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Duan X, Liu H, Hu X, Yu Q, Kuang G, Liu L, Zhang S, Wang X, Li J, Yu D, Huang J, Wang T, Lin Z, Xiong N. Insomnia in Parkinson's Disease: Causes, Consequences, and Therapeutic Approaches. Mol Neurobiol 2025; 62:2292-2313. [PMID: 39103716 PMCID: PMC11772535 DOI: 10.1007/s12035-024-04400-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Accepted: 07/24/2024] [Indexed: 08/07/2024]
Abstract
Sleep disorders represent prevalent non-motor symptoms in Parkinson's disease (PD), affecting over 90% of the PD population. Insomnia, characterized by difficulties in initiating and maintaining sleep, emerges as the most frequently reported sleep disorder in PD, with prevalence rates reported from 27 to 80% across studies. Insomnia not only significantly impacts the quality of life of PD patients but is also associated with cognitive impairment, motor disabilities, and emotional deterioration. This comprehensive review aims to delve into the mechanisms underlying insomnia in PD, including neurodegenerative changes, basal ganglia beta oscillations, and circadian rhythms, to gain insights into the neural pathways involved. Additionally, the review explores the risk factors and comorbidities associated with insomnia in PD, providing valuable insights into its management. Special attention is given to the challenges faced by healthcare providers in delivering care to PD patients and the impact of caregiving roles on patients' quality of life. Overall, this review provides a comprehensive understanding of insomnia in PD and highlights the importance of addressing this common sleep disorder in PD patients.
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Affiliation(s)
- Xiaoyu Duan
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Duke Kunshan University, No. 8 Duke Avenue, Kunshan, 215316, Jiangsu, China
| | - Hanshu Liu
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xinyu Hu
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qinwei Yu
- Department of Neurology, Wuhan Red Cross Hospital, 392 Hongkong Road, Wuhan, Hubei, China
| | - Guiying Kuang
- Department of Neurology, Wuhan Red Cross Hospital, 392 Hongkong Road, Wuhan, Hubei, China
| | - Long Liu
- Department of Neurology, Wuhan Red Cross Hospital, 392 Hongkong Road, Wuhan, Hubei, China
| | - Shurui Zhang
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xinyi Wang
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jingwen Li
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Danfang Yu
- Department of Neurology, Wuhan Red Cross Hospital, 392 Hongkong Road, Wuhan, Hubei, China
| | - Jinsha Huang
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tao Wang
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhicheng Lin
- Laboratory of Psychiatric Neurogenomics, McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA
| | - Nian Xiong
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Galvez V, Romero-Rebollar C, Estudillo-Guerra MA, Fernandez-Ruiz J. Resting-state networks and their relationship with MoCA performance in PD patients. Brain Imaging Behav 2024; 18:612-621. [PMID: 38332386 DOI: 10.1007/s11682-024-00860-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/30/2024] [Indexed: 02/10/2024]
Abstract
Although mild cognitive impairment is a common non-motor symptom experienced by individuals with Parkinson's Disease, the changes in intrinsic resting-state networks associated with its onset in Parkinson's remain underexamined. To address the issue, our study sought to examine resting-state network alterations and their association with total performance in the Montreal Cognitive Assessment and its cognitive domains in Parkinson's by means of functional magnetic resonance imaging of 29 Parkinson's patients with normal cognition, 25 Parkinson's patients with mild cognitive impairment, and 13 healthy controls. To contrast the Parkinson's groups with each other and the controls, the images were used to estimate the Z-score coefficient between the regions of interest from the default mode network, the salience network and the central executive network. Our first finding was that default mode and salience network connectivity decreased significantly in Parkinson's patients regardless of their cognitive status. Additionally, default mode network nodes had a negative and salience network nodes a positive correlation with the global assessment in Parkinson's with normal cognition; this inverse relationship of both networks to total score was not found in the group with cognitive impairment. Finally, a positive correlation was found between executive scores and anterior and posterior cortical network connectivity and, in the group with cognitive impairment, between language scores and salience network connectivity. Our results suggest that specific resting-state networks of Parkinson's patients with cognitive impairment differ from those of Parkinson's patients with normal cognition, supporting the evidence that cognitive impairment in Parkinson's Disease displays a differentiated neurodegenerative pattern.
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Affiliation(s)
- Victor Galvez
- Laboratorio de Neurociencias Cognitivas y Desarrollo, Escuela de Psicología, Universidad Panamericana, Ciudad de México, México.
| | - César Romero-Rebollar
- Escuela de Pedagogía, Universidad Panamericana, Ciudad de México, México
- Universidad Tecnológica de México-UNITEC MÉXICO-Campus en línea, Ciudad de México, México
| | - M Anayali Estudillo-Guerra
- Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Juan Fernandez-Ruiz
- Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México
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Tuena C, Maestri S, Serino S, Pedroli E, Stramba-Badiale M, Riva G. Prognostic relevance of gait-related cognitive functions for dementia conversion in amnestic mild cognitive impairment. BMC Geriatr 2023; 23:462. [PMID: 37525134 PMCID: PMC10388514 DOI: 10.1186/s12877-023-04175-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 07/15/2023] [Indexed: 08/02/2023] Open
Abstract
BACKGROUND Increasing research suggests that gait abnormalities can be a risk factor for Alzheimer's Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up. METHODS Four hundred two individuals with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests. RESULTS While controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abnormal gait (HR = 1.7), MMSE (HR = 1.09), and DSST (HR = 1.03) covariates showed a higher impact on AD dementia conversion. CONCLUSIONS The importance of the link between gait and related cognitive functions in terms of diagnosis, prognosis, and rehabilitation in aMCI is critical. We showed that in aMCI gait abnormalities lead to executive functions/attention deterioration and conversion to AD dementia.
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Affiliation(s)
- Cosimo Tuena
- Applied Technology for Neuro-Psychology Lab, IRCCS Istituto Auxologico Italiano, Milan, Italy.
| | - Sara Maestri
- Applied Technology for Neuro-Psychology Lab, IRCCS Istituto Auxologico Italiano, Milan, Italy
| | - Silvia Serino
- Department of Psychology, Università degli Studi Milano-Bicocca, Milan, Italy
| | - Elisa Pedroli
- Applied Technology for Neuro-Psychology Lab, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Faculty of Psychology, Università eCampus, Novedrate, Italy
| | - Marco Stramba-Badiale
- Department of Geriatrics and Cardiovascular Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy
| | - Giuseppe Riva
- Applied Technology for Neuro-Psychology Lab, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Humane Technology Lab, Università Cattolica del Sacro Cuore, Milan, Italy
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Manceau C, Constant E, Brugallé E, Wawrziczny E, Sokolowski C, Flinois B, Baille G, Defebvre L, Dujardin K, Antoine P. Couples facing the “honeymoon period” of Parkinson's disease: A qualitative study of dyadic functioning. Br J Health Psychol 2022; 28:366-382. [PMID: 36301684 DOI: 10.1111/bjhp.12629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 10/09/2022] [Accepted: 10/12/2022] [Indexed: 11/28/2022]
Abstract
INTRODUCTION The public health issue of the Parkinson's disease (PD) has led to a great deal of research that has highlighted the individual challenges faced by the person with the Parkinson's disease (PwPD) and the caregiving spouse. Few studies, however, have sought to understand the functioning of couples facing PD, by differentiating each stage, each of which has its own issues. In particular, the "honeymoon period", characterized by a symptomatic respite allowed by the effectiveness of treatments for motor symptoms, has been poorly documented, especially at the dyadic level. DESIGN AND METHOD This qualitative study, based on Interpretative Phenomenological Analysis, aimed to understand the experience of couples and their functioning at this stage. Fifteen couples participated in separate semi-structured interviews for each partner. The analyses highlighted four dyadic dynamics, which call into question the relevance of the term "honeymoon" to describe the experience of couples. RESULTS While some couples appear to adjust by means of flexible functioning and a positive reinterpretation of this experience, other dyads oscillate between rigid hyperprotection in the face of perceived distress or a vicious circle of control/avoidance and, in some cases, gradually slipping towards the erosion of the relationship. DISCUSSION These results show that the relational difficulties suffered by partners at this stage should be taken into account as soon as possible after the diagnosis. Strengthening the communication and the togetherness between partners, as well as working on dyadic emotional regulation, are particularly relevant options for these couples.
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Affiliation(s)
- Charlotte Manceau
- Univ. Lille, CNRS, UMR 9193 – SCALab – Sciences Cognitives et Sciences Affectives Villeneuve d'Ascq France
| | - Emilie Constant
- Univ. Lille, CNRS, UMR 9193 – SCALab – Sciences Cognitives et Sciences Affectives Villeneuve d'Ascq France
| | - Elodie Brugallé
- Neurology and Movement Disorders Department CHU‐Lille Lille France
| | - Emilie Wawrziczny
- Univ. Lille, CNRS, UMR 9193 – SCALab – Sciences Cognitives et Sciences Affectives Villeneuve d'Ascq France
| | - Céline Sokolowski
- Univ. Lille, CNRS, UMR 9193 – SCALab – Sciences Cognitives et Sciences Affectives Villeneuve d'Ascq France
| | | | - Guillaume Baille
- Neurology and Movement Disorders Department Univ. Lille, Inserm, Lille Neurosciences and Cognition, CHU‐Lille Lille France
| | - Luc Defebvre
- Neurology and Movement Disorders Department Univ. Lille, Inserm, Lille Neurosciences and Cognition, CHU‐Lille Lille France
| | - Kathy Dujardin
- Neurology and Movement Disorders Department Univ. Lille, Inserm, Lille Neurosciences and Cognition, CHU‐Lille Lille France
| | - Pascal Antoine
- Univ. Lille, CNRS, UMR 9193 – SCALab – Sciences Cognitives et Sciences Affectives Villeneuve d'Ascq France
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Nishikawa N, Murata M, Hatano T, Mukai Y, Saitoh Y, Sakamoto T, Hanakawa T, Kamei Y, Tachimori H, Hatano K, Matsuda H, Taruno Y, Sawamoto N, Kajiyama Y, Ikenaka K, Kawabata K, Nakamura T, Iwaki H, Kadotani H, Sumi Y, Inoue Y, Hayashi T, Ikeuchi T, Shimo Y, Mochizuki H, Watanabe H, Hattori N, Takahashi Y, Takahashi R. Idiopathic rapid eye movement sleep behavior disorder in Japan: An observational study. Parkinsonism Relat Disord 2022; 103:129-135. [PMID: 36113390 DOI: 10.1016/j.parkreldis.2022.08.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 07/12/2022] [Accepted: 08/10/2022] [Indexed: 11/27/2022]
Abstract
INTRODUCTION Idiopathic rapid eye movement sleep behavior disorder (iRBD) is one of the most specific prodromal symptoms of synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy. The Japan Parkinson's Progression Markers Initiative (J-PPMI) was a prospective cohort study conducted in Japanese patients with iRBD to investigate biomarkers for prodromal synucleinopathies. We carried out an initial assessment of the J-PPMI study to reveal the factors correlated with dopamine transporter single-photon emission computed tomography (DaT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy. METHODS This cross-sectional study was conducted in 108 patients with iRBD, selected from the J-PPMI study. We divided the patients into four groups based on the MIBG and DaT results. We also recorded the patients' demographics and clinical data. Following PD probability calculation, we examined the biomarkers associated with DaT and MIBG. RESULTS Ninety-five of the enrolled patients (88%) met the diagnostic criteria for prodromal PD based on the probability score. Only five patients had normal MIBG and DaT. We identified 29 cases with decreased DaT and MIBG, all of whom met the above diagnostic criteria. Both DaT and MIBG were significantly correlated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J) score. CONCLUSION Both DaT and MIBG are important biomarkers for confirming synucleinopathies and/or staging disease progression. Although 95% of iRBD patients were consistent with the body-first subtype concept, alpha-synuclein pathologies of iRBD might have widespread systemic involvement rather than being confined to the lower brainstem, particularly in patients with reduced MoCA-J scores.
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Affiliation(s)
- Noriko Nishikawa
- Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
| | - Miho Murata
- Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Taku Hatano
- Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yohei Mukai
- Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Yuji Saitoh
- Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Takashi Sakamoto
- Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Takashi Hanakawa
- Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Yuichi Kamei
- Department of Sleep-Wake Disorder, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Psychiatry, Kamisuwa Hospital, Nagano, Japan
| | - Hisateru Tachimori
- Department of Clinical Data Science, Clinical Research & Education Promotion Division, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Kenji Hatano
- Department of Clinical Data Science, Clinical Research & Education Promotion Division, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Hiroshi Matsuda
- Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Yosuke Taruno
- Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Nobukatsu Sawamoto
- Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yuta Kajiyama
- Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kensuke Ikenaka
- Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kazuya Kawabata
- Brain and Mind Research Centre, Nagoya University, Nagoya, Japan; Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomohiko Nakamura
- Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan
| | | | - Hiroshi Kadotani
- Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan
| | - Yukiyoshi Sumi
- Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan
| | - Yuichi Inoue
- Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan; Department of Somnology, Tokyo Medical University, Tokyo, Japan
| | - Toshihiro Hayashi
- Department of Neurology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan; Department of Physiology, Teikyo University School of Medicine, Tokyo, Japan
| | - Takeshi Ikeuchi
- Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
| | - Yasushi Shimo
- Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Neurology, Juntendo University Nerima Hospital, Tokyo, Japan
| | - Hideki Mochizuki
- Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hirohisa Watanabe
- Brain and Mind Research Centre, Nagoya University, Nagoya, Japan; Department of Neurology, School of Medicine, Fujita Health University, Aichi, Japan
| | - Nobutaka Hattori
- Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yuji Takahashi
- Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Ryosuke Takahashi
- Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Whiteley N, Pluim CF, Split M, Cabrera Tuazon A, Moore RC, Irene Litvan, Lessig S, Filoteo JV, Schiehser DM. Prospective predictors of care partner burden and depression in Parkinson's disease. Int J Geriatr Psychiatry 2022; 37. [PMID: 35996353 DOI: 10.1002/gps.5795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 07/22/2022] [Indexed: 11/11/2022]
Abstract
OBJECTIVES Care partners who provide informal care to individuals with Parkinson's disease (PD) report higher levels of burden and depression; however, longitudinal research on these symptoms is scarce. The current study assessed changes in care partner burden and depression, and patient and care partner predictors of these symptoms over time. Such knowledge may provide important information for assessment and treatment of depression and burden in care partners of individuals with PD. RESEARCH DESIGN AND METHODS Participants were 88 PD patients without dementia and their self-identified care partner (n = 88). Care partners completed the Geriatric Depression Scale and Zarit Burden Interview. PD participants completed mood questionnaires and a motor exam at baseline and 2 year follow-up. Relationships among care partner burden and depression over time with patient and care partner predictors (i.e., demographic, mood, and disease characteristics) were assessed using correlations and regression analyses. RESULTS Care partner burden and depression significantly increased over an approximate 2 year period. Greater baseline disease severity predicted worsening of care partner burden (p = 0.028), while baseline patient depression predicted worsening of care partner depression (p = 0.002). CONCLUSIONS Results highlight differential impacts of specific PD symptoms on worsening care partner burden compared to depression; increased PD disease severity predicts increased burden, while patient mood predicts worsening of depression over time. Targeting PD disease severity and mood symptoms may prevent the progression of care partner burden and depression.
