AUTHOR=Bubu Omonigho M. , Williams Ellita T. , Umasabor-Bubu Ogie Q. , Kaur Sonya S. , Turner Arlener D. , Blanc Judite , Cejudo Jaime Ramos , Mullins Anna E. , Parekh Ankit , Kam Korey , Osakwe Zainab T. , Nguyen Ann W. , Trammell Antoine R. , Mbah Alfred K. , de Leon Mony , Rapoport David M. , Ayappa Indu , Ogedegbe Gbenga , Jean-Louis Girardin , Masurkar Arjun V. , Varga Andrew W. , Osorio Ricardo S. 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.763264

DOI=10.3389/fnagi.2021.763264

ISSN=1663-4365

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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 (<italic>n</italic> = 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.</p><p><bold>Results:</bold> 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, <italic>p</italic> &lt; 0.01 for both). The interaction of SD and FHS-CVD risk-score with time was significant (aOR: 2.87, <italic>p</italic> &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 (<italic>n</italic> = 361) (aOR: 2.55, <italic>p</italic> &lt; 0.01), and approximated risk-estimates of each biomarker in the sample where data was available.</p><p><bold>Conclusions:</bold> Clinical measures of sleep and vascular risk may complement current AD biomarkers in assessing risk of cognitive decline in older adults.</p>