APOE ε4 allele status similarly predicts a latent dementia index as clinical diagnosis of dementia

Abstract

AbstractBackgