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Sankhe K, Bawa KK, Miller DS, Bateman D, Cummings JL, Ereshefsky L, Husain M, Ismail Z, Manera V, Mintzer J, Moebius HJ, Mortby M, Porsteinsson A, Robert P, Lanctôt KL. Mapping of validated apathy scales onto the apathy diagnostic criteria for neurocognitive disorders. Int Psychogeriatr 2025:100074. [PMID: 40280825 DOI: 10.1016/j.inpsyc.2025.100074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 04/02/2025] [Accepted: 04/09/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND Diagnostic criteria for apathy in neurocognitive disorders (DCA-NCD) have recently been updated. OBJECTIVES We investigated whether validated scales measuring apathy severity capture the three dimensions of the DCA-NCD (diminished initiative, diminished interest, diminished emotional expression). MEASUREMENTS Degree of mapping ("not at all", "weakly", or "strongly") between items on two commonly used apathy scales, the Neuropsychiatric Inventory-Clinician (NPI-C) apathy and Apathy Evaluation Scale (AES), with the DCA-NCD overall and its 3 dimensions was evaluated by survey. DESIGN Survey participants, either experts (n = 12, DCA-NCD authors) or scientific community members (n = 19), rated mapping for each item and mean scores were calculated. Interrater reliability between expert and scientific community members was assessed using Cohen's kappa. RESULTS According to experts, 9 of 11 (81.8%) NPI-C apathy items and 6 of 18 (33.3%) AES items mapped strongly onto the DCA-NCD overall. For the scientific community group, 10 of 11 (90.9%) NPI-C apathy items and 7 of 18 (38.8%) AES items mapped strongly onto the DCA-NCD overall. The overall mean mapping scores were higher for the NPI-C apathy compared to the AES for both expert (t (11) = 3.13, p = .01) and scientific community (t (17) = 3.77, p = .002) groups. There was moderate agreement between the two groups on overall mapping for the NPI-C apathy (kappa= 0.74 (0.57, 1.00)) and AES (kappa= 0.63 (0.35, 1.00)). CONCLUSIONS More NPI-C apathy than AES items mapped strongly and uniquely onto the DCA-NCD and its dimensions. The NPI-C apathy may better capture the DCA-NCD and its dimensions compared with the AES.
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Affiliation(s)
- K Sankhe
- Neuropsychopharmacology Research Group, Toronto, ON, Canada; Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada
| | - K K Bawa
- Neuropsychopharmacology Research Group, Toronto, ON, Canada; Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
| | | | - D Bateman
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA
| | - J L Cummings
- Chambers-Grundy Center for Transformative Neuroscience, University of Nevada, Las Vegas, NV, USA
| | - L Ereshefsky
- University of Texas Health Sciences, San Antonio, TX, USA; Follow the Molecule: CNS Consulting LLC, Marina del Rey, CA, USA
| | - M Husain
- University of Oxford, Oxford, UK
| | - Z Ismail
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
| | - V Manera
- Université Côte d'Azur, Cognition Behaviour Technology Lab, Nice, France; Association Innovation Alzheimer, Nice, France
| | - J Mintzer
- Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Health Care System, Charleston, SC, USA
| | | | - M Mortby
- Neuroscience Research Australia, Sydney, NSW, Australia; UNSW Ageing Futures Institute, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia
| | - A Porsteinsson
- University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - P Robert
- Association Innovation Alzheimer, Nice, France; Centre Memoire, Centre Hospitalier Universitaire de Nice, Nice, France
| | - K L Lanctôt
- Neuropsychopharmacology Research Group, Toronto, ON, Canada; Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
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Greig Custo MT, Lang MK, Barker WW, Gonzalez J, Vélez-Uribe I, Arruda F, Conniff J, Rodriguez MJ, Loewenstein DA, Duara R, Adjouadi M, Curiel RE, Rosselli M. The association of depression and apathy with Alzheimer's disease biomarkers in a cross-cultural sample. APPLIED NEUROPSYCHOLOGY. ADULT 2024; 31:849-865. [PMID: 35764422 PMCID: PMC9930412 DOI: 10.1080/23279095.2022.2079414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Cross-cultural differences in the association between neuropsychiatric symptoms and Alzheimer's disease (AD) biomarkers are not well understood. This study aimed to (1) compare depressive symptoms and frequency of reported apathy across diagnostic groups of participants with normal cognition (CN), mild cognitive impairment (MCI), and dementia, as well as ethnic groups of Hispanic Americans (HA) and European Americans (EA); (2) evaluate the relationship between depression and apathy with Aβ deposition and brain atrophy. Statistical analyses included ANCOVAs, chi-squared, nonparametric tests, correlations, and logistic regressions. Higher scores on the Geriatric Depression Scale (GDS-15) were reported in the MCI and dementia cohorts, while older age corresponded with lower GDS-15 scores. The frequency of apathy differed across diagnoses within each ethnicity, but not when comparing ethnic groups. Reduced volume in the rostral anterior cingulate cortex (ACC) significantly correlated with and predicted apathy for the total sample after applying false discovery rate corrections (FDR), controlling for covariates. The EA group separately demonstrated a significant negative relationship between apathy and superior frontal volume, while for HA, there was a relationship between rostral ACC volume and apathy. Apathy corresponded with higher Aβ levels for the total sample and for the CN and HA groups.
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Affiliation(s)
- María T. Greig Custo
- Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA
- Florida Alzheimer’s Disease Research Center, Miami Beach, FL, USA
| | - Merike K. Lang
- Department of Psychology, Charles E Schmidt College of Science, Florida Atlantic University, Davie, FL, USA
| | - Warren W. Barker
- Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA
- Florida Alzheimer’s Disease Research Center, Miami Beach, FL, USA
| | - Joanna Gonzalez
- Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA
| | - Idaly Vélez-Uribe
- Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA
- Department of Psychology, Charles E Schmidt College of Science, Florida Atlantic University, Davie, FL, USA
| | - Fernanda Arruda
- Department of Psychology, Charles E Schmidt College of Science, Florida Atlantic University, Davie, FL, USA
| | - Joshua Conniff
- Department of Psychology, Charles E Schmidt College of Science, Florida Atlantic University, Davie, FL, USA
| | | | - David A. Loewenstein
- Florida Alzheimer’s Disease Research Center, Miami Beach, FL, USA
- Department of Psychiatry and Behavioral Sciences and Center for Cognitive Neuroscience and Aging, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Ranjan Duara
- Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA
- Florida Alzheimer’s Disease Research Center, Miami Beach, FL, USA
| | - Malek Adjouadi
- Florida Alzheimer’s Disease Research Center, Miami Beach, FL, USA
- Center for Advanced Technology and Education, College of Engineering, Florida International University, Miami, FL, USA
| | - Rosie E. Curiel
- Florida Alzheimer’s Disease Research Center, Miami Beach, FL, USA
- Department of Psychiatry and Behavioral Sciences and Center for Cognitive Neuroscience and Aging, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Mónica Rosselli
- Florida Alzheimer’s Disease Research Center, Miami Beach, FL, USA
- Department of Psychology, Charles E Schmidt College of Science, Florida Atlantic University, Davie, FL, USA
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3
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Teixeira AL, Martins LB, Cordeiro TME, Jose L, Suchting R, Holmes HM, Acierno R, Ahn H. Home-based tDCS for apathy in Alzheimer's disease: a protocol for a randomized double-blinded controlled pilot study. Pilot Feasibility Stud 2023; 9:74. [PMID: 37147739 PMCID: PMC10161588 DOI: 10.1186/s40814-023-01310-5] [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: 08/29/2022] [Accepted: 04/21/2023] [Indexed: 05/07/2023] Open
Abstract
BACKGROUND Apathy is among the most common behavioral symptoms in dementia and is consistently associated with negative outcomes in Alzheimer's disease (AD). Despite its prevalence and clinical relevance, available pharmacological and non-pharmacological strategies to treat apathy in AD have been marked, respectively, by potentially severe side effects and/or limited efficacy. Transcranial direct current stimulation (tDCS) is a relatively novel non-pharmacological method of neuromodulation with promising results. Compared to previous tDCS formats, recent technological advances have increased the portability of tDCS, which creates the potential for caregiver-administered, home use. Our study aims to evaluate the feasibility, safety, and efficacy of home-based tDCS for the treatment of apathy in AD. METHODS/DESIGN This is an experimenter- and participant-blinded, randomized, sham-controlled, parallel-group (1:1 for two groups) pilot clinical trial, involving 40 subjects with AD. After a brief training, caregivers will administer tDCS for participants at home under remote televideo supervision by research staff to ensure the use of proper technique. Participants will be assessed at baseline, during treatment (week 2, week 4, and week 6), and 6 weeks post-treatment. Dependent measures will cover cognitive performance, apathy, and other behavioral symptoms. Data about side effects and acceptability will also be collected. DISCUSSION Our study will address apathy, an overlooked clinical problem in AD. Our findings will advance the field of non-pharmacological strategies for neuropsychiatric symptoms, presenting a great potential for clinical translation. TRIAL REGISTRATION ClinicalTrials.gov, NCT04855643.
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Affiliation(s)
- Antonio L Teixeira
- Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center, 1941 East Road, Houston, TX, 77054, USA.
| | - Laís Bhering Martins
- Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center, 1941 East Road, Houston, TX, 77054, USA
| | - Thiago Macedo E Cordeiro
- Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center, 1941 East Road, Houston, TX, 77054, USA
| | - Lijin Jose
- Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center, 1941 East Road, Houston, TX, 77054, USA
| | - Robert Suchting
- Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center, 1941 East Road, Houston, TX, 77054, USA
| | - Holly M Holmes
- Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, TX, USA
| | - Ron Acierno
- Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center, 1941 East Road, Houston, TX, 77054, USA
| | - Hyochol Ahn
- College of Nursing, Florida State University, Tallahassee, FL, USA
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Mehak SF, Shivakumar AB, Saraf V, Johansson M, Gangadharan G. Apathy in Alzheimer's disease: A neurocircuitry based perspective. Ageing Res Rev 2023; 87:101891. [PMID: 36871779 DOI: 10.1016/j.arr.2023.101891] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/25/2023] [Accepted: 02/21/2023] [Indexed: 03/07/2023]
Abstract
In addition to memory deficits and other cognitive disturbances, patients with Alzheimer's disease (AD) experience neuropsychiatric symptoms, notably apathy, which is a state of impaired motivation observed by deficits in goal directed behavior. Apathy is a multifaceted neuropsychiatric condition and appears to be a prognostic indicator, correlating with the progression of AD. Strikingly, recent studies point out that the neurodegenerative pathology of AD may drive apathy independent of cognitive decline. These studies also highlight that neuropsychiatric symptoms, in particular apathy, might manifest early in AD. Here, we review the current understanding of the neurobiological underpinnings of apathy as a neuropsychiatric symptom of AD. Specifically, we highlight the neural circuits and brain regions recognized to be correlated with the apathetic symptomatology. We also discuss the current evidence that supports the notion that apathy and cognitive deficits may develop as independent but concurrent phenomena driven by AD pathology, suggesting its efficacy as an additional outcome measure in Alzheimer's disease clinical trials. The current and prospective therapeutic interventions for apathy in AD from a neurocircuitry based perspective are also reviewed.
