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Gabriel V, Bousiges O, Mondino M, Cretin B, Philippi N, Muller C, Anthony P, Demuynck C, de Sousa PL, Botzung A, Sanna L, Chabran E, Blanc F. Aβ42 biomarker linked to insula, striatum, thalamus and claustrum in dementia with Lewy bodies. GeroScience 2025:10.1007/s11357-025-01513-z. [PMID: 39821801 DOI: 10.1007/s11357-025-01513-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 01/06/2025] [Indexed: 01/19/2025] Open
Abstract
The differential mechanisms between proteinopathies and neurodegeneration in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) remain unclear. To address this issue, we conducted a voxel-based morphometry and cerebrospinal fluid biomarker (α-synuclein, Aβ42, t-Tau and p-Tau181) level correlation study in patients with DLB, AD and mixed cases (AD + DLB). Cerebrospinal fluid samples obtained by lumbar puncture and whole-brain T1-weighted images were collected in the AlphaLewyMA cohort. Within the cohort, 65 DLB patients, 18 AD patients, 24 AD + DLB patients and 16 neurological control subjects (NC) were clinically diagnosed. Correlation analyses were performed between cerebrospinal fluid biomarker levels and gray matter volumes using a voxel-based morphometry approach. A mediation analysis was performed to explore the role of gray matter volumes in the relationship between Aβ42 levels and clinical severity (MMSE scores). We observed a significant positive correlation between gray matter volumes and cerebrospinal fluid Aβ42 levels in the insula, the striatal regions, the right thalamus, and the claustrum in DLB patients (pFDR < 0.05). Mediation analysis revealed that gray matter volumes significantly mediated the relationship between Aβ42 levels and MMSE scores in DLB patients. We found no significant correlation with gray matter volumes for α-synuclein, p-Tau181 or t-Tau in DLB patients (pFDR < 0.05). We found no significant correlations in the AD, AD + DLB and NC groups for any of the biomarkers (pFDR < 0.05). The specific correlation between a reduced cerebrospinal fluid Aβ42 level and lower gray matter volumes in insula, striatum, thalamus, and claustrum in DLB patients suggests a prominent role for amyloidopathy in promoting brain atrophy in key regions of the disease.
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Affiliation(s)
- Vincent Gabriel
- ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France.
| | - Olivier Bousiges
- ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France
- Laboratory of Biochemistry and Molecular Biology, University Hospital of Strasbourg, Strasbourg, France
| | - Mary Mondino
- ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France
- Laboratory of Biochemistry and Molecular Biology, University Hospital of Strasbourg, Strasbourg, France
| | - Benjamin Cretin
- ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France
- CM2R (Centre de Mémoire Ressources Et Recherche), Geriatric Day Hospital and Neuropsychological Unit, Geriatrics Department and Neurology Service, University Hospital of Strasbourg, Strasbourg, France
| | - Nathalie Philippi
- ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France
- CM2R (Centre de Mémoire Ressources Et Recherche), Geriatric Day Hospital and Neuropsychological Unit, Geriatrics Department and Neurology Service, University Hospital of Strasbourg, Strasbourg, France
| | - Candice Muller
- CM2R (Centre de Mémoire Ressources Et Recherche), Geriatric Day Hospital and Neuropsychological Unit, Geriatrics Department and Neurology Service, University Hospital of Strasbourg, Strasbourg, France
| | - Pierre Anthony
- CM2R (Centre de Mémoire Ressources Et Recherche), Geriatric Day Hospital and Neuropsychological Unit, Geriatrics Department and Neurology Service, University Hospital of Strasbourg, Strasbourg, France
- CM2R, Geriatric Day Hospital, Geriatrics Division, Civil Hospitals of Colmar, Colmar, France
| | - Catherine Demuynck
- CM2R (Centre de Mémoire Ressources Et Recherche), Geriatric Day Hospital and Neuropsychological Unit, Geriatrics Department and Neurology Service, University Hospital of Strasbourg, Strasbourg, France
| | - Paulo Loureiro de Sousa
- ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France
| | - Anne Botzung
- ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France
- CM2R (Centre de Mémoire Ressources Et Recherche), Geriatric Day Hospital and Neuropsychological Unit, Geriatrics Department and Neurology Service, University Hospital of Strasbourg, Strasbourg, France
| | - Léa Sanna
- CM2R (Centre de Mémoire Ressources Et Recherche), Geriatric Day Hospital and Neuropsychological Unit, Geriatrics Department and Neurology Service, University Hospital of Strasbourg, Strasbourg, France
| | - Eléna Chabran
- ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France
| | - Frédéric Blanc
- ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France
- CM2R (Centre de Mémoire Ressources Et Recherche), Geriatric Day Hospital and Neuropsychological Unit, Geriatrics Department and Neurology Service, University Hospital of Strasbourg, Strasbourg, France
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Carrarini C, Nardulli C, Titti L, Iodice F, Miraglia F, Vecchio F, Rossini PM. Neuropsychological and electrophysiological measurements for diagnosis and prediction of dementia: a review on Machine Learning approach. Ageing Res Rev 2024; 100:102417. [PMID: 39002643 DOI: 10.1016/j.arr.2024.102417] [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] [Received: 11/09/2023] [Revised: 04/29/2024] [Accepted: 07/07/2024] [Indexed: 07/15/2024]
Abstract
INTRODUCTION Emerging and advanced technologies in the field of Artificial Intelligence (AI) represent promising methods to predict and diagnose neurodegenerative diseases, such as dementia. By using multimodal approaches, Machine Learning (ML) seems to provide a better understanding of the pathological mechanisms underlying the onset of dementia. The purpose of this review was to discuss the current ML application in the field of neuropsychology and electrophysiology, exploring its results in both prediction and diagnosis for different forms of dementia, such as Alzheimer's disease (AD), Vascular Dementia (VaD), Dementia with Lewy bodies (DLB), and Frontotemporal Dementia (FTD). METHODS Main ML-based papers focusing on neuropsychological assessments and electroencephalogram (EEG) studies were analyzed for each type of dementia. RESULTS An accuracy ranging between 70 % and 90 % or even more was observed in all neurophysiological and electrophysiological results trained by ML. Among all forms of dementia, the most significant findings were observed for AD. Relevant results were mostly related to diagnosis rather than prediction, because of the lack of longitudinal studies with appropriate follow-up duration. However, it remains unclear which ML algorithm performs better in diagnosing or predicting dementia. CONCLUSIONS Neuropsychological and electrophysiological measurements, together with ML analysis, may be considered as reliable instruments for early detection of dementia.
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Affiliation(s)
- Claudia Carrarini
- Department of Neuroscience & Neurorehabilitation, IRCCS San Raffaele, via della Pisana 235, Rome 00163, Italy; Department of Neuroscience, Catholic University of Sacred Heart, Largo Agostino Gemelli 8, Rome 00168, Italy
| | - Cristina Nardulli
- Department of Neuroscience & Neurorehabilitation, IRCCS San Raffaele, via della Pisana 235, Rome 00163, Italy
| | - Laura Titti
- Department of Neuroscience & Neurorehabilitation, IRCCS San Raffaele, via della Pisana 235, Rome 00163, Italy
| | - Francesco Iodice
- Department of Neuroscience & Neurorehabilitation, IRCCS San Raffaele, via della Pisana 235, Rome 00163, Italy
| | - Francesca Miraglia
- Department of Neuroscience & Neurorehabilitation, IRCCS San Raffaele, via della Pisana 235, Rome 00163, Italy; Department of Theoretical and Applied Sciences, eCampus University, via Isimbardi 10, Novedrate 22060, Italy
| | - Fabrizio Vecchio
- Department of Neuroscience & Neurorehabilitation, IRCCS San Raffaele, via della Pisana 235, Rome 00163, Italy; Department of Theoretical and Applied Sciences, eCampus University, via Isimbardi 10, Novedrate 22060, Italy
| | - Paolo Maria Rossini
- Department of Neuroscience & Neurorehabilitation, IRCCS San Raffaele, via della Pisana 235, Rome 00163, Italy.
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Armstrong MJ, Barnes LL. Under-Diagnosis of Dementia with Lewy Bodies in Individuals Racialized as Black: Hypotheses Regarding Potential Contributors. J Alzheimers Dis 2024; 97:1571-1580. [PMID: 38277299 PMCID: PMC10894581 DOI: 10.3233/jad-231177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/07/2023] [Indexed: 01/28/2024]
Abstract
Dementia with Lewy bodies (DLB) is one of the most common degenerative dementias after Alzheimer's disease (AD) dementia. DLB is under-diagnosed across populations but may be particularly missed in older Black adults. The object of this review was to examine key features of DLB and potential associations with race in order to hypothesize why DLB may be under-diagnosed in Black adults in the U.S. In terms of dementia, symptoms associated with high rates of co-pathology (e.g., AD, vascular disease) in older Black adults may obscure the clinical picture that might suggest Lewy body pathology. Research also suggests that clinicians may be predisposed to give AD dementia diagnoses to Black adults, potentially missing contributions of Lewy body pathology. Hallucinations in Black adults may be misattributed to AD or primary psychiatric disease rather than Lewy body pathology. Research on the prevalence of REM sleep behavior in diverse populations is lacking, but REM sleep behavior disorder could be under-diagnosed in Black adults due to sleep patterns or reporting by caregivers who are not bed partners. Recognition of parkinsonism could be reduced in Black adults due to clinician biases, cultural effects on self-report, and potentially underlying differences in the frequency of parkinsonism. These considerations are superimposed on structural and systemic contributions to health (e.g., socioeconomic status, education, structural racism) and individual-level social exposures (e.g., social interactions, discrimination). Improving DLB recognition in Black adults will require research to investigate reasons for diagnostic disparities and education to increase identification of core symptoms in this population.
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Affiliation(s)
- Melissa J. Armstrong
- Department of Neurology, University of Florida College of Medicine, Gainesville, FL, USA
- 1Florida Alzheimer Disease Research Center, Gainesville, FL, USA
| | - Lisa L. Barnes
- Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA
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Isik AT, Kaya D, Ontan MS, Mutlay F, Bulut EA, Dost FS, Erken N, Aydin AE. Neuroleptic Malignant Syndrome in Patients With Dementia: Experiences of A Single Memory Clinic. Clin Neuropharmacol 2023; 46:209-213. [PMID: 37962307 DOI: 10.1097/wnf.0000000000000570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2023]
Abstract
OBJECTIVES Neuroleptic malignant syndrome (NMS) is a life-threatening condition that occurs as an adverse reaction to antipsychotic and antiemetic agents or sudden withdrawal of dopaminergic medications. Given the metabolic and functional reserves and the comorbidities in older adults, NMS may show an atypical course. METHODS The medical records of patients with neurodegenerative diseases leading to dementia between 2013 and 2020 were reviewed for the diagnosis of NMS. Demographic and clinical characteristics of the patients were obtained from the records of laboratory parameters, management, and length of stay. RESULTS Fifteen older adults (19 episodes) diagnosed with NMS were included. The median age was 76 years, and 5 were female. Ten of 15 NMS patients were atypical. Most of them had an infection accompanying NMS. Neuroleptic malignant syndrome was caused by antidopaminergic agents (5 antipsychotics, 1 metoclopramide) in 6 episodes and discontinuation of a dopaminergic agent, l -DOPA, in 12 episodes. In 1 patient, it was associated with simultaneous use of domperidone and amantadine withdrawal. Rigidity in NMS due to l -DOPA discontinuation was higher than in those due to antipsychotic use ( P = 0.027). Two of our patients needed intensive care, and 1 died. CONCLUSIONS This study highlights the high frequency of atypical NMS and the importance of early recognition of this potentially fatal syndrome, which can accompany neurodegenerative diseases and infections in older adults.
