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, we explored the contribution of co-pathologies.
We evaluated 219 participants (135 EOAD, 84 LOAD) meeting NIA-AA criteria for AD (115 amyloid-PET/CSF biomarkers, 104 postmortem diagnosis) at UCSF. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was assessed at baseline and during follow-up. NPI-Q mean comparisons and regression models adjusting by cognitive (MMSE) and functional status (CDR SoB) 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.
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 nighttime behaviors scores (p<0.05). No differences between amnestics/non-amnestics were found. Argyrophilic grain disease (AGD) co-pathology predicted higher severity of NPI-Q scores in LOAD.
Anxiety, nighttime 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 AGD in LOAD may also play a role in increasing neuropsychiatric symptoms.

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