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Affiliation(s)
- Nicole Whiteley
- Research Service, VA San Diego Healthcare System, San Diego, California, USA
| | - Celina F Pluim
- Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts, USA
| | - Molly Split
- Department of Psychological and Brain Sciences, Drexel University, Philadelphia, Pennsylvania, USA
| | | | - Raeanne C Moore
- Department of Psychiatry, University of California San Diego, La Jolla, California, USA
| | - Irene Litvan
- Department of Neurosciences, Parkinson and Other Movement Disorders Center, University of California San Diego, La Jolla, California, USA
| | - Stephanie Lessig
- Research Service, VA San Diego Healthcare System, San Diego, California, USA.,Department of Neurosciences, Parkinson and Other Movement Disorders Center, University of California San Diego, La Jolla, California, USA
| | - J Vincent Filoteo
- Research Service, VA San Diego Healthcare System, San Diego, California, USA.,Department of Psychiatry, University of California San Diego, La Jolla, California, USA.,Department of Neurosciences, Parkinson and Other Movement Disorders Center, University of California San Diego, La Jolla, California, USA
| | - Dawn M Schiehser
- Research Service, VA San Diego Healthcare System, San Diego, California, USA.,Department of Psychiatry, University of California San Diego, La Jolla, California, USA
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Saunders-Pullman R, Ortega RA, Wang C, Raymond D, Elango S, Leaver K, Urval N, Katsnelson V, Gerber R, Swan M, Shanker V, Alcalay RN, Mirelman A, Brumm MC, Mejia-Santana H, Coffey CS, Marek K, Ozelius LJ, Giladi N, Marder KS, Bressman SB. Association of Olfactory Performance With Motor Decline and Age at Onset in People With Parkinson Disease and the LRRK2 G2019S Variant. Neurology 2022; 99:e814-e823. [PMID: 35995594 PMCID: PMC9484727 DOI: 10.1212/wnl.0000000000200737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 03/30/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND AND OBJECTIVES There is clinical and phenotypic heterogeneity in LRRK2 G2019S Parkinson disease (PD), including loss of smell. Olfactory scores have defined subgroups of LRRK2 PD at baseline. We now extend this work longitudinally to better determine features associated with olfactory classes and to gain further insight into this heterogeneity. METHODS Evaluation of 162 patients with LRRK2 PD and 198 patients with idiopathic PD (IPD) from the LRRK2 Ashkenazi Jewish Consortium was performed, with follow-up available for 92 patients with LRRK2 PD and 74 patients with IPD. Olfaction (University of Pennsylvania Smell Identification Test [UPSIT]), motor function (Unified Parkinson Disease Rating Scale), and cognition (Montreal Cognitive Assessment), as well as sleep, nonmotor, and mood, were measured. Gaussian mixture models were applied on the UPSIT percentile score to determine subgroups based on olfactory performance. Linear mixed effects models, using PD duration as the time scale, assessed the relationship between UPSIT subgroup membership and motor/cognitive change. RESULTS Baseline olfaction was better in LRRK2 PD compared with IPD (mean UPSIT ± SD: 24.2 ± 8.8 vs 18.9 ± 7.6), with higher mean percentile scores (difference: 15.3 ± 11.6) (p < 0.001) and less frequent hyposmia (55.6% vs 85.4%; p < 0.001). Analysis suggested 3 classes among LRRK2 PD. Age at onset in LRRK2 PD was earlier in the worst olfaction group (group 1), compared with groups 2 and 3 (54.5 ± 11.1 vs 61.7 ± 9.3) (p = 0.012), and separately in the hyposmic group overall (55.0 ± 11.3 vs 61.7 ± 9.1) (p < 0.001). Longitudinal motor deterioration in LRRK2 PD was also significantly faster in the worst UPSIT group than the best UPSIT group (group 3 vs group 1: B = 0.31, SE = 0.35 vs B = 0.96, SE = 0.28) (rate difference = -0.65, SE = 0.29) (p = 0.03). However, olfactory group membership was not significantly associated with cognitive decline. DISCUSSION In this large LRRK2 cohort with longitudinal analysis, we extend prior work demonstrating subgroups defined by olfaction in LRRK2 G2019S PD and show that the worst olfaction group has earlier age at PD onset and more rapid motor decline. This supports a subgroup of LRRK2 PD that might show more rapid change in a clinical trial of LRRK2-related agents and highlights the need to integrate careful phenotyping into allocation schema in clinical trials of LRRK2-related agents. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that worse olfactory scores were associated with an earlier age at symptomatic onset and a faster rate of motor deterioration in patients with LRRK2 PD.
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Affiliation(s)
- Rachel Saunders-Pullman
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston.
| | - Roberto Angel Ortega
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Cuiling Wang
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Deborah Raymond
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Sonya Elango
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Katherine Leaver
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Nikita Urval
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Viktoriya Katsnelson
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Rachel Gerber
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Matthew Swan
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Vicki Shanker
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Roy N Alcalay
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Anat Mirelman
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Michael C Brumm
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Helen Mejia-Santana
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Christopher S Coffey
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Kenneth Marek
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Laurie J Ozelius
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Nir Giladi
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Karen S Marder
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
| | - Susan B Bressman
- From the Department of Neurology (R.S.-P., R.A.O., D.R., S.E., K.L., N.U., V.K., R.G., M.S., V.S., S.B.B.), Mount Sinai Beth Israel; Albert Einstein College of Medicine (C.W.), Bronx, NY; Department of Neurology (R.N.A., H.M.-S., K.S.M.), Columbia University Irving Medical Center, New York; Neurological Institute (A.M., N.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine and Sagol School of Neurosciences, Tel Aviv University, Israel; University of Iowa Carver College of Medicine (M.C.B., C.S.C.), and Biostatistics (M.C.B., C.S.C.), University of Iowa, Iowa City; Department of Neurology (K.M.), Institute for Neurodegenerative Disorders, New Haven, CT; and Department of Genetics (L.J.O.), Massachusetts General Hospital, Boston
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Lee Y, Chang YY, Chen YF, Lin TK, Hung CF, Chiou YJ, Wang LJ. Prevalence and Risk Factors of Depression between Patients with Parkinson’s Disease and Their Caregivers: A One-Year Prospective Study. Healthcare (Basel) 2022; 10:healthcare10071305. [PMID: 35885832 PMCID: PMC9318994 DOI: 10.3390/healthcare10071305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/07/2022] [Accepted: 07/12/2022] [Indexed: 11/20/2022] Open
Abstract
Depression is a common comorbidity in patients with Parkinson’s disease (PD) and in their caregivers. This study aimed to compare the prevalence and risk factors of depression between patients with PD and their caregivers. In total, 113 patients with PD and 101 caregivers were enrolled. Patients with PD were assessed using the Mini International Neuropsychiatric Interview, Unified Parkinson’s Disease Rating Scale (UPDRS), Activities of Daily Living (ADL), Hospital Anxiety and Depression Scale, Beck Hopelessness Scale, Brief Fatigue Inventory, Connor–Davidson Resilience Scale, and Big Five Inventory-10. Caregivers of patients with PD were also assessed using the above-mentioned instruments, with the exception of the UPDRS and ADL. During a 12-month follow-up period, depressive disorders were the most common psychiatric diagnosis of PD patients (27.4%) and their caregivers (17.8%). Depressive disorders were more prevalent in PD patients than in caregivers of PD patients throughout the entire follow-up phase. The severity of fatigue and severity of suicide risk were significantly associated with depression among patients with PD. The severity of pain and severity of anxiety were predictors of depression in caregivers of PD patients. The findings in this study provide references for early detection and treatment of depressive disorders in PD patients and their caregivers.
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Affiliation(s)
- Yu Lee
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (Y.L.); (C.-F.H.); (Y.-J.C.)
| | - Yung-Yee Chang
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (Y.-Y.C.); (Y.-F.C.); (T.-K.L.)
| | - Ying-Fa Chen
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (Y.-Y.C.); (Y.-F.C.); (T.-K.L.)
| | - Tsu-Kung Lin
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (Y.-Y.C.); (Y.-F.C.); (T.-K.L.)
| | - Chi-Fa Hung
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (Y.L.); (C.-F.H.); (Y.-J.C.)
| | - Yu-Jie Chiou
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (Y.L.); (C.-F.H.); (Y.-J.C.)
| | - Liang-Jen Wang
- Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
- Correspondence: ; Tel.: +886-7-7317123 (ext. 8753); Fax: +886-7-7326817
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Santos-García D, de Deus Fonticoba T, Cores Bartolomé C, Íñiguez Alvarado MC, Feal Panceiras MJ, Suárez Castro E, Canfield H, Martínez Miró C, Jesús S, Aguilar M, Pastor P, Planellas L, Cosgaya M, García Caldentey J, Caballol N, Legarda I, Hernández Vara J, Cabo I, López Manzanares L, González Aramburu I, Ávila Rivera MA, Gómez Mayordomo V, Nogueira V, Puente V, Dotor García-Soto J, Borrué C, Solano Vila B, Álvarez Sauco M, Vela L, Escalante S, Cubo E, Carrillo Padilla F, Martínez Castrillo JC, Sánchez Alonso P, Alonso Losada MG, Ariztegui NL, Gastón I, Kulisevsky J, Blázquez Estrada M, Seijo M, Martínez JR, Valero C, Kurtis M, de Fábregues O, González Ardura J, Alonso Redondo R, Ordás C, López DíazL LM, McAfee D, Martinez-Martin P, Mir P. Predictors of the change in burden, strain, mood, and quality of life among caregivers of Parkinson's disease patients. Int J Geriatr Psychiatry 2022; 37. [PMID: 35633051 DOI: 10.1002/gps.5761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 05/12/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND AND OBJECTIVE Caregiver burden in Parkinson's disease (PD) has been studied in many cross-sectional studies but poorly in longitudinal ones. The aim of the present study was to analyze the change in burden, strain, mood, and quality of life (QoL) after a 2-year follow-up in a cohort of caregivers of patients with PD and also to identify predictors of these changes. PATIENTS AND METHODS PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centers of Spain from the COPPADIS cohort were included in the study. They were evaluated again at 2-year follow-up. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), and EUROHIS-QOL 8-item index (EUROHIS-QOL8) at baseline (V0) and at 2-year follow-up (V2). General linear model repeated measure and lineal regression models were applied. RESULTS Significant changes, indicating an impairment, were detected on the total score of the ZCBI (p < 0.0001), CSI (p < 0.0001), BDI-II (p = 0.024), and EUROHIS-QOL8 (p = 0.002) in 192 PD caregivers (58.82 ± 11.71 years old; 69.3% were females). Mood impairment (BDI-II; β = 0.652; p < 0.0001) in patients from V0 to V2 was the strongest factor associated with caregiver's mood impairment after the 2-year follow-up. Caregiver's mood impairment was the strongest factor associated with an increase from V0 to V2 on the total score of the ZCBI (β = 0.416; p < 0.0001), CSI (β = 0.277; p = 0.001), and EUROHIS-QOL (β = 0.397; p = 0.002). CONCLUSION Burden, strain, mood, and QoL were impaired in caregivers of PD patients after a 2-year follow-up. Mood changes in both the patient and the caregiver are key aspects related to caregiver burden increase.
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Affiliation(s)
| | | | | | | | | | | | - Héctor Canfield
- CHUF, Complejo Hospitalario Universitario de Ferrol, A Coruña, Spain
| | | | - Silvia Jesús
- Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain
- CIBERNED (Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas), Madrid, Spain
| | - Miquel Aguilar
- Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain
| | - Pau Pastor
- Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain
| | | | | | | | - Nuria Caballol
- Consorci Sanitari Integral, Hospital Moisés Broggi, Sant Joan Despí, Barcelona, Spain
| | - Ines Legarda
- Hospital Universitario Son Espases, Palma de Mallorca, Spain
| | - Jorge Hernández Vara
- CIBERNED (Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas), Madrid, Spain
- Hospital Universitario Vall d'Hebron, Barcelona, Spain
| | - Iria Cabo
- Complejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, Spain
| | | | - Isabel González Aramburu
- CIBERNED (Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas), Madrid, Spain
- Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Maria A Ávila Rivera
- Consorci Sanitari Integral, Hospital General de L'Hospitalet, L'Hospitalet de Llobregat, Barcelona, Spain
| | | | | | | | | | | | - Berta Solano Vila
- Institut d'Assistència Sanitària (IAS) - Institut Català de la Salut, Girona, Spain
| | | | - Lydia Vela
- Fundación Hospital de Alcorcón, Madrid, Spain
| | - Sonia Escalante
- Hospital de Tortosa Verge de la Cinta (HTVC), Tortosa, Tarragona, Spain
| | - Esther Cubo
- Complejo Asistencial Universitario de Burgos, Burgos, Spain
| | | | | | | | - Maria G Alonso Losada
- Hospital Álvaro Cunqueiro, Complejo Hospitalario Universitario de Vigo (CHUVI), Vigo, Spain
| | | | | | - Jaime Kulisevsky
- CIBERNED (Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas), Madrid, Spain
- Hospital de Sant Pau, Barcelona, Spain
| | | | - Manuel Seijo
- Complejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, Spain
| | | | | | | | | | | | | | | | | | - Darrian McAfee
- University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Pablo Martinez-Martin
- CIBERNED (Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas), Madrid, Spain
| | - Pablo Mir
- Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain
- CIBERNED (Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas), Madrid, Spain
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10
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Kalampokini S, Hommel ALAJ, Lorenzl S, Ferreira JJ, Meissner WG, Odin P, Bloem BR, Dodel R, Schrag AE. Caregiver Burden in Late-Stage Parkinsonism and Its Associations. J Geriatr Psychiatry Neurol 2022; 35:110-120. [PMID: 33094677 DOI: 10.1177/0891988720968263] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Patients in the late stages of parkinsonism are highly dependent on others in their self-care and activities of daily living. However, few studies have assessed the physical, psychological and social consequences of caring for a person with late-stage parkinsonism. PATIENTS AND METHODS Five hundred and six patients and their caregivers from the Care of Late Stage Parkinsonism (CLaSP) study were included. Patients' motor and non-motor symptoms were assessed using the UPDRS and Non-motor symptom scale (NMSS), Neuropsychiatric inventory (NPI-12), and caregivers' health status using the EQ-5D-3 L. Caregiver burden was assessed by the Zarit Burden Interview (ZBI). RESULTS The majority of caregivers were the spouse or life partner (71.2%), and were living with the patient at home (67%). Approximately half of caregivers reported anxiety/depression and pain/discomfort (45% and 59% respectively). The factors most strongly associated with caregiver burden were patients' neuropsychiatric features on the total NPI score (r = 0.38, p < 0.0001), total NMSS score (r = 0.28, p < 0.0001), caring for male patients and patients living at home. Being the spouse, the hours per day assisting and supervising the patient as well as caregivers' EQ-5D mood and pain scores were also associated with higher ZBI scores (all p < 0.001). CONCLUSION The care of patients with late stage parkinsonism is associated with significant caregiver burden, particularly when patients manifest many neuropsychiatric and non-motor features and when caring for a male patient at home.
