Depression and anxiety modify cognitive concerns associated with amyloid and early clinical impairment

Cognitive concerns (CCs) are common for patients with Alzheimer's disease (AD) dementia. We explore anxiety, depression, and clinical impairment as moderators of CCs in early AD. Understanding these associations may help inform efforts to advance early identification of disease progression in AD.

Data sources, selected based on requirements for availability of biomarker data and clinical assessment data, generated a pooled sample of adults ages 65+ with known amyloid status and cognitive function ranging from unimpaired (Clinical Dementia Rating global score [CDR-GS] = 0, n = 5,498) to early impairment (CDR-GS = 0.5, n = 504). Measures of CCs, anxiety, and depression were standardized to cognitively unimpaired groups. To model the difference in effects for different levels of anxiety and depression, we used mixed-effects quantile regression for median adjusted for age, sex, race, and educational years. All reported findings are p < .05.

Higher CCs were associated with early clinical impairment (estimated change in median [β] = 15.5). CCs were higher with higher versus lower anxiety, except in unimpaired persons with elevated amyloid. In this latter group of unimpaired persons with elevated amyloid, CCs were higher with higher versus lower depression.

In combination elevated amyloid, anxiety, and depression may offer data to guide clinical interpretation of CCs in early clinical impairment. The findings advance understanding of mood effects in early AD and inform specific measurement considerations. Future longitudinal studies are needed. (PsycInfo Database Record (c) 2026 APA, all rights reserved).