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. 2022 Apr;29(4):957-967.
doi: 10.1111/ene.15203. Epub 2021 Dec 20.

The severity of neuropsychiatric symptoms is higher in early-onset than late-onset Alzheimer's disease

Neus Falgàs  1   2   3 , Isabel E Allen  4 , Salvatore Spina  1 , Harli Grant  1 , Stefanie D Piña Escudero  1   2 , Jennifer Merrilees  1 , Rosalie Gearhart  1 , Howard J Rosen  1   2 , Joel H Kramer  1   2 , William W Seeley  1 , Thomas C Neylan  1   5 , Bruce L Miller  1 , Gil D Rabinovici  1   2 , Lea T Grinberg  1   2   6   7 , Christine M Walsh  1
Affiliations

The severity of neuropsychiatric symptoms is higher in early-onset than late-onset Alzheimer's disease

Neus Falgàs et al. Eur J Neurol. 2022 Apr.

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.

Keywords: Alzheimer's disease; behavioral symptoms; locus coeruleus; phenotype; sleep.

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Conflict of interest statement

CONFLICT OF INTEREST

Authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Baseline NPI-Q scores in EOAD and LOAD groups. (a) Mean NPI-Q total scores in EOAD and LOAD. (b) Mean scores across the different NPI-Q domains in EOAD and LOAD. Significant difference *p < 0.05, **p < 0.01
FIGURE 2
FIGURE 2
Longitudinal trajectories of NPI-Q scores in EOAD and LOAD. The individual and mean differential group trajectories between EOAD and LOAD (p < 0.05) adjusted by MMSE and CDR SoB in (a) NPI-Q total score, (b) anxiety score, (c) motor disturbances score and (d) night-time behaviors score
FIGURE 3
FIGURE 3
Baseline NPI-Q scores in amnestic and non-amnestic groups in EOAD and LOAD. (a) Mean NPI-Q total scores in amnestic and non-amnestic phenotypes in EOAD patients. (b) Means of the different NPI-Q domains in amnestic and non-amnestic phenotypes in EOAD. (c) Mean NPI-Q total scores in amnestic and non-amnestic phenotypes in LOAD patients. (d) Means of the different NPI-Q domains in amnestic and non-amnestic phenotypes in LOAD. No statistically significant difference was found between groups
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