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Affiliation(s)
- Stefania Kalampokini
- UCL Queen Square Institute of Neurology, 61554University College London, United Kingdom
| | - Adrianus L A J Hommel
- Department of Neurology, Donders Institute for Brain, Cognition and Behavior, 6029Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
| | - Stefan Lorenzl
- Institute of Nursing Science and Practice, 162199Paracelsus Medical University, Salzburg, Austria.,Interdisziplinäres Zentrum für Palliativmedizin und Klinik für Neurologie Universität München-Klinikum Großhadern, Munich, Germany.,Department of Neurology, Agatharied Hospital, Hausham, Germany
| | - Joaquim J Ferreira
- Instituto de Medicina Molecular 37809Universidade di Lisboa, Lisboa, Portugal
| | - Wassilios G Meissner
- Service de Neurologie, CHU de Bordeaux, Bordeaux, France.,Institut des Maladies Neurodégénératives, 27086University de Bordeaux, Bordeaux, France.,Department of Medicine, University of Otago, Christchurch, New Zealand.,New Zealand Brain Research Institute, Christchurch, New Zealand
| | - Per Odin
- Department of Neurology, 59568Lund University Hospital, Sweden
| | - Bastiaan R Bloem
- Department of Neurology, Donders Institute for Brain, Cognition and Behavior, 6029Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
| | - Richard Dodel
- Department of Geriatric Medicine, University Duisburg-Essen, Germany.,Department of Neurology, Philipps-University Marburg, Germany
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11
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Patient and caregiver outcomes with levodopa-carbidopa intestinal gel in advanced Parkinson’s disease. NPJ Parkinsons Dis 2021; 7:108. [PMID: 34848716 PMCID: PMC8633325 DOI: 10.1038/s41531-021-00246-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 06/07/2021] [Indexed: 01/02/2023] Open
Abstract
Levodopa-carbidopa intestinal gel (LCIG) has shown to be efficacious in motor and non-motor symptoms (NMS). Nevertheless, studies with patient Quality of Life (QoL) as a primary endpoint are scarce. To assess the effect of LCIG on Advanced Parkinson’s Disease (APD) patients QoL. Secondarily, the impact on motor symptoms and NMS, emotional well-being, treatment satisfaction, and caregiver QoL, stress, disease burden, anxiety, depression, and work impairment were also investigated. In this prospective, 6-month multicenter postmarketing observational study, LCIG was administered to 59 patients with APD. Endpoints were assessed using validated scales and questionnaires. LCIG significantly improved patient QoL (PDQ-39 mean change ± standard deviation from baseline, −12.8 ± 14.6; P < 0.0001), motor symptoms (UPDRS-III in “On,” −6.5 ± 11.8; P = 0.0002), NMS (NMSS, −35.7 ± 31.1; P < 0.0001), mood (Norris/Bond-Lader VAS, −6.6 ± 21.1; P = 0.0297), fatigue (PFS-16, −0.6 ± 1.0; P = 0.0003), depression (BDI-II, −5.1 ± 9.4; P = 0.0002), anxiety (BAI, −6.2 ± 9.6; P < 0.0001), and patient treatment satisfaction (SATMED-Q, 16.1 ± 16.8; P < 0.0001). There were significant correlations between the change from baseline to 6 months between PDQ-39 and UPDRS-IV, NMSS, BAI, BDI-II, AS, and PFS-16 scores, and Norris/Bond-Lader alertness/sedation factor. Caregiver anxiety also improved (Goldberg anxiety scale, −1.1 ± 1.0; P = 0.0234), but the clinical relevance of this finding is questionable. The serious adverse events reported were similar to those previously described for LCIG. In patients with APD, LCIG improves QoL, motor symptoms and NMS, emotional well-being, and satisfaction with the treatment. Improvement in patient QoL is associated with improvements in motor complications, NMS, anxiety, depression, apathy and fatigue. Improvements in patients’ QoL does not correspond with improvements in caregivers’ QoL or burden.
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12
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Lee Y, Chiou YJ, Hung CF, Chang YY, Chen YF, Lin TK, Wang LJ. Prevalence and Associated Factors of Depressive Disorder in Caregivers of Individuals With Parkinson Disease. J Geriatr Psychiatry Neurol 2021; 34:418-425. [PMID: 32588710 DOI: 10.1177/0891988720933359] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Parkinson disease (PD) is a debilitating neurodegenerative disease. Caring for an individual with PD can have a variety of negative physical and psychological effects on caregivers which may challenge their ability to continue in their caretaking role. The aim of this study was to assess the prevalence and associated factors of depressive disorders in caregivers of individuals with PD using standardized instruments. METHODS This study used a cross-sectional design with consecutive sampling. Study participants were recruited from the neurological ward or neurological outpatient clinic of a medical center from August 2018 to July 2019. Caregivers of persons with PD were enrolled and assessed using the Mini International Neuropsychiatric Interview, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Hopelessness Scale, Brief Fatigue Inventory, Connor-Davidson Resilience Scale, and Big Five Inventory-10. RESULTS Of the 162 caregivers that completed the study, 67.3% (n = 109) were females. The most common psychiatric diagnosis was depressive disorder (11.1%), followed by insomnia disorder (7.4%) and anxiety disorder not otherwise specified (4.3%); 28% of the caregivers had a psychiatric diagnosis. Using logistic regression analysis, it was found that duration of caregiving (odds ratio [OR] = 1.28; 95% CI, 1.05-1.58), severity of anxiety (OR = 1.86; 95% CI, 1.36-2.53), and severity of fatigue (OR = 1.08; 95% CI, 1.01-1.16) were 3 significant associated factors for the development of depression. CONCLUSION Depression was the most prevalent psychiatric diagnosis in caregivers of people with PD. Early diagnosis of these caregivers is crucial to the offering of suitable support and treatment and might improve caregivers' quality of life.
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Affiliation(s)
- Yu Lee
- Department of Psychiatry, 63328Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Jie Chiou
- Department of Psychiatry, 63328Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chi-Fa Hung
- Department of Psychiatry, 63328Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yung-Yee Chang
- Department of Neurology, 63328Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ying-Fa Chen
- Department of Neurology, 63328Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsu-Kung Lin
- Department of Neurology, 63328Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Liang-Jen Wang
- Department of Child and Adolescent Psychiatry, 63328Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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13
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Combs HL, Wyman-Chick KA, Erickson LO, York MK. Development of standardized regression-based formulas to assess meaningful cognitive change in early Parkinson's disease. Arch Clin Neuropsychol 2021; 36:734-745. [PMID: 33103727 DOI: 10.1093/arclin/acaa104] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 07/29/2020] [Accepted: 10/01/2020] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVE Longitudinal assessment of cognitive and emotional functioning in patients with Parkinson's disease (PD) is helpful in tracking progression of the disease, developing treatment plans, evaluating outcomes, and educating patients and families. Determining whether change over time is meaningful in neurodegenerative conditions, such as PD, can be difficult as repeat assessment of neuropsychological functioning is impacted by factors outside of cognitive change. Regression-based prediction formulas are one method by which clinicians and researchers can determine whether an observed change is meaningful. The purpose of the current study was to develop and validate regression-based prediction models of cognitive and emotional test scores for participants with early-stage idiopathic PD and healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI). METHODS Participants with de novo PD and HC were identified retrospectively from the PPMI archival database. Data from baseline testing and 12-month follow-up were utilized in this study. In total, 688 total participants were included in the present study (NPD = 508; NHC = 185). Subjects from both groups were randomly divided into development (70%) and validation (30%) subsets. RESULTS Early-stage idiopathic PD patients and healthy controls were similar at baseline. Regression-based models were developed for all cognitive and self-report mood measures within both populations. Within the validation subset, the predicted and observed cognitive test scores did not significantly differ, except for semantic fluency. CONCLUSIONS The prediction models can serve as useful tools for researchers and clinicians to study clinically meaningful cognitive and mood change over time in PD.
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14
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Cuneus/precuneus as a central hub for brain functional connectivity of mild cognitive impairment in idiopathic REM sleep behavior patients. Eur J Nucl Med Mol Imaging 2021; 48:2834-2845. [PMID: 33511424 DOI: 10.1007/s00259-021-05205-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 01/17/2021] [Indexed: 10/22/2022]
Abstract
PURPOSE To investigate brain functional correlates of mild cognitive impairment (MCI) in idiopathic REM sleep behavior disorder (iRBD). METHODS Thirty-nine consecutive iRBD patients, 17 with (RBD-MCI, 73.6±6.5 years), and 22 without (RBD-NC, 69.6±6.1 years) MCI underwent neuropsychological assessment, 18F-FDG-PET, and 123I-FP-CIT-SPECT as a marker of nigro-striatal dopaminergic function. Forty-two healthy subjects (69.6±8.5 years) were used as control for 18F-FDG-PET analysis. Brain metabolism was compared between the three groups by univariate analysis of variance. Post hoc comparison between RBD-MCI and RBD-NC was performed to investigate the presence of an MCI-related volume of interest (MCI-VOI). Brain functional connectivity was explored by interregional correlation analysis (IRCA), using the whole-brain normalized MCI-VOI uptake as the independent variable. Moreover, the MCI-VOI uptake was correlated with 123I-FP-CIT-SPECT specific-to-non displaceable binding ratios (SBR) and neuropsychological variables. Finally, the MCI-VOI white matter structural connectivity was analyzed by using a MRI-derived human atlas. RESULTS The MCI-VOI was characterized by a relative hypometabolism involving precuneus and cuneus (height threshold p<0.0001). IRCA (height threshold p<0.0001) revealed a brain functional network involving regions in frontal, temporal, parietal, and occipital lobes, thalamus, caudate, and red nuclei in iRBD patients. In controls, the network was smaller and involved temporal, occipital, cingulate cortex, and cerebellum. Moreover, MCI-VOI metabolism was correlated with verbal memory (p=0.01), executive functions (p=0.0001), and nigro-putaminal SBR (p=0.005). Finally, MCI-VOI was involved in a white matter network including cingulate fasciculus and corpus callosum. CONCLUSION Our data suggest that cuneus/precuneus is a hub of a large functional network subserving cognitive function in iRBD.
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15
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A dyadic study of psychological well-being of individuals with Parkinson's disease and their caregivers. Sci Rep 2021; 11:957. [PMID: 33441640 PMCID: PMC7806607 DOI: 10.1038/s41598-020-79609-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 12/10/2020] [Indexed: 01/11/2023] Open
Abstract
Parkinson's disease (PD) is an incapacitating neurodegenerative disease. Patients with PD and their caregivers may have interactive effects on each other’s psychological well-being. This study aimed to assess the dyadic dynamics of resilience, fatigue, and suicidal ideation on the depression severity of PD patients and their caregivers. In total, 175 PD patients and 175 caregivers were recruited at a medical center from August 2018 to May 2020. Structural equation modeling (SEM) was used to examine the actor/partner effects on the psychological well-being of both the PD patients and their caregivers. The most common psychiatric diagnoses of both the PD patients (28.6%) and their caregivers (11.4%) were depressive disorders. The PD patients’ and their caregivers’ fatigue, suicidal ideation, and lack of resilience were significantly associated with the severity of their depression, respectively. Interactive effects existed between psychological well-being of individuals with PD and their caregivers. Clinicians must be aware of, and manage, these contributing factors between PD patients and their caregivers in order to prevent them from worsening each other’s depression.
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16
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Bejr-Kasem H, Sampedro F, Marín-Lahoz J, Martínez-Horta S, Pagonabarraga J, Kulisevsky J. Minor hallucinations reflect early gray matter loss and predict subjective cognitive decline in Parkinson's disease. Eur J Neurol 2020; 28:438-447. [PMID: 33032389 DOI: 10.1111/ene.14576] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 10/02/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND PURPOSE Well-structured hallucinations in Parkinson's disease (PD) are associated with poor prognosis and dementia. However, the predictive value of minor psychotic phenomena in cognitive deterioration is not well known. Cross-sectional studies have shown that PD patients with minor hallucinations have more severe cortical atrophy than non-hallucinators, but baseline and longitudinal studies addressing the evolution of these brain differences are lacking. The impact of developing minor hallucinations on cognitive impairment and cortical atrophy progression in early PD was explored. METHODS One hundred and thirty-one de novo PD patients from the Parkinson's Progression Marker Initiative for whom brain magnetic resonance imaging scans were available were included. Cognitive outcome at 5 years was compared between patients with and without minor hallucinations during follow-up. Additionally, using gray matter volume (GMV) voxel-based morphometry, cross-sectional (at baseline) and longitudinal (1- and 2-year GMV loss) structural brain differences between groups were studied. RESULTS During follow-up, 35.1% of patients developed minor hallucinations. At 5 years, these patients showed an increased prevalence of subjective cognitive decline compared to non-hallucinators (44.1% vs. 13.9%; p < 0.001), but not formal cognitive impairment. Additionally, compared to non-hallucinators, they exhibited reduced GMV at baseline in visuoperceptive areas and increased GMV loss in left temporal areas (p < 0.05 corrected). CONCLUSIONS Minor hallucinations seem to be an early clinical marker of increased neurodegeneration and are associated with mid-term subjective cognitive decline. Longer follow-up analyses would be needed to further define if these findings could reflect a higher risk of future cognitive deterioration.