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Affiliation(s)
- Ahmet Turan Isik
- Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir
| | - Derya Kaya
- Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir
| | - Mehmet Selman Ontan
- Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir
| | - Feyza Mutlay
- Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir
| | - Esra Ates Bulut
- Department of Geriatric Medicine, Adana City Research and Training Hospital, Adana
| | - Fatma Sena Dost
- Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir
| | - Neziha Erken
- Department of Geriatric Medicine, University of Gazi Antep, Gaziantep
| | - Ali Ekrem Aydin
- Department of Geriatric Medicine, Sivas Numune Hospital, Sivas, Turkey
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Kang S, Yoon SH, Na HK, Lee YG, Jeon S, Baik K, Sohn YH, Ye BS. Neuropsychological Comparison of Patients With Alzheimer's Disease and Dementia With Lewy Bodies. J Clin Neurol 2023; 19:521-529. [PMID: 37455503 PMCID: PMC10622731 DOI: 10.3988/jcn.2022.0358] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 12/20/2022] [Accepted: 12/21/2022] [Indexed: 07/18/2023] Open
Abstract
BACKGROUND AND PURPOSE This study aimed to determine the neuropsychological differences between patients with early-stage Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) with a Clinical Dementia Rating (CDR) score of ≤1. METHODS We examined 168 patients with AD (126 with CDR score=0.5, 42 with CDR score=1) and 169 patients with DLB (104 with CDR score=0.5, 65 with CDR score=1) whose diagnoses were supported by 18F-flobetaben positron-emission tomography (PET) and 18F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane PET. Neuropsychological test scores were compared after controlling for age, sex, and education duration. Using a cutoff motor score on the Unified Parkinson's Disease Rating Scale of 20, patients with AD were further divided into AD with parkinsonism (ADP+, n=86) and AD without parkinsonism (ADP-, n=82). RESULTS At CDR scores of both 0.5 and 1, the DLB group had lower scores on the attention (digit-span forward at CDR score=0.5 and backward at CDR score=1), visuospatial, and executive (color reading Stroop test at CDR score=0.5 and phonemic fluency test, Stroop tests, and digit symbol coding at CDR score=1) tests than the AD group, but higher scores on the memory tests. The ADP- and ADP+ subgroups had comparable scores on most neuropsychological tests, but the ADP+ subgroup had lower scores on the color reading Stroop test. CONCLUSIONS Patients with DLB had worse attention, visuospatial, and executive functions but better memory function than patients with AD. Parkinsonism was not uncommon in the patients with AD and could be related to attention and executive dysfunction.
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Affiliation(s)
- Sungwoo Kang
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - So Hoon Yoon
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Han Kyu Na
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Young-Gun Lee
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Seun Jeon
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
- Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Kyoungwon Baik
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Young H Sohn
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | - Byoung Seok Ye
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
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Pires PC, Paiva-Santos AC, Veiga F. Liposome-Derived Nanosystems for the Treatment of Behavioral and Neurodegenerative Diseases: The Promise of Niosomes, Transfersomes, and Ethosomes for Increased Brain Drug Bioavailability. Pharmaceuticals (Basel) 2023; 16:1424. [PMID: 37895895 PMCID: PMC10610493 DOI: 10.3390/ph16101424] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 09/29/2023] [Accepted: 10/06/2023] [Indexed: 10/29/2023] Open
Abstract
Psychiatric and neurodegenerative disorders are amongst the most prevalent and debilitating diseases, but current treatments either have low success rates, greatly due to the low permeability of the blood-brain barrier, and/or are connected to severe side effects. Hence, new strategies are extremely important, and here is where liposome-derived nanosystems come in. Niosomes, transfersomes, and ethosomes are nanometric vesicular structures that allow drug encapsulation, protecting them from degradation, and increasing their solubility, permeability, brain targeting, and bioavailability. This review highlighted the great potential of these nanosystems for the treatment of Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, anxiety, and depression. Studies regarding the encapsulation of synthetic and natural-derived molecules in these systems, for intravenous, oral, transdermal, or intranasal administration, have led to an increased brain bioavailability when compared to conventional pharmaceutical forms. Moreover, the developed formulations proved to have neuroprotective, anti-inflammatory, and antioxidant effects, including brain neurotransmitter level restoration and brain oxidative status improvement, and improved locomotor activity or enhancement of recognition and working memories in animal models. Hence, albeit being relatively new technologies, niosomes, transfersomes, and ethosomes have already proven to increase the brain bioavailability of psychoactive drugs, leading to increased effectiveness and decreased side effects, showing promise as future therapeutics.
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Affiliation(s)
- Patrícia C. Pires
- Faculty of Pharmacy, Faculty of Pharmacy of the University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal;
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
- Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal
| | - Ana Cláudia Paiva-Santos
- Faculty of Pharmacy, Faculty of Pharmacy of the University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal;
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Francisco Veiga
- Faculty of Pharmacy, Faculty of Pharmacy of the University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal;
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
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Seebaluck J, Colebatch JG, Chan BS. Butyrophenone-induced neuroleptic malignant syndrome in Lewy body dementia: A cautionary tale. Emerg Med Australas 2023; 35:183-184. [PMID: 36316025 DOI: 10.1111/1742-6723.14113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 10/04/2022] [Accepted: 10/06/2022] [Indexed: 01/19/2023]
Affiliation(s)
- Jason Seebaluck
- South Eastern Area Toxicology Service, Prince of Wales Hospital, Sydney, New South Wales, Australia.,Emergency Department, Prince of Wales Hospital, Sydney, New South Wales, Australia
| | - James G Colebatch
- Department of Neurology, Institute of Neurological Sciences, Prince of Wales Hospital, Sydney, New South Wales, Australia.,School of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - Betty S Chan
- South Eastern Area Toxicology Service, Prince of Wales Hospital, Sydney, New South Wales, Australia.,Emergency Department, Prince of Wales Hospital, Sydney, New South Wales, Australia.,Critical Care Discipline, The University of New South Wales, Sydney, New South Wales, Australia.,NSW Poisons Information Centre, Sydney, New South Wales, Australia
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Silva-Rodríguez J, Labrador-Espinosa MA, Moscoso A, Schöll M, Mir P, Grothe MJ, for the Alzheimer’s Disease Neuroimaging Initiative. Differential Effects of Tau Stage, Lewy Body Pathology, and Substantia Nigra Degeneration on 18F-FDG PET Patterns in Clinical Alzheimer Disease. J Nucl Med 2023; 64:274-280. [PMID: 36008119 PMCID: PMC9902861 DOI: 10.2967/jnumed.122.264213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 08/03/2022] [Accepted: 08/03/2022] [Indexed: 02/04/2023] Open
Abstract
Comorbid Lewy body (LB) pathology is common in Alzheimer disease (AD). The effect of LB copathology on 18F-FDG PET patterns in AD is yet to be studied. We analyzed associations of neuropathologically assessed tau pathology, LB pathology, and substantia nigra neuronal loss (SNnl) with antemortem 18F-FDG PET hypometabolism in patients with a clinical AD presentation. Methods: Twenty-one patients with autopsy-confirmed AD without LB neuropathologic changes (LBNC) (pure-AD), 24 with AD and LBNC copathology (AD-LB), and 7 with LBNC without fulfilling neuropathologic criteria for AD (pure-LB) were studied. Pathologic groups were compared regarding regional and voxelwise 18F-FDG PET patterns, the cingulate island sign ratio (CISr), and neuropathologic ratings of SNnl. Additional analyses assessed continuous associations of Braak tangle stage and SNnl with 18F-FDG PET patterns. Results: Pure-AD and AD-LB showed highly similar patterns of AD-typical temporoparietal hypometabolism and did not differ in CISr, regional 18F-FDG SUVR, or SNnl. By contrast, pure-LB showed the expected pattern of pronounced posterior-occipital hypometabolism typical for dementia with LB (DLB), and both CISr and SNnl were significantly higher compared with the AD groups. In continuous analyses, Braak tangle stage correlated significantly with more AD-like, and SNnl with more DLB-like, 18F-FDG PET patterns. Conclusion: In autopsy-confirmed AD dementia patients, comorbid LB pathology did not have a notable effect on the regional 18F-FDG PET pattern. A more DLB-like 18F-FDG PET pattern was observed in relation to SNnl, but advanced SNnl was mostly limited to relatively pure LB cases. AD pathology may have a dominant effect over LB pathology in determining the regional neurodegeneration phenotype.
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Affiliation(s)
- Jesús Silva-Rodríguez
- 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
| | - Miguel A. Labrador-Espinosa
- 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;,Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain;,Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Seville, Spain
| | - Alexis Moscoso
- Wallenberg Center for Molecular and Translational Medicine and Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; and
| | - Michael Schöll
- Wallenberg Center for Molecular and Translational Medicine and Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; and,Dementia Research Centre, Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - 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; .,Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.,Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Seville, Spain
| | - Michel J. Grothe
- 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;,Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain;,Wallenberg Center for Molecular and Translational Medicine and Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; and
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Orsolini L, Corona D, Salvi V, Volpe U. Long-acting paliperidone in Ekbom's syndrome in Lewy body dementia: A case report. Transl Neurosci 2022; 13:201-210. [PMID: 35975126 PMCID: PMC9334881 DOI: 10.1515/tnsci-2022-0230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/15/2022] [Accepted: 06/22/2022] [Indexed: 12/29/2022] Open
Abstract
Introduction Ekbom Syndrome (ES) is characterised by fixed, delusional beliefs that one's body is infested by parasites or other vermin in absence of supporting clinical evidence. Antipsychotic (AP) treatment, including long-acting injectable (LAI) AP in subjects with poor compliance, is prescribed to manage behavioural and psychotic symptomatology. Objectives We describe a 70-year-old woman who was hospitalised after experiencing new-onset delusions of infestation with visual and tactile hallucinations that led to bizarre behaviours and progressive social withdrawal. Methods She was diagnosed with ES and was initially treated with risperidone 3 mg; however, due to poor compliance and a lack of insight, she was switched to LAI palmitate paliperidone (LAI-PP). She was followed up for 8 months, administering Positive and Negative Syndrome Scale, Montreal Cognitive Assessment, Global Assessment of Functioning, Brief Psychiatric Rating Scale, neurocognitive assessment, and neuroimaging. Results After a progressive cognitive deterioration, she was diagnosed with an ES secondary to Lewy body dementia (DLB). Conclusion The LAI-PP treatment determined a complete clinical remission of psychotic symptoms despite the emergence of an iatrogenic akinetic-rigid syndrome. The delay of confirmatory neurological diagnosis, the associated risky behaviours of the patient, and poor treatment adherence led clinicians to prescribe LAI-PP following a good clinical response to oral paliperidone. However, in the case of a suspected DLB diagnosis, the prescription of an LAI-PP as a first-line strategy should be carefully evaluated.
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Affiliation(s)
- Laura Orsolini
- Department of Clinical Neurosciences/DIMSC, Unit of Clinical Psychiatry, Polytechnic University of Marche, 60126, Ancona, Italy
| | - Diana Corona
- Department of Clinical Neurosciences/DIMSC, Unit of Clinical Psychiatry, Polytechnic University of Marche, 60126, Ancona, Italy
| | - Virginio Salvi
- Department of Clinical Neurosciences/DIMSC, Unit of Clinical Psychiatry, Polytechnic University of Marche, 60126, Ancona, Italy
| | - Umberto Volpe
- Department of Clinical Neurosciences/DIMSC, Unit of Clinical Psychiatry, Polytechnic University of Marche, 60126, Ancona, Italy
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Al-Harrasi AM, Iqbal E, Tsamakis K, Lasek J, Gadelrab R, Soysal P, Kohlhoff E, Tsiptsios D, Rizos E, Perera G, Aarsland D, Stewart R, Mueller C. Motor signs in Alzheimer's disease and vascular dementia: Detection through natural language processing, co-morbid features and relationship to adverse outcomes. Exp Gerontol 2021; 146:111223. [PMID: 33450346 DOI: 10.1016/j.exger.2020.111223] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 11/09/2020] [Accepted: 12/21/2020] [Indexed: 11/21/2022]
Abstract
BACKGROUND Motor signs in patients with dementia are associated with a higher risk of cognitive decline, institutionalisation, death and increased health care costs, but prevalences differ between studies. The aims of this study were to employ a natural language processing pipeline to detect motor signs in a patient cohort in routine care; to explore which other difficulties occur co-morbid to motor signs; and whether these, as a group and individually, predict adverse outcomes. METHODS A cohort of 11,106 patients with dementia in Alzheimer's disease, vascular dementia or a combination was assembled from a large dementia care health records database in Southeast London. A natural language processing algorithm was devised in order to establish the presence of motor signs (bradykinesia, Parkinsonian gait, rigidity, tremor) recorded around the time of dementia diagnosis. We examined the co-morbidity profile of patients with these symptoms and used Cox regression models to analyse associations with survival and hospitalisation, adjusting for twenty-four potential confounders. RESULTS Less than 10% of patients were recorded to display any motor sign, and tremor was most frequently detected. Presence of motor signs was associated with younger age at diagnosis, neuropsychiatric symptoms, poor physical health and higher prescribing of psychotropics. Rigidity was independently associated with a 23% increased mortality risk after adjustment for confounders (p = 0.014). A non-significant trend for a 15% higher risk of hospitalisation was detected in those with a recorded Parkinsonian gait (p = 0.094). CONCLUSIONS With the exception of tremor, motor signs appear to be under-recorded in routine care. They are part of a complex clinical picture and often accompanied by neuropsychiatric and functional difficulties, and thereby associated with adverse outcomes. This underlines the need to establish structured examinations in routine clinical practice via easy-to-use tools.