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Affiliation(s)
- Sonam Fathima Mehak
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
| | - Apoorva Bettagere Shivakumar
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
| | - Vikyath Saraf
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
| | - Maurits Johansson
- Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, SUS, Sweden; Division of Clinical Sciences, Helsingborg, Department of Clinical Sciences Lund, Lund University, Sweden; Department of Psychiatry, Helsingborg Hospital, Sweden.
| | - Gireesh Gangadharan
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
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Manca R, Jones SA, Venneri A. Macrostructural and Microstructural White Matter Alterations Are Associated with Apathy across the Clinical Alzheimer's Disease Spectrum. Brain Sci 2022; 12:1383. [PMID: 36291317 PMCID: PMC9599811 DOI: 10.3390/brainsci12101383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/04/2022] [Accepted: 10/09/2022] [Indexed: 11/30/2022] Open
Abstract
Apathy is the commonest neuropsychiatric symptom in Alzheimer's disease (AD). Previous findings suggest that apathy is caused by a communication breakdown between functional neural networks involved in motivational-affective processing. This study investigated the relationship between white matter (WM) damage and apathy in AD. Sixty-one patients with apathy (AP-PT) and 61 without apathy (NA-PT) were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and matched for cognitive status, age and education. Sixty-one cognitively unimpaired (CU) participants were also included as controls. Data on cognitive performance, cerebrospinal fluid biomarkers, brain/WM hyperintensity volumes and diffusion tensor imaging indices were compared across groups. No neurocognitive differences were found between patient groups, but the AP-PT group had more severe neuropsychiatric symptoms. Compared with CU participants, only apathetic patients had deficits on the Clock Drawing Test. AP-PT had increased WM damage, both macrostructurally, i.e., larger WM hyperintensity volume, and microstructurally, i.e., increased radial/axial diffusivity and reduced fractional anisotropy in the fornix, cingulum, anterior thalamic radiations and superior longitudinal and uncinate fasciculi. AP-PT showed signs of extensive WM damage, especially in associative tracts in the frontal lobes, fornix and cingulum. Disruption in structural connectivity might affect crucial functional inter-network communication, resulting in motivational deficits and worse cognitive decline.
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Affiliation(s)
- Riccardo Manca
- Department of Life Sciences, Brunel University London, Uxbridge UB8 3BH, UK
| | - Sarah A. Jones
- Rotherham Doncaster and South Humber NHS Foundation Trust, Rotherham DN4 8QN, UK
| | - Annalena Venneri
- Department of Life Sciences, Brunel University London, Uxbridge UB8 3BH, UK
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
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6
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The Apathy Evaluation Scale (AES-C): Psychometric Properties and Invariance of Italian Version in Mild Cognitive Impairment and Alzheimer's Disease. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18189597. [PMID: 34574524 PMCID: PMC8467636 DOI: 10.3390/ijerph18189597] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/06/2021] [Accepted: 09/09/2021] [Indexed: 12/14/2022]
Abstract
Apathy is a neuropsychiatric symptom observed in different neurological and psychiatric disorders. Although apathy is considered a symptom, it has been recently reconsidered as a syndrome characterised by three dimensions: cognitive symptoms, affective symptoms and behavioural symptoms. Recent studies have shown that apathy can be considered as a prodromal symptom of Alzheimer's disease (AD), but also an indicator of the transition from mild cognitive impairment to AD. According to this scenario, an early detection of apathy in subjects with Mild Cognitive Impairment (MCI) and Mild AD can be a valid psychometric strategy to improve an early diagnosis and promote a prompt intervention. The Apathy Evaluation Scale is a validated tool composed of 18 items that assess and quantify emotional, behavioural and cognitive aspects of apathy. The aim of this study is to assess the specific reliability and validity of the Italian version of the Apathy Evaluation Scale-Clinician Version (AES-C) to detect apathy both in amnestic MCI and mild AD patients. In the present paper, we therefore examined the psychometric properties and the invariance of the Italian Version of the AES-C conducted on a sample composed of an experimental group of amnestic MCI and AD patients (N = 107) and a control group (N = 107) constituted by Age- and Sex-matched healthy controls. Results confirm the goodness of the scale. Confirmatory factory analysis confirmed that the AES-C Italian Version presents the same stability of one second-order factor and three first-order factors identified in the original version, and all items are predicted by a single general factor. Moreover, the scale was found to be invariant across both populations. Moreover, reliability and discriminant analysis showed good values. We found in the experimental group a negative correlation between the AES-C and Frontal Assessment Battery (FAB) (rs = -0.21, p < 0.001) and Mini Mental State Examination (MMSE) (rs = -0.04, p < 0.001), while a positive correlation was found between the AES-C and Hamilton psychiatric Rating scale for Depression (HAM-D) scores (rs = 0.58, p < 0.001) Overall, our data demonstrated the validity of the Italian version of the AES-C for the assessment of apathy both in MCI and in AD patients.
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7
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Revisiting Apathy in Alzheimer's Disease: From Conceptualization to Therapeutic Approaches. Behav Neurol 2021; 2021:6319826. [PMID: 34394772 PMCID: PMC8356015 DOI: 10.1155/2021/6319826] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 07/02/2021] [Accepted: 07/28/2021] [Indexed: 11/24/2022] Open
Abstract
Apathy is a neurobehavioral syndrome characterized by impaired motivation for goal-directed behaviors and cognitive activity, alongside blunted affect. Apathy is a common neuropsychiatric syndrome in Alzheimer's disease (AD), with a 5-year prevalence over 70%. Apathy also serves as a prognostic indicator, correlating with the progression of AD. Despite advances in its conceptualization and understanding of its neural basis, there is very limited empirical evidence to support the available strategies for the treatment of apathy in AD. Given its complex pathophysiology, including distinct substrates for different apathy dimensions (affective, cognitive, and behavioral), it is unlikely that a single pharmacological or nonpharmacological strategy will be effective for all cases of apathy in AD. High-quality evidence research is needed to better understand the role of specific strategies aiming at a personalized approach.
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8
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De Paepe AE, Ara A, Garcia-Gorro C, Martinez-Horta S, Perez-Perez J, Kulisevsky J, Rodriguez-Dechicha N, Vaquer I, Subira S, Calopa M, Muñoz E, Santacruz P, Ruiz-Idiago J, Mareca C, de Diego-Balaguer R, Camara E. Gray Matter Vulnerabilities Predict Longitudinal Development of Apathy in Huntington's Disease. Mov Disord 2021; 36:2162-2172. [PMID: 33998063 DOI: 10.1002/mds.28638] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 04/15/2021] [Accepted: 04/16/2021] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Apathy, a common neuropsychiatric disturbance in Huntington's disease (HD), is subserved by a complex neurobiological network. However, no study has yet employed a whole-brain approach to examine underlying regional vulnerabilities that may precipitate apathy changes over time. OBJECTIVES To identify whole-brain gray matter volume (GMV) vulnerabilities that may predict longitudinal apathy development in HD. METHODS Forty-five HD individuals (31 female) were scanned and evaluated for apathy and other neuropsychiatric features using the short-Problem Behavior Assessment for a maximum total of six longitudinal visits (including baseline). In order to identify regions where changes in GMV may describe changes in apathy, we performed longitudinal voxel-based morphometry (VBM) on those 33 participants with a magnetic resonance imaging (MRI) scan on their second visit at 18 ± 6 months follow-up (78 MRI datasets). We next employed a generalized linear mixed-effects model (N = 45) to elucidate whether initial and specific GMV may predict apathy development over time. RESULTS Utilizing longitudinal VBM, we revealed a relationship between increases in apathy and specific GMV atrophy in the right middle cingulate cortex (MCC). Furthermore, vulnerability in the right MCC volume at baseline successfully predicted the severity and progression of apathy over time. CONCLUSIONS This study highlights that individual differences in apathy in HD may be explained by variability in atrophy and initial vulnerabilities in the right MCC, a region implicated in action-initiation. These findings thus serve to facilitate the prediction of an apathetic profile, permitting targeted, time-sensitive interventions in neurodegenerative disease with potential implications in otherwise healthy populations. © 2021 International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Audrey E De Paepe
- Cognition and Brain Plasticity Unit, Bellvitge Biomedical Research Institute - IDIBELL, Barcelona, Spain.,Department of Cognition, Development and Educational Psychology, Universitat de Barcelona, Barcelona, Spain
| | - Alberto Ara
- Cognition and Brain Plasticity Unit, Bellvitge Biomedical Research Institute - IDIBELL, Barcelona, Spain.,Department of Cognition, Development and Educational Psychology, Universitat de Barcelona, Barcelona, Spain.,Institute of Neurosciences, Universitat de Barcelona, Barcelona, Spain
| | - Clara Garcia-Gorro
- Cognition and Brain Plasticity Unit, Bellvitge Biomedical Research Institute - IDIBELL, Barcelona, Spain.,Department of Cognition, Development and Educational Psychology, Universitat de Barcelona, Barcelona, Spain
| | - Saül Martinez-Horta
- European Huntington's Disease Network, Ulm, Germany.,Movement Disorders Unit, Department of Neurology, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases), Carlos III Institute, Madrid, Spain
| | - Jesus Perez-Perez
- European Huntington's Disease Network, Ulm, Germany.,Movement Disorders Unit, Department of Neurology, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases), Carlos III Institute, Madrid, Spain
| | - Jaime Kulisevsky
- European Huntington's Disease Network, Ulm, Germany.,Movement Disorders Unit, Department of Neurology, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases), Carlos III Institute, Madrid, Spain
| | | | - Irene Vaquer
- Hestia Duran i Reynals, Hospital Duran i Reynals, Hospitalet de Llobregat, Barcelona, Spain
| | - Susana Subira
- Hestia Duran i Reynals, Hospital Duran i Reynals, Hospitalet de Llobregat, Barcelona, Spain.,Departament de Psicologia Clínica i de la Salut, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Matilde Calopa
- Movement Disorders Unit, Neurology Service, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Esteban Muñoz
- European Huntington's Disease Network, Ulm, Germany.,Movement Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain.,IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.,Facultat de Medicina, University of Barcelona, Barcelona, Spain
| | - Pilar Santacruz
- Movement Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain
| | - Jesus Ruiz-Idiago
- Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.,Hospital Mare de Deu de la Mercè, Barcelona, Spain
| | - Celia Mareca
- Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Ruth de Diego-Balaguer
- Cognition and Brain Plasticity Unit, Bellvitge Biomedical Research Institute - IDIBELL, Barcelona, Spain.,Department of Cognition, Development and Educational Psychology, Universitat de Barcelona, Barcelona, Spain.,Institute of Neurosciences, Universitat de Barcelona, Barcelona, Spain.,European Huntington's Disease Network, Ulm, Germany.,ICREA (Catalan Institute for Research and Advanced Studies), Barcelona, Spain
| | - Estela Camara
- Cognition and Brain Plasticity Unit, Bellvitge Biomedical Research Institute - IDIBELL, Barcelona, Spain.,Department of Cognition, Development and Educational Psychology, Universitat de Barcelona, Barcelona, Spain.,European Huntington's Disease Network, Ulm, Germany
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9
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Mariano LI, Caramelli P, Guimarães HC, Gambogi LB, Moura MVB, Yassuda MS, Teixeira AL, de Souza LC. Can Social Cognition Measurements Differentiate Behavioral Variant Frontotemporal Dementia from Alzheimer's Disease Regardless of Apathy? J Alzheimers Dis 2021; 74:817-827. [PMID: 32116247 DOI: 10.3233/jad-190861] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) share cognitive and behavioral symptoms, such as apathy. Social cognition measurements are useful in distinguishing bvFTD from AD, but their accuracies may be affected by apathy. OBJECTIVE To investigate whether social cognition measurements can distinguish bvFTD from either apathetic or non-apathetic AD patients. METHODS Three groups of participants were enrolled in the present study: bvFTD (n = 22), AD (n = 20), and healthy controls (HC, n = 23). The AD group was divided into apathetic (n = 10) and non-apathetic (n = 10). All subjects underwent comprehensive neuropsychological examination, including the short version of the Social and Emotional Assessment (Mini-SEA), which comprises the facial emotion recognition test and the faux-pas recognition test (Faux-Pas Test). Apathy was assessed according to the Starkstein's Apathy (SA) Scale. RESULTS The bvFTD and AD groups did not differ on global cognitive efficiency and on executive functions. In comparison to the whole AD group, bvFTD displayed lower Faux-Pas Test and Mini-SEA scores. Both AD subgroups, apathetic or non-apathetic, exhibited similar performance on all social cognition measurements. In comparison to either apathetic AD or non-apathetic AD, bvFTD patients underperformed on the Faux-Pas Test and on the Mini-SEA. The area under the curve values for the Mini-SEA total score were 0.87 (bvFTD versus AD), 0.90 (bvFTD versus apathetic AD), and 0.83 (bvFTD versus non-apathetic AD). CONCLUSION Social cognition tests provide accurate distinction between bvFTD against either apathetic AD or non-apathetic AD. Social cognition measurements did not correlate with apathy severity.