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Affiliation(s)
- H Bejr-Kasem
- Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Universitat Autònoma de Barcelona (U.A.B.), Department of Medicine, Barcelona, Spain.,Institut d´Investigacions Biomèdiques- Sant Pau (IIB-Sant Pau), Barcelona, Spain.,Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
| | - F Sampedro
- Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Universitat Autònoma de Barcelona (U.A.B.), Department of Medicine, Barcelona, Spain.,Institut d´Investigacions Biomèdiques- Sant Pau (IIB-Sant Pau), Barcelona, Spain.,Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
| | - J Marín-Lahoz
- Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Universitat Autònoma de Barcelona (U.A.B.), Department of Medicine, Barcelona, Spain.,Institut d´Investigacions Biomèdiques- Sant Pau (IIB-Sant Pau), Barcelona, Spain.,Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
| | - S Martínez-Horta
- Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Universitat Autònoma de Barcelona (U.A.B.), Department of Medicine, Barcelona, Spain.,Institut d´Investigacions Biomèdiques- Sant Pau (IIB-Sant Pau), Barcelona, Spain.,Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
| | - J Pagonabarraga
- Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Universitat Autònoma de Barcelona (U.A.B.), Department of Medicine, Barcelona, Spain.,Institut d´Investigacions Biomèdiques- Sant Pau (IIB-Sant Pau), Barcelona, Spain.,Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
| | - J Kulisevsky
- Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Universitat Autònoma de Barcelona (U.A.B.), Department of Medicine, Barcelona, Spain.,Institut d´Investigacions Biomèdiques- Sant Pau (IIB-Sant Pau), Barcelona, Spain.,Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
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17
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Wang L, Wang X, Song P, Han P, Fu L, Chen X, Yu H, Hou L, Yu X, Zhang Y, Zhang W, Guo Q. Combined Depression and Malnutrition As an Effective Predictor of First Fall Onset in a Chinese Community-Dwelling Population: A 2-Year Prospective Cohort Study. Rejuvenation Res 2020; 23:498-507. [PMID: 32303149 DOI: 10.1089/rej.2019.2188] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
This study aims to explore the single and joint effects of depression and malnutrition on the incidence of first fall onset in a Chinese community-dwelling elderly population. This cohort study consisted of 739 residents without a history of falls who were aged 60 years and older (mean age: 67.08 ± 5.79 years, female: 58.2%). Depression was defined with the Geriatric Depression Scale (GDS)-30; a score of ≥11 was considered to be depressed, while malnutrition was defined with the Mini Nutritional Assessment where a score <17 was defined as malnourished. Over a 2-year follow-up period, older adults who experienced at least one fall were allocated to the first fall onset group. The prevalence of baseline falls was 21.36%. During the 2-year follow-up, incidence of first fall onset was 13.13%. After adjusting for all confounders, depression alone (adjusted odds ratio [OR] = 3.545, 95% confidence interval [CI] = 1.318-9.535) and malnutrition alone (adjusted OR = 2.204, 95% CI = 1.183-4.108) were observed to be independent risk factors for first fall onset, while comorbidity of depression and malnutrition showed progressively increased risk of promoting first fall (adjusted OR = 8.161, 95% CI = 3.591-18.545) than those with only depression or malnutrition or without both depression and malnutrition. Malnutrition mediated 56% effects in the association between depression and first fall onset, while depression mediated 76% effects in the promoting role of malnutrition in first fall. Depression and malnutrition were found to be independent causes for promoting first fall, while mental health and nutrition should be treated as commonly prior interventions to delay first fall onset. Meanwhile, for malnourished Chinese community-dwelling older adults, avoidance or treatment of depression should be addressed at first.
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Affiliation(s)
- Lu Wang
- Department of Rehabilitation Medicine, TEDA International Cardiovascular Hospital, Cardiovascular Clinical College of Tianjin Medical University, Tianjin, China.,Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin, China
| | - Xing Wang
- Department of neurology, Tianjin Medical University General Hospital, Tianjin, China
| | - Peiyu Song
- Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin, China
| | - Peipei Han
- Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin, China
| | - Liyuan Fu
- Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin, China
| | - Xioayu Chen
- Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin, China
| | - Hairui Yu
- Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin, China
| | - Lin Hou
- Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin, China
| | - Xing Yu
- Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin, China
| | - Yuanyuan Zhang
- Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin, China
| | - Wen Zhang
- Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin, China
| | - Qi Guo
- College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, China
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18
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Bayram E, Banks SJ, Shan G, Kaplan N, Caldwell JZK. Sex Differences in Cognitive Changes in De Novo Parkinson's Disease. J Int Neuropsychol Soc 2020; 26:241-249. [PMID: 31822306 PMCID: PMC7282562 DOI: 10.1017/s1355617719001085] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
OBJECTIVE To evaluate the sex differences in cognitive course over 4 years in Parkinson's disease (PD) patients with and without mild cognitive impairment (MCI) compared to controls. METHODS Four-year longitudinal cognitive scores of 257 cognitively intact PD, 167 PD-MCI, and 140 controls from the Parkinson's Progression Markers Initiative were included. Longitudinal scores of men and women, and PD with and without MCI were compared. RESULTS Women had better verbal memory, men had better visuospatial function. There was no interaction between sex, diagnostic group, and/or time (4-year follow-up period). CONCLUSIONS Sex differences in cognitive course in de novo PD are similar to healthy aging. Cognitive decline rates in PD with and without MCI are similar for the first 4 years of PD.
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Affiliation(s)
- Ece Bayram
- University of California San Diego, Department of Neurosciences, La Jolla, CA, USA
| | - Sarah J. Banks
- University of California San Diego, Department of Neurosciences, La Jolla, CA, USA
| | - Guogen Shan
- University of Nevada Las Vegas, Department of Environmental and Occupational Health, Las Vegas, NV, USA
| | - Nikki Kaplan
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA
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19
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Prevalence and factors related to orthostatic syndromes in recently diagnosed, drug-naïve patients with Parkinson disease. Clin Auton Res 2019; 30:265-271. [DOI: 10.1007/s10286-019-00652-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 12/02/2019] [Indexed: 12/15/2022]
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20
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Zhang H, Wang S, Wang L, Yi X, Jia X, Jia C. Comparison of the Geriatric Depression Scale-15 and the Patient Health Questionnaire-9 for screening depression in older adults. Geriatr Gerontol Int 2019; 20:138-143. [PMID: 31820572 DOI: 10.1111/ggi.13840] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 11/05/2019] [Accepted: 11/17/2019] [Indexed: 11/29/2022]
Abstract
AIM To examine the reliability and validity of the Geriatric Depression Scale-15 (GDS-15) and the Patient Health Questionnaire-9 (PHQ-9) for evaluating depression in older adults. METHODS A total of 1546 participants aged ≥60 years were investigated face-to-face with the PHQ-9 and GDS-15 anonymously. Internal consistency reliability was evaluated with Cronbach's α, and structural equation modeling was used to study the construct validity of the scale. Logistic regression was used to discusses the impact of demographic characteristics on the scale. RESULTS The consistency rate between the GDS-15 and PHQ-9 was 96.10%. The Cronbach's α and split-half reliability in the scales were >0.7. The model fit indices χ2 /df., comparative fit index and root mean square error of approximation in the GDS-15 were 2.769, 0.815 and 0.077, respectively. The minimum fit function χ2 in the PHQ-9 model was 93.742, with 27 df., the comparative fit index was acceptably low (comparative fit index 0.837) and the root mean square error of approximation was acceptably high (root mean square error of approximation 0.118). Item standardized path regression coefficients of the GDS-15 model varied between 0.07 and 0.76, among which the coefficients of item 2 and item 9 were 0.12 and 0.07, respectively. Whereas in the PHQ-9, the item standardized path regression coefficients were high (r > 0.45), except for item 3 (r = 0.34). The GDS-15 was affected by urban-rural distribution (OR = 2.104, P = 0.027), whereas the PHQ-9 was affected by sex (OR = 4.266, P = 0.007). CONCLUSIONS The similar psychometric performance of the PHQ-9, along with its ease of use and relative brevity, makes it attractive compared with the longer GDS-15 for use in Chinese older adults, whereas the influence of sex distribution on the PHQ-9 should be paid attention to. Geriatr Gerontol Int 2020; 20: 138-143.
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Affiliation(s)
- Hong Zhang
- Department of Epidemiology, School of Public Health, Shandong University, Jinan, China
| | - Shumei Wang
- Department of Epidemiology, School of Public Health, Shandong University, Jinan, China
| | - Lijie Wang
- Department of Epidemiology, School of Public Health, Shandong University, Jinan, China
| | - Xiangren Yi
- The School of Physical Education of Shandong University, Jinan, China
| | - Xiaoxian Jia
- Department of Epidemiology, School of Public Health, Shandong University, Jinan, China
| | - Cunxian Jia
- Department of Epidemiology, School of Public Health, Shandong University, Jinan, China
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21
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Kozlovski T, Mitelpunkt A, Thaler A, Gurevich T, Orr-Urtreger A, Gana-Weisz M, Shachar N, Galili T, Marcus-Kalish M, Bressman S, Marder K, Giladi N, Benjamini Y, Mirelman A. Hierarchical Data-Driven Analysis of Clinical Symptoms Among Patients With Parkinson's Disease. Front Neurol 2019; 10:531. [PMID: 31164863 PMCID: PMC6536639 DOI: 10.3389/fneur.2019.00531] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Accepted: 05/03/2019] [Indexed: 12/13/2022] Open
Abstract
Mutations in the LRRK2 and GBA genes are the most common inherited causes of Parkinson's disease (PD). Studies exploring phenotypic differences based on genetic status used hypothesis-driven data-gathering and statistical-analyses focusing on specific symptoms, which may influence the validity of the results. We aimed to explore phenotypic expression in idiopathic PD (iPD) patients, G2019S-LRRK2-PD, and GBA-PD using a data-driven approach, allowing screening of large numbers of features while controlling selection bias. Data was collected from 1525 Ashkenazi Jews diagnosed with PD from the Tel-Aviv Medical center; 161 G2019S-LRRK2-PD, 222 GBA-PD, and 1142 iPD (no G2019S-LRRK2 or any of the 7 AJ GBA mutations tested). Data included 771 measures: demographics, cognitive, physical and neurological functions, performance-based measures, and non-motor symptoms. The association of the genotypes with each of the measures was tested while accounting for age at motor symptoms onset, gender, and disease duration; p-values were reported and corrected in a hierarchical approach for an average over the selected measures false discovery rate control, resulting in 32 measures. GBA-PD presented with more severe symptoms expression while LRRK2-PD had more benign symptoms compared to iPD. GBA-PD presented greater cognitive and autonomic involvement, more frequent hyposmia and REM sleep behavior symptoms while these were less frequent among LRRK2-PD compared to iPD. Using a data-driven analytical approach strengthens earlier studies and extends them to portray a possible unique disease phenotype based on genotype among AJ PD. Such findings could help direct a more personalized therapeutic approach.
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Affiliation(s)
- Tal Kozlovski
- Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel
| | - Alexis Mitelpunkt
- Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Pediatric Neurology Unit, Dana Children Hospital, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Avner Thaler
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Movement Disorders Unit, Tel Aviv Medical Center, Neurological Institute, Tel Aviv, Israel.,Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
| | - Tanya Gurevich
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Movement Disorders Unit, Tel Aviv Medical Center, Neurological Institute, Tel Aviv, Israel.,Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
| | - Avi Orr-Urtreger
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Genetic Institute, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Mali Gana-Weisz
- Genetic Institute, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Netta Shachar
- Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel
| | - Tal Galili
- Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel
| | - Mira Marcus-Kalish
- Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel
| | - Susan Bressman
- Department of Neurology, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel Medical Center, New York, NY, United States
| | - Karen Marder
- Department of Neurology, Taub Institute for Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, United States
| | - Nir Giladi
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Movement Disorders Unit, Tel Aviv Medical Center, Neurological Institute, Tel Aviv, Israel.,Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
| | - Yoav Benjamini
- Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel.,Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.,Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel
| | - Anat Mirelman
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Movement Disorders Unit, Tel Aviv Medical Center, Neurological Institute, Tel Aviv, Israel.,Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.,Laboratory of Early Markers of Neurodegeneration, Tel Aviv Medical Center, Neurological Institute, Tel Aviv, Israel
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22
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Garrido A, Fairfoul G, Tolosa ES, Martí MJ, Green A. α-synuclein RT-QuIC in cerebrospinal fluid of LRRK2-linked Parkinson's disease. Ann Clin Transl Neurol 2019; 6:1024-1032. [PMID: 31211166 PMCID: PMC6562027 DOI: 10.1002/acn3.772] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 03/04/2019] [Indexed: 11/17/2022] Open
Abstract
Background Leucine‐rich kinase 2 (LRRK2)‐linked Parkinson's disease (PD) is clinically indistinguishable from idiopathic PD (IPD). A pleiotropic neuropathology has been recognized but the majority of studies in LRRK2 p.G2019S patients reveal Lewy‐type synucleinopathy as its principal histological substrate. To date no in vivo biomarkers of synucleinopathy have been found in LRRK2 mutation carriers. Objectives We used real‐time quaking‐induced conversion (RT‐QuIC) technique to assess the presence of alpha‐synuclein (a‐syn) aggregates in cerebrospinal fluid (CSF) of LRRK2 p.G2019S carriers. Methods CSF samples of 51 subjects were analyzed: 15 LRRK2 p.G2019S PD, 10 IPD, 16 LRRK2 p.G2019S nonmanifesting carriers (NMC) and 10 healthy controls. The presence of parkinsonism and prodromal symptoms was assessed in all study subjects. Results Forty percent (n = 6) LRRK2‐PD, and 18.8% (n = 3) LRRK2‐NMC had a positive a‐syn RT‐QuIC response. RT‐QuIC detected IPD with 90% sensitivity and 80% specificity. No clinical differences were detected between LRRK2‐PD patients with positive and negative RT‐QuIC. A positive RT‐QuIC result in LRRK2‐NMC occurred in a higher proportion of subjects meeting the Movement Disorder Society research criteria for prodromal PD. Interpretation RT‐QuIC detects a‐syn aggregation in CSF in a significant number of patients with LRRK2‐PD, but less frequently than in IPD. A small percentage of LRRK2‐NMC tested also positive. If appropriately validated in long‐term studies with large number of mutation carriers, and hopefully, postmortem or in vivo confirmation of histopathology, RT‐QuIC could contribute to the selection of candidates to receive disease modifying drugs, in particular treatments targeting a‐syn deposition.
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Affiliation(s)
- Alicia Garrido
- Parkinson's Disease and Movement Disorders Unit Institut Clínic de Neurociències Hospital Clinic de Barcelona Barcelona Spain.,Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) Madrid Spain
| | - Graham Fairfoul
- The National CJD Research & Surveillance Unit Centre for Clinical Brain Sciences University of Edinburgh Edinburgh EH4 2XU United Kingdom
| | - Eduardo S Tolosa
- Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) Madrid Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) University of Barcelona (UB) Barcelona Spain
| | - Maria José Martí
- Parkinson's Disease and Movement Disorders Unit Institut Clínic de Neurociències Hospital Clinic de Barcelona Barcelona Spain.,Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) Madrid Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) University of Barcelona (UB) Barcelona Spain
| | - Alison Green
- The National CJD Research & Surveillance Unit Centre for Clinical Brain Sciences University of Edinburgh Edinburgh EH4 2XU United Kingdom
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23
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Ma HI, Gunnery SD, Stevenson MT, Saint-Hilaire M, Thomas CA, Tickle-Degnen L. Experienced facial masking indirectly compromises quality of life through stigmatization of women and men with Parkinson's disease. STIGMA AND HEALTH 2019; 4:462-472. [PMID: 33225063 PMCID: PMC7678084 DOI: 10.1037/sah0000168] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/09/2023]
Abstract
This study examined the relationship between self-reported facial masking and quality of life (QoL) in people with Parkinson's disease (PD), and tested experienced stigma as a mediator and gender as a moderator of this relationship. The strength of stigma as a mediator was compared against an alternative mediator, depression. Ninety people with PD (34 women) rated difficulty showing facial expression (masking), and completed the Stigma Scale for Chronic Illness, Geriatric Depression Scale (15-item), and Parkinson's Disease Questionnaire-39. A conditional process model tested the indirect effect of facial masking on QoL through stigma, separately for women and men. A parallel indirect model included both stigma and depression to compare their statistical and clinical significance as mediators. Gender-moderated mediation of stigma reduced the association between facial masking and QoL to non-significance, suggesting stigma explained the association between facial masking and QoL. While facial masking was more stigmatizing for women than for men, stigma mediated the facial masking-QoL association for both women and men. Stigma (controlling for depression) reached a statistically and clinically significant level of mediation, whereas depression (controlling for stigma) reached a statistically yet not clinically significant level of mediation. People with PD who experience more severe facial masking feel more stigmatized, especially women. Regardless of gender, an increase in stigma from facial masking increases the likelihood of compromised QoL that reaches both statistical and clinical levels of significance.
