- Falgàs, Neus;
- Allen, Isabel E;
- Spina, Salvatore;
- Grant, Harli;
- Escudero, Stefanie D Piña;
- Merrilees, Jennifer;
- Gearhart, Rosalie;
- Rosen, Howard J;
- Kramer, Joel H;
- Seeley, William W;
- Neylan, Thomas C;
- Miller, Bruce L;
- Rabinovici, Gil D;
- Grinberg, Lea T;
- Walsh, Christine M
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.