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Affiliation(s)
- Ahmed M Al-Harrasi
- King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK; Sultan Qaboos University Hospital, Muscat, Oman
| | - Ehtesham Iqbal
- King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK
| | - Konstantinos Tsamakis
- King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK; National and Kapodistrian University of Athens, School of Medicine, Second Department of Psychiatry, University General Hospital 'ATTIKON', Athens, Greece
| | - Judista Lasek
- South London and Maudsley NHS Foundation Trust, London, UK
| | | | - Pinar Soysal
- Department of Geriatric Medicine, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Enno Kohlhoff
- Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain
| | - Dimitrios Tsiptsios
- Neurophysiology Department, Sunderland Royal Hospital, South Tyneside & Sunderland NHS Foundation Trust, Sunderland, UK
| | - Emmanouil Rizos
- National and Kapodistrian University of Athens, School of Medicine, Second Department of Psychiatry, University General Hospital 'ATTIKON', Athens, Greece
| | - Gayan Perera
- King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK
| | - Dag Aarsland
- King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK; South London and Maudsley NHS Foundation Trust, London, UK; Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway
| | - Robert Stewart
- King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK; South London and Maudsley NHS Foundation Trust, London, UK
| | - Christoph Mueller
- King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK; South London and Maudsley NHS Foundation Trust, London, UK.
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11
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Orlović I, Bartolović M, Marušić K, Vlahović D, Šiško Markoš I, Karlović D, Peitl V. THE ENIGMA OF LEWY BODY DEMENTIA: A CASE REPORT. Acta Clin Croat 2020; 59:771-776. [PMID: 34285451 PMCID: PMC8253061 DOI: 10.20471/acc.2020.59.04.27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 11/12/2019] [Indexed: 11/24/2022] Open
Abstract
Lewy body dementia is a progressive neurodegenerative disease and is considered to be the second most common cause of dementia in the elderly. Because of the complexity of clinical presentation, it is often misdiagnosed and mistaken for other dementias, which may result in administering inappropriate therapy, and thus worsening of the patient condition. We reviewed a case of a 71-year-old patient whose clinical presentation gradually occurred with complex visual hallucinations, atypical extrapyramidal motor symptoms, fluctuating cognitive impairments with delirious episodes, and oscillating syncope. Depressive mood, impaired daily functioning and sensitivity to antipsychotics were also noted. Extensive diagnostic workup was performed with neuropsychological testing and use of single-photon emission computerized tomography. Considering the clinical presentation and diagnostic procedures performed, the diagnosis of Lewy body dementia was set and pharmacotherapy was revised. We discuss the importance of taking overall clinical presentation and diagnostic treatment in consideration and applying appropriate therapy to slow down the progression of the disease and exacerbation of the patient's psychological functions.
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Affiliation(s)
- Ivona Orlović
- 1Department of Psychiatry, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 2Department of Oncology and Nuclear Medicine, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 3Catholic University of Croatia, Zagreb, Croatia; 4School of Dental Medicine, University of Zagreb, Zagreb, Croatia
| | - Matija Bartolović
- 1Department of Psychiatry, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 2Department of Oncology and Nuclear Medicine, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 3Catholic University of Croatia, Zagreb, Croatia; 4School of Dental Medicine, University of Zagreb, Zagreb, Croatia
| | - Katarina Marušić
- 1Department of Psychiatry, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 2Department of Oncology and Nuclear Medicine, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 3Catholic University of Croatia, Zagreb, Croatia; 4School of Dental Medicine, University of Zagreb, Zagreb, Croatia
| | - Darko Vlahović
- 1Department of Psychiatry, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 2Department of Oncology and Nuclear Medicine, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 3Catholic University of Croatia, Zagreb, Croatia; 4School of Dental Medicine, University of Zagreb, Zagreb, Croatia
| | - Ines Šiško Markoš
- 1Department of Psychiatry, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 2Department of Oncology and Nuclear Medicine, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 3Catholic University of Croatia, Zagreb, Croatia; 4School of Dental Medicine, University of Zagreb, Zagreb, Croatia
| | - Dalibor Karlović
- 1Department of Psychiatry, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 2Department of Oncology and Nuclear Medicine, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 3Catholic University of Croatia, Zagreb, Croatia; 4School of Dental Medicine, University of Zagreb, Zagreb, Croatia
| | - Vjekoslav Peitl
- 1Department of Psychiatry, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 2Department of Oncology and Nuclear Medicine, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 3Catholic University of Croatia, Zagreb, Croatia; 4School of Dental Medicine, University of Zagreb, Zagreb, Croatia
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12
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Treatment of psychosis in Parkinson's disease and dementia with Lewy Bodies: A review. Parkinsonism Relat Disord 2020; 75:55-62. [PMID: 32480308 DOI: 10.1016/j.parkreldis.2020.05.026] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 05/21/2020] [Accepted: 05/23/2020] [Indexed: 12/16/2022]
Abstract
There is a considerable overlap between Parkinson's Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB). They present a challenge therapeutically, with regard to morbidity and mortality risk. In particular, symptoms of psychosis in these conditions augur a considerably increased burden. To date, there has been a myriad of prospective, retrospective and case studies examining the use of neuroleptics in the treatment of psychotic symptoms in PDD/DLB. Clozapine has the most robust evidence base however its use is limited by agranulocytosis risk and the associated need for frequent blood count monitoring. Quetiapine is more readily used, however, it has a more equivocal evidence base, in terms of efficacy. Other neuroleptics have thus far demonstrated mixed results with increased risk of extrapyramidal worsening. In addition to the atypical agents, the introduction of pimavanserin has provided another treatment option for Parkinson's Disease Psychosis (PDP), decreasing concern for deterioration in motor function. We await further research to confidently demonstrate its efficacy and safety in DLB psychosis. Cholinesterase inhibitors likely have a limited role in treating milder psychosis symptomatology in DLB and perhaps PDD. After review of the current literature for antipsychotic therapy in both PDD and DLB, we provide a logical framework for addressing psychotic symptoms in each condition.
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13
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Salman A, Lapidot I, Shufan E, Agbaria AH, Porat Katz BS, Mordechai S. Potential of infrared microscopy to differentiate between dementia with Lewy bodies and Alzheimer's diseases using peripheral blood samples and machine learning algorithms. JOURNAL OF BIOMEDICAL OPTICS 2020; 25:1-15. [PMID: 32329265 PMCID: PMC7177186 DOI: 10.1117/1.jbo.25.4.046501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 04/09/2020] [Indexed: 06/11/2023]
Abstract
SIGNIFICANCE Accurate and objective identification of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is of major clinical importance due to the current lack of low-cost and noninvasive diagnostic tools to differentiate between the two. Developing an approach for such identification can have a great impact in the field of dementia diseases as it would offer physicians a routine objective test to support their diagnoses. The problem is especially acute because these two dementias have some common symptoms and characteristics, which can lead to misdiagnosis of DLB as AD and vice versa, mainly at their early stages. AIM The aim is to evaluate the potential of mid-infrared (IR) spectroscopy in tandem with machine learning algorithms as a sensitive method to detect minor changes in the biochemical structures that accompany the development of AD and DLB based on a simple peripheral blood test, thus improving the diagnostic accuracy of differentiation between DLB and AD. APPROACH IR microspectroscopy was used to examine white blood cells and plasma isolated from 56 individuals: 26 controls, 20 AD patients, and 10 DLB patients. The measured spectra were analyzed via machine learning. RESULTS Our encouraging results show that it is possible to differentiate between dementia (AD and DLB) and controls with an ∼86 % success rate and between DLB and AD patients with a success rate of better than 93%. CONCLUSIONS The success of this method makes it possible to suggest a new, simple, and powerful tool for the mental health professional, with the potential to improve the reliability and objectivity of diagnoses of both AD and DLB.
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Affiliation(s)
- Ahmad Salman
- Shamoon College of Engineering, Department of Physics, Beer-Sheva, Israel
| | - Itshak Lapidot
- Afeka Tel-Aviv Academic College of Engineering, Afeka Center for Language Processing, Department of Electrical and Electronics Engineering, Tel-Aviv, Israel
| | - Elad Shufan
- Shamoon College of Engineering, Department of Physics, Beer-Sheva, Israel
| | - Adam H. Agbaria
- Ben-Gurion University of the Negev, Department of Physics, Faculty of Natural Sciences, Beer-Sheva, Israel
| | - Bat-Sheva Porat Katz
- The Hebrew University of Jerusalem, School of Nutritional Sciences, The Robert H. Smith Faculty of Agriculture, Food, and Environment, Rehovot, Israel
- Kaplan Medical Center, Rehovot, Israel
| | - Shaul Mordechai
- Ben-Gurion University of the Negev, Department of Physics, Faculty of Natural Sciences, Beer-Sheva, Israel
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14
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Russo M, Carrarini C, Dono F, Rispoli MG, Di Pietro M, Di Stefano V, Ferri L, Bonanni L, Sensi SL, Onofrj M. The Pharmacology of Visual Hallucinations in Synucleinopathies. Front Pharmacol 2019; 10:1379. [PMID: 31920635 PMCID: PMC6913661 DOI: 10.3389/fphar.2019.01379] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 10/30/2019] [Indexed: 12/13/2022] Open
Abstract
Visual hallucinations (VH) are commonly found in the course of synucleinopathies like Parkinson's disease and dementia with Lewy bodies. The incidence of VH in these conditions is so high that the absence of VH in the course of the disease should raise questions about the diagnosis. VH may take the form of early and simple phenomena or appear with late and complex presentations that include hallucinatory production and delusions. VH are an unmet treatment need. The review analyzes the past and recent hypotheses that are related to the underlying mechanisms of VH and then discusses their pharmacological modulation. Recent models for VH have been centered on the role played by the decoupling of the default mode network (DMN) when is released from the control of the fronto-parietal and salience networks. According to the proposed model, the process results in the perception of priors that are stored in the unconscious memory and the uncontrolled emergence of intrinsic narrative produced by the DMN. This DMN activity is triggered by the altered functioning of the thalamus and involves the dysregulated activity of the brain neurotransmitters. Historically, dopamine has been indicated as a major driver for the production of VH in synucleinopathies. In that context, nigrostriatal dysfunctions have been associated with the VH onset. The efficacy of antipsychotic compounds in VH treatment has further supported the notion of major involvement of dopamine in the production of the hallucinatory phenomena. However, more recent studies and growing evidence are also pointing toward an important role played by serotonergic and cholinergic dysfunctions. In that respect, in vivo and post-mortem studies have now proved that serotonergic impairment is often an early event in synucleinopathies. The prominent cholinergic impairment in DLB is also well established. Finally, glutamatergic and gamma aminobutyric acid (GABA)ergic modulations and changes in the overall balance between excitatory and inhibitory signaling are also contributing factors. The review provides an extensive overview of the pharmacology of VH and offers an up to date analysis of treatment options.