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Affiliation(s)
- Luciano Inácio Mariano
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Instituto de Ciências Biológicas, Pampulha, Belo Horizonte, Minas Gerais (MG), Brazil.,Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil
| | - Paulo Caramelli
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Instituto de Ciências Biológicas, Pampulha, Belo Horizonte, Minas Gerais (MG), Brazil.,Departamento de Clínica Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil
| | - Henrique Cerqueira Guimarães
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Instituto de Ciências Biológicas, Pampulha, Belo Horizonte, Minas Gerais (MG), Brazil
| | - Leandro Boson Gambogi
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Instituto de Ciências Biológicas, Pampulha, Belo Horizonte, Minas Gerais (MG), Brazil
| | | | - Mônica Sanches Yassuda
- Grupo de Neurologia Cognitiva e do Comportamento (GNCC), Departamento de Neurologia, Faculdade de Medicina, Universidade de São Paulo, Cerqueira César, São Paulo, SP, Brazil.,Programa de Pós-Graduação em Gerontologia, Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Antônio Lúcio Teixeira
- Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.,Santa Casa BH Ensino e Pesquisa, Santa Efigênia, Belo Horizonte, MG, Brazil
| | - Leonardo Cruz de Souza
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Instituto de Ciências Biológicas, Pampulha, Belo Horizonte, Minas Gerais (MG), Brazil.,Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil.,Departamento de Clínica Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil
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10
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Zhào H, Liu Y, Xia Z, Xie H, Huang Y. Diagnosis and Assessment of Apathy in Elderly Chinese Patients With Cerebral Small Vessel Disease. Front Psychiatry 2021; 12:688685. [PMID: 34413797 PMCID: PMC8368720 DOI: 10.3389/fpsyt.2021.688685] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 07/08/2021] [Indexed: 11/13/2022] Open
Abstract
Objective: The study aimed to estimate the frequency of apathy in Chinese patients with cerebral small vessel disease (CSVD) and investigate the relationship between apathy and neuroimaging markers of CSVD. Methods: A total of 150 CSVD aged patients were recruited for a cross-sectional observational study. Following the new revised version of diagnostic criteria for apathy (DCA), each patient was evaluated successively by the neuropsychiatric inventory (NPI-apathy), geriatric depression scale (GDS), and caregiver burden scale (CBS). The MRI presence of lacunes, white matter hyperintensities, cerebral microbleeds, and perivascular spaces were rated independently. Furthermore, presence of all these MRI markers were summed in a score of 0-4 representing all CSVD features combined. Results: According to the DCA, we found that the frequency of apathy in Chinese Alzheimer's disease patients reached 37.33%, with lack of and diminished goal-directed activities in the dimension of behavior/cognition. We did not find a close relationship between apathy and depression. Caregiver burden was positively correlated with apathy severity. Apathy, but not depression, was positively associated with total CSVD burden, rather than a separate MRI marker of CSVD. Conclusion: As a key component of neuropsychiatric symptoms, apathy was common in Chinese elderly with CSVD, more attention should be paid to apathy in clinical practice of CSVD.
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Affiliation(s)
- Hóngyi Zhào
- Department of Neurology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, China.,Department of Psychiatry, NO 984 Hospital of People's Liberation Army, Beijing, China
| | - Yu Liu
- Department of Neurology, NO 984 Hospital of People's Liberation Army, Beijing, China
| | - Zhenxi Xia
- Department of Neurology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Hongyang Xie
- Department of Neurology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yonghua Huang
- Department of Neurology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
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11
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Sassi KLM, Rocha NP, Colpo GD, John V, Teixeira AL. Amphetamine Use in the Elderly: A Systematic Review of the Literature. Curr Neuropharmacol 2020; 18:126-135. [PMID: 31660835 PMCID: PMC7324882 DOI: 10.2174/1570159x17666191010093021] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 08/01/2019] [Accepted: 09/30/2019] [Indexed: 11/25/2022] Open
Abstract
Objective: To systematically review the literature on the therapeutic use of amphetamine, lisdexamfetamine and methylphenidate in elderly population with and without dementia. Methods: We conducted two researches on the PubMed, Scopus and Embase using the keywords (“elderly”) AND (“amphetamine” OR “methylphenidate” OR “lisdexamfetamine”) and then (“Alzheimer” OR “dementia”) AND (“amphetamine” OR “methylphenidate” OR “lisdexamfetamine”). Results: Twenty-nine papers met all the eligibility criteria. The results are encouraging as 81.5% of the studies showed clinical improvement of the investigated condition. Conclusion: Amphetamines and methylphenidate are probably effective strategies for different conditions in the elderly population. However, further studies are needed to provide more robust evidence on efficacy, dosage and safety for this population.
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Affiliation(s)
- Karina Lúcia Moreira Sassi
- Department of Psychiatry and Behavioral Science, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Natalia Pessoa Rocha
- Department of Psychiatry and Behavioral Science, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Gabriela Delevati Colpo
- Department of Psychiatry and Behavioral Science, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Vineeth John
- Department of Psychiatry and Behavioral Science, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Antonio Lucio Teixeira
- Department of Psychiatry and Behavioral Science, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
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12
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Lazcano-Ocampo C, Wan YM, van Wamelen DJ, Batzu L, Boura I, Titova N, Leta V, Qamar M, Martinez-Martin P, Ray Chaudhuri K. Identifying and responding to fatigue and apathy in Parkinson’s disease: a review of current practice. Expert Rev Neurother 2020; 20:477-495. [DOI: 10.1080/14737175.2020.1752669] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Claudia Lazcano-Ocampo
- King’s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
- Department of Neurology, Hospital Sotero Del Rio, Santiago, Chile
| | - Yi Min Wan
- King’s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
- Department of Psychiatry, Ng Teng Fong General Hospital, Singapore
| | - Daniel J van Wamelen
- King’s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
- Cognition and Behaviour; Department of Neurology; Nijmegen, Radboud University Medical Centre; Donders Institute for Brain, The Netherlands
| | - Lucia Batzu
- King’s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
| | - Iro Boura
- King’s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
| | - Nataliya Titova
- Department of Neurology, Neurosurgery and Medical Genetics, Federal State Budgetary Educational Institution of Higher Education «N.I. Pirogov Russian National Research Medical University» of the Ministry of Healthcare of the Russian Federation, Moscow, Russia
| | - Valentina Leta
- King’s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
| | - Mubasher Qamar
- King’s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
- Queen Elizabeth the Queen Mother Hospital, East Kent Hospitals University NHS Foundation Trust, Margate, UK
| | - Pablo Martinez-Martin
- Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Carlos III Institute of Health. Madrid, Spain
| | - K Ray Chaudhuri
- King’s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
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13
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Gonçalves SDAB, Caramelli P, Mariano LI, Guimarães HC, Gambogi LB, Resende EDPF, Teixeira AL, de Souza LC. Apathy in frontotemporal dementia is related to medial prefrontal atrophy and is independent of executive dysfunction. Brain Res 2020; 1737:146799. [PMID: 32198120 DOI: 10.1016/j.brainres.2020.146799] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 02/28/2020] [Accepted: 03/16/2020] [Indexed: 10/24/2022]
Abstract
INTRODUCTION Apathy is the most common neuropsychiatric syndrome in behavioral variant frontotemporal dementia (bvFTD), and encompasses cognitive, behavioral and affective symptoms. The neural basis of apathy in bvFTD is not completely understood. Previous neuroimaging studies have poorly considered executive impairment and dementia severity as possible confounding factors. Herein we investigated the neural basis of apathy in bvFTD through structural neuroimaging taking into account these factors. METHODS We included patients with probable bvFTD (n = 21) and cognitively healthy controls (HC, n = 22). Participants were matched for age, sex and schooling. All subjects underwent a thorough neuropsychological examination, including tests for executive functions and social cognition. Apathy was assessed with the Starkstein Apathy Scale (SAS). All subjects underwent 3T brain MRI. We investigated correlations between SAS scores and gray matter atrophy within the bvFTD group. Executive function (Frontal Assessment Battery) and disease severity were considered as covariates in neuroimaging analyses. RESULTS Compared to HC, bvFTD patients had lower scores on global cognitive efficiency, executive functions and social cognition. All bvFTD had clinically relevant apathy (scores greater than 14 in the SAS). Performance in executive function tests did not correlate with apathy scores. The severity of apathy was negatively correlated with gray matter volumes in midline prefrontal regions, namely orbitofrontal cortex and both anterior and dorsal regions of cingulate cortex. CONCLUSIONS Apathy in bvFTD is related to a specific network of prefrontal cortical areas critically involved in effort-based behavior for rewards and appears to be independent of executive dysfunction.
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Affiliation(s)
| | - Paulo Caramelli
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil; Departamento de Clínica Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil
| | - Luciano Inácio Mariano
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Henrique Cerqueira Guimarães
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | - Leandro Boson Gambogi
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
| | | | - Antônio Lúcio Teixeira
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil; Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; Santa Casa BH Ensino e Pesquisa, Belo Horizonte, MG, Brazil
| | - Leonardo Cruz de Souza
- Programa de Pós-Graduação em Neurociências, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil; Departamento de Clínica Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil.