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Affiliation(s)
- Hui-Ing Ma
- Department of Occupational Therapy, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 701, Taiwan
| | - Sarah D. Gunnery
- Department of Psychology, New England College, 98 Bridge St., Henniker, NH, 03242
| | - Michael T. Stevenson
- Department of Occupational Therapy, Tufts University, 574 Boston Ave., Medford, MA 02155, USA
| | - Marie Saint-Hilaire
- Department of Neurology, Boston University Medical Center, 725 Albany St., Boston, MA, 02118, USA
| | - Cathi A. Thomas
- Department of Neurology, Boston University Medical Center, 725 Albany St., Boston, MA, 02118, USA
| | - Linda Tickle-Degnen
- Department of Occupational Therapy, Tufts University, 574 Boston Ave., Medford, MA 02155, USA
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24
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Wang Z, Jia X, Chen H, Feng T, Wang H. Abnormal Spontaneous Brain Activity in Early Parkinson's Disease With Mild Cognitive Impairment: A Resting-State fMRI Study. Front Physiol 2018; 9:1093. [PMID: 30154730 PMCID: PMC6102476 DOI: 10.3389/fphys.2018.01093] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Accepted: 07/23/2018] [Indexed: 01/27/2023] Open
Abstract
Mild cognitive impairment (MCI) is a common symptom at the baseline of early Parkinson's disease (PD) diagnosis, but the neural mechanism is unclear. To address the issue, the present study employed resting-state functional magnetic resonance imaging data of 19 drug-naïve PD patients with normal cognition (PD-NC), 10 PD patients with MCI (PD-MCI) and 13 age- and gender-matched healthy controls (HC) from the Parkinson's progression markers initiative (PPMI) (http://www.ppmi-info.org/), and examined abnormal spontaneous brain activities in the PD-MCI. The pattern of spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) of blood oxygen level dependent signal. Voxel-wise one-way analysis of covariance and post hoc analyses of ALFF were performed under non-parametric permutation tests in a general linear model among the three groups, with age, gender and data center as additional covariates. Statistical significances in the post hoc analysis were corrected by a small volume correction with a cluster-level threshold of p < 0.05 (n = 10000 permutations, FWE-corrected). Correlations of clinical and neuropsychological assessments [i.e., Unified Parkinson's Disease Rating Scale (UPDRS) total score, Montreal Cognitive Assessment (MoCA) and cognitive domains] with the regional ALFF were performed in the PD-MCI group. Compared with the HC, both PD groups exhibited reduced ALFF in the occipital area (Calcarine_R/Cuneus_R). Specially, the PD-MCI group additionally exhibited increased ALFF in the opercular part of right inferior frontal gyrus (Frontal_Inf_Oper_R). Comparing with the PD-NC, the PD-MCI group exhibited significantly higher ALFF in the Frontal_Inf_Oper_R and left fusiform gyus (ps < 0.05). The correlation analysis revealed that the ALFF in the Frontal_Inf_Oper_R was positively correlated with the UPDRS total score (p < 0.05), but marginally negatively correlated with the MoCA score. For cognitive domains, the ALFF in the region also showed a significantly negative correlation with the score of SF test (p < 0.01) and a marginally negative correlation with the score of Symbol-Digit Modalities Test. Together, we concluded hyperactivity in the right inferior frontal gyrus in early PD with MCI, suggesting a compensatory recruitment in response to cognitive decline, which may shed light on thought of dementia progression and potentially comprehensive treatment in PD.
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Affiliation(s)
- Zhijiang Wang
- Peking University Institute of Mental Health (Sixth Hospital), Beijing, China
- National Clinical Research Center for Mental Disorders and Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China
- Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, China
| | - Xiuqin Jia
- Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Huimin Chen
- Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Tao Feng
- Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Huali Wang
- Peking University Institute of Mental Health (Sixth Hospital), Beijing, China
- National Clinical Research Center for Mental Disorders and Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China
- Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, China
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25
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Kojima Y, Kumagai T, Hidaka T, Kakamu T, Endo S, Mori Y, Tsukamoto T, Sakamoto T, Murata M, Hayakawa T, Fukushima T. Characteristics of facial expression recognition ability in patients with Lewy body disease. Environ Health Prev Med 2018; 23:32. [PMID: 30021532 PMCID: PMC6052637 DOI: 10.1186/s12199-018-0723-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 06/28/2018] [Indexed: 11/16/2022] Open
Abstract
Background The facial expression of medical staff has been known to greatly affect the psychological state of patients, making them feel uneasy or conversely, cheering them up. By clarifying the characteristics of facial expression recognition ability in patients with Lewy body disease, the aim of this study is to examine points to facilitate smooth communication between caregivers and patients with the disease whose cognitive function has deteriorated. Methods During the period from March 2016 to July 2017, we examined the characteristics of recognition of the six facial expressions of “happiness,” “sadness,” “fear,” “anger,” “surprise,” and “disgust” for 107 people aged 60 years or more, both outpatient and inpatient, who hospital specialists had diagnosed with Lewy body diseases of Parkinson’s disease, Parkinson’s disease with dementia, and dementia with Lewy bodies. Based on facial expression recognition test results, we classified them by cluster analysis and clarified features of each type. Results In patients with Lewy body disease, happiness was kept unaffected by aging, age of onset, duration of the disease, cognitive function, and apathy; however, recognizing the facial expression of fear was difficult. In addition, due to aging, cognitive decline, and apathy, the facial expression recognition ability for sadness and anger decreased. In particular, cognitive decline reduced recognition of all of the facial expressions except for happiness. The test accuracy rates were classified into three types using the cluster analysis: “stable type,” “mixed type,” and “reduced type”. In the “reduced type”, the overall facial recognition ability declined except happiness, and in the mixed type, recognition ability of anger particularly declined. Conclusion There were several facial expressions that the Lewy body disease patients were unable to accurately identify. Caregivers are recommended to make an effort to compensate for such situations with language or body contact, etc., as a way to convey correct feeling to the patients of each type.
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Affiliation(s)
- Yuriko Kojima
- Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, 960-1295, Japan.
| | - Tomohiro Kumagai
- Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, 960-1295, Japan
| | - Tomoo Hidaka
- Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, 960-1295, Japan
| | - Takeyasu Kakamu
- Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, 960-1295, Japan
| | - Shota Endo
- Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, 960-1295, Japan
| | - Yayoi Mori
- Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, 960-1295, Japan
| | - Tadashi Tsukamoto
- Department of Neurology, National Center of Neurology and Psychiatry, Kogawahigashi-cho 4-1-1, Kodaira, Tokyo, 187-8551, Japan
| | - Takashi Sakamoto
- Department of Neurology, National Center of Neurology and Psychiatry, Kogawahigashi-cho 4-1-1, Kodaira, Tokyo, 187-8551, Japan
| | - Miho Murata
- Department of Neurology, National Center of Neurology and Psychiatry, Kogawahigashi-cho 4-1-1, Kodaira, Tokyo, 187-8551, Japan
| | - Takehito Hayakawa
- Research Center for Social Studies of Health and Community, Ritsumeikan University, Tojiinkita-machi 56-1, Kita-ku, Kyoto, 603-8577, Japan
| | - Tetsuhito Fukushima
- Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, 960-1295, Japan
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26
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Mirelman A, Saunders-Pullman R, Alcalay RN, Shustak S, Thaler A, Gurevich T, Raymond D, Mejia-Santana H, Orbe Reilly M, Ozelius L, Clark L, Gana-Weisz M, Bar-Shira A, Orr-Utreger A, Bressman SB, Marder K, Giladi N. Application of the Movement Disorder Society prodromal criteria in healthy G2019S-LRRK2 carriers. Mov Disord 2018; 33:966-973. [PMID: 29603409 DOI: 10.1002/mds.27342] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 01/10/2018] [Accepted: 01/17/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND In 2015, the International Parkinson and Movement Disorder Society Task Force recommended research criteria for the estimation of prodromal PD. OBJECTIVES We aimed to evaluate, for the first time, the criteria in first-degree relatives of Ashkenazi Jewish G2019S-LRRK2 PD patients, who are considered a population at risk for developing PD, and assess the sensitivity and specificity of the criteria in identifying phenoconverters. METHODS Participants were evaluated longitudinally over a period of 5 years (average follow-up: 49.2 ± 12.3 months). Likelihood ratios and probability estimations were calculated based on the International Parkinson and Movement Disorder Society Research Criteria for Prodromal Parkinson's Disease markers and examined for each assessment point. RESULTS One hundred twenty healthy carriers (49.53 ± 13.4 years; 54% female) and 111 healthy noncarriers (48.43 ± 15.79 years; 49% female) participated in this study. Probability scores were significantly higher in healthy carriers than healthy noncarriers (P < 0.0001). Of the 20 participants (8.6%) who met criteria for probable prodromal PD at baseline, 17 were healthy carriers. Participants who reached the threshold were older (P < 0.0001), had higher UPDRS-III (P < 0.001), lower cognitive function (P = 0.001), and more nonmotor symptoms (P < 0.0001), compared to those who did not. Ten participants were diagnosed with incident PD within 5 years from baseline resulting in a specificity of 91.82% (95% confidence interval: 86.69-96.94), sensitivity of 80% (95% confidence interval: 55.21-100), positive predictive value of 47.06% (95% confidence interval: 23.33-70.79), and negative predictive value of 98.06% (95% confidence interval: 95.39-100). All 10 phenoconvertors were G2019S-LRRK2 carriers. CONCLUSIONS The results showed the utility of using the criteria and high sensitivity and specificity in identifying prodromal PD in this high-risk unique cohort. These results may be valuable for future disease modification clinical trials. © 2018 International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Anat Mirelman
- Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel-Aviv, Israel.,Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Tel-Aviv, Israel
| | - Rachel Saunders-Pullman
- Departments of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA.,Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Roy N Alcalay
- Department of Neurology, College of Physicians and Surgeons, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA
| | - Shiran Shustak
- Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel-Aviv, Israel
| | - Avner Thaler
- Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel-Aviv, Israel.,Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Tel-Aviv, Israel
| | - Tanya Gurevich
- Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel-Aviv, Israel.,Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Tel-Aviv, Israel
| | - Deborah Raymond
- Departments of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA
| | - Helen Mejia-Santana
- Department of Neurology, College of Physicians and Surgeons, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA
| | - Martha Orbe Reilly
- Department of Neurology, College of Physicians and Surgeons, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA
| | - Laurie Ozelius
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Lorraine Clark
- Department of Neurology, College of Physicians and Surgeons, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.,Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA
| | - Mali Gana-Weisz
- Genetics Institute, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Anat Bar-Shira
- Genetics Institute, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Avi Orr-Utreger
- Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Tel-Aviv, Israel.,Genetics Institute, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Susan B Bressman
- Departments of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, USA.,Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Karen Marder
- Department of Neurology, College of Physicians and Surgeons, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA
| | - Nir Giladi
- Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel-Aviv, Israel.,Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Tel-Aviv, Israel
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27
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Hsu CL, Liang CK, Liao MC, Chou MY, Lin YT. Slow gait speed as a predictor of 1-year cognitive decline in a veterans' retirement community in southern Taiwan. Geriatr Gerontol Int 2018; 17 Suppl 1:14-19. [PMID: 28436187 DOI: 10.1111/ggi.13034] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/01/2017] [Indexed: 12/19/2022]
Abstract
AIM Slow gait speed has been associated with mortality, poor physical function and disability in older people. Our aim was to evaluate the association between slow gait speed and rapid cognitive decline among oldest-old men in Taiwan. METHODS We carried out a longitudinal cohort study in a veterans' retirement community, and enrolled 249 male residents aged 80 years and older. Slow gait speed was defined as <1 m/s, and rapid cognitive decline was defined as a Mini-Mental State Examination (MMSE) decline of ≥3 points over 1 year. Body mass index, Charlson's Comorbidity Index, handgrip strength, gait speed and Mini-Mental State Examination datasets were collected, and a logistic regression model was built to evaluate the association between fast cognitive decline and slow gait speed. RESULTS In all, 249 residents (mean age 86.4 ± 4.01 years) were recruited, including 58 (23.3%) with rapid cognitive decline. Univariate analysis showed that slow gait speed could predict rapid cognitive decline (OR 4.10, 95% CI 1.20-14.00, P = 0.024). After adjusting for age, Charlson's Comorbidity Index, polypharmacy, psychiatric drug usage, cigarette smoking experience, baseline cognitive function, depressive mood, handgrip strength, nutritional status and history of fall, slow gait speed was still independently associated with rapid cognitive decline (adjusted OR 4.58, 95% CI 1.22-17.2, P = 0.024). CONCLUSIONS Slow gait speed was thus an independent predictor of rapid cognitive decline in oldest-old men in a veterans' retirement community in Taiwan. Geriatr Gerontol Int 2017: 17 (Suppl. 1): 14-19.
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Affiliation(s)
- Chiao-Lin Hsu
- Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan.,Center of Health Examination, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan
| | - Chih-Kuang Liang
- Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan.,Division of Neurology, Department of Internal Medicine.,Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan
| | - Mei-Chen Liao
- Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan
| | - Ming-Yueh Chou
- Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan.,Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan
| | - Yu-Te Lin
- Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan.,Division of Neurology, Department of Internal Medicine
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28
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Sasaki Y, Aida J, Tsuji T, Miyaguni Y, Tani Y, Koyama S, Matsuyama Y, Sato Y, Tsuboya T, Nagamine Y, Kameda Y, Saito T, Kakimoto K, Kondo K, Kawachi I. Does Type of Residential Housing Matter for Depressive Symptoms in the Aftermath of a Disaster? Insights From the Great East Japan Earthquake and Tsunami. Am J Epidemiol 2018; 187:455-464. [PMID: 28992035 PMCID: PMC5860436 DOI: 10.1093/aje/kwx274] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 07/06/2017] [Indexed: 12/19/2022] Open
Abstract
The 2011 Great East Japan Earthquake and Tsunami resulted in widespread property destruction and over 250,000 displaced residents. We sought to examine whether the type of housing arrangement available to the affected victims was associated with a differential incidence of depressive symptoms. In this prospective cohort study, which comprised participants aged ≥65 years from Iwanuma as a part of the Japan Gerontological Evaluation Study, we had information about the residents' mental health both before the disaster in 2010 and 2.5 years afterward. The Geriatric Depression Scale was used. Type of accommodation after the disaster was divided into 5 categories: no move, prefabricated housing (temporary housing), existing private accommodations (temporary apartment), newly established housing, and other. Poisson regression analysis was adopted, with and without multiple imputation. Among the 2,242 participants, 16.2% reported depressive symptoms at follow-up. The adjusted rate ratio for depressive symptoms among persons moving into prefabricated housing, compared with those who did not, was 2.07 (95% confidence interval: 1.45, 2.94). Moving into existing private accommodations or other types of accommodations was not associated with depression. The relationship between living environment and long-term mental health should be considered for disaster recovery planning.
