The severity of neuropsychiatric symptoms is higher in early-onset than late-onset Alzheimer's disease
Eur J Neurol. 2022 Apr;29(4):957-967. doi: 10.1111/ene.15203. Epub 2021 Dec 20.
ABSTRACT
BACKGROUND AND PURPOSE: The faster rates of cognitive decline and predominance of atypical forms in early-onset Alzheimer's disease (EOAD) suggest that neuropsychiatric symptoms could be different in EOAD compared to late-onset AD (LOAD); however, prior studies based on non-biomarker-diagnosed cohorts show discordant results. Our goal was to determine the profile of neuropsychiatric symptoms in EOAD and LOAD, in a cohort with biomarker/postmortem-confirmed diagnoses. Additionally, the contribution of co-pathologies was explored.
METHODS: In all, 219 participants (135 EOAD, 84 LOAD) meeting National Institute on Aging and Alzheimer's Association criteria for AD (115 amyloid positron emission tomography/cerebrospinal fluid biomarkers, 104 postmortem diagnosis) at the University of California San Francisco were evaluated. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was assessed at baseline and during follow-up. The NPI-Q mean comparisons and regression models adjusted by cognitive (Mini-Mental State Examination) and functional status (Clinical Dementia Rating Sum of Boxes) were performed to determine the effect of EOAD/LOAD and amnestic/non-amnestic diagnosis on NPI-Q. Regression models assessing the effect of co-pathologies on NPI-Q were performed.
RESULTS: At baseline, the NPI-Q scores were higher in EOAD compared to LOAD (p < 0.05). Longitudinally, regression models showed a significant effect of diagnosis, where EOAD had higher NPI-Q total, anxiety, motor disturbances and night-time behavior scores (p < 0.05). No differences between amnestics/non-amnestics were found. Argyrophilic grain disease co-pathology predicted a higher severity of NPI-Q scores in LOAD.
CONCLUSIONS: Anxiety, night-time behaviors and motor disturbances are more severe in EOAD than LOAD across the disease course. The differential patterns of neuropsychiatric symptoms observed between EOAD/LOAD could suggest a pattern of selective vulnerability extending to the brain's subcortical structures. Further, co-pathologies such as argyrophilic grain disease in LOAD may also play a role in increasing neuropsychiatric symptoms.
PMID:34862834 | PMC:PMC8901553 | DOI:10.1111/ene.15203
Authors
![Neus Falgas](/sites/default/files/styles/image_1x1_small/public/profile/neus_falgas.jpg?h=87136cbf&itok=TquqlhVe)
Neus Falgàs, MD, PhD
Neurologist
![Isabel Elaine Allen headshot](/sites/default/files/styles/image_1x1_small/public/profile/IEA-9-2023.jpg?h=ca48db8a&itok=4ZwlRswy)
Isabel Elaine Allen, PhD, MA
Professor of Biostatistics & Epidemiology
![Salvo Spina](/sites/default/files/styles/image_1x1_small/public/profile/Salvo_Spina.jpg?h=ca529fcb&itok=-h2xiPYX)
Salvo Spina, MD, PhD
Associate Professor of Neurology
![Stefanie Pina Escudero 2023](/sites/default/files/styles/image_1x1_small/public/profile/GBHI_2023-Conference-Photos_125%20%281%29%20%281%29.jpg?h=301bf149&itok=H795CwKR)
Stefanie Piña Escudero, MD
Geriatrician
![Jennifer Merrilees, RN, PhD](/sites/default/files/styles/image_1x1_small/public/profile/JenniferMerrilees_2021_1100px.jpg?h=947fc1b2&itok=dwzQOdgq)
Jennifer Merrilees, RN, PhD
Clinical Nurse Specialist in Geriatrics
![Rosalie Gearhart](/sites/default/files/styles/image_1x1_small/public/profile/Rosalie_Gearhart.jpg?h=ef18c1a9&itok=8HX65JwS)
Rosalie Gearhart, RN, MS
Geriatric Clinical Nurse Specialist
![Howie Rosen headshot](/sites/default/files/styles/image_1x1_small/public/profile/20211019_1_0128%20%281%29.jpg?h=c2857175&itok=0k88_56I)
Howie Rosen, MD
Professor of Neurology
![Joel Kramer](/sites/default/files/styles/image_1x1_small/public/profile/Joel_Kramer.jpg?h=17c4d544&itok=WDjIGUzD)
Joel Kramer, PsyD
Professor of Neuropsychology
![Bill Seeley](/sites/default/files/styles/image_1x1_small/public/profile/Bill-Seeley.jpg?h=0d3353d8&itok=iyfBQb_O)
Bill Seeley, MD
Professor of Neurology and Pathology
![Bruce Miller](/sites/default/files/styles/image_1x1_small/public/profile/Bruce%20Miller.jpg?h=3334e0bf&itok=3zITuREU)
Bruce Miller, MD
Founding Director, University of California, San Francisco
![Lea Grinberg headshot 2021](/sites/default/files/styles/image_1x1_small/public/profile/Grinberg_Lea%20%281%29.jpg?h=a09a6676&itok=ispOx_-8)
Lea Tenenholz Grinberg, MD, PhD
Professor of Neurology and Pathology