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14
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Ehrenberg AJ, Suemoto CK, França Resende EDP, Petersen C, Leite REP, Rodriguez RD, Ferretti-Rebustini REDL, You M, Oh J, Nitrini R, Pasqualucci CA, Jacob-Filho W, Kramer JH, Gatchel JR, Grinberg LT. Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer's Disease. J Alzheimers Dis 2019; 66:115-126. [PMID: 30223398 DOI: 10.3233/jad-180688] [Citation(s) in RCA: 152] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Clarifying the relationships between neuropsychiatric symptoms and Alzheimer's disease (AD)-related pathology may open avenues for effective treatments. Here, we investigate the odds of developing neuropsychiatric symptoms across increasing burdens of neurofibrillary tangle and amyloid-β pathology. Participants who passed away between 2004 and 2014 underwent comprehensive neuropathologic evaluation at the Biobank for Aging Studies from the Faculty of Medicine at the University of São Paulo. Postmortem interviews with reliable informants were used to collect information regarding neuropsychiatric and cognitive status. Of 1,092 cases collected, those with any non-Alzheimer pathology were excluded, bringing the cohort to 455 cases. Braak staging was used to evaluate neurofibrillary tangle burden, and the CERAD neuropathology score was used to evaluate amyloid-β burden. The 12-item neuropsychiatric inventory was used to evaluate neuropsychiatric symptoms and CDR-SOB score was used to evaluate dementia status. In Braak I/II, significantly increased odds were detected for agitation, anxiety, appetite changes, depression, and sleep disturbances, compared to controls. Increased odds of agitation continue into Braak III/IV. Braak V/VI is associated with higher odds for delusions. No increased odds for neuropsychiatric symptoms were found to correlate with amyloid-β pathology. Increased odds of neuropsychiatric symptoms are associated with early neurofibrillary tangle pathology, suggesting that subcortical neurofibrillary tangle accumulation with minimal cortical pathology is sufficient to impact quality of life and that neuropsychiatric symptoms are a manifestation of AD biological processes.
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Affiliation(s)
- Alexander J Ehrenberg
- Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.,Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, USA
| | | | - Elisa de Paula França Resende
- Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.,Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, USA
| | - Cathrine Petersen
- Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA
| | | | | | | | - Michelle You
- Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA
| | - Jun Oh
- Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA
| | | | | | | | - Joel H Kramer
- Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA
| | | | - Lea T Grinberg
- Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.,University of São Paulo Medical School, São Paulo, Brazil.,Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, USA
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15
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Lavallé L, Aleman A. rTMS for treatment of negative symptoms in schizophrenia: Clinical effects and neural basis. L'ENCEPHALE 2019; 45 Suppl 2:S50-S51. [PMID: 31101378 DOI: 10.1016/j.encep.2019.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- L Lavallé
- Inserm U1028, CNRS UMR5292, PSYR2 Team, Lyon Neuroscience Research Center, université Claude Bernard Lyon 1, centre hospitalier Le Vinatier, 69678 Lyon, France.
| | - A Aleman
- University Medical Center Groningen and University of Groningen, Groningen, The Netherlands
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16
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Vergallo A, Giampietri L, Pagni C, Giorgi FS, Nicoletti V, Miccoli M, Libertini P, Petrozzi L, Bonuccelli U, Tognoni G. Association Between CSF Beta-Amyloid and Apathy in Early-Stage Alzheimer Disease. J Geriatr Psychiatry Neurol 2019; 32:164-169. [PMID: 30913958 DOI: 10.1177/0891988719838627] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
AIM The apathetic syndrome is a common clinical feature in patients with Alzheimer diseases (AD), from preclinical phases to late stages of dementia, and it is strongly related to major disease outcomes. Unfortunately, no specific pharmacological treatments for apathy have been accomplished so far. Translational evidences have previously shown that a link between apathy and hallmarks of AD-related pathophysiology, that is, β-amyloid (Aβ) plaques and neurofibrillary tangles, exists. However, only few studies investigated the association between core biomarkers of AD and apathy scores, finding conflicting results. METHODS Thirty-seven patients were identified as having AD dementia according to National Institute on Aging-Alzheimer Association 2011 criteria. All participants underwent an extensive diagnostic workup including cerebrospinal fluid (CSF) assessment to measure the concentrations of Aβ42, t-tau, and pTau181. To follow, they were stratified as: apathy absence, apathy mild, and apathy severe according to the Neuro Psychiatric Inventory-apathy item scores. We investigated for potential associations between apathy scores and CSF biomarkers concentrations as well as for differences in terms of clinical and CSF biomarkers data across the 3 apathy groups. RESULTS The CSF Aβ42 concentrations were negatively correlated with apathy scores. In addition, patients with severe apathy had significantly lower Aβ42 levels compared to nonapathetic ones. CONCLUSION Based on our results, we encourage further studies to untangle the potential association between the complex pathophysiological dynamics of AD and apathy which may represent an innovative reliable clinical outcome measure to use in clinical trials, investigating treatments with either a symptomatic or a disease-modifying effect.
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Affiliation(s)
- A Vergallo
- 1 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
| | - L Giampietri
- 1 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
| | - C Pagni
- 1 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
| | - F S Giorgi
- 1 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
| | - V Nicoletti
- 1 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
| | - M Miccoli
- 1 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
| | - P Libertini
- 1 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
| | - L Petrozzi
- 1 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
| | - U Bonuccelli
- 1 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
| | - G Tognoni
- 1 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
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17
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Jones SA, De Marco M, Manca R, Bell SM, Blackburn DJ, Wilkinson ID, Soininen H, Venneri A. Altered frontal and insular functional connectivity as pivotal mechanisms for apathy in Alzheimer's disease. Cortex 2019; 119:100-110. [PMID: 31091485 DOI: 10.1016/j.cortex.2019.04.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 01/10/2019] [Accepted: 04/11/2019] [Indexed: 11/26/2022]
Abstract
BACKGROUND Apathy is a common and early symptom in Alzheimer's disease (AD) and is linked to poorer prognosis. Theoretical interpretations of apathy implicate alterations of connections amongst fronto-striatal and limbic regions. OBJECTIVE To test the association between presence of apathy and patterns of brain functional connectivity in patients with clinically-established AD. METHODS Seventy AD patients were included. Thirty-five patients experienced apathy as defined by the screening question of the Neuropsychiatric Inventory, and thirty-five did not. All patients agreed to undergo an MRI protocol inclusive of resting-state acquisitions. The hemodynamic-dependent signal was extracted bilaterally from five regions of interest: ventromedial prefrontal cortices, anterior cingulate cortices, dorsolateral prefrontal cortices, insulae and amygdalae. t tests were run to compare connectivity maps of apathetic and non-apathetic patients. Age, education, Mini Mental State Examination score, gray matter volumes and gray matter fractions served as covariates. RESULTS At a pFWE < .05 threshold, apathetic patients had reduced connectivity between the left insula and right superior parietal cortex. Apathetic patients had also increased connectivity between the right dorsolateral prefrontal seed and the right superior parietal cortex. Patients with apathy were significantly more likely to experience other psychiatric symptoms. CONCLUSION Our findings support a role of frontal and insular connections in coordinating value-based decisions in AD. Both down-regulation and maladaptive up-regulation mechanisms appear to be at play in these regions.
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Affiliation(s)
- Sarah A Jones
- Sheffield Health and Social Care NHS Foundation Trust, Sheffield, UK
| | - Matteo De Marco
- Department of Neuroscience, University of Sheffield, Sheffield, UK
| | - Riccardo Manca
- Department of Neuroscience, University of Sheffield, Sheffield, UK
| | - Simon M Bell
- Department of Neuroscience, University of Sheffield, Sheffield, UK
| | | | - Iain D Wilkinson
- Academic Unit of Radiology, University of Sheffield, Sheffield, UK
| | - Hilkka Soininen
- Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
| | - Annalena Venneri
- Department of Neuroscience, University of Sheffield, Sheffield, UK.
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18
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Lateral parietal cortex in the generation of behavior: Implications for apathy. Prog Neurobiol 2019; 175:20-34. [DOI: 10.1016/j.pneurobio.2018.12.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Revised: 11/20/2018] [Accepted: 12/23/2018] [Indexed: 11/21/2022]
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19
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Working definitions, subjective and objective assessments and experimental paradigms in a study exploring social withdrawal in schizophrenia and Alzheimer’s disease. Neurosci Biobehav Rev 2019; 97:38-46. [DOI: 10.1016/j.neubiorev.2018.06.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2017] [Revised: 04/10/2018] [Accepted: 06/21/2018] [Indexed: 11/24/2022]
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20
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Lanni C, Fagiani F, Racchi M, Preda S, Pascale A, Grilli M, Allegri N, Govoni S. Beta-amyloid short- and long-term synaptic entanglement. Pharmacol Res 2019; 139:243-260. [DOI: 10.1016/j.phrs.2018.11.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 11/06/2018] [Accepted: 11/09/2018] [Indexed: 12/17/2022]
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21
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Van Dam D, Vermeiren Y, Dekker AD, Naudé PJW, Deyn PPD. Neuropsychiatric Disturbances in Alzheimer's Disease: What Have We Learned from Neuropathological Studies? Curr Alzheimer Res 2017; 13:1145-64. [PMID: 27137218 PMCID: PMC5070416 DOI: 10.2174/1567205013666160502123607] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 03/04/2016] [Accepted: 04/27/2016] [Indexed: 12/16/2022]
Abstract
Neuropsychiatric symptoms (NPS) are an integral part of the dementia syndrome and were therefore recently included in the core diagnostic criteria of dementia. The near universal prevalence of NPS in Alzheimer's disease (AD), combined with their disabling effects on patients and caregivers, is contrasted by the fact that few effective and safe treatments exist, which is in part to be attributed to our incomplete understanding of the neurobiology of NPS. In this review, we describe the pathological alterations typical for AD, including spreading and evolution of burden, effect on the molecular and cellular integrity, functional consequences and atrophy of NPS-relevant brain regions and circuits in correlation with specific NPS assessments. It is thereby clearly established that NPS are fundamental expressions of the underlying neurodegenerative brain disease and not simply reflect the patients' secondary response to their illness. Neuropathological studies, moreover, include a majority of end-stage patient samples, which may not correctly represent the pathophysiological environment responsible for particular NPS that may already be present in an early stage, or even prior to AD diagnosis. The burdensome nature and high prevalence of NPS, in combination with the absence of effective and safe pharmacotherapies, provide a strong incentive to continue neuropathological and neurochemical, as well as imaging and other relevant approaches to further improve our apprehension of the neurobiology of NPS.
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Affiliation(s)
| | | | | | | | - Peter P De Deyn
- Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, and, Faculty of Medical and Health Care Sciences, University of Antwerp, Universiteitsplein 1, BE-2610 Wilrijk (Antwerp), Belgium
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22
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Ferris CF, Kulkarni P, Yee JR, Nedelman M, de Jong IEM. The Serotonin Receptor 6 Antagonist Idalopirdine and Acetylcholinesterase Inhibitor Donepezil Have Synergistic Effects on Brain Activity-A Functional MRI Study in the Awake Rat. Front Pharmacol 2017; 8:279. [PMID: 28659792 PMCID: PMC5467007 DOI: 10.3389/fphar.2017.00279] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 05/03/2017] [Indexed: 12/05/2022] Open
Abstract
The 5-HT6 receptor is a promising target for cognitive disorders, in particular for Alzheimer's disease (AD) and other CNS disorders. The high-affinity and selective 5-HT6 receptor antagonist idalopirdine (Lu AE58054) is currently in development for mild-moderate AD as adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We studied the effects of idalopirdine alone and in combination with the AChEI donepezil on brain activity using BOLD (Blood Oxygen Level Dependent) functional magnetic resonance imaging (fMRI) in the awake rat. Idalopirdine (2 mg/kg, i.v.) alone had a modest effect on brain activity, resulting in activation of eight brain regions at the peak response. Of these, the cholinergic diagonal band of Broca, the infralimbic cortex, the ventral pallidum, the nucleus accumbens shell, and the magnocellular preoptic area were shared with the effects of donepezil (0.3 mg/kg, i.v.). Donepezil alone activated 19 brain regions at the peak response, including several cortical regions, areas of the septo-hippocampal system and the serotonergic raphe nucleus. When idalopirdine and donepezil were combined, there was a robust stimulation pattern with activation of 36 brain regions spread across the extended-amygdala-, striato-pallidal, and septo-hippocampal networks as well as the cholinergic system. These findings indicate that, whilst idalopirdine and donepezil recruit a number of overlapping regions including one of the forebrain cholinergic nuclei, the synergistic effect of both compounds extends beyond the cholinergic system and the effects of donepezil alone toward recruitment of multiple neural circuits and neurotransmitter systems. These data provide new insight into the mechanisms via which idalopirdine might improve cognition in donepezil-treated AD patients.