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Affiliation(s)
- Yuri Sasaki
- Department of Social Preventive Medical Sciences, Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
- Correspondence to Dr. Yuri Sasaki, Department of Social Preventive Medical Sciences, Center for Preventive Medical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan (e-mail: )
| | - Jun Aida
- Department of International and Community Oral Health, Graduate School of Dentistry, Tohoku University, Miyagi, Japan
| | - Taishi Tsuji
- Department of Social Preventive Medical Sciences, Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
| | - Yasuhiro Miyaguni
- Department of Social Preventive Medical Sciences, Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
| | - Yukako Tani
- Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan
- Japan Society for the Promotion of Science, Tokyo, Japan
| | - Shihoko Koyama
- Department of International and Community Oral Health, Graduate School of Dentistry, Tohoku University, Miyagi, Japan
- Department of Community Medical Supports, Tohoku Medical Megabank Organization, Miyagi, Japan
| | - Yusuke Matsuyama
- Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan
- Japan Society for the Promotion of Science, Tokyo, Japan
| | - Yukihiro Sato
- Department of International and Community Oral Health, Graduate School of Dentistry, Tohoku University, Miyagi, Japan
| | - Toru Tsuboya
- Department of International and Community Oral Health, Graduate School of Dentistry, Tohoku University, Miyagi, Japan
| | - Yuiko Nagamine
- Department of Social Preventive Medical Sciences, Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
| | - Yoshihito Kameda
- Department of Social Preventive Medical Sciences, Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
| | - Tami Saito
- Department of Social Science, National Center for Geriatrics and Gerontology, Aichi, Japan
| | - Kazuhiro Kakimoto
- Kansai International Airport Quarantine Station, Ministry of Health, Labour and Welfare, Osaka, Japan
| | - Katsunori Kondo
- Department of Social Preventive Medical Sciences, Center for Preventive Medical Sciences, Chiba University, Chiba, Japan
- Department of Gerontological Evaluation, National Center for Geriatrics and Gerontology, Aichi, Japan
| | - Ichiro Kawachi
- Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, Massachusetts
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29
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Arnaldi D, De Carli F, Famà F, Brugnolo A, Girtler N, Picco A, Pardini M, Accardo J, Proietti L, Massa F, Bauckneht M, Morbelli S, Sambuceti G, Nobili F. Prediction of cognitive worsening in de novo Parkinson's disease: Clinical use of biomarkers. Mov Disord 2017; 32:1738-1747. [DOI: 10.1002/mds.27190] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Revised: 08/02/2017] [Accepted: 09/10/2017] [Indexed: 01/10/2023] Open
Affiliation(s)
- Dario Arnaldi
- Clinical Neurology, Dept. of Neuroscience (DINOGMI); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Fabrizio De Carli
- Institute of Molecular Bioimaging and Physiology; National Research Council; Genoa Italy
| | - Francesco Famà
- Clinical Neurology, Dept. of Neuroscience (DINOGMI); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Andrea Brugnolo
- Clinical Neurology, Dept. of Neuroscience (DINOGMI); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Nicola Girtler
- Clinical Neurology, Dept. of Neuroscience (DINOGMI); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Agnese Picco
- Clinical Neurology, Dept. of Neuroscience (DINOGMI); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Matteo Pardini
- Clinical Neurology, Dept. of Neuroscience (DINOGMI); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Jennifer Accardo
- Clinical Neurology, Dept. of Neuroscience (DINOGMI); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Luca Proietti
- Clinical Neurology, Dept. of Neuroscience (DINOGMI); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Federico Massa
- Clinical Neurology, Dept. of Neuroscience (DINOGMI); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Matteo Bauckneht
- Nuclear Medicine, Department of Health Sciences (DISSAL); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Silvia Morbelli
- Nuclear Medicine, Department of Health Sciences (DISSAL); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Gianmario Sambuceti
- Nuclear Medicine, Department of Health Sciences (DISSAL); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
| | - Flavio Nobili
- Clinical Neurology, Dept. of Neuroscience (DINOGMI); University of Genoa and IRCCS AOU San Martino-IST; Genoa Italy
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Mosley PE, Moodie R, Dissanayaka N. Caregiver Burden in Parkinson Disease: A Critical Review of Recent Literature. J Geriatr Psychiatry Neurol 2017; 30:235-252. [PMID: 28743212 DOI: 10.1177/0891988717720302] [Citation(s) in RCA: 168] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Burden is a negative psychological state induced in caregivers by the demands of providing care to a person with an illness or a disability. Managing caregiver burden in Parkinson disease (PD) is significant because informal caregivers make a substantial contribution to the well-being of persons with PD, incurring financial, social, and personal losses. Failure to recognize and manage caregiver burden may lead to burnout and premature institutionalization of the person with PD. We conducted a comprehensive literature review to identify and summarize factors that may amplify burden, including motor and nonmotor symptoms of PD, caregiver psychiatric symptoms, and caregiver coping style. We review instruments designed to sample the construct of burden among caregivers and evaluate interventions that may reduce burden, either by directly targeting caregivers or by treating PD symptoms associated with burden. We aim to provide a concise synopsis of these issues for the clinician or researcher working with this population in order to facilitate recognition of caregiver burden, provide accurate assessment, administer appropriate interventions, and stimulate further research in this area.
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Affiliation(s)
- Philip E Mosley
- 1 Systems Neuroscience Group, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.,2 Neurosciences Queensland, St Andrew's War Memorial Hospital, Spring Hill, Queensland, Australia.,3 Queensland Brain Institute, University of Queensland, St Lucia, Queensland, Australia.,4 School of Medicine, University of Queensland, Herston, Queensland, Australia
| | - Rebecca Moodie
- 1 Systems Neuroscience Group, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
| | - Nadeeka Dissanayaka
- 5 UQ Centre for Clinical Research, University of Queensland, Herston, Queensland, Australia.,6 School of Psychology, University of Queensland, St Lucia, Queensland, Australia.,7 Department of Neurology, Royal Brisbane & Woman's Hospital, Herston, Queensland, Australia
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Schrag A, Siddiqui UF, Anastasiou Z, Weintraub D, Schott JM. Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson's disease: a cohort study. Lancet Neurol 2017; 16:66-75. [PMID: 27866858 PMCID: PMC5377592 DOI: 10.1016/s1474-4422(16)30328-3] [Citation(s) in RCA: 299] [Impact Index Per Article: 37.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 10/20/2016] [Accepted: 10/20/2016] [Indexed: 01/15/2023]
Abstract
BACKGROUND Parkinson's disease is associated with an increased incidence of cognitive impairment and dementia. Predicting who is at risk of cognitive decline early in the disease course has implications for clinical prognosis and for stratification of participants in clinical trials. We assessed the use of clinical information and biomarkers as predictive factors for cognitive decline in patients with newly diagnosed Parkinson's disease. METHODS The Parkinson's Progression Markers Initiative (PPMI) study is a cohort study in patients with newly diagnosed Parkinson's disease. We evaluated cognitive performance (Montreal Cognitive Assessment [MoCA] scores), demographic and clinical data, APOE status, and biomarkers (CSF and dopamine transporter [DAT] imaging results). Using change in MoCA scores over 2 years, MoCA scores at 2 years' follow-up, and a diagnosis of cognitive impairment (combined mild cognitive impairment or dementia) at 2 years as outcome measures, we assessed the predictive values of baseline clinical variables and separate or combined additions of APOE status, DAT imaging, and CSF biomarkers. We did univariate and multivariate linear analyses with MoCA change scores between baseline and 2 years, and with MoCA scores at 2 years as dependent variables, using backwards linear regression analysis. Additionally, we constructed a prediction model for diagnosis of cognitive impairment using logistic regression analysis. FINDINGS 390 patients with Parkinson's disease recruited between July 1, 2010, and May 31, 2013, and for whom data on MoCA scores at baseline and 2 years were available. In multivariate analyses, baseline age, University of Pennsylvania Smell Inventory Test (UPSIT) scores, CSF amyloid - (Aβ42) to t-tau ratio, and APOE status were associated with change in MoCA scores over time. Baseline age, MoCA and UPSIT scores, and CSF Aβ42 to t-tau ratio were associated with MoCA score at 2 years (using a backwards p-removal threshold of 0·1). Accuracy of prediction of cognitive impairment using age alone (area under the curve 0·68, 95% CI 0·60-0·76) significantly improved by addition of clinical scores (UPSIT, Rapid Eye Movement Sleep Behaviour Disorder Screening Questionnaire [RBDSQ], Geriatric Depression Scale, and Movement Disorder Society Unified Parkinson's Disease Rating Scale motor scores; 0·76, 0·68-0·83), CSF variables (0·74, 0·68-0·81), or DAT imaging results (0·76, 0·68-0·83). In combination, the five variables showing the most significant associations with cognitive impairment (age, UPSIT, RBDSQ, CSF Aβ42, and caudate uptake on DAT imaging) allowed prediction of cognitive impairment at 2 years (0·80, 0·74-0·87; p=0·0003 compared to age alone). INTERPRETATION In newly diagnosed Parkinson's disease, the occurrence of cognitive impairment at 2 year follow-up can be predicted with good accuracy using a model combining information on age, non-motor assessments, DAT imaging, and CSF biomarkers. FUNDING None.
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Affiliation(s)
- Anette Schrag
- Department of Clinical Neurosciences, Royal Free Campus, UCL Institute of Neurology, University College London, London, UK.
| | - Uzma Faisal Siddiqui
- Department of Clinical Neurosciences, Royal Free Campus, UCL Institute of Neurology, University College London, London, UK
| | - Zacharias Anastasiou
- Department of Clinical Neurosciences, Royal Free Campus, UCL Institute of Neurology, University College London, London, UK
| | - Daniel Weintraub
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA
| | - Jonathan M Schott
- Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK
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Deck BL, Rick J, Xie SX, Chen-Plotkin A, Duda JE, Morley JF, Chahine LM, Dahodwala N, Trojanowski JQ, Weintraub D. Statins and Cognition in Parkinson's Disease. JOURNAL OF PARKINSON'S DISEASE 2017; 7:661-667. [PMID: 28922167 PMCID: PMC5675567 DOI: 10.3233/jpd-171113] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND The relationship between statins and cognition in Parkinson's disease (PD) is poorly understood. OBJECTIVES Analyses were performed to determine associations between statin use and cross-sectional and longitudinal cognitive performance in PD. METHODS Neuropsychological tests, medication logs, and ratings of functional abilities were collected from 313 PD participants longitudinally. RESULTS At baseline, statin users (SU; N = 129) were older, more likely male, and had shorter PD duration than non-statin users (NSU; N = 184). In Cross-sectional analysis, SU performed better on global cognition, Trails B, semantic fluency, and phonemic fluency tasks. Rate of long-term global cognitive (Dementia Rating Scale-2 and MoCA) decline was significantly less in SU.
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Affiliation(s)
- Benjamin L. Deck
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jacqueline Rick
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Sharon X. Xie
- Department of Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Alice Chen-Plotkin
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - John E. Duda
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Parkinson’s Disease Research, Education and Clinical Center (PADRECC), Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA
| | - James F. Morley
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Parkinson’s Disease Research, Education and Clinical Center (PADRECC), Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA
| | - Lana M. Chahine
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Nabila Dahodwala
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - John Q. Trojanowski
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Daniel Weintraub
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Parkinson’s Disease Research, Education and Clinical Center (PADRECC), Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA
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Schrag A, Taddei RN. Depression and Anxiety in Parkinson's Disease. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2017; 133:623-655. [DOI: 10.1016/bs.irn.2017.05.024] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Cognitive impairment in elderly patients with type 2 diabetes mellitus: prevalence and related clinical factors. Diabetol Int 2016; 8:193-198. [PMID: 30603321 DOI: 10.1007/s13340-016-0292-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 10/16/2016] [Indexed: 12/20/2022]
Abstract
Aim Diabetes mellitus is reported to be a risk factor for dementia. We evaluated the cognitive function in elderly diabetic patients and estimated the prevalence of patients with cognitive impairment and looked for any related clinical factors. Subjects and methods Using 281 elderly (65 years of age or older) Japanese patients with type 2 diabetes mellitus who were free of clinically evident cognitive impairment, we evaluated their cognitive function with the Mini Mental State Examination (MMSE). Results The MMSE score of all the participants was 27.3 ± 2.4 with 31.3% of them being in the abnormal range (tentatively defined normal range as having an MMSE score of 27-30). Multiple regression analysis disclosed that fasting serum non-esterified fatty acid (NEFA), estimated glomerular filtration ratio (eGFR) and insulin treatment were significantly related factors for the MMSE score, in addition to age and schooling history, which are extremely strong factors. Conclusions We revealed that approximately one-third of elderly type 2 diabetic patients who were free of clinically evident cognitive impairment had impaired cognitive function, demonstrating that the MMSE score was significantly correlated with fasting NEFA level, renal function, insulin treatment, age and schooling history.
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Davis LL, Weaver M, Zamrini E, Stevens A, Kang DH, Parker CR. Biopsychological Markers of Distress in Informal Caregivers. Biol Res Nurs 2016; 6:90-9. [PMID: 15388906 DOI: 10.1177/1099800404267353] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background. Thirty caregiving wives participated in a study of caregiving distress and negative mood (depressive symptoms) by making diary entries on stressful caregiving situations and collecting saliva samples 4 times a day. At the end of the 7-day study period, caregivers’ salivary cortisol production was compared with their diary entries and correlated with pencil and paper self-report scores of caregiver distress and depressive symptoms. Findings. Despite the inability to control a number of factors thought to confound cortisol production (exercise, smoking, alcohol ingestion, and prescription medications), there was a statistically significant difference between No Caregiving and Caregiving cortisol, F( 1,739) = 7.67, P = 0.006, with cortisol production higher when caregiving events occurred. However, efforts to code specific types of caregiving situations (e.g., 1 = indirect care; 4 = AD problem behavior care) did not further differentiate cortisol production. Although caregivers’ self-reports for the same 7-day period indicated they were depressed, pencil-and-paper measures of distress and negative affect were not significantly correlated with cortisol production. Conclusions and Recommendations. The finding that this caregiving group was significantly stressed by caregiving, as evidenced by increased cortisol production during caregiving episodes, verifies the importance of further exploration of specific caregiving situations as contributory factors in caregiver health and well-being. In that saliva is a relatively economical and comparatively noninvasive biological data source for community-based stress studies, methodological limitations of the study are identified and 5 recommendations are made for future biological marker studies of caregiver distress in community-based settings.