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Affiliation(s)
- Mirella Russo
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - Claudia Carrarini
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - Fedele Dono
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - Marianna Gabriella Rispoli
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - Martina Di Pietro
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - Vincenzo Di Stefano
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - Laura Ferri
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - Laura Bonanni
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - Stefano Luca Sensi
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
- Behavioral Neurology and Molecular Neurology Units, Center of Excellence on Aging and Translational Medicine—CeSI-MeT, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
- Departments of Neurology and Pharmacology, Institute for Mind Impairments and Neurological Disorders—iMIND, University of California, Irvine, Irvine, CA, United States
| | - Marco Onofrj
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy
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15
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Inskip M, Mavros Y, Sachdev PS, Fiatarone Singh MA. Promoting independence in Lewy body dementia through exercise (PRIDE) study: Protocol for a pilot study. Contemp Clin Trials Commun 2019; 16:100466. [PMID: 31701040 PMCID: PMC6831670 DOI: 10.1016/j.conctc.2019.100466] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Revised: 09/23/2019] [Accepted: 10/10/2019] [Indexed: 11/18/2022] Open
Abstract
Background Lewy Body dementia (LBD) is the second most prevalent neurodegenerative dementia. This form of dementia is notable for an aggressive disease course consisting of a combination of cognitive, Parkinsonian, affective, and physiological symptoms that significantly increase morbidity and mortality, and decrease life expectancy in this population compared to more common dementias. Additionally, those diagnosed with LBD are often excluded from trials evaluating exercise in similar diseases such as Alzheimer's disease or Parkinson's disease due to the complexity and concurrency of motor and cognitive symptoms. Consequently, there is scarce research evaluating the effect of exercise on individuals with LBD. Methods The PRomoting Independence in Lewy Body Dementia through Exercise (PRIDE) trial is a novel non-randomised, crossover pilot study consisting of an 8-week wait-list usual care period, followed by an 8-week exercise intervention targeting progressive resistance and balance training. The trial aim is to evaluate the effect of exercise on the primary outcome of functional independence and secondary outcomes including cognitive, physical, psychosocial and quality of life measures in people living with LBD and their caregivers. The intervention involves 3 supervised 1-h sessions per week (24 sessions in total) administered by an Accredited Exercise Physiologist in a clinical facility at the University of Sydney in Lidcombe, Australia. Discussion The PRIDE study is the first controlled trial to evaluate a robust exercise intervention within a LBD cohort and will provide crucial information required to inform robust future clinical trials. Trial registration Australia and New Zealand Trial Register (ANZCTR): ACTRN12616000466448; Key words: Lewy body; dementia; exercise; anabolic; functional independence.
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Affiliation(s)
- Michael Inskip
- The University of Sydney Faculty of Health Sciences, Discipline of Exercise and Sports Science, Cumberland Campus, Lidcombe, NSW, 2141, Australia
- Corresponding author. Office K220, The University of Sydney, Faculty of Health Sciences, Cumberland Campus, Lidcombe, NSW, 2141, Australia.
| | - Yorgi Mavros
- The University of Sydney Faculty of Health Sciences, Discipline of Exercise and Sports Science, Cumberland Campus, Lidcombe, NSW, 2141, Australia
| | - Perminder S. Sachdev
- Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, 2031, Australia
- Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, NSW, 2031, Australia
| | - Maria A. Fiatarone Singh
- The University of Sydney Faculty of Health Sciences, Discipline of Exercise and Sports Science, Cumberland Campus, Lidcombe, NSW, 2141, Australia
- The University of Sydney, Sydney Medical School, Sydney, 2006, Australia
- Hebrew SeniorLife, Roslindale, MA, 02131, USA
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02155, USA
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16
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Lee G, Cummings J, Decourt B, Leverenz JB, Sabbagh MN. Clinical drug development for dementia with Lewy bodies: past and present. Expert Opin Investig Drugs 2019; 28:951-965. [PMID: 31614096 PMCID: PMC6823159 DOI: 10.1080/13543784.2019.1681398] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 10/14/2019] [Indexed: 12/25/2022]
Abstract
Introduction: Dementia with Lewy bodies (DLB) is an under-researched area despite being the second most common type of degenerative dementia after Alzheimer's disease. It is an area of unmet need with no approved symptomatic or disease-modifying therapies. The pharmacological management of DLB is complex and challenging because early trials of drugs for DLB have resulted in no demonstrable efficacy. Randomized controlled trials (RCTs) in the DLB population have only recently been initiated. Understanding results from previous and current clinical trials in DLB can provide insights for future research and development.Areas covered: We provide an overview of the DLB drug development landscape and the current treatment strategies. We reviewed ClinicalTrials.gov to identify all clinical trials for the treatment of DLB.Expert opinion: DLB drug development has significantly improved in recent years with eight agents now in clinical trials. However, more rigorous RCTs are urgently needed. Diagnostic criteria must be optimized to accurately diagnose patients for clinical trials and care. New biomarker strategies are necessary to improve diagnostic capabilities and trial designs, and novel drug targets should be identified to develop DLB specific disease-modifying therapies. Evaluating the current drug development landscape can provide insight into how best to optimize development practices.
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Affiliation(s)
- Garam Lee
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA
| | - Jeffrey Cummings
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA
- Department of Brain Health, School of Integrated Health Science, University of Nevada Las Vegas, Las Vegas, NV, USA
| | - Boris Decourt
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA
| | - James B Leverenz
- Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland, OH, USA
| | - Marwan N Sabbagh
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA
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17
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Berardelli I, Belvisi D, Pasquini M, Fabbrini A, Petrini F, Fabbrini G. Treatment of psychiatric disturbances in hypokinetic movement disorders. Expert Rev Neurother 2019; 19:965-981. [PMID: 31241368 DOI: 10.1080/14737175.2019.1636648] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 06/24/2019] [Indexed: 12/26/2022]
Abstract
Introduction: We reviewed studies that assessed the treatment of psychiatric disturbances in Parkinson's disease and atypical parkinsonisms. Neuropsychiatric disturbances in these conditions are frequent and have a profound impact on quality of life of patients and of their caregivers. It is therefore important to be familiar with the appropriate pharmacological and non-pharmacological interventions for treating these disorders. Areas covered: The authors searched for papers in English in Pubmed using the following keywords: Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, Lewy body dementia, depression, apathy, anxiety, fatigue, sleep disorders, obsessive compulsive disorders, psychosis, hallucinations, delusions, impulse control disorders. Expert opinion: In Parkinson's disease, depression may benefit from the optimization of dopaminergic therapy, from the use of antidepressants acting on both the serotoninergic and noradrenergic pathways and from cognitive behavioral therapy. Psychosis in Parkinson's disease may improve with the use of clozapine; the serotonin inverse agonist pimavanserin has been shown to be effective. Treatment of impulse control disorders is primarily based on the removal of dopamine agonists. No controlled studies have investigated the treatment of neuropsychiatric disorders in multiple system atrophy, progressive supranuclear palsy or corticobasal degeneration. Acethylcholinesterase inhibitors may be used to treat hallucinations in Lewy body dementia.
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Affiliation(s)
- Isabella Berardelli
- Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome , Rome , Italy
| | | | - Massimo Pasquini
- Department of Human Neurosciences, Sapienza University of Rome , Rome , Italy
| | - Andrea Fabbrini
- Department of Human Neurosciences, Sapienza University of Rome , Rome , Italy
| | - Federica Petrini
- Department of Neurosciences and Mental Health, Azienda Universitaria Policlinico Umberto I° , Rome , Italy
| | - Giovanni Fabbrini
- IRCCS Neuromed , Pozzilli , Italy
- Department of Human Neurosciences, Sapienza University of Rome , Rome , Italy
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18
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Sestini S, Alongi P, Berti V, Calcagni ML, Cecchin D, Chiaravalloti A, Chincarini A, Cistaro A, Guerra UP, Pappatà S, Tiraboschi P, Nobili F. The role of molecular imaging in the frame of the revised dementia with Lewy body criteria. Clin Transl Imaging 2019. [DOI: 10.1007/s40336-019-00321-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Chin KS, Teodorczuk A, Watson R. Dementia with Lewy bodies: Challenges in the diagnosis and management. Aust N Z J Psychiatry 2019; 53:291-303. [PMID: 30848660 DOI: 10.1177/0004867419835029] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE Dementia with Lewy bodies is the second most common form of neurodegenerative dementia in older age yet is often under-recognised and misdiagnosed. This review aims to provide an overview of the clinical features of dementia with Lewy bodies, discussing the frequent challenges clinicians experience in diagnosing dementia with Lewy bodies, and outlines a practical approach to the clinical management, particularly in the Australian setting. METHODS This paper is a narrative review and a semi-structured database (PubMed and MEDLINE) search strategy was implemented. Articles were screened and clinically relevant studies were selected for inclusion. RESULTS Dementia with Lewy bodies is clinically characterised by complex visual hallucinations, spontaneous motor parkinsonism, prominent cognitive fluctuations and rapid eye movement sleep behaviour disorder. Neuropsychiatric features and autonomic dysfunction are also common. The new diagnostic criteria and specific diagnostic biomarkers help to improve detection rates and diagnostic accuracy, as well as guide appropriate management. Clinical management of dementia with Lewy bodies is challenging and requires an individualised multidisciplinary approach with specialist input. CONCLUSION Dementia with Lewy bodies is a common form of dementia. It often presents as a diagnostic challenge to clinicians, particularly at early stages of disease, and in patients with mixed neuropathological changes, which occur in over 50% of people with dementia with Lewy bodies. Prompt diagnosis and comprehensive treatment strategies are important in improving patients' care.
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Affiliation(s)
- Kai Sin Chin
- 1 The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.,2 Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia
| | - Andrew Teodorczuk
- 3 School of Medicine, Griffith University, Gold Coast, QLD, Australia.,4 Metro North Mental Health, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Rosie Watson
- 1 The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.,2 Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia
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Cousins O, Yousaf T, Wilson H, Pagano G, Politis M. Molecular Imaging of Dementia With Lewy Bodies. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2018; 144:59-93. [PMID: 30638457 DOI: 10.1016/bs.irn.2018.10.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia. The core clinical features of DLB include fluctuating cognition, visual hallucinations, rapid eye movement sleep behavior disorder, and parkinsonism. Molecular imaging is a powerful tool to assess the brain function in vivo. In this chapter, we reviewed the positron emission tomography, single-photon emission computed tomography, and [123I]-metaiodobenzylguanidine scintigraphy studies evaluating the pathological processes underlying DLB, including altered brain metabolism and neurotransmitter pathways, abnormal protein aggregation, and neuroinflammation. These techniques can aid in the differential diagnosis of DLB (versus Alzheimer's disease and related dementia) and in the monitoring disease progression and treatment efficacy of disease-modifying drugs. Furthermore, we explored the limitations of current imaging biomarkers and future directions, particularly focusing on the vital need for tracers that have high affinity for alpha-synuclein.
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Affiliation(s)
- Oliver Cousins
- Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom
| | - Tayyabah Yousaf
- Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom
| | - Heather Wilson
- Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom
| | - Gennaro Pagano
- Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom
| | - Marios Politis
- Neurodegeneration Imaging Group, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.
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Abstract
Byrne provides an excellent clinical overview. However, I have selected four areas of clinical interest for more detailed consideration.