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Affiliation(s)
- Craig F Ferris
- Department of Psychology, Center for Translational NeuroImaging, Northeastern UniversityBoston, MA, United States
| | - Praveen Kulkarni
- Department of Psychology, Center for Translational NeuroImaging, Northeastern UniversityBoston, MA, United States
| | - Jason R Yee
- Department of Psychology, Center for Translational NeuroImaging, Northeastern UniversityBoston, MA, United States
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Pharmacological Therapy for Apathy in Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Can J Neurol Sci 2017; 44:267-275. [PMID: 28148339 DOI: 10.1017/cjn.2016.426] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
AbstractIntroduction:Apathy is highly prevalent in Alzheimer’s disease (AD), but whether pharmacotherapy is effective in managing apathy is unclear.Methods:To assess the efficacy of pharmacotherapy for apathy in AD we searched for randomized controlled trials (RCT) and aggregate data reporting on apathy in several search engines, reference lists of articles, and reviews. Demographic characteristics and relevant data were extracted to assess apathy.Results:Fifteen RCTs’ were examined, and 11 were used in aggregate meta-analytic statistics. Drugs included were cholinesterase inhibitors, memantine, and psycho-stimulants. We found no significant treatment effect in favour of any of the drugs, and the effect-size estimates under a random effect model were heterogeneous. Most RCTs had a high attrition rate and used the NPI apathy subscale to measure apathy.Conclusion:The lack of an effect could be explained by methodological limitations, publication bias, and heterogeneity.
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Moretti R, Signori R. Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits. Front Aging Neurosci 2016; 8:289. [PMID: 28018207 PMCID: PMC5145860 DOI: 10.3389/fnagi.2016.00289] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2016] [Accepted: 11/15/2016] [Indexed: 01/10/2023] Open
Abstract
Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional involvement; it is an important and heavy-burden clinical condition which strongly impacts in everyday life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC) and basal ganglia; "emotional affective" apathy may be related to the orbitomedial PFC and ventral striatum; "cognitive apathy" may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of "autoactivation" may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to gray matter atrophy in the anterior cingulate (ACC) and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies, and a reduced speedness in action decision, major responsible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control. We will discuss the importance of these circuits in different pathologies, degenerative or vascular, acute or chronic.
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Affiliation(s)
- Rita Moretti
- Neurology Clinic, Department of Medicine, Surgery and Health Sciences, University of TriesteTrieste, Italy
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Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders. Neurosci Biobehav Rev 2016; 69:381-401. [DOI: 10.1016/j.neubiorev.2016.08.012] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Revised: 03/11/2016] [Accepted: 08/06/2016] [Indexed: 11/21/2022]
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Boublay N, Schott AM, Krolak-Salmon P. Neuroimaging correlates of neuropsychiatric symptoms in Alzheimer's disease: a review of 20 years of research. Eur J Neurol 2016; 23:1500-9. [PMID: 27435186 DOI: 10.1111/ene.13076] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 06/08/2016] [Indexed: 11/28/2022]
Abstract
Assessing morphological, perfusion and metabolic brain changes preceding or associated with neuropsychiatric symptoms (NPSs) will help in the understanding of pathophysiological underlying processes in Alzheimer's disease (AD). This review aimed to highlight the main findings on significant associations between neuroimaging and NPSs, the pathophysiology to elucidate possible underlying mechanisms, and methodological issues to aid future research. Research papers published from January 1990 to October 2015 were identified in the databases PsycInfo, Embase, PubMed and Medline, using key words related to NPSs and imaging techniques. In addition to a semi-systematic search in the databases, we also performed hand searches based on reported citations identified to be of interest. Delusions, apathy and depression symptoms were particularly associated with brain changes in AD. The majority of studies disclosed an association between frontal lobe structural and/or metabolic changes and NPSs, implicating, interestingly, for all 12 NPSs studied, the anterior cingulate cortex although temporal, subcortical and parietal regions, and insula were also involved. Given the high degree of connectivity of these brain areas, frontal change correlates of NPSs may help in the understanding of neural network participation. This review also highlights crucial methodological issues that may reduce the heterogeneity of results to enable progress on the pathophysiological mechanisms and aid research on NPS treatments in AD. Based on a broad review of the current literature, a global brain pattern to support the huge heterogeneity of neuroimaging correlates of NPSs in AD and methodological strategies are suggested to help direct future research.
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Affiliation(s)
- N Boublay
- Memory Clinical and Research Center of Lyon, Hospital of Charpennes, University Hospital of Lyon, Lyon, France. .,University of Lyon, Lyon, France. .,Hospices Civils de Lyon, Pôle Information Médicale Evaluation Recherche, Lyon, France. .,INSERM, U1028, CNRS, UMR5292, Lyon Neuroscience Research Center, Brain Dynamics and Cognition Team, Lyon, France.
| | - A M Schott
- Hospices Civils de Lyon, Pôle Information Médicale Evaluation Recherche, Lyon, France.,University Lyon 1, Lyon, France
| | - P Krolak-Salmon
- Memory Clinical and Research Center of Lyon, Hospital of Charpennes, University Hospital of Lyon, Lyon, France.,University of Lyon, Lyon, France.,Clinical Research Centre CRC - VCF (Vieillissement - Cerveau - Fragilité), Hospital of Charpennes, University Hospital of Lyon, Lyon, France.,INSERM, U1028, CNRS, UMR5292, Lyon Neuroscience Research Center, Brain Dynamics and Cognition Team, Lyon, France
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Baquero M, Martín N. Depressive symptoms in neurodegenerative diseases. World J Clin Cases 2015; 3:682-693. [PMID: 26301229 PMCID: PMC4539408 DOI: 10.12998/wjcc.v3.i8.682] [Citation(s) in RCA: 114] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Revised: 02/12/2015] [Accepted: 05/27/2015] [Indexed: 02/05/2023] Open
Abstract
Depressive symptoms are very common in chronic conditions. This is true so for neurodegenerative diseases. A number of patients with cognitive decline and dementia due to Alzheimer’s disease and related conditions like Parkinson’s disease, Lewy body disease, vascular dementia, frontotemporal degeneration amongst other entities, experience depressive symptoms in greater or lesser grade at some point during the course of the illness. Depressive symptoms have a particular significance in neurological disorders, specially in neurodegenerative diseases, because brain, mind, behavior and mood relationship. A number of patients may develop depressive symptoms in early stages of the neurologic disease, occurring without clear presence of cognitive decline with only mild cognitive deterioration. Classically, depression constitutes a reliable diagnostic challenge in this setting. However, actually we can recognize and evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in order to establish their clinical significance and to plan some therapeutic strategies. Depressive symptoms can appear also lately, when the neurodegenerative disease is fully developed. The presence of depression and other neuropsychiatric symptoms have a negative impact on the quality-of-life of patients and caregivers. Besides, patients with depressive symptoms also tend to further decrease function and reduce cognitive abilities and also uses to present more affected clinical status, compared with patients without depression. Depressive symptoms are treatable. Early detection of depressive symptoms is very important in patients with neurodegenerative disorders, in order to initiate the most adequate treatment. We review in this paper the main neurodegenerative diseases, focusing in depressive symptoms of each other entities and current recommendations of management and treatment.
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Resende EDPF, Caramelli P. Mapping the affective syndrome in Alzheimer's disease. ARQUIVOS DE NEURO-PSIQUIATRIA 2015. [PMID: 26200047 DOI: 10.1590/0004-282x20150095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Elisa de Paula França Resende
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Paulo Caramelli
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
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Moretti R, Cavressi M, Tomietto P. Gait and apathy as relevant symptoms of subcortical vascular dementia. Am J Alzheimers Dis Other Demen 2015; 30:390-399. [PMID: 25204314 PMCID: PMC10852560 DOI: 10.1177/1533317514550329] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Subcortical vascular dementia relates to small-vessel disease and hypoperfusion, resulting in focal and diffuse ischemic white matter lesions. The main target of the disease are the frontal subcortical neural networks. There is no clinical standard definition of the pathology, on the contrary, everyday clinical practice suggests dominant behavioral alterations and dysexecutive syndrome. METHODS The aim of this study was to investigate gait disorders, behavioral alteration, and drug intake of a subcortical population with dementia (n = 1155). A complete neuropsychological examination was conducted at baseline and every 6 months, and the results were compared. RESULTS Our data suggest that there is a significant increment in apathy levels and a dramatic decrease in gait and equilibrium control in the patients examined during follow-up. CONCLUSION Subcortical vascular dementia may be associated with gait and balance alteration and apathy per se; we suggest to implement clinical data with these major aspects.
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Affiliation(s)
- Rita Moretti
- Clinica Neurologica, Responsabile Ambulatorio Complicanze Internistiche Cerebrali, Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e della Salute, Università degli Studi di Trieste, Trieste, Italy
| | | | - Paola Tomietto
- Medicina Clinica, Servizio Reumatologia, Ospedale Cattinara, Trieste, Italy
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30
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Mørch-Johnsen L, Nesvåg R, Faerden A, Haukvik UK, Jørgensen KN, Lange EH, Andreassen OA, Melle I, Agartz I. Brain structure abnormalities in first-episode psychosis patients with persistent apathy. Schizophr Res 2015; 164:59-64. [PMID: 25818626 DOI: 10.1016/j.schres.2015.03.001] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Revised: 03/02/2015] [Accepted: 03/02/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Apathy is an enduring and debilitating feature related to poor outcome in patients with first-episode psychosis (FEP). The biological underpinnings of apathy are unknown. We tested if FEP patients with persistent apathy (PA) differed from FEP patients without persistent apathy (NPA) in specific brain structure measures in the early phase of illness. METHODS A total of 70 Norwegian FEP patients were recruited within 1 year of first adequate treatment. They were defined as having PA (N=18) or NPA (N=52) based on Apathy Evaluation Scale score at baseline and 1 year later. MRI measures of cortical thickness and subcortical structure volumes were compared between the PA and NPA groups. RESULTS The PA group had significantly thinner left orbitofrontal cortex and left anterior cingulate cortex. The results remained significant after controlling for depressive symptoms and antipsychotic medication. DISCUSSION FEP patients with persistent apathy in the early phase of their illness show brain structural changes compared to FEP patients without persistent apathy. The changes are confined to regions associated with motivation, occur early in the disease course and appear selectively in PA patients when both groups are compared to healthy controls.