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Stigma as a key determinant of health-related quality of life in Parkinson's disease. Qual Life Res 2016; 25:3037-3045. [PMID: 27259581 DOI: 10.1007/s11136-016-1329-z] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/25/2016] [Indexed: 10/21/2022]
Abstract
PURPOSE People with Parkinson's disease (PD) may experience stigma due to their visible features of movement and communication difficulties. This paper aimed to examine the role of experienced stigma in health-related quality of life (QOL), after controlling for personal and clinical characteristics. METHODS This is a preliminary analysis of a subset of baseline data from the Social Self-Management of Parkinson's Disease Study (SocM-PD), an ongoing 3-year prospective cohort study. Seventy-three people with PD (M age = 65.72, 29 women) participated in this study. Hierarchical multiple regression analyses were used to determine the role of stigma in QOL, after controlling for gender, disease severity, depression, and motor difficulties of daily living. RESULTS Significant correlations were found between QOL with gender (r = .26), disease severity (r = .38), depression (r = .65), motor difficulties of daily living (r = .71), and stigma (r = .83). After controlling for the significant covariates, stigma made a significant and unique contribution to the explanation of QOL by 13.7 % (p < 0.001). A final hierarchical multiple regression with stigma and the 4 covariates revealed an overall model that explained 77.8 % of the total variance of QOL (F [5, 63] = 48.79, p < 0.001). CONCLUSIONS Experienced stigma appears to be a key determinant of QOL in people with PD. The results suggest the importance of further understanding stigma in PD to develop possible intervention strategies. Future work is also needed to verify the results with a larger and longitudinal dataset of the SocM-PD.
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Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial. Lancet Neurol 2015; 14:795-803. [PMID: 26116315 DOI: 10.1016/s1474-4422(15)00144-1] [Citation(s) in RCA: 200] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Revised: 05/21/2015] [Accepted: 06/18/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. METHODS Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0·10. The study is registered at ClinicalTrials.gov, number NCT01280123. FINDINGS 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4·42 (95% CI 2·55-6·28) for 15 mg pioglitazone, 5·13 (95% CI 3·17-7·08) for 45 mg pioglitazone, and 6·25 (95% CI 4·35-8·15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was -1·83 (80% CI -3·56 to -0·10) and the null hypothesis could not be rejected (p=0·19). The mean difference between the 45 mg and placebo groups was -1·12 (80% CI -2·93 to 0·69) and the null hypothesis was rejected in favour of futility (p=0·09). Planned sensitivity analyses of the primary outcome, using last value carried forward (LVCF) to handle missing data and using the completers' only sample, suggested that the 15 mg dose is also futile (p=0·09 for LVCF, p=0·09 for completers) but failed to reject the null hypothesis for the 45 mg dose (p=0·12 for LVCF, p=0·19 for completers). Six serious adverse events occurred in the 15 mg group, nine in the 45 mg group, and three in the placebo group; none were thought to be definitely or probably related to the study interventions. INTERPRETATION These findings suggest that pioglitazone at the doses studied here is unlikely to modify progression in early Parkinson's disease. Further study of pioglitazone in a larger trial in patients with Parkinson's disease is not recommended. FUNDING National Institute of Neurological Disorders and Stroke.
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Santos-García D, de la Fuente-Fernández R. Factors contributing to caregivers' stress and burden in Parkinson's disease. Acta Neurol Scand 2015; 131:203-10. [PMID: 25212106 DOI: 10.1111/ane.12305] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/13/2014] [Indexed: 11/27/2022]
Abstract
BACKGROUND AND OBJECTIVE To analyze the main determinants of burden and stress in caregivers of Spanish Parkinson's disease (PD) patients. METHODS One-hundred and twenty-one non-demented patients with PD (57.9% males; 70.9 ± 8.2 years old) were included in this cross-sectional, monocenter, evaluation study. Caregivers (n = 121; 71.9% females; 60.2 ± 15 years old) were assessed using the Zarit Caregiver Burden Inventory (ZCBI) and Caregiver Strain Index (CSI). Multiple linear regression methods were used to evaluate factors contributing to caregivers' stress and burden: (i) PD motor dysfunction (ON-state Hoehn & Yahr/Unified Parkinson's Disease Rating Scale [UPDRS] part III and motor complications [UPDRS part IV]); (ii) Mood (Beck Depression Inventory [BDI]); (iii) Non-motor symptoms (Non-Motor Symptoms Scale [NMSS]); (iv) Disability (Schwab & England Activities of Daily Living Scale [ADLS]); and (v) Socio-demographic and other disease-related variables. RESULTS Zarit Caregiver Burden Inventory and CSI mean scores were 16 ± 13.9 and 2.1 ± 2.3, respectively. High correlation was found between ZCBI and CSI (r = 0.819; P < 0.0001). Moderate to severe burden (ZCBI > 40) was present in 9.1% of caregivers; 5.8% had high levels of stress (CSI ≥ 7). Moderate to strong correlations were observed between patient-related variables (Hoehn&Yahr, UPDRS-III, UPDRS-IV, BDI, NMSS, and ADLS) and ZCBI and CSI (P < 0.0001). Linear regression methods showed that ADLS had the strongest influence on ZCBI and CSI, followed by BDI on ZCBI. CONCLUSIONS Disability (ADLS) and mood (BDI) of patients with PD are the main factors contributing to burden and stress in caregivers.
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Affiliation(s)
- D. Santos-García
- Section of Neurology; Complejo Hospitalario Universitario de Ferrol (CHUF); Hospital A. Marcide; Ferrol Spain
| | - R. de la Fuente-Fernández
- Section of Neurology; Complejo Hospitalario Universitario de Ferrol (CHUF); Hospital A. Marcide; Ferrol Spain
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Mirelman A, Alcalay RN, Saunders-Pullman R, Yasinovsky K, Thaler A, Gurevich T, Mejia-Santana H, Raymond D, Gana-Weisz M, Bar-Shira A, Ozelius L, Clark L, Orr-Urtreger A, Bressman S, Marder K, Giladi N. Nonmotor symptoms in healthy Ashkenazi Jewish carriers of the G2019S mutation in the LRRK2 gene. Mov Disord 2015; 30:981-6. [PMID: 25809001 DOI: 10.1002/mds.26213] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Revised: 02/18/2015] [Accepted: 02/19/2015] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND The asymptomatic carriers of the Leucine rich repeat kinase 2 (LRRK2) G2019S mutation represent a population at risk for developing PD. The aim of this study was to assess differences in nonmotor symptoms between nonmanifesting carriers and noncarriers of the G2019S mutation. METHODS Two hundred fifty-three subjects participated in this observational cross-sectional multicenter study. Standard questionnaires assessing anxiety, depression, cognition, smell, nonmotor symptoms, and rapid eye movement (REM) sleep behavior were administered. Analyses were adjusted for age, sex, family relations, education, and site. RESULTS One hundred thirty-four carriers were identified. Carriers had higher nonmotor symptoms score on the Nonmotor symptoms (NMS) questionnaire (P = 0.02). These findings were amplified in carriers older than age 50 y, with higher nonmotor symptoms scores and trait anxiety scores (P < 0.03). CONCLUSIONS In this cross-section study, carriers of the G2019S LRRK2 mutation endorsed subtle nonmotor symptoms. Whether these are early features of PD will require a longitudinal study. © 2015 International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Anat Mirelman
- Movement Disorders Unit, Department of Neurology, Tel-Aviv Medical Center, Department of Neurology, Israel
| | - Roy N Alcalay
- College of Physicians and Surgeons, Columbia University, New York, NY, USA.,Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA
| | - Rachel Saunders-Pullman
- The Alan and Barbara Mirken Department of Neurology, Mount Sinai-Beth Israel Medical Center, New York, New York, USA.,Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Kira Yasinovsky
- Movement Disorders Unit, Department of Neurology, Tel-Aviv Medical Center, Department of Neurology, Israel
| | - Avner Thaler
- Movement Disorders Unit, Department of Neurology, Tel-Aviv Medical Center, Department of Neurology, Israel
| | - Tanya Gurevich
- Movement Disorders Unit, Department of Neurology, Tel-Aviv Medical Center, Department of Neurology, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Deborah Raymond
- The Alan and Barbara Mirken Department of Neurology, Mount Sinai-Beth Israel Medical Center, New York, New York, USA
| | - Mali Gana-Weisz
- Genetics Institute, Tel Aviv Sourasky Medical Center, Israel
| | - Anat Bar-Shira
- Genetics Institute, Tel Aviv Sourasky Medical Center, Israel
| | - Laurie Ozelius
- Departments of Genetics and Genomic Sciences and Neurology, Mount Sinai School of Medicine, New York, NY, USA
| | - Lorraine Clark
- Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.,Center for Human Genetics, College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - Avi Orr-Urtreger
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Genetics Institute, Tel Aviv Sourasky Medical Center, Israel
| | - Susan Bressman
- The Alan and Barbara Mirken Department of Neurology, Mount Sinai-Beth Israel Medical Center, New York, New York, USA.,Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Karen Marder
- College of Physicians and Surgeons, Columbia University, New York, NY, USA.,Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA
| | - Nir Giladi
- Movement Disorders Unit, Department of Neurology, Tel-Aviv Medical Center, Department of Neurology, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Sieratzki Chair in Neurology, Tel-Aviv University, New York, NY, USA
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Transdermal Rotigotine Improves Sleep Fragmentation in Parkinson's Disease: Results of the Multicenter, Prospective SLEEP-FRAM Study. PARKINSONS DISEASE 2015; 2015:131508. [PMID: 25793143 PMCID: PMC4352510 DOI: 10.1155/2015/131508] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 02/03/2015] [Accepted: 02/05/2015] [Indexed: 01/23/2023]
Abstract
Sleep disturbances occur frequently in patients with Parkinson's disease (PD). The aim of this study was to investigate the effects of rotigotine on sleep fluctuations in a sample of PD patients with self-reported complaints of nocturnal awakenings. This prospective, open-label, observational, and multicenter study enrolled consecutive outpatients with PD and administered rotigotine (mean dose 8.9 mg/day) for 3 months. The primary endpoint was the change from baseline in sleep fragmentation, assessed using the sleep maintenance subscale score of the Parkinson's Disease Sleep Scale (PDSS). The newly designed Parkinson's Disease Sleep Fragmentation Questionnaire (PD-SFQ) was used to measure other sleep parameters. A total of 62 patients were enrolled (mean age 70.2 years; 66% male). At 3 months, rotigotine significantly improved sleep fragmentation from baseline on the PDSS-2 sleep maintenance subscale (from 3.4 ± 0.9 to 1.9 ± 1.4; P < 0.0001). Rotigotine also significantly improved nocturnal motor symptoms (P < 0.0001), restless legs-like symptoms (P < 0.005), and nocturia (P = 0.004). Rotigotine significantly improved self-reported complaints of sleep fragmentation in PD patients and could be a useful treatment to improve this specific sleep problem in PD. However, these results are based on a small and clinically heterogeneous sample so they must be taken cautiously.
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Caillava-Santos F, Margis R, de Mello Rieder CR. Wearing-off in Parkinson's disease: neuropsychological differences between on and off periods. Neuropsychiatr Dis Treat 2015; 11:1175-80. [PMID: 25999721 PMCID: PMC4435249 DOI: 10.2147/ndt.s77060] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Levodopa-associated motor fluctuations are common complications observed in Parkinson's disease (PD) patients. Although nonmotor fluctuations are a significant cause of morbidity, they frequently are not properly identified. Few studies have characterized the nonmotor emotional fluctuations and their relation to motor fluctuations. AIMS The objective of the present study is to analyze the occurrence of fluctuations in anxiety and depression symptoms, as well as in cognitive function (memory, language, executive function, and attention), and their relation to motor fluctuations in PD patients presenting wearing-off phenomenon. METHODS Twenty-four patients were assessed during the wearing on-off periods. The State-Trait Anxiety Inventory (STAI-State) and Beck Depression Inventory (BDI) were used to assess anxiety and depression, respectively, and the Wisconsin Card Sorting Test (WCST), Stroop Test, Rey Auditory Verbal Learning Test (RAVLT), Weschler Memory Scale - digits (WMS) and Controlled Oral Word Association (COWA) for assessing executive functions, verbal memory, attention and work memory and verbal fluency, respectively. RESULTS Patients presented higher depression and anxiety scores in the wearing-off period (P<0.05). Differences were also found in the semantic verbal fluency (P=0.017) and executive function (P=0.008) tests performance. CONCLUSIONS Nonmotor symptoms such as anxiety and depression, verbal fluency, and executive function performance are influenced by motor fluctuations.
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Affiliation(s)
- Fabiane Caillava-Santos
- Psychology Department, Universidade da Região da Campanha, Bagé, RS, Brazil ; Curso de Pós-Graduação em Medicina, Ciências Médicas da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Regina Margis
- Curso de Pós-Graduação em Medicina, Ciências Médicas da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Carlos Roberto de Mello Rieder
- Curso de Pós-Graduação em Medicina, Ciências Médicas da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil ; Movement Disorders Center, Division of Neurology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil ; Movement Disorder Clinic, Division of Neurology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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Baillon S, Dennis M, Lo N, Lindesay J. Screening for depression in Parkinson's disease: the performance of two screening questions. Age Ageing 2014; 43:200-5. [PMID: 24132854 DOI: 10.1093/ageing/aft152] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND the study objective was to evaluate the validity of the two questions recommended by the UK. National Institute for Health and Clinical Excellence for depression screening in Parkinson's disease (PD). METHODS one hundred and twenty patients attending a PD out-patient clinic were interviewed in a standardised manner using relevant sections of the Present State Examination- Schedules for Clinical Assessment in Neuropsychiatry to identify depression according to Diagnostic and Statistical Manual (4th edition) criteria. Participants then completed the two depression screening questions and the 15-item Geriatric Depression Scale (GDS-15). RESULTS sensitivity, specificity, positive and negative predictive values of the two questions and GDS-15 for major and minor depression combined were calculated for different cut-off scores and a receiver operating characteristics (ROC) analysis was conducted. A threshold of one or more positive responses to the two screening questions gave a sensitivity of 100% and specificity of 84% (positive predictive value 54%, negative predictive value 100%). The area under the ROC curve was 0.95. The optimal cut-off for the GDS-15 was 5/6, which gave a sensitivity of 84% and specificity of 89% (positive predictive value 59%, negative predictive value 97%), and the area under the curve was 0.92. CONCLUSION this study shows that the two depression screening questions can be used as an initial screen for depression in patients with PD who have no significant cognitive impairment. A positive response to either of the questions would indicate that further diagnostic assessment may be warranted.