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Babiloni C, Del Percio C, Lizio R, Noce G, Lopez S, Soricelli A, Ferri R, Nobili F, Arnaldi D, Famà F, Aarsland D, Orzi F, Buttinelli C, Giubilei F, Onofrj M, Stocchi F, Stirpe P, Fuhr P, Gschwandtner U, Ransmayr G, Garn H, Fraioli L, Pievani M, Frisoni GB, D'Antonio F, De Lena C, Güntekin B, Hanoğlu L, Başar E, Yener G, Emek-Savaş DD, Triggiani AI, Franciotti R, Taylor JP, Vacca L, De Pandis MF, Bonanni L. Abnormalities of resting-state functional cortical connectivity in patients with dementia due to Alzheimer's and Lewy body diseases: an EEG study. Neurobiol Aging 2017; 65:18-40. [PMID: 29407464 DOI: 10.1016/j.neurobiolaging.2017.12.023] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 12/21/2017] [Accepted: 12/21/2017] [Indexed: 11/30/2022]
Abstract
Previous evidence showed abnormal posterior sources of resting-state delta (<4 Hz) and alpha (8-12 Hz) rhythms in patients with Alzheimer's disease with dementia (ADD), Parkinson's disease with dementia (PDD), and Lewy body dementia (DLB), as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis of additional abnormalities in functional cortical connectivity computed in those sources, in ADD, considered as a "disconnection cortical syndrome", in comparison with PDD and DLB. Resting-state eyes-closed electroencephalographic (rsEEG) rhythms had been collected in 42 ADD, 42 PDD, 34 DLB, and 40 normal healthy older (Nold) participants. Exact low-resolution brain electromagnetic tomography (eLORETA) freeware estimated the functional lagged linear connectivity (LLC) from rsEEG cortical sources in delta, theta, alpha, beta, and gamma bands. The area under receiver operating characteristic (AUROC) curve indexed the classification accuracy between Nold and diseased individuals (only values >0.7 were considered). Interhemispheric and intrahemispheric LLCs in widespread delta sources were abnormally higher in the ADD group and, unexpectedly, normal in DLB and PDD groups. Intrahemispheric LLC was reduced in widespread alpha sources dramatically in ADD, markedly in DLB, and moderately in PDD group. Furthermore, the interhemispheric LLC in widespread alpha sources showed lower values in ADD and DLB than PDD groups. At the individual level, AUROC curves of LLC in alpha sources exhibited better classification accuracies for the discrimination of ADD versus Nold individuals (0.84) than for DLB versus Nold participants (0.78) and PDD versus Nold participants (0.75). Functional cortical connectivity markers in delta and alpha sources suggest a more compromised neurophysiological reserve in ADD than DLB, at both group and individual levels.
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Affiliation(s)
- Claudio Babiloni
- Department of Physiology and Pharmacology "Vittorio Erspamer", University of Rome "La Sapienza", Rome, Italy; Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy.
| | | | - Roberta Lizio
- Department of Physiology and Pharmacology "Vittorio Erspamer", University of Rome "La Sapienza", Rome, Italy; Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy
| | - Giuseppe Noce
- Department of Integrated Imaging, IRCCS SDN, Naples, Italy
| | - Susanna Lopez
- Department of Physiology and Pharmacology "Vittorio Erspamer", University of Rome "La Sapienza", Rome, Italy
| | - Andrea Soricelli
- Department of Integrated Imaging, IRCCS SDN, Naples, Italy; Department of Motor Sciences and Healthiness, University of Naples Parthenope, Naples, Italy
| | - Raffaele Ferri
- Department of Neurology, IRCCS Oasi Institute for Research on Mental Retardation and Brain Aging, Troina, Enna, Italy
| | - Flavio Nobili
- Clinical Neurology, Department of Neuroscience (DiNOGMI), University of Genoa and IRCCS AOU S Martino-IST, Genoa, Italy
| | - Dario Arnaldi
- Clinical Neurology, Department of Neuroscience (DiNOGMI), University of Genoa and IRCCS AOU S Martino-IST, Genoa, Italy
| | - Francesco Famà
- Clinical Neurology, Department of Neuroscience (DiNOGMI), University of Genoa and IRCCS AOU S Martino-IST, Genoa, Italy
| | - Dag Aarsland
- Department of Old Age Psychiatry, King's College University, London, UK
| | - Francesco Orzi
- Department of Neuroscience, Mental Health and Sensory Organs, University of Rome "La Sapienza", Rome, Italy
| | - Carla Buttinelli
- Department of Neuroscience, Mental Health and Sensory Organs, University of Rome "La Sapienza", Rome, Italy
| | - Franco Giubilei
- Department of Neuroscience, Mental Health and Sensory Organs, University of Rome "La Sapienza", Rome, Italy
| | - Marco Onofrj
- Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - Fabrizio Stocchi
- Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy
| | - Paola Stirpe
- Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy
| | - Peter Fuhr
- Universitätsspital Basel, Abteilung Neurophysiologie, Basel, Switzerland
| | - Ute Gschwandtner
- Universitätsspital Basel, Abteilung Neurophysiologie, Basel, Switzerland
| | - Gerhard Ransmayr
- Department of Neurology and Psychiatry and Faculty of Medicine, Johannes Kepler University Linz, General Hospital of the City of Linz, Linz, Austria
| | - Heinrich Garn
- AIT Austrian Institute of Technology GmbH, Vienna, Austria
| | | | - Michela Pievani
- Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Giovanni B Frisoni
- Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland
| | - Fabrizia D'Antonio
- Department of Neurology and Psychiatry, Sapienza, University of Rome, Rome, Italy
| | - Carlo De Lena
- Department of Neurology and Psychiatry, Sapienza, University of Rome, Rome, Italy
| | - Bahar Güntekin
- Department of Biophysics, Istanbul Medipol University, Istanbul, Turkey
| | - Lutfu Hanoğlu
- Department of Neurology, University of Istanbul-Medipol, Istanbul, Turkey
| | - Erol Başar
- IBG, Departments of Neurology and Neurosciences, Dokuz Eylül University, Izmir, Turkey
| | - Görsev Yener
- IBG, Departments of Neurology and Neurosciences, Dokuz Eylül University, Izmir, Turkey
| | - Derya Durusu Emek-Savaş
- Department of Psychology and Department of Neurosciences, Dokuz Eylül University, Izmir, Turkey
| | | | - Raffaella Franciotti
- Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d'Annunzio of Chieti-Pescara, Chieti, Italy
| | | | - Laura Vacca
- Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy; Casa di Cura Privata del Policlinico (CCPP) Milano SpA, Milan, Italy
| | | | - Laura Bonanni
- Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d'Annunzio of Chieti-Pescara, Chieti, Italy
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Price A, Farooq R, Yuan JM, Menon VB, Cardinal RN, O’Brien JT. Mortality in dementia with Lewy bodies compared with Alzheimer's dementia: a retrospective naturalistic cohort study. BMJ Open 2017; 7:e017504. [PMID: 29101136 PMCID: PMC5695389 DOI: 10.1136/bmjopen-2017-017504] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVES To use routine clinical data to investigate survival in dementia with Lewy bodies (DLB) compared with Alzheimer's dementia (AD). DLB is the second most common dementia subtype after AD, accounting for around 7% of dementia diagnoses in secondary care, though studies suggest that it is underdiagnosed by up to 50%. Most previous studies of DLB have been based on select research cohorts, so little is known about the outcome of the disease in routine healthcare settings. SETTING Cambridgeshire & Peterborough NHS Foundation Trust, a mental health trust providing secondary mental health care in England. SAMPLE 251 DLB and 222 AD identified from an anonymised database derived from electronic clinical case records across an 8-year period (2005-2012), with mortality data updated to May 2015. RESULTS Raw (uncorrected) median survival was 3.72 years for DLB (95% CI 3.33 to 4.14) and 6.95 years for AD (95% CI 5.78 to 8.12). Controlling for age at diagnosis, comorbidity and antipsychotic prescribing the model predicted median survival for DLB was 3.3 years (95% CI 2.88 to 3.83) for males and 4.0 years (95% CI 3.55 to 5.00) for females, while median survival for AD was 6.7 years (95% CI 5.27 to 8.51) for males and 7.0 years (95% CI 5.92 to 8.73) for females. CONCLUSION Survival from first presentation with cognitive impairment was markedly shorter in DLB compared with AD, independent of age, sex, physical comorbidity or antipsychotic prescribing. This finding, in one of the largest clinical cohorts of DLB cases assembled to date, adds to existing evidence for poorer survival for DLB versus AD. There is an urgent need for further research to understand possible mechanisms accounting for this finding.
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Affiliation(s)
- Annabel Price
- Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - Redwan Farooq
- School of Clinical Medicine, University of Cambridge, London, UK
| | - Jin-Min Yuan
- School of Clinical Medicine, University of Cambridge, London, UK
| | | | - Rudolf N Cardinal
- Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - John T O’Brien
- Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
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Reeve E, Trenaman SC, Rockwood K, Hilmer SN. Pharmacokinetic and pharmacodynamic alterations in older people with dementia. Expert Opin Drug Metab Toxicol 2017; 13:651-668. [DOI: 10.1080/17425255.2017.1325873] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Emily Reeve
- NHMRC Cognitive Decline Partnership Centre, Kolling Institute of Medical Research, Northern Clinical School, Faculty of Medicine, University of Sydney, Sydney, Australia
- Geriatric Medicine Research, Faculty of Medicine, Dalhousie University and Nova Scotia Health Authority, Halifax, NS, Canada
| | - Shanna C Trenaman
- Dalhousie University and Nova Scotia Health Authority, Halifax, NS, Canada
| | - Kenneth Rockwood
- Geriatric Medicine Research, Faculty of Medicine, Dalhousie University and Nova Scotia Health Authority, Halifax, NS, Canada
- Division of Geriatric Medicine, Dalhousie University, Halifax, NS, Canada
- DGI Clinical Inc., Halifax, Canada
| | - Sarah N Hilmer
- NHMRC Cognitive Decline Partnership Centre, Kolling Institute of Medical Research, Northern Clinical School, Faculty of Medicine, University of Sydney, Sydney, Australia
- Departments of Aged Care and Clinical Pharmacology, Royal North Shore Hospital, St Leonards, NSW, Australia
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Bonanni L, Franciotti R, Nobili F, Kramberger MG, Taylor JP, Garcia-Ptacek S, Falasca NW, Famá F, Cromarty R, Onofrj M, Aarsland D. EEG Markers of Dementia with Lewy Bodies: A Multicenter Cohort Study. J Alzheimers Dis 2016; 54:1649-1657. [DOI: 10.3233/jad-160435] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Laura Bonanni
- Department of Neuroscience, Imaging and Clinical Science, and Aging Research Centre, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
| | - Raffaella Franciotti
- Department of Neuroscience, Imaging and Clinical Science, and Aging Research Centre, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
| | - Flavio Nobili
- Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy
| | | | - John-Paul Taylor
- Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK
| | - Sara Garcia-Ptacek
- Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, and Memory Clinic Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - N. Walter Falasca
- BIND – Behavioral Imaging and Neural Dynamics Center, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
| | - Francesco Famá
- Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy
| | - Ruth Cromarty
- Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK
| | - Marco Onofrj
- Department of Neuroscience, Imaging and Clinical Science, and Aging Research Centre, G. d’Annunzio University of Chieti-Pescara, Chieti, Italy
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Bonanni L, Di Giacomo R, D'Amico A, Frazzini V, Franciotti R, Manzoli L, Thomas A, Onofrj M. Akinetic crisis in dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2016; 87:1123-6. [PMID: 27068351 DOI: 10.1136/jnnp-2015-312914] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Accepted: 03/22/2016] [Indexed: 11/03/2022]
Abstract
BACKGROUND AND PURPOSE Dementia with Lewy bodies (DLB) is characterised by neuroleptic hypersensitivity. It is unclear, however, whether the neuroleptic hypersensitivity implies an increased incidence of neuroleptic malignant syndrome (NMS) or of akinetic crisis (AC), which are expressions of the same possibly lethal clinical event, and whether AC in DLB can appear independently of neuroleptic treatment. In our prospective study, we assessed the incidence of AC in a cohort of DLB as compared with that in patients with Parkinson disease (PD). METHODS In total, 614 patients with PD and 236 DLB were recruited and followed during 2005-2013. AC was diagnosed as sudden akinetic state unresponsive to dopaminergic rescue drugs, dysphagia and serological alterations without recovery for 48 h or more requiring hospital admission. Exposure to neuroleptics was specifically evaluated, because of the high implicit risk in DLB. RESULTS 24 patients with PD (3.9%) and 16 patients with DLB (6.8%) developed AC. 77 (32.6%) DLB and 32 (5.2%) PD were exposed to typical neuroleptics, but only 8 DLB and 3 PD presented with AC. Disease duration before AC was lower in DLB than in PD group (p<0.01). Outcome was fatal in 8 patients with (50%) DLB and 3 (12.5%) PD (p=0.05). When age and use of neuroleptics were adjusted for into a Cox proportional hazards model predicting time to AC, the HR of patients with DLB was 13.0 (95% CI 4.23 to 39.9; p<0.001). CONCLUSIONS AC in DLB can appear independently of neuroleptic treatment, occurs earlier and is more frequently fatal than in PD.