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Affiliation(s)
- Lynn Mørch-Johnsen
- Department of Psychiatric Research, Diakonhjemmet Hospital, 0319 Oslo, Norway; NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway.
| | - Ragnar Nesvåg
- Norwegian Institute of Public Health, 0403 Oslo, Norway
| | - Ann Faerden
- Division of Mental Health and Addiction, Oslo University Hospital, 0424 Oslo, Norway
| | - Unn K Haukvik
- Department of Psychiatric Research, Diakonhjemmet Hospital, 0319 Oslo, Norway; NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway
| | - Kjetil N Jørgensen
- Department of Psychiatric Research, Diakonhjemmet Hospital, 0319 Oslo, Norway; NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway
| | - Elisabeth H Lange
- Department of Psychiatric Research, Diakonhjemmet Hospital, 0319 Oslo, Norway; NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway
| | - Ole A Andreassen
- NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, 0424 Oslo, Norway
| | - Ingrid Melle
- NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, 0424 Oslo, Norway
| | - Ingrid Agartz
- Department of Psychiatric Research, Diakonhjemmet Hospital, 0319 Oslo, Norway; NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, 0424 Oslo, Norway
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Abstract
BACKGROUND Apathy is one of the most frequent "behavioral and psychological signs and symptoms of dementia" (BPSD) encountered in Alzheimer's disease (AD). There is a growing interest in the early diagnosis of apathetic elderly patients in the community since apathy has been associated with reduced daily functioning, caregiver distress, and poor outcome. The generalization of neuroimaging techniques might be able to offer help in this domain. METHODS Within this context we conducted an extensive electronic search from the databases included in the National Library of Medicine as well as PsychInfo and Google Scholar for neuroimaging findings of apathy in AD. RESULTS Neuroimaging findings lend support to the notion that frontal-subcortical networks are involved in the occurrence of apathy in AD. CONCLUSIONS Longitudinal studies comparing patients and normal individuals might allow us to infer on the association between apathy and neurodegenerative diseases and what can brain imaging markers tell us about the characterization of this association, thus revealing disease patterns, helping to distinguish clinically distinct cognitive syndromes, and allowing predictions.
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Affiliation(s)
- Christos Theleritis
- First Department of Psychiatry, National and Kapodistrian University of Athens, Eginition Hospital, 74 Vas. Sofias Ave., 11528 Athens, Greece
- University Mental Health Research Institute, 2 Soranou Efesiou Str., Papagou 156 01, Athens, Greece
- Department of Psychosis Studies, Institute of Psychiatry, De Crespigny Park, King’s College London, UK
| | - Antonios Politis
- First Department of Psychiatry, National and Kapodistrian University of Athens, Eginition Hospital, 74 Vas. Sofias Ave., 11528 Athens, Greece
- The Johns Hopkins University, Baltimore, MD, USA
| | - Kostas Siarkos
- First Department of Psychiatry, National and Kapodistrian University of Athens, Eginition Hospital, 74 Vas. Sofias Ave., 11528 Athens, Greece
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32
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Horning SM, Melrose R, Sultzer D. Insight in Alzheimer's disease and its relation to psychiatric and behavioral disturbances. Int J Geriatr Psychiatry 2014; 29:77-84. [PMID: 23671016 PMCID: PMC3796120 DOI: 10.1002/gps.3972] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2013] [Accepted: 03/14/2013] [Indexed: 11/12/2022]
Abstract
OBJECTIVE Individuals suffering from Alzheimer's disease (AD) often have impaired awareness or a lack of insight into their cognitive deficits and functional abilities, especially in the later stages of the disease. Previous research has documented a relationship between depression and insight in AD, such that greater awareness of one's disease has been associated with a higher degree of depression. However, little is known about the relationship between insight, cognitive decline, and other psychiatric or behavioral problems associated with AD. METHODS This study included 107 outpatients who met criteria for probable AD. Instruments included the Neurobehavioral Rating Scale, the Apathy Evaluation Scale, and the mini mental state exam. A series of hierarchical regression analyses were conducted to determine the relationship between insight and depressed mood, anxiety, psychosis, apathy, agitation, and behavioral retardation in AD patients after controlling for cognitive skills. RESULTS Insight was found to significantly predict depressed mood, anxiety, and apathy even after controlling for global cognition. Greater insight was found to be associated with depressed mood and anxiety. However, impaired insight was associated with higher levels of apathy. CONCLUSION Insight may be differentially related to mood symptoms and apathy within AD, such that patients with intact insight are more depressed, whereas patients with impaired insight are more apathetic. This suggests that assessment of insight in AD may complement the clinical evaluation of depression and apathy in AD and help guide the most appropriate interventions. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
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Affiliation(s)
- Sheena M. Horning
- Brain, Behavior, and Aging Research Center, VA Greater Los Angeles Healthcare System
| | - Rebecca Melrose
- Brain, Behavior, and Aging Research Center, VA Greater Los Angeles Healthcare System,Dept. of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA
| | - David Sultzer
- Brain, Behavior, and Aging Research Center, VA Greater Los Angeles Healthcare System,Dept. of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA
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33
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Tascone LDS, Bottino CMDC. Neurobiology of neuropsychiatric symptoms in Alzheimer's disease: A critical review with a focus on neuroimaging. Dement Neuropsychol 2013; 7:236-243. [PMID: 29213845 PMCID: PMC5619193 DOI: 10.1590/s1980-57642013dn70300002] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The objective of this critical review of the literature was to reveal the neural
circuits involved in the occurrence of neuropsychiatric symptoms (NPS) in
Alzheimer's disease (AD) patients through the association of these symptoms with
neuroimaging findings. The search for articles was performed on PUBMED from
January 2000 to May 2013, using the key words: Dementia AND BPSD; Dementia AND
Neuropsychiatric Symptoms; and Dementia AND Psychosis, Delusions,
Hallucinations, Agitation, Depression, Anxiety, Apathy, Euphoria, Disinhibition,
Irritability, Aberrant Motor Behavior, Sleep or Eating Disorders. Forty-six
articles were reviewed and important contributions, especially regarding the
psychopathological concepts discussed, were also considered even if not included
in this time period. The available evidence suggests the three most relevant
neurobiological models for neuropsychiatric symptoms in Alzheimer's disease are
the frontal-subcortical circuits, the cortico-cortical networks, and the
monoaminergic system. We discussed the association of the individual symptoms or
syndromes with these models.
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34
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Guimarães HC, Caramelli P, Fialho PPA, França EDP, Afonso MPD, Teixeira AL. Serum levels of soluble TNF-α receptors but not BDNF are associated with apathy symptoms in mild Alzheimer's disease and amnestic mild cognitive impairment. Dement Neuropsychol 2013; 7:298-303. [PMID: 29213854 PMCID: PMC5619202 DOI: 10.1590/s1980-57642013dn70300011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2013] [Accepted: 08/18/2013] [Indexed: 11/24/2022] Open
Abstract
Apathy is intimately associated with dementia. Unfortunately, its pathophysiology remains poorly understood. The motivational impairment that characterizes this disorder might share the same inflammatory mechanisms, as suggested by the sickness behavior theory. OBJECTIVE The primary aim of this study was to investigate the association between apathy symptoms and serum levels of tumor necrosis factor alpha (TNF-α) and its soluble receptors. Brain-derived neurotrophic factor (BDNF) levels were also analyzed since these have been associated with depression, a condition which shares abulic features with apathy. METHODS The sample consisted of 27 subjects with mild Alzheimer's disease or amnestic mild cognitive impairment, who were submitted to specific apathy evaluation using the Apathy Scale (AS) and provided blood samples for biomarker analysis. Participants were categorized into two groups according to median AS scores (17 points). RESULTS Subjects with higher apathy symptoms (n=13) displayed higher levels of TNF-α soluble receptors (type 1: p=0.03; type 2: p=0.04). No other difference was found between groups. CONCLUSION These findings point to the involvement of inflammatory mediators in the genesis of apathy symptoms, as suggested by the sickness behavior theory.
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Affiliation(s)
- Henrique Cerqueira Guimarães
- Behavioral and Cognitive Neurology Research Group,
Department of Internal Medicine, Faculty of Medicine of the Federal University of
Minas Gerais, Belo Horizonte (MG), Brazil
| | - Paulo Caramelli
- Behavioral and Cognitive Neurology Research Group,
Department of Internal Medicine, Faculty of Medicine of the Federal University of
Minas Gerais, Belo Horizonte (MG), Brazil
| | - Patricia Paes Araujo Fialho
- Behavioral and Cognitive Neurology Research Group,
Department of Internal Medicine, Faculty of Medicine of the Federal University of
Minas Gerais, Belo Horizonte (MG), Brazil
| | - Elisa de Paula França
- Behavioral and Cognitive Neurology Research Group,
Department of Internal Medicine, Faculty of Medicine of the Federal University of
Minas Gerais, Belo Horizonte (MG), Brazil
| | - Marcelo Pelizzaro Dias Afonso
- Behavioral and Cognitive Neurology Research Group,
Department of Internal Medicine, Faculty of Medicine of the Federal University of
Minas Gerais, Belo Horizonte (MG), Brazil
| | - Antonio Lucio Teixeira
- Behavioral and Cognitive Neurology Research Group,
Department of Internal Medicine, Faculty of Medicine of the Federal University of
Minas Gerais, Belo Horizonte (MG), Brazil
- Translational Psychoneuroimmunology Group, Department of
Internal Medicine, Faculty of Medicine of the Federal University of Minas Gerais,
Belo Horizonte (MG), Brazil
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Knutson KM, Dal Monte O, Raymont V, Wassermann EM, Krueger F, Grafman J. Neural correlates of apathy revealed by lesion mapping in participants with traumatic brain injuries. Hum Brain Mapp 2013; 35:943-53. [PMID: 23404730 DOI: 10.1002/hbm.22225] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2012] [Revised: 09/07/2012] [Accepted: 10/25/2012] [Indexed: 01/18/2023] Open
Abstract
Apathy, common in neurological disorders, is defined as disinterest and loss of motivation, with a reduction in self-initiated activity. Research in diseased populations has shown that apathy is associated with variations in the volume of brain regions such as the anterior cingulate and the frontal lobes. The goal of this study was to determine the neural signatures of apathy in people with penetrating traumatic brain injuries (pTBIs), as to our knowledge, these have not been studied in this sample. We studied 176 male Vietnam War veterans with pTBIs using voxel-based lesion-symptom mapping (VLSM) and apathy scores from the UCLA Neuropsychiatric Inventory (NPI), a structured inventory of symptoms completed by a caregiver. Our results revealed that increased apathy symptoms were associated with brain damage in limbic and cortical areas of the left hemisphere including the anterior cingulate, inferior, middle, and superior frontal regions, insula, and supplementary motor area. Our results are consistent with the literature, and extend them to people with focal pTBI. Apathy is a significant symptom since it can reduce participation of the patient in family and other social interactions, and diminish affective decision-making.