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Affiliation(s)
- Sarah Baillon
- Department of Health Sciences, University of Leicester, Leicester, Leics, UK
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Ghorbani Saeedian R, Nagyova I, Krokavcova M, Skorvanek M, Rosenberger J, Gdovinova Z, Groothoff JW, van Dijk JP. The role of social support in anxiety and depression among Parkinson's disease patients. Disabil Rehabil 2014; 36:2044-9. [PMID: 24533876 DOI: 10.3109/09638288.2014.886727] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE To explore how social support is associated with anxiety and depression in Parkinson's disease (PD) patients controlling for gender, disease duration and disease severity. METHODS The sample consisted of 124 patients (52.4% male; mean age 68.1 ± 8.4 years; mean disease duration 6.3 ± 5.5 years). Anxiety and depression were measured with the Hospital Anxiety and Depression Scale, social support with the Multidimensional Scale of Perceived Social Support and disease severity with the Unified Parkinson Disease Rating Scale. Data were analyzed using linear regression. RESULTS Gender, disease duration, disease severity and social support explained 31% of the total variance in anxiety in younger PD patients but did not significantly contribute to the explanation of depression. In the older group, this model explained 41% of the variance in depression but did not significantly contribute to the explanation of anxiety. CONCLUSION PD patients experience the positive influence of social support differently according to age. In the younger group, disease duration plays the primary role regarding anxiety. In the older group, poor social support especially from friends is associated with more depression after controlling for the relevant variables. Implications of Rehabilitation PD is a disease of older age with a neurodegenerative character and treatment should focus on increasing quality of life. Anxiety and depression are common co-morbidities in PD patients. The support network should also be screened regularly and involved in enhancing the quality of life.
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Lagopoulos J, Malhi GS, Ivanovski B, Cahill CM, Morris JGL. A matter of motion or an emotional matter? Management of depression in Parkinson’s disease. Expert Rev Neurother 2014; 5:803-10. [PMID: 16274337 DOI: 10.1586/14737175.5.6.803] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Depression is one of the most frequent comorbidities occurring in Parkinson's disease, affecting up to 50% of patients. Depression is associated with severe negative symptoms and has been shown to contribute to an increased rate of decline of both cognitive and motor function, profoundly impacting on the patient's quality of life. The symptoms of depression overlap with the motor features of Parkinson's disease, making detection difficult. Moreover, the lack of specialized screening tools means that depression remains undiagnosed and untreated in a high percentage of patients. However, depression in Parkinson's disease, when identified early, can be effectively treated with a variety of antidepressant medications, improving quality of life and preserving daily function. The focus of this review is to provide an overview of current knowledge regarding depression in Parkinson's disease, followed by a practical discussion addressing the issues of the detection, diagnosis and treatment.
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Affiliation(s)
- Jim Lagopoulos
- School of Psychiatry, The University of New South Wales, Australia
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Henderson EJ, Lord SR, Close JCT, Lawrence AD, Whone A, Ben-Shlomo Y. The ReSPonD trial--rivastigmine to stabilise gait in Parkinson's disease a phase II, randomised, double blind, placebo controlled trial to evaluate the effect of rivastigmine on gait in patients with Parkinson's disease who have fallen. BMC Neurol 2013; 13:188. [PMID: 24299497 PMCID: PMC3880104 DOI: 10.1186/1471-2377-13-188] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Accepted: 11/11/2013] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Gait impairment is common in people with Parkinson's disease. There is a lack of effective interventions to target this debilitating complication and therefore a need to identify new therapeutic options. An underlying cholinergic deficit contributes to both the gait and cognitive dysfunction seen in Parkinson's disease. The combined impact of both impairments can be assessed in gait tasks performed with concomitant cognitive tasks. The aim of this trial is to evaluate the impact of a cholinesterase inhibitor on cognitive function and gait performance in people with established Parkinson's disease. METHODS/DESIGN This is a single centre, double-blind, randomised placebo-controlled trial in 130 people with Hoehn and Yahr stage 2-3 idiopathic Parkinson's disease who have fallen in the past year. Participants will be randomised to two groups, receiving either rivastigmine capsules or identical placebo capsules for 8 months. Assessment will be undertaken at baseline and at the end of medication prescription (i.e. 8 months) with participants remaining enrolled in the trial for a further 4 months to monitor for falls and adverse events. The primary outcome is step time variability, assessed with and without the addition of concurrent cognitive tasks. Secondary outcomes will include other gait parameters, sensorimotor and balance performances, cognitive indices, falls and fall related injury, fear of falling, Parkinson's symptoms and data pertaining to possible harms. DISCUSSION This randomised controlled trial will examine the effect of cholinesterase inhibitor therapy on gait, balance and falls in Parkinson's disease. If effective, it would offer a new therapeutic option to ameliorating gait and cognitive deficits in a population at high risk of falls. TRIAL REGISTRATION ISRCTN19880883, UTN U1111-1124-0244.
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Affiliation(s)
- Emily J Henderson
- Department of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, BS8 2PS Bristol, UK.
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Alcalay RN, Mirelman A, Saunders-Pullman R, Tang MX, Mejia Santana H, Raymond D, Roos E, Orbe-Reilly M, Gurevich T, Bar Shira A, Gana Weisz M, Yasinovsky K, Zalis M, Thaler A, Deik A, Barrett MJ, Cabassa J, Groves M, Hunt AL, Lubarr N, San Luciano M, Miravite J, Palmese C, Sachdev R, Sarva H, Severt L, Shanker V, Swan MC, Soto-Valencia J, Johannes B, Ortega R, Fahn S, Cote L, Waters C, Mazzoni P, Ford B, Louis E, Levy O, Rosado L, Ruiz D, Dorovski T, Pauciulo M, Nichols W, Orr-Urtreger A, Ozelius L, Clark L, Giladi N, Bressman S, Marder KS. Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. Mov Disord 2013; 28:1966-71. [PMID: 24243757 DOI: 10.1002/mds.25647] [Citation(s) in RCA: 125] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Revised: 07/11/2013] [Accepted: 07/28/2013] [Indexed: 12/12/2022] Open
Abstract
The phenotype of Parkinson's disease (PD) in patients with and without leucine-rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking. The objective of this study was to characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. We studied 553 AJ PD patients, including 65 patients who were previously reported, from three sites (two in New York and one in Tel-Aviv). Glucocerebrosidase (GBA) mutation carriers were excluded. Evaluations included the Montreal Cognitive Assessment (MoCA), the Unified Parkinson's Disease Rating Scale (UPDRS), the Geriatric Depression Scale (GDS) and the Non-Motor Symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features and LRRK2 status (outcome) in 488 newly recruited participants. LRRK2 G2019S carriers (n = 97) and non-carriers (n = 391) were similar in age and age at onset of PD. Carriers had longer disease duration (8.6 years vs. 6.1 years; P < 0.001), were more likely to be women (51.5% vs. 37.9%; P = 0.015), and more often reported first symptoms in the lower extremities (40.0% vs. 19.2%; P < 0.001). In logistic models that were adjusted for age, disease duration, sex, education, and site, carriers were more likely to have lower extremity onset (P < 0.001), postural instability and gait difficulty (PIGD) (P = 0.043), and a persistent levodopa response for >5 years (P = 0.042). Performance on the UPDRS, MoCA, GDS, and NMS did not differ by mutation status. PD in AJ LRRK2 G2019S mutation carriers is similar to idiopathic PD but is characterized by more frequent lower extremity involvement at onset and PIGD without the associated cognitive impairment.
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Affiliation(s)
- Roy N Alcalay
- Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA
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Chiu M, Wesson V, Sadavoy J. Improving caregiving competence, stress coping, and mental well-being in informal dementia carers. World J Psychiatry 2013; 3:65-73. [PMID: 24255878 PMCID: PMC3832864 DOI: 10.5498/wjp.v3.i3.65] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 07/18/2013] [Accepted: 10/16/2013] [Indexed: 02/05/2023] Open
Abstract
AIM: To study the effectiveness of Reitman Centre “Coaching, Advocacy, Respite, Education, Relationship, and Simulation” (CARERS) program, which uses problem-solving techniques and simulation to train informal dementia carers.
METHODS: Seventy-three carers for family members with dementia were included in the pilot study. Pre- and post-intervention data were collected from carers using validated measures of depression, mastery, role captivity and overload, caregiving competence and burden, and coping styles. To assess program effectiveness, mean differences for these measures were calculated. One-way ANOVA was used to determine if change in scores is dependent on the respective baseline scores. Clinical effects for measures were expressed as Cohen’s D values.
RESULTS: Data from 73 carers were analyzed. The majority of these participants were female (79.5%). A total of 69.9% were spouses and 30.1% were children of the care recipient. Participants had an overall mean age of 68.34 ± 12.01 years. About 31.5% of participating carers had a past history of psychiatric illness (e.g., depression), and 34.2% sustained strained relationships with their respective care recipients. Results from carers demonstrated improvement in carers’ self-perception of competence (1.26 ± 1.92, P < 0.0001), and significant reduction in emotion-focused coping (measured by the Coping Inventory of Stressful Situations, -2.37 ± 6.73, P < 0.01), Geriatric Depression scale (-0.67 ± 2.63, P < 0.05) and Pearlin’s overload scale (-0.55 ± 2.07, P < 0.05), upon completion of the Program. Secondly, it was found that carers with more compromised baseline scores benefited most from the intervention, as they experienced statistically significant improvement in the following constructs: competence, stress-coping style (less emotion-oriented), sense of mastery, burden, overload.
CONCLUSION: Study results supported the effectiveness of the CARERS Program in improving caregiving competence, stress coping ability and mental well-being in carers caring for family members with dementia.
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Chagas MHN, Tumas V, Rodrigues GR, Machado-de-Sousa JP, Filho AS, Hallak JEC, Crippa JAS. Validation and internal consistency of Patient Health Questionnaire-9 for major depression in Parkinson's disease. Age Ageing 2013; 42:645-9. [PMID: 23761457 DOI: 10.1093/ageing/aft065] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND depression is common in Parkinson's disease (PD), although frequently under-recognised. Among the scales used to investigate depressive features in PD, the Patient Health Questionnaire-9 (PHQ-9) has been largely used, but no specific cut-off scores for depression have been established thus far, which hinders the use of the PHQ-9 in clinical and research settings. OBJECTIVE we assessed the discriminant validity of the PHQ-9 in order to establish the best cut-off score for the diagnosis of major depression in PD patients. METHOD one hundred and ten patients with a diagnosis of PD without dementia were evaluated with the Structured Clinical Interview for DSM-IV (SCID), considered as the gold standard for the diagnosis of major depression. Eighty-four PD patients completed the PHQ-9, the 15-item Geriatric Depression Scale (GDS-15) and the Zung Self-rating Depression Scale (SDS). RESULTS the prevalence of current depression in the sample of PD patients was 25.5%. Maximal discrimination between depressed and non-depressed patients was reached with a cut-off score of 9 in the PHQ-9 (sensitivity of 100% and specificity of 83.1%). The internal consistency of the scale was 0.83 and, when used as a diagnostic instrument, the PHQ-9 had a sensitivity of 52.6% and specificity of 95.4%. The correlation coefficient between the PHQ-9 and the other two scales was 0.63. CONCLUSIONS the PHQ-9 is an adequate instrument for the screening-but not diagnosis-of depression in PD patients, with optimal sensitivity and specificity attained with a cut-off score of 9.
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Affiliation(s)
- Marcos Hortes N Chagas
- Behavior and Neurosciences Department, University of São Paulo, Av., Bandeirantes, 3900, Ribeirão Preto, SP 14048-900, Brazil.
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Oyama G, Okun MS, Schmidt P, Tröster AI, Nutt J, Go CL, Foote KD, Malaty IA. Deep Brain Stimulation May Improve Quality of Life in People With Parkinson's Disease Without Affecting Caregiver Burden. Neuromodulation 2013; 17:126-32. [DOI: 10.1111/ner.12097] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2012] [Revised: 04/30/2013] [Accepted: 05/22/2013] [Indexed: 11/29/2022]
Affiliation(s)
- Genko Oyama
- Department of Neurology; University of Florida Center for Movement Disorders and Neurorestoration; Gainesville FL USA
| | - Michael S. Okun
- Department of Neurology; University of Florida Center for Movement Disorders and Neurorestoration; Gainesville FL USA
- Department of Neurosurgery; University of Florida Center for Movement Disorders and Neurorestoration; Gainesville FL USA
| | | | - Alexander I. Tröster
- Department of Neurology; University of North Carolina School of Medicine; Chapel Hill NC USA
| | - John Nutt
- Department of Neurology; Oregon Health & Science University; Portland OR USA
| | - Criscely L. Go
- Department of Neurology; University of Florida Center for Movement Disorders and Neurorestoration; Gainesville FL USA
| | - Kelly D. Foote
- Department of Neurology; University of Florida Center for Movement Disorders and Neurorestoration; Gainesville FL USA
- Department of Neurosurgery; University of Florida Center for Movement Disorders and Neurorestoration; Gainesville FL USA
| | - Irene A. Malaty
- Department of Neurology; University of Florida Center for Movement Disorders and Neurorestoration; Gainesville FL USA
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Ambulatory activity in incident Parkinson's: more than meets the eye? J Neurol 2013; 260:2964-72. [PMID: 23900754 DOI: 10.1007/s00415-013-7037-5] [Citation(s) in RCA: 135] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Revised: 07/04/2013] [Accepted: 07/05/2013] [Indexed: 01/22/2023]
Abstract
Physical activity is important for people with Parkinson's disease (PD) to improve disease-specific impairment and ameliorate secondary consequences related to deconditioning. Activity may also have a neuroprotective role if instigated early. Ambulatory activity has not been examined in incident PD. Eighty-nine newly diagnosed PD cases [mean (SD) age 67.3 (9.9) years] and 97 controls [mean (SD) 69.2 (7.7) years] wore an activity monitor (activPAL™) for 7 days. Volume, pattern and variability outcomes were compared. Accumulation of activity (α) was classified as short (< 30 s), medium (30 s-2 min) and long (> 2 min) bouts of walking. Associations between sustained walking (> 2 min) and motor, cognitive and affective characteristics were identified. Activity outcomes were considered with respect to global health recommendations. Total steps (volume), accumulation of bout length (α), and variability (S2w) outcomes were significantly different (all P < 0.001). PD participants (including Hoehn & Yahr (H&Y) stage I) accumulated significantly less time in long bouts (> 2 min) of walking compared with controls, due to performing fewer long bouts, rather than a reduction in time spent in walking per bout. For PD and controls there were weak but significant correlations for a range of characteristics and sustained walking. Fewer people with PD achieved the recommended 30 min of walking per day comprised of bouts > 10 min (P = 0.02) and bouts > 2 min (P < 0.001). People with PD were significantly less active than controls, with an inability to sustain levels of walking, and with differences apparent very early on in the disease process. A focus on increasing general ambulatory activity and exercise from the outset is recommended.
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