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Affiliation(s)
- L Bonanni
- Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - R Di Giacomo
- Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - A D'Amico
- Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - V Frazzini
- Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - R Franciotti
- Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - L Manzoli
- Section of Epidemiology, Department of Medicine and Aging, University G d'Annunzio of Chieti-Pescara, Chieti, Italy Regional Healthcare Agency of Abruzzo, Abruzzo, Italy
| | - A Thomas
- Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d'Annunzio of Chieti-Pescara, Chieti, Italy
| | - M Onofrj
- Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d'Annunzio of Chieti-Pescara, Chieti, Italy
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Bonanni L, Cagnin A, Agosta F, Babiloni C, Borroni B, Bozzali M, Bruni AC, Filippi M, Galimberti D, Monastero R, Muscio C, Parnetti L, Perani D, Serra L, Silani V, Tiraboschi P, Padovani A. The Italian dementia with Lewy bodies study group (DLB-SINdem): toward a standardization of clinical procedures and multicenter cohort studies design. Neurol Sci 2016; 38:83-91. [DOI: 10.1007/s10072-016-2713-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Accepted: 09/08/2016] [Indexed: 01/23/2023]
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Shiga Y, Kanaya Y, Kono R, Takeshima S, Shimoe Y, Kuriyama M. [Dementia with Lewy bodies presenting marked tongue protrusion and bite due to lingual dystonia: A case report]. Rinsho Shinkeigaku 2016; 56:418-423. [PMID: 27212676 DOI: 10.5692/clinicalneurol.cn-000843] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
We report the patient of a 53-year-old woman who developed subacute-onset marked tonge protrusion and bite. She was diagnosed as dementia with Lewy bodies (DLB) from the clinical features including progressive cognitive decline, visual hallucinations, parkinsonism, and severe insomnia and depression, and the radiological finding of low dopamine transported uptake in basal ganglia by Dat SCAN and low blood circulation in occipital lobe of cerebrum. The patient received 600 mg doses of levodopa for over a year, followed by rotigotine and ropinirole with a rapid increase of dosage. It is believed that these treatments stimulated and sensitized dopamine D1 receptors, thereby inducing lingual dystonia. Furthermore, the patient demonstrated dyspnea and attacks of apnea caused by the closure of bilateral vocal cords due to laryngeal dyskinesia. After initiation of the neuroleptic, olanzapine, for a short duration, the high dose of levodopa overlapped with neuroleptic sensitivity, suggesting DOPA-induced dystonia and dyskinesia. This interaction can sometimes lead to lethal adverse events, and must be considered very important when treating patients with DLB.
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Affiliation(s)
- Yuji Shiga
- Department of Neurology, Brain Attack Center Ota Memorial Hospital
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Abstract
This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@ku.edu .
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Affiliation(s)
- Kimberly A. Madson
- Department of Pharmacy Practice, University of Montana, Skaggs School of Pharmacy, Missoula, Montana
| | - Sherrill Brown
- Department of Pharmacy Practice, University of Montana, Skaggs School of Pharmacy, Missoula, Montana
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Brigo F, Turri G, Tinazzi M. 123I-FP-CIT SPECT in the differential diagnosis between dementia with Lewy bodies and other dementias. J Neurol Sci 2015; 359:161-71. [PMID: 26671107 DOI: 10.1016/j.jns.2015.11.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 10/20/2015] [Accepted: 11/02/2015] [Indexed: 10/22/2022]
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Walker Z, Moreno E, Thomas A, Inglis F, Tabet N, Rainer M, Pizzolato G, Padovani A. Clinical usefulness of dopamine transporter SPECT imaging with 123I-FP-CIT in patients with possible dementia with Lewy bodies: randomised study. Br J Psychiatry 2015; 206:145-52. [PMID: 25431431 DOI: 10.1192/bjp.bp.114.148643] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Dementia with Lewy bodies (DLB) is underrecognised in clinical settings. AIMS To investigate whether performing a (123)I-ioflupane injection ((123)I-FP-CIT also called DaTSCAN™) single photon emission computed tomography (SPECT) scan in patients with possible DLB would lead to a more certain diagnosis (probable DLB or non-DLB dementia). METHOD We randomised 187 patients with possible DLB 2:1 to have a scan or not (control group). The outcome measure was a change in diagnosis to probable DLB or non-DLB. RESULTS There were 56 controls and 114 scanned patients, of whom 43% had an abnormal scan. More patients in the imaging group had a change in diagnosis compared with controls at 8 and 24 weeks (61% (n = 70) v. 4% (n = 2) and 71% (n = 77) v. 16% (n = 9); both P<0.0001). Clinicians were more likely to change the diagnosis if the scan was abnormal (82%) than if it was normal (46%). CONCLUSIONS Imaging significantly contributed to a more certain diagnosis, proving to be a useful adjunct in the work-up of patients with possible DLB.
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Affiliation(s)
- Zuzana Walker
- Zuzana Walker, MD, FRCPsych, Division of Psychiatry, University College London, London, and North Essex Partnership University NHS Foundation Trust, Essex, UK; Emilio Moreno, MD, PhD, GE Healthcare, Amersham, UK; Alan Thomas, PhD, FRCPsych, Biological Research Building, Newcastle University, Newcastle, UK; Fraser Inglis, FRCP, Glasgow Memory Clinic, Glasgow, UK; Naji Tabet, MD, MRCPsych, Postgraduate Medicine, Brighton and Sussex Medical School, Brighton, UK; Michael Rainer, MD, Karl Landsteiner Institut für Gedächtnis- und Alzheimerforschung, Vienna, Austria; Gilberto Pizzolato (deceased), MD, previously at Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Alessandro Padovani, MD, PhD, Scienze Cliniche e Sperimentali, University of Brescia, Brescia, Italy
| | - Emilio Moreno
- Zuzana Walker, MD, FRCPsych, Division of Psychiatry, University College London, London, and North Essex Partnership University NHS Foundation Trust, Essex, UK; Emilio Moreno, MD, PhD, GE Healthcare, Amersham, UK; Alan Thomas, PhD, FRCPsych, Biological Research Building, Newcastle University, Newcastle, UK; Fraser Inglis, FRCP, Glasgow Memory Clinic, Glasgow, UK; Naji Tabet, MD, MRCPsych, Postgraduate Medicine, Brighton and Sussex Medical School, Brighton, UK; Michael Rainer, MD, Karl Landsteiner Institut für Gedächtnis- und Alzheimerforschung, Vienna, Austria; Gilberto Pizzolato (deceased), MD, previously at Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Alessandro Padovani, MD, PhD, Scienze Cliniche e Sperimentali, University of Brescia, Brescia, Italy
| | - Alan Thomas
- Zuzana Walker, MD, FRCPsych, Division of Psychiatry, University College London, London, and North Essex Partnership University NHS Foundation Trust, Essex, UK; Emilio Moreno, MD, PhD, GE Healthcare, Amersham, UK; Alan Thomas, PhD, FRCPsych, Biological Research Building, Newcastle University, Newcastle, UK; Fraser Inglis, FRCP, Glasgow Memory Clinic, Glasgow, UK; Naji Tabet, MD, MRCPsych, Postgraduate Medicine, Brighton and Sussex Medical School, Brighton, UK; Michael Rainer, MD, Karl Landsteiner Institut für Gedächtnis- und Alzheimerforschung, Vienna, Austria; Gilberto Pizzolato (deceased), MD, previously at Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Alessandro Padovani, MD, PhD, Scienze Cliniche e Sperimentali, University of Brescia, Brescia, Italy
| | - Fraser Inglis
- Zuzana Walker, MD, FRCPsych, Division of Psychiatry, University College London, London, and North Essex Partnership University NHS Foundation Trust, Essex, UK; Emilio Moreno, MD, PhD, GE Healthcare, Amersham, UK; Alan Thomas, PhD, FRCPsych, Biological Research Building, Newcastle University, Newcastle, UK; Fraser Inglis, FRCP, Glasgow Memory Clinic, Glasgow, UK; Naji Tabet, MD, MRCPsych, Postgraduate Medicine, Brighton and Sussex Medical School, Brighton, UK; Michael Rainer, MD, Karl Landsteiner Institut für Gedächtnis- und Alzheimerforschung, Vienna, Austria; Gilberto Pizzolato (deceased), MD, previously at Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Alessandro Padovani, MD, PhD, Scienze Cliniche e Sperimentali, University of Brescia, Brescia, Italy
| | - Naji Tabet
- Zuzana Walker, MD, FRCPsych, Division of Psychiatry, University College London, London, and North Essex Partnership University NHS Foundation Trust, Essex, UK; Emilio Moreno, MD, PhD, GE Healthcare, Amersham, UK; Alan Thomas, PhD, FRCPsych, Biological Research Building, Newcastle University, Newcastle, UK; Fraser Inglis, FRCP, Glasgow Memory Clinic, Glasgow, UK; Naji Tabet, MD, MRCPsych, Postgraduate Medicine, Brighton and Sussex Medical School, Brighton, UK; Michael Rainer, MD, Karl Landsteiner Institut für Gedächtnis- und Alzheimerforschung, Vienna, Austria; Gilberto Pizzolato (deceased), MD, previously at Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Alessandro Padovani, MD, PhD, Scienze Cliniche e Sperimentali, University of Brescia, Brescia, Italy
| | - Michael Rainer
- Zuzana Walker, MD, FRCPsych, Division of Psychiatry, University College London, London, and North Essex Partnership University NHS Foundation Trust, Essex, UK; Emilio Moreno, MD, PhD, GE Healthcare, Amersham, UK; Alan Thomas, PhD, FRCPsych, Biological Research Building, Newcastle University, Newcastle, UK; Fraser Inglis, FRCP, Glasgow Memory Clinic, Glasgow, UK; Naji Tabet, MD, MRCPsych, Postgraduate Medicine, Brighton and Sussex Medical School, Brighton, UK; Michael Rainer, MD, Karl Landsteiner Institut für Gedächtnis- und Alzheimerforschung, Vienna, Austria; Gilberto Pizzolato (deceased), MD, previously at Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Alessandro Padovani, MD, PhD, Scienze Cliniche e Sperimentali, University of Brescia, Brescia, Italy
| | - Gilberto Pizzolato
- Zuzana Walker, MD, FRCPsych, Division of Psychiatry, University College London, London, and North Essex Partnership University NHS Foundation Trust, Essex, UK; Emilio Moreno, MD, PhD, GE Healthcare, Amersham, UK; Alan Thomas, PhD, FRCPsych, Biological Research Building, Newcastle University, Newcastle, UK; Fraser Inglis, FRCP, Glasgow Memory Clinic, Glasgow, UK; Naji Tabet, MD, MRCPsych, Postgraduate Medicine, Brighton and Sussex Medical School, Brighton, UK; Michael Rainer, MD, Karl Landsteiner Institut für Gedächtnis- und Alzheimerforschung, Vienna, Austria; Gilberto Pizzolato (deceased), MD, previously at Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Alessandro Padovani, MD, PhD, Scienze Cliniche e Sperimentali, University of Brescia, Brescia, Italy
| | - Alessandro Padovani
- Zuzana Walker, MD, FRCPsych, Division of Psychiatry, University College London, London, and North Essex Partnership University NHS Foundation Trust, Essex, UK; Emilio Moreno, MD, PhD, GE Healthcare, Amersham, UK; Alan Thomas, PhD, FRCPsych, Biological Research Building, Newcastle University, Newcastle, UK; Fraser Inglis, FRCP, Glasgow Memory Clinic, Glasgow, UK; Naji Tabet, MD, MRCPsych, Postgraduate Medicine, Brighton and Sussex Medical School, Brighton, UK; Michael Rainer, MD, Karl Landsteiner Institut für Gedächtnis- und Alzheimerforschung, Vienna, Austria; Gilberto Pizzolato (deceased), MD, previously at Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Alessandro Padovani, MD, PhD, Scienze Cliniche e Sperimentali, University of Brescia, Brescia, Italy
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Abstract
BACKGROUND The clinical condition of dementia is now recognized as a diagnosis that can only be applied too late in the disease process to be useful for therapeutic approaches centring on disease modification. As a result, in recent years increasing attention has been given to mild cognitive impairment (MCI) and the diagnosis of prodromal dementia. This paper reviews the evidence for the clinical presentation of prodromal dementia with Lewy bodies (DLB). METHOD A Medline search was carried out to identify articles with original data on the prodromal presentation of DLB. RESULTS In MCI cohorts that progress to dementia, the proportion diagnosed with DLB is similar to that reported in dementia cohorts. Prodromal DLB may present as any MCI subtype, although visuospatial and executive domains may be most commonly affected. Rapid eye movement (REM) sleep behaviour disorder (RBD), autonomic symptoms, hyposmia, hallucinations and motor symptoms seem to be more common in prodromal DLB than in prodromal Alzheimer's disease (AD). Some of these symptoms can precede the diagnosis of DLB by several years. There has been little research into the use of biomarkers in prodromal DLB, although in RBD cohorts, clinical and imaging biomarkers have been associated with the development of DLB. CONCLUSIONS The evidence available suggests that prodromal DLB may be differentiated from other dementia prodromes in most cases. Further research is needed to confirm this, and to assess the utility of biomarkers such as 123I-FP-CIT and 123I-MIBG imaging.
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Affiliation(s)
- P C Donaghy
- Institute for Ageing and Health, Newcastle University,Campus for Ageing and Vitality, Newcastle upon Tyne,UK
| | - J T O'Brien
- Department of Psychiatry,University of Cambridge,Cambridge Biomedical Campus, Cambridge,UK
| | - A J Thomas
- Institute for Ageing and Health, Newcastle University,Campus for Ageing and Vitality, Newcastle upon Tyne,UK
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Yap KZ, Chan SY. Role of antipsychotics for treating behavioral and psychological symptoms of dementia. World J Pharmacol 2014; 3:174-185. [DOI: 10.5497/wjp.v3.i4.174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 10/02/2014] [Accepted: 10/27/2014] [Indexed: 02/06/2023] Open
Abstract
Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes (NHs) for the management of behavioral and psychological symptoms of dementia continue to be emphasized and intervened by many. However, despite the numerous side effects and the recent blackbox warning by the United States Food and Drug Administration about the increased risks for stroke and sudden death associated with the use of antipsychotics in dementia, the prevalence of antipsychotic use in NHs remains high. While the use of antipsychotics appeared to have modest efficacy in reducing symptoms of aggression and psychosis in dementia, there is insufficient evidence to routinely recommend the use of alternative psychopharmacological treatments for these symptoms. Hence, clinicians have to balance the safety warnings against the need to treat these symptoms in order to prevent harm to the resident that may result from his/her dangerous behaviors. Although the use of antipsychotics may be warranted in some cases, organizational, resource and training support should be provided to encourage and equip NH staff to participate in interventions so as to minimize inappropriate use of these medicines in NHs. This review will discuss the place in therapy, the trend and appropriateness of antipsychotic use in NHs, as well as the effectiveness of current and future strategies for reducing antipsychotic use in the NHs.
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Camicioli R, Gauthier S. Clinical Trials in Parkinson's Disease Dementia and Dementia with Lewy Bodies. Can J Neurol Sci 2014; 34 Suppl 1:S109-17. [PMID: 17469693 DOI: 10.1017/s0317167100005679] [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: 11/07/2022]
Abstract
Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are pathological overlapping and important causes of dementia for which clinical trials are in their infancy. Cholinesterase inhibitors may be of benefit in DLB and PDD, as suggested by placebo-controlled clinical trials of rivastigmine and donepezil. The anti-psychotic agent clozapine has been of benefit in PD and PDD, but other agents, such as quetiapine, require adequate assessment. Barriers to trials include pathological overlap that can lead to inaccuracies in clinical diagnosis, unavailability of a consensus definition for PDD, unanswered questions regarding natural history and the paucity of validated outcome measures. Motor impairment must be considered in patients with PDD and DLB; conversely, cognitive impairment should be assessed in trials targeting motor impairment in advanced PD. Potential targets for treatment include onset of dementia, cognitive impairment, behavioral impairment, functional decline, falls, nursing home placement, mortality, quality of life and economic impact. Biomarkers including neuroimaging and cerebrospinal fluid markers are not currently established. At present PDD and DLB are distinct entities by definition. Future studies, including clinical trials and biomarker studies, will help to further define the clinical and therapeutic implications of this distinction.
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Magnetic resonance spectroscopy in the diagnosis of dementia with Lewy bodies. BIOMED RESEARCH INTERNATIONAL 2014; 2014:809503. [PMID: 25110697 PMCID: PMC4109391 DOI: 10.1155/2014/809503] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/25/2014] [Revised: 05/21/2014] [Accepted: 06/20/2014] [Indexed: 01/03/2023]
Abstract
Dementia with Lewy bodies (DLB) is considered to be the second most frequent primary degenerative dementing illness after Alzheimer's disease (AD). DLB, together with Parkinson's disease (PD), Parkinson's disease with dementia (PDD) belong to α-synucleinopathies—a group of neurodegenerative diseases associated with pathological accumulation of the α-synuclein protein. Dementia due to PD and DLB shares clinical symptoms and neuropsychological profiles. Moreover, the core features and additional clinical signs and symptoms for these two very similar diseases are largely the same. Neuroimaging seems to be a promising method in differential diagnosis of dementia studies. The development of imaging methods or other objective measures to supplement clinical criteria for DLB is needed and a method which would accurately facilitate diagnosis of DLB prior to death is still being searched. Proton magnetic resonance spectroscopy (1H-MRS) provides a noninvasive method of assessing an in vivo biochemistry of brain tissue. This review summarizes the main results obtained from the application of neuroimaging techniques in DLB cases focusing on 1H-MRS.
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36
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Marvanova M. Antipsychotic use in elderly patients with dementia: Efficacy and safety concerns. Ment Health Clin 2014. [DOI: 10.9740/mhc.n204371] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Behavioral and psychiatric symptoms of dementia (BPSD) refer to a heterogeneous group of symptoms that represent non-cognitive complications of Alzheimer's disease (AD) and other dementias. Currently, there are no FDA-approved antipsychotic medications for management of BPSD in the United States. Second generation antipsychotics (SGAs) should only be used for appropriate and justified BPSD targets including distressing and severe physical aggression and/or disturbing hallucinations or delusions that pose a risk of harm to self or others after non-pharmacologic interventions have failed. At best, SGAs provide only modest effects and are associated with increased risk for mortality and cerebrovascular complications in addition to other agent-specific side effects. Current evidence and recommendations support use of risperidone, aripiprazole or olanzapine for Alzheimer's disease (AD) and vascular dementia (VaD), and use of quetiapine or clozapine for Lewy body dementia (LBD) and Parkinson's disease dementia (PDD). Any SGA should be initiated at low dosages with slow titration; and the lowest effective dose should be used as a maintenance dose only for a short period of time. Patients should be monitored for clinical response and adverse effects and should be periodically evaluated for continued need for medication. Appropriate use of SGAs for management of BPSD is critical to increase safety for our growing elderly population with dementia.
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Affiliation(s)
- Marketa Marvanova
- 1 Associate Professor, Pharmacy Practice, Chicago State University College of Pharmacy, Adjunct Associate Professor of Neurology, Northwestern University Feinberg School of Medicine, Department of Neurology, Clinical Pharmacy Specialist, Neurology, Rush University Medical Center, Chicago, IL
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37
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Vann Jones SA, O'Brien JT. The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychol Med 2014; 44:673-683. [PMID: 23521899 DOI: 10.1017/s0033291713000494] [Citation(s) in RCA: 336] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Dementia with Lewy bodies (DLB) is increasingly recognized as a common cause of dementia in older people. However, its true frequency remains unclear, with previous studies reporting a prevalence range from zero to 22.8% of all dementia cases. This review aimed to establish the population prevalence and incidence for DLB and to compare this to its prevalence in secondary care settings. METHOD A literature review of all relevant population and clinical studies was conducted using PubMed. Additional references from papers found during that process were added to this. RESULTS DLB accounted for 4.2% of all diagnosed dementias in the community. In secondary care this increased to 7.5%. The incidence of DLB was 3.8% of new dementia cases. There was a significant increase in DLB diagnoses when using the revised (2005) International Consensus Criteria (ICC) for DLB compared to the original (1996) criteria. CONCLUSIONS DLB currently accounts for around one in 25 dementia cases diagnosed in the community and one in 13 cases in secondary care. The significantly higher rates of DLB in secondary care may reflect enhanced diagnostic accuracy in specialist settings and/or the increased morbidity and carer burden of the DLB syndrome compared to other dementias. However, the true prevalence is likely to be much higher because DLB diagnoses are often missed, although there is evidence that new criteria aid case identification.
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Affiliation(s)
- S A Vann Jones
- Institute for Ageing and Health, Newcastle University, UK
| | - J T O'Brien
- Institute for Ageing and Health, Newcastle University, UK
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38
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Mitolo M, Salmon DP, Gardini S, Galasko D, Grossi E, Caffarra P. The new Qualitative Scoring MMSE Pentagon Test (QSPT) as a valid screening tool between autopsy-confirmed dementia with Lewy bodies and Alzheimer's disease. J Alzheimers Dis 2014; 39:823-832. [PMID: 24284368 PMCID: PMC4346244 DOI: 10.3233/jad-131403] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Visual-constructional apraxia is a prominent feature of dementia with Lewy bodies (DLB) that might help to clinically distinguish it from Alzheimer's disease (AD). The main goal of this study was to assess performance on the copy intersecting-pentagon item of the Mini-Mental State Examination with the new Qualitative Scoring method for the Pentagon copy Test (QSPT). In order to determine which aspects of the drawings might differentiate DLB from AD, pentagon drawings of autopsy-verified DLB (n = 16) and AD (n = 15) patients were assessed using the QSPT. The qualitative scoring encompasses the assessment of different parameters of the drawing, such as number of angles, distance/intersection, closure/opening, rotation, and closing-in. The QSPT scores were compared between groups using linear analyses and artificial neural network analyses at four different time points. Linear analyses showed that during the first evaluation, number of angles was the only parameter that showed a significant difference between DLB and AD patients. A gradual decline in other parameters and total pentagon score occurred in both groups during subsequent years, with greater decline for the DLB group. The artificial neural network analyses using auto-contractive maps showed that, with disease progression, DLB became related to relatively lower qualitative pentagon scores, whereas AD became related to relatively higher qualitative scores. These findings suggest that the QSPT might be a sensitive measure of visuo-constructive abilities able to differentiate DLB from AD at disease onset and as the diseases progress, but further studies on larger population are necessary in order to establish its clinical relevance.
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Affiliation(s)
- Micaela Mitolo
- Department of Psychology, University of Padua, Padua, Italy
- Alzheimer's Disease Research Center, University of California, San Diego, CA, USA
| | - David P. Salmon
- Alzheimer's Disease Research Center, University of California, San Diego, CA, USA
| | - Simona Gardini
- Department of Neuroscience, University of Parma and Center for Cognitive Disorders, AUSL of Parma, Parma, Italy
| | - Douglas Galasko
- Alzheimer's Disease Research Center, University of California, San Diego, CA, USA
| | - Enzo Grossi
- Villa Santa Maria, Neuropsychiatric Rehabilitation Centre, Tavernerio, Como, Italy
| | - Paolo Caffarra
- Department of Neuroscience, University of Parma and Center for Cognitive Disorders, AUSL of Parma, Parma, Italy
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39
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Abstract
OPINION STATEMENT Dementia with Lewy bodies (DLB) is a multisystem disorder with diverse disease expression. A treatment regime restricted to the cognitive aspects of the disease does no favor to patients. Instead, patients should be educated to recognize the symptoms of this multisystem involvement. There are no treatments that slow the progression of disease, but symptomatic treatments can be effective. When thinking about treatment, we find it useful to divide the symptoms and signs into five categories: (a) cognitive features, (b) neuropsychiatric features, (c) motor dysfunction, (d) autonomic dysfunction, and (e) sleep dysfunction. Clinicians, funding bodies and industry are increasingly recognizing the importance of this common and debilitating disease.
