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Background:  To determine whether sleep disturbance (SD) and vascular-risk interact to promote Alzheimer’s disease (AD) stage-progression in normal, community-dwelling older adults and evaluate their combined risk beyond that of established AD biomarkers.   Methods:  Longitudinal data from the National Alzheimer’s Coordinating Center Uniform-Dataset. SD data (i.e., SD+ vs. SD-), as characterized by the Neuropsychiatric Inventory-Questionnaire, were derived from 10,600 participants at baseline, with at-least one follow-up visit. A subset ( n  = 361) had baseline cerebrospinal fluid (CSF) biomarkers and MRI data. The Framingham heart study general cardiovascular disease (FHS-CVD) risk-score was used to quantify vascular risk. Amnestic mild cognitive impairment (aMCI) diagnosis during follow-up characterized AD stage-progression. Logistic mixed-effects models with random intercept and slope examined the interaction of SD and vascular risk on prospective aMCI diagnosis.   Results:  Of the 10,600 participants, 1,017 (9.6%) reported SD and 6,572 (62%) were female. The overall mean (SD) age was 70.5 (6.5), and follow-up time was 5.1 (2.7) years. SD and the FHS-CVD risk-score were each associated with incident aMCI (aOR: 1.42 and aOR: 2.11,  p  &amp;lt; 0.01 for both). The interaction of SD and FHS-CVD risk-score with time was significant (aOR: 2.87,  p  &amp;lt; 0.01), suggesting a synergistic effect. SD and FHS-CVD risk-score estimates remained significantly associated with incident aMCI even after adjusting for CSF (Aβ, T-tau, P-tau) and hippocampal volume ( n  = 361) (aOR: 2.55,  p  &amp;lt; 0.01), and approximated risk-estimates of each biomarker in the sample where data was available.   Conclusions:  Clinical measures of sleep and vascular risk may complement current AD biomarkers in assessing risk of cognitive decline in older adults.

frontiers in aging neuroscience

Interactive Associations of Neuropsychiatry Inventory-Questionnaire Assessed Sleep Disturbance and Vascular Risk on Alzheimer’s Disease Stage Progression in Clinically Normal Older Adults