Genetic risk for alzheimer’s disease, cognition, and mild behavioral impairment in healthy older adults

Abstract

Background: The neuropsychiatric syndrome mild behavioral impairment (MBI) describes an at-risk state for dementia and may be a useful screening tool for sample enrichment. We hypothesized that stratifying a cognitively normal sample on MBI status would enhance the association between genetic risk for Alzheimer’s disease (AD) and cognition. Methods: Data from 4458 participants over age 50 without dementia was analyzed. A cognitive composite score was constructed and the MBI Checklist was used to stratify those with MBI and those without. Polygenic scores for AD were generated using summary statistics from the IGAP study. Results: AD genetic risk was associated with worse cognition in the MBI group but not in the no MBI group (MBI: β = –0.09, 95% confidence interval: –0.13 to –0.03, P = 0.002, R2 = 0.003). The strongest association was in those with more severe MBI aged ≥65. Conclusions: MBI is an important feature of aging; screening on MBI may be a useful sample enrichment strategy for clinical research.