Abstract INTRODUCTION Anxiety and depressive symptoms are common in Alzheimer's disease (AD), yet their relationships with amyloid, tau, and sleep remain unclear. We examined whether amyloid status and sleep duration moderate the relationships between anxiety and depressive symptoms and amygdalar tau burden in cognitively unimpaired older adults at risk for AD. METHODS Participants ( n = 393) from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies underwent tau and amyloid positron emission tomography imaging. Anxiety and depressive symptoms were evaluated using the State‐Trait Anxiety Inventory and Geriatric Depression Scale. Sleep duration was self‐reported. RESULTS Positive amyloid status moderated the relationship between depressive symptoms and amygdalar tau. Sleep duration moderated the relationship between anxiety and amygdalar tau, such that greater anxiety symptoms were associated with higher tau levels at shorter sleep durations. DISCUSSION Findings suggest biological and behavioral factors jointly influence neuropsychiatric symptom–tau relationships in preclinical AD, supporting an interactive model of early disease vulnerability.
Bonta et al. (Wed,) studied this question.