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Affiliation(s)
- Kristine M Knutson
- Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
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36
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Hahn C, Lim HK, Won WY, Ahn KJ, Jung WS, Lee CU. Apathy and white matter integrity in Alzheimer's disease: a whole brain analysis with tract-based spatial statistics. PLoS One 2013; 8:e53493. [PMID: 23301077 PMCID: PMC3536751 DOI: 10.1371/journal.pone.0053493] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Accepted: 11/29/2012] [Indexed: 11/18/2022] Open
Abstract
The aim of this study was to investigate the microstructural alterations of white matter (WM) in Alzheimer's disease (AD) patients with apathy and to observe the relationships with the severity of apathy. Sixty drug-naïve subjects took part in this study (30 apathetic and 30 nonapathetic subjects with AD). The loss of integrity in WM was compared in AD patients with and without apathy through measurement of fractional anisotropy (FA) using by tract-based spatial statistics (TBSS). In addition, we explored the correlation pattern between FA values and the severity of apathy in AD patients with apathy. The apathy group had significantly reduced FA values (p(corrected)<0.05) in the genu of the corpus callosum compared to the nonapathy group. The severity of apathy was negatively correlated with FA values of the left anterior and posterior cingulum, right superior longitudinal fasciculus, splenium, body and genu of the corpus callosum and bilateral uncinate fasciculusin the apathy group (p(corrected)<0.05). This study was the first to explore FA values in whole brain WM in AD patients with apathy. The findings of these microstructural alterations of WM may be the key to the understanding of underlying neurobiological mechanism and clinical significances of apathy in AD.
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Affiliation(s)
- Changtae Hahn
- Department of Psychiatry, Seoul Saint Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyun-Kook Lim
- Department of Psychiatry, Saint Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea
| | - Wang Yeon Won
- Department of Psychiatry, The Saint Paul Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kook Jin Ahn
- Department of Radiology, Seoul Saint Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Won-Sang Jung
- Department of Radiology, Saint Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea
| | - Chang Uk Lee
- Department of Psychiatry, Seoul Saint Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- * E-mail:
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Hernandez SSS, Vital TM, Garuffi M, Stein AM, Teixeira CVL, Costa JLR, Stella F. Apathy, cognitive function and motor function in Alzheimer's disease. Dement Neuropsychol 2012; 6:236-243. [PMID: 29213803 PMCID: PMC5619335 DOI: 10.1590/s1980-57642012dn06040007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2012] [Accepted: 09/09/2012] [Indexed: 11/24/2022] Open
Abstract
The aims of this study were to characterize the presence of apathy in patients with AD, determine the relationship between apathy, motor function and cognitive function, and to verify differences among patients stratified by level of apathy in relation to cognitive and motor abilities. METHODS A cross-sectional study was conducted of 37 patients with AD. The following tests were used: MoCA, the Frontal Assessment Battery, Verbal Fluency, Clock Drawing Test, Andreotti & Okuma Battery Tests, Sit and Reach, Resistance of Upper Limbs - AAHPERD Battery Test, Sit and Lift Chair and the Apathy domain of the Neuropsychiatric Inventory. After verifying the normality of the data distribution, comparisons were made using Student's t-test and the U Mann Whitney test; relationships were also assessed using Pearson's and Spearman's correlation coefficients. All analyses were considered to be statistically significant at a p-value of 0.05. RESULTS 46% of participants in this study showed mild symptoms of apathy. Significant and weak associations were found (p=0.04) between apathy and the attention domain on the MoCA and between apathy and the Walk Test. Analysis of differences in cognitive and motor functions according to participants' level of apathy revealed no significant differences for any of the variables. CONCLUSION Apathy was reflected in attention and the Walk Test, suggesting these variables may be related to cognitive and functional decline in AD patients.
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Affiliation(s)
- Salma S. Soleman Hernandez
- Institute of Biosciences, Universidade Estadual Paulista
(UNESP), Department of Physical Education, Physical Activity and Aging Lab (LAFE),
Rio Claro SP, Brazil
| | - Thays Martins Vital
- Institute of Biosciences, Universidade Estadual Paulista
(UNESP), Department of Physical Education, Physical Activity and Aging Lab (LAFE),
Rio Claro SP, Brazil
| | - Marcelo Garuffi
- Institute of Biosciences, Universidade Estadual Paulista
(UNESP), Department of Physical Education, Physical Activity and Aging Lab (LAFE),
Rio Claro SP, Brazil
| | - Angélica Miki Stein
- Institute of Biosciences, Universidade Estadual Paulista
(UNESP), Department of Physical Education, Physical Activity and Aging Lab (LAFE),
Rio Claro SP, Brazil
| | - Camila Vieira Ligo Teixeira
- Institute of Biosciences, Universidade Estadual Paulista
(UNESP), Department of Physical Education, Physical Activity and Aging Lab (LAFE),
Rio Claro SP, Brazil
| | - José Luiz Riani Costa
- Institute of Biosciences, Universidade Estadual Paulista
(UNESP), Department of Physical Education, Physical Activity and Aging Lab (LAFE),
Rio Claro SP, Brazil
| | - Florindo Stella
- Institute of Biosciences, Universidade Estadual Paulista
(UNESP), Department of Physical Education, Physical Activity and Aging Lab (LAFE),
Rio Claro SP, Brazil
- Clinic of Geriatric Psychiatry, Universidade Estadual de
Campinas (UNICAMP), Campinas SP, Brazil
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Jellinger KA. Cerebral correlates of psychotic syndromes in neurodegenerative diseases. J Cell Mol Med 2012; 16:995-1012. [PMID: 21418522 PMCID: PMC4365880 DOI: 10.1111/j.1582-4934.2011.01311.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2011] [Accepted: 03/01/2011] [Indexed: 12/20/2022] Open
Abstract
Psychosis has been recognized as a common feature in neurodegenerative diseases and a core feature of dementia that worsens most clinical courses. It includes hallucinations, delusions including paranoia, aggressive behaviour, apathy and other psychotic phenomena that occur in a wide range of degenerative disorders including Alzheimer's disease, synucleinopathies (Parkinson's disease, dementia with Lewy bodies), Huntington's disease, frontotemporal degenerations, motoneuron and prion diseases. Many of these psychiatric manifestations may be early expressions of cognitive impairment, but often there is a dissociation between psychotic/behavioural symptoms and the rather linear decline in cognitive function, suggesting independent pathophysiological mechanisms. Strictly neuropathological explanations are likely to be insufficient to explain them, and a large group of heterogeneous factors (environmental, neurochemical changes, genetic factors, etc.) may influence their pathogenesis. Clinico-pathological evaluation of behavioural and psychotic symptoms (PS) in the setting of neurodegenerative and dementing disorders presents a significant challenge for modern neurosciences. Recognition and understanding of these manifestations may lead to the development of more effective preventive and therapeutic options that can serve to delay long-term progression of these devastating disorders and improve the patients' quality of life. A better understanding of the pathophysiology and distinctive pathological features underlying the development of PS in neurodegenerative diseases may provide important insights into psychotic processes in general.
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Schroeter ML, Vogt B, Frisch S, Becker G, Seese A, Barthel H, Mueller K, Villringer A, Sabri O. Dissociating behavioral disorders in early dementia-An FDG-PET study. Psychiatry Res 2011; 194:235-244. [PMID: 22044532 DOI: 10.1016/j.pscychresns.2011.06.009] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2011] [Revised: 04/30/2011] [Accepted: 06/08/2011] [Indexed: 11/26/2022]
Abstract
Behavioral impairments occur frequently in dementia. Studies with magnetic resonance imaging, measuring atrophy, have systematically investigated their neural correlates. Such a systematic approach has not yet been applied to imaging with [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET), although regional hypometabolism may precede and exceed atrophy in dementia. The present study related all behavioral disorders as assessed with the Neuropsychiatric Inventory to reductions in brain glucose utilization as measured by FDG-PET with Statistical Parametric Mapping (SPM5). It included 54 subjects mainly with early Alzheimer's disease, frontotemporal lobar degeneration, and subjective cognitive impairment. Apathy, disinhibition and eating disorders - most frequent in frontotemporal lobar degeneration - correlated significantly with regional brain hypometabolism. Whereas a single regressor analysis and conjunction analysis revealed largely overlapping frontomedian regions that were associated with all three behavioral domains, a disjunction analysis identified three specific neural networks for each behavioral disorder, independent of dementia severity. Apathy was related to the ventral tegmental area, a component of the motivational dopaminergic network; disinhibition to both anterior temporal lobes including the anterior hippocampi and left amygdala, caudate head, orbitofrontal cortex and insulae; and eating disorders to the right lateral (orbito) frontal cortex/insula. Our study contributes to the understanding of behavioral deficits in early dementia and suggests specific diagnostic and therapeutic approaches.
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Affiliation(s)
- Matthias L Schroeter
- Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Day Clinic of Cognitive Neurology, University of Leipzig, 04103 Leipzig, Germany; LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
| | - Barbara Vogt
- Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Day Clinic of Cognitive Neurology, University of Leipzig, 04103 Leipzig, Germany
| | - Stefan Frisch
- Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Day Clinic of Cognitive Neurology, University of Leipzig, 04103 Leipzig, Germany
| | - Georg Becker
- Department of Nuclear Medicine, University of Leipzig, 04103 Leipzig, Germany
| | - Anita Seese
- Department of Nuclear Medicine, University of Leipzig, 04103 Leipzig, Germany
| | - Henryk Barthel
- LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany; Department of Nuclear Medicine, University of Leipzig, 04103 Leipzig, Germany
| | - Karsten Mueller
- Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany
| | - Arno Villringer
- Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Day Clinic of Cognitive Neurology, University of Leipzig, 04103 Leipzig, Germany; LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
| | - Osama Sabri
- LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany; Department of Nuclear Medicine, University of Leipzig, 04103 Leipzig, Germany
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40
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Clinicopathological correlates of behavioral and psychological symptoms of dementia. Acta Neuropathol 2011; 122:117-35. [PMID: 21455688 DOI: 10.1007/s00401-011-0821-3] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2011] [Revised: 03/18/2011] [Accepted: 03/21/2011] [Indexed: 10/18/2022]
Abstract
Behavioral and psychological symptoms are commonly observed in a majority of demented patients at some time during the course of their illness. Many of these psychiatric manifestations, especially those related to mood, may be early expressions of dementia and/or mild cognitive impairment. The literature suggests that behavioral and psychological symptoms of dementia (BPSD) are an integral part of the disease process. The dissociation, in many cases, between BPSD and the rather linear decline in cognitive functions suggests that independent pathophysiological mechanisms give rise to these symptoms. A review of the neuroimaging and neuropathology literature indicates that BPSD are the expression of regional rather than diffuse brain pathology. Psychotic symptoms in demented patients usually demonstrate preferential involvement of the frontal lobe and/or limbic regions. Visual hallucinations differentiate themselves from other psychotic symptoms by their tendency to involve the occipital lobes. There is a significant association between apathy and structural changes of the anterior cingulate gyrus. White matter hyperintensities occur in a significant number of depressed patients; otherwise, there is lack of association between depression and either specific brain changes or affected regions. Strictly neuropathological explanations are likely to be insufficient to explain BPSD. Environmental changes, neurochemical abnormalities, past psychiatric history (including premorbid personality), social history (e.g., intellectual achievement and life-long learning), family history, and genetic susceptibility are factors, among others, that influence BPSD.