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Affiliation(s)
- Brendon P Boot
- Department of Neurology, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA, 02115, USA,
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40
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Ballard C, Aarsland D, Francis P, Corbett A. Neuropsychiatric symptoms in patients with dementias associated with cortical Lewy bodies: pathophysiology, clinical features, and pharmacological management. Drugs Aging 2013; 30:603-11. [PMID: 23681401 DOI: 10.1007/s40266-013-0092-x] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are synucleinopathies that lead to neurodegeneration and dementia. Although they result in symptoms common to Alzheimer's disease, they are associated with early emergence of parkinsonism and high frequency of neuropsychiatric symptoms, most commonly hallucinations and delusions. This review summarizes the current understanding of the underlying biology of neuropsychiatric symptoms in DLB and PDD and the evidence base for treatment to address them. Disruption to cholinergic and serotonergic neurotransmission and synapse activity are highlighted as primary pathological factors in neuropsychiatric symptoms, particularly loss of key neurotransmitter functions, alterations to neuronal receptors in the serotonergic pathway, and regionally specific structural changes that are linked to specific symptoms. Review of options for pharmacological treatment of neuropsychiatric symptoms suggests that the best evidence for the value of treatment is for cholinesterase inhibitors, with an indication that people with visual hallucinations are particularly likely to benefit. Evidence for the benefits of antipsychotics other than clozapine is limited, and there are serious safety concerns about the use of antipsychotics in these patients. Evidence to support other pharmacological interventions is very preliminary. Nonpharmacological approaches based on person-centered care and cholinesterase inhibitors should be considered as the first-line treatment for neuropsychiatric symptoms except in extreme cases.
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Affiliation(s)
- Clive Ballard
- Wolfson Centre for Age-Related Diseases, King's College London, Wolfson Building, Guy's Campus, London, SE1 1UL, UK.
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41
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Burke A, Hall G, Tariot PN. The clinical problem of neuropsychiatric signs and symptoms in dementia. Continuum (Minneap Minn) 2013; 19:382-96. [PMID: 23558484 PMCID: PMC10563909 DOI: 10.1212/01.con.0000429177.14354.83] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
PURPOSE OF REVIEW This article reviews behavioral signs and symptoms of dementia that can lead to increased mortality, excessive cognitive and functional disability, early institutionalization, and increased caregiver burnout. RECENT FINDINGS Almost all patients with a dementia will develop significant behavioral disturbances at some point over the course of their illness. These behavioral signs and symptoms rarely fit into usual diagnostic classifications or meet full criteria for a formal major psychiatric disorder. SUMMARY Treatment of behavioral signs and symptoms of dementia should include both pharmacologic and nonpharmacologic interventions. There are currently no treatments for these disturbances approved by the US Food and Drug Administration. Best judgment should be used in identifying dominant target symptoms and matching them to the most relevant drug class. Implementing nonpharmacologic interventions before the development of neuropsychiatric symptoms may prevent triggers related to a progressively lowered stress threshold and therefore is key in the treatment of all patients with a dementia.
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Affiliation(s)
- Anna Burke
- Banner Alzheimer’s Institute 901 East Willetta St, Phoenix, AZ 85006, USA.
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42
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Rice T, Dobry Y, Wang E, Novakovic V, Sher L. Cognitive effects of quetiapine in a patient with dementia with Lewy bodies. Psychogeriatrics 2013; 13:52-7. [PMID: 23551413 DOI: 10.1111/j.1479-8301.2012.00414.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
A recent large-scale randomized controlled clinical trial, the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study, found a significant worsening of cognitive functioning in a sample of patients with Alzheimer's disease. To date there have been no equally powered studies examining the cognitive effects of atypical antipsychotics in patients with dementia with Lewy bodies, the second most prevalent neurodegenerative disorder. This case report describes a significant cognitive improvement observed through the use of an atypical antipsychotic in a patient with dementia with Lewy bodies. The observed divergence in cognitive responsiveness is discussed mechanistically on both the clinical and neuromolecular level. Limitations to this case study design are presented and discussed. The prudence of caution in importing the results of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study to the dementia with Lewy bodies population is summarized and presented for psychiatrists, neurologists and primary care providers, with an intent to stimulate discussion and further research.
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Affiliation(s)
- Timothy Rice
- The Mount Sinai School of Medicine, New York, New York 10029, USA.
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43
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Utilidad de la imagen precoz de la gammagrafía de inervación miocárdica en el diagnóstico de la demencia con cuerpos de Lewy. Rev Esp Med Nucl Imagen Mol 2013. [DOI: 10.1016/j.remn.2012.03.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Camacho V, Estorch M, Marquié M, Domènech A, Flotats A, Fernández A, Duch J, Geraldo L, Deportos J, Artigas C, Lleó A, Carrió I. Utility of early imaging of myocardial innervation scintigraphy in the diagnosis of Lewy body dementia. Rev Esp Med Nucl Imagen Mol 2013. [DOI: 10.1016/j.remnie.2013.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Mori E, Ikeda M, Kosaka K. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial. Ann Neurol 2012; 72:41-52. [PMID: 22829268 PMCID: PMC3504981 DOI: 10.1002/ana.23557] [Citation(s) in RCA: 158] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Objective: Because cholinergic deficits are prominent in dementia with Lewy bodies (DLB), we investigated the effects of a cholinesterase inhibitor, donepezil, in such patients in a randomized, double-bilnd- placebo-controlled exploratory phase 2 trial. Methods: One-hundred forty patients with DLB, recruited from 48 specialty centers in Japan, were randomly assigned to receive placebo or 3, 5, or 10mg of donepezil hydrochloride daily for 12 weeks (n = 35, 35, 33, and 37, respectively). Effects on cognitive function were assessed using the Mini-Mental State Examination (MMSE) and several domain-specific neuropsychological tests. Changes in behavior were evaluated using the Neuropsychiatric Inventory, caregiver burden using the Zarit Caregiver Burden Interview, and global function using the Clinician’s Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus). Safety measures included the Unified Parkinson’s Disease Rating Scale part III. Results: Donepezil at 5 and 10mg/day was significantly superior to placebo on both the MMSE (5mg: mean difference, 3.8; 95% confidence interval [CI], 2.3-5.3; p < 0.001; 10 mg: mean difference, 2.4; 95% CI, 0.9-3.9; p = 0.001) and CIBIC-plus (p < 0.001 for each); 3mg/day was significantly superior to placebo on CIBIC-plus (p < 0.001), but not on the MMSE (p = 0.017). Significant improvements were found also in behavioral measures (p < 0.001) at 5 and 10mg/day and caregiver burden (p = 0.004) at 10 mg/day. The safety results were consistent with the known profile of donepezil and similar among groups. Interpretation: Donepezil at 5 and 10mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose. Donepezil is safe and well tolerated.
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Affiliation(s)
- Etsuro Mori
- Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan.
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46
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Abstract
Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia in older people, accounting for 10% to 15% of all cases, it occupies part of a spectrum that includes Parkinson's disease and primary autonomic failure. All these diseases share a neuritic pathology based upon abnormal aggregation of the synaptic protein α-synuciein. It is important to identify DLB patients accurately because they have specific symptoms, impairments, and functional disabilities thai differ from other common dementia syndromes such as Alzheimer's disease, vascular cognitive impairment, and frontotemporal dementia. Clinical diagnostic criteria for DLB have been validated against autopsy, but fail to detect a substantial minority of cases with atypical presentations that are often due to the presence of mixed pathology. DLB patients frequently have severe neuroleptic sensitivity reactions, which are associated with significantly increased morbidity and mortality. Cholinesterase inhibitor treatment is usually well tolerated and substantially improves cognitive and neuropsychiatrie symptoms. Although virtually unrecognized 20 years ago, DLB could within this decade become one of the most treatable neurodegenerative disorders of late life.
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Affiliation(s)
- Ian McKeith
- Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK
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47
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Ballard C, Kahn Z, Corbett A. Treatment of Dementia with Lewy Bodies and Parkinsonʼs Disease Dementia. Drugs Aging 2011; 28:769-77. [DOI: 10.2165/11594110-000000000-00000] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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Bittner V, Ullrich G, Thormann M, Müller NG, Friederichs C, Amthauer H, Heinze HJ, Bittner DM. Positive FP-CIT SPECT (DaTSCAN) in Clinical Alzheimer's Disease - An Unexpected Finding? Dement Geriatr Cogn Dis Extra 2011; 1:283-91. [PMID: 22545039 PMCID: PMC3235939 DOI: 10.1159/000330470] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Clinically, Alzheimer's disease (AD) is by far the most common cause of dementia. Criteria for the diagnosis of dementia with Lewy bodies (DLB) are highly specific but not at all sensitive, which is reflected by the higher number of DLB cases detected histopathologically at autopsy. Imaging of dopamine transporter with FP-CIT SPECT is one possibility to increase sensitivity. Pathological confirmation was also included in the revised consensus criteria for the diagnosis of DLB. However, in the absence of parkinsonism, one of the core features, a clinical diagnosis of AD is more likely. The role of FP-CIT SPECT in DLB diagnosis remains to be clarified. Based on our 3 case reports and a review of the literature, the utility of this imaging method in the differential diagnosis of AD and DLB is highlighted.
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Affiliation(s)
- Verena Bittner
- Departments of Neurology, Magdeburg, University of Magdeburg, Magdeburg, Germany
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Arslankoylu AE, Kutuk MO, Okuyaz C, Toros F. Neuroleptic malignant syndrome due to risperidone misdiagnosed as status epilepticus. Pediatr Rep 2011; 3:e19. [PMID: 22053263 PMCID: PMC3207307 DOI: 10.4081/pr.2011.e19] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2011] [Accepted: 06/21/2011] [Indexed: 11/23/2022] Open
Abstract
Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal disease characterized by fever, muscle rigidity, delirium and autonomic instability. Here we report a child, with NMS due to the risperidone misdiagnosed as status epilepticus. Nine year old boy, who had been under high dose risperidone treatment for 8 weeks, admitted to the emergency room because of the contractions (evaluated as status epilepticus) persisting for 7 hours. Since there was neuroleptic treatment in the past medical history and, unconsciousness, muscular rigidity, diaphoresis, hypertermi and, hypotension in physical examination, leucocytosis and elevated creatininphosphokinase levels in laboratory tests, the patient was evaluated as NMS and discharged without any complications. We reported this case to point out that; NMS may be misdiagnosed as status epilepticus in children when EEG monitoring is unavailable. When a child admitted to the emergency room because of suspicious convulsion neuroleptic drug use must surely be asked.
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Affiliation(s)
- Ali Ertug Arslankoylu
- Mersin University Faculty of Medicine, Department of Pediatrics, Pediatric Intensive Care Unit, Mersin, Turkey
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50
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Abstract
The risk of developing dementia is associated with increasing age, lifestyle, and cardiovascular health. Alzheimer dementia is characterized by progressive cognitive deficits and decline in functional ability. Using history, examination, and laboratory testing, the clinician can evaluate the patient with dementia. Specific to these conditions are assessments of cognition, neuropsychiatric symptoms, and level of functioning. Managing neuropsychiatric symptoms is challenging and requires a team approach in which nonpharmacological strategies are preferred before medications are considered. Various diagnostic methods are being developed to discriminate disease from nondisease and track progression. Drug discovery is identifying novel molecules that target underlying disease mechanisms.
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Affiliation(s)
- Milap A Nowrangi
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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