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Tunnard C, Whitehead D, Hurt C, Wahlund LO, Mecocci P, Tsolaki M, Vellas B, Spenger C, Kłoszewska I, Soininen H, Lovestone S, Simmons A. Apathy and cortical atrophy in Alzheimer's disease. Int J Geriatr Psychiatry 2011; 26:741-8. [PMID: 20872914 DOI: 10.1002/gps.2603] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2010] [Accepted: 06/14/2010] [Indexed: 01/13/2023]
Abstract
OBJECTIVES Apathy has been reported as the most prevalent behavioural symptom experienced in Alzheimer's disease (AD), associated with greater functional decline and caregiver distress. The aim of the current study was to investigate structural correlates of apathy in AD using magnetic resonance imaging (MRI) regional volume and regional cortical thickness measures. METHODS Semi-structured interviews were conducted with 111 AD patients and their caregivers as part of the European multi-centre study AddNeuroMed. Apathy was measured using the apathy domain of the Neuropsychiatric Inventory (NPI). All AD patients were scanned using a 1.5T MRI scanner and the images analysed using an automated analysis pipeline. RESULTS We found apathy to be the most prevalent neuropsychiatric symptom occurring in 57% of patients. Apathetic patients had significantly greater cortical thinning in left caudal anterior cingulate cortex (ACC) and left lateral orbitofrontal cortex (OFC), as well as left superior and ventrolateral frontal regions, than those without apathy symptoms. CONCLUSIONS Apathy is mediated by frontocortical structures but this is specific to the left hemisphere at least for patients in the mild to moderate stages of AD.
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Affiliation(s)
- C Tunnard
- MRC Centre for Neurodegeneration, King's College London, Institute of Psychiatry, De Crespigny Park, UK
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Stella F, de Andrade LP, Vital TM, Coelho FGDM, Nascimento CMC, Hernández SSS. Apathy in Alzheimer's disease: Contribution to a clinical view on progression of dementia. Dement Neuropsychol 2010; 4:188-193. [PMID: 29213685 PMCID: PMC5619288 DOI: 10.1590/s1980-57642010dn40300007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
In addition to cognitive impairment, apathy is increasingly recognized as an
important neuropsychiatric syndrome in Alzheimer’s disease (AD).
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Affiliation(s)
- Florindo Stella
- UNESP, Universidade Estadual Paulista, Biosciences Institute, Campus of Rio Claro, Aging and Physical Activity Laboratory, São Paulo SP, Brazil.,Geriatric Psychiatry Clinic, State University of Campinas, CRUESP Cooperation Program, Campinas SP, Brazil
| | - Larissa Pires de Andrade
- UNESP, Universidade Estadual Paulista, Biosciences Institute, Campus of Rio Claro, Aging and Physical Activity Laboratory, São Paulo SP, Brazil
| | - Thays Martins Vital
- UNESP, Universidade Estadual Paulista, Biosciences Institute, Campus of Rio Claro, Aging and Physical Activity Laboratory, São Paulo SP, Brazil
| | - Flávia Gomes de Melo Coelho
- UNESP, Universidade Estadual Paulista, Biosciences Institute, Campus of Rio Claro, Aging and Physical Activity Laboratory, São Paulo SP, Brazil
| | - Carla Manuela Crispim Nascimento
- UNESP, Universidade Estadual Paulista, Biosciences Institute, Campus of Rio Claro, Aging and Physical Activity Laboratory, São Paulo SP, Brazil
| | - Salma Stephany Soleman Hernández
- UNESP, Universidade Estadual Paulista, Biosciences Institute, Campus of Rio Claro, Aging and Physical Activity Laboratory, São Paulo SP, Brazil
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Vidoni ED, Honea RA, Burns JM. Neural correlates of impaired functional independence in early Alzheimer's disease. J Alzheimers Dis 2010; 19:517-27. [PMID: 20110598 DOI: 10.3233/jad-2010-1245] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Cognitive and physical decline are important predictors of functional independence in Alzheimer's disease (AD). However, little is known about AD-related neural change leading to decreased independence. We hypothesized that regional gray matter atrophy, including the medial frontal cortex, would be related to cognition, physical function, and functional independence. Individuals without dementia (n=56) and subjects with early-stage AD (n=58) underwent MRI and a comprehensive cognitive and physical function evaluation. The relationship of cognitive and physical function measures and independence performing complex daily activities was explored using correlation and mediation analysis. These results suggest that cognition had both a strong direct effect and mediated the influence of physical function on independence for those with AD. We followed this with a voxel-based morphometric global conjunction analysis of imaging data within each group to identify neural substrates common to our function measures. Imaging evidence supported our mediation analysis results. Imaging evidence revealed that in AD, regional gray matter atrophy measures in medial frontal and temporo-parietal areas were related to decreased cognition, physical function, and independence. Loss of independence in early AD is closely related to impaired cognition associated with performing complex behaviors. People with early AD may have decreased gray matter volume in the medial frontal and temporal-parietal cortices that is associated with loss of independence in activities of daily living. These results are the first to identify regionally specific brain volume changes that may be related to functional dependence seen in early AD.
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Affiliation(s)
- Eric D Vidoni
- Department of Neurology, KU Alzheimer and Memory Program, University of Kansas Medical Center, Kansas City, KS, USA
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Guimarães HC, Fialho PPA, Carvalho VA, Dos Santos EL, Caramelli P. Brazilian caregiver version of the Apathy Scale. Dement Neuropsychol 2009; 3:321-326. [PMID: 29213647 PMCID: PMC5619419 DOI: 10.1590/s1980-57642009dn30400010] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
No Brazilian version of a specific scale for evaluating apathy in dementia is
available.
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Affiliation(s)
- Henrique Cerqueira Guimarães
- Behavioral and Cognitive Neurology Unit, Department of Internal Medicine, Faculty of Medicine of the Federal University of Minas Gerais, Belo Horizonte MG, Brazil.,Post-graduate Program in Neurology, University of São Paulo School of Medicine, São Paulo SP, Brazil
| | - Patricia Paes Araujo Fialho
- Behavioral and Cognitive Neurology Unit, Department of Internal Medicine, Faculty of Medicine of the Federal University of Minas Gerais, Belo Horizonte MG, Brazil
| | - Viviane Amaral Carvalho
- Behavioral and Cognitive Neurology Unit, Department of Internal Medicine, Faculty of Medicine of the Federal University of Minas Gerais, Belo Horizonte MG, Brazil
| | - Etelvina Lucas Dos Santos
- Behavioral and Cognitive Neurology Unit, Department of Internal Medicine, Faculty of Medicine of the Federal University of Minas Gerais, Belo Horizonte MG, Brazil
| | - Paulo Caramelli
- Post-graduate Program in Neurology, University of São Paulo School of Medicine, São Paulo SP, Brazil
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Kummer A, Teixeira AL. Neuropsychiatry of Parkinson's disease. ARQUIVOS DE NEURO-PSIQUIATRIA 2009; 67:930-9. [DOI: 10.1590/s0004-282x2009000500033] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2009] [Accepted: 08/03/2009] [Indexed: 12/22/2022]
Abstract
Parkinson's disease (PD) is traditionally regarded as a movement disorder. In recent years, however, non-motor symptoms have been considered significant factors of disability at all stages of the illness. Behavioral and psychological symptoms or neuropsychiatric syndromes associated with PD are frequent and may represent a challenge in the management of these patients. They include anxiety, depression, psychosis, sleep, sexual and impulse control disorders, apathy and cognitive dysfunction. Their pathogenesis in PD is complex, involving neurodegenerative, drug-related and psychological mechanisms. We will review the current knowledge of this growing field, also focusing on the management of theses syndromes.
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Machado S, Cunha M, Minc D, Portella CE, Velasques B, Basile LF, Cagy M, Piedade R, Ribeiro P. Alzheimer's disease and implicit memory. ARQUIVOS DE NEURO-PSIQUIATRIA 2009; 67:334-42. [DOI: 10.1590/s0004-282x2009000200034] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2008] [Accepted: 02/21/2009] [Indexed: 11/21/2022]
Abstract
Specific neuropsychiatric disorders, such as Alzheimer's disease (AD) affect some forms of memory while leaving others relatively intact. In this review, we investigate particularities of the relationship between explicit and implicit memories in AD. It was found that implicit memory is preserved in AD, irrespective of the task used; in other words, there was not interference from explicit memory. In addition, it was verified that is possible through implicit memory compensatory strategies such as, activities of daily living (ADL) to compensate for the explicit memory deficits. In this sense, cognitive rehabilitation (CR) demonstrates reasonable results in the process of compensation of explicit memory deficits. Concluding, the decline in explicit memory suggests that both systems are functionally independent even if the other is compromised. We expect that when explicit memory system is not involved in competition with the implicit system, the final effect of learning is better, because all of the implicit memory capacity is engaged in learning and not in competition with the explicit system.
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Affiliation(s)
- Sergio Machado
- Federal University of Rio de Janeiro, Brazil; Brazilian Institute of Neural Bioscience, Brazil
| | - Marlo Cunha
- Federal University of Rio de Janeiro, Brazil; Brazilian Institute of Neural Bioscience, Brazil
| | - Daniel Minc
- Federal University of Rio de Janeiro, Brazil
| | | | - Bruna Velasques
- Federal University of Rio de Janeiro, Brazil; Brazilian Institute of Neural Bioscience, Brazil
| | - Luis F. Basile
- University of São Paulo Medical School, Brazil; UMESP, Brazil
| | | | | | - Pedro Ribeiro
- Federal University of Rio de Janeiro, Brazil; UFRJ, Brazil; Brazilian Institute of Neural Bioscience, Brazil
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47
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Laks J, Engelhardt E. Behavioral and psychological symptoms in dementia is not a unitary concept: A critical review with emphasis on Alzheimer's disease. Dement Neuropsychol 2008; 2:272-277. [PMID: 29213584 PMCID: PMC5619079 DOI: 10.1590/s1980-57642009dn20400007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2008] [Accepted: 11/08/2008] [Indexed: 01/21/2023] Open
Abstract
Behavioral and Psychological Symptoms of Dementia (BPSD) is an important feature of dementia. However, this definition comprises a large array of symptoms and syndromes. This hampers understanding of the behavior of patients with dementia and the devising of strategies to ameliorate these symptoms. OBJECTIVES This review aimed to describe the main factors and syndromes that comprise BPSD, as well as neuroimaging, psychopharmacological, and genetic data derived from studies of these factors. METHODS A search on the Medline, Scielo, and ISI databases was performed using the keyword BPSD for articles published within the last five years. Selected publications were favored, so this review should not be regarded as a systematic study on the subject. RESULTS The main factors and syndromes comprising BPSD were identified, namely psychosis, depression, and activity. Different ways of clustering symptoms were considered. The main manifestations of psychosis, apathy and depression were focused, relating phenomenology to neuroimaging and pharmacological issues. CONCLUSIONS BPSD is a heterogeneous array of symptoms which can be better understood as clusters. At least three factors can be separated in BSPD, namely psychosis, depression, and activity. This division may offer guidance to clinicians regarding treatment management and follow up of the chosen therapeutic strategy.
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Affiliation(s)
- Jerson Laks
- Center for Alzheimer’s Disease/ Institute of
Psychiatry/Federal University of Rio de Janeiro; School of Medical Sciences, State
University of Rio de Janeiro
| | - Eliasz Engelhardt
- Institute of Neurology Deolindo Couto of the Federal
University of Rio de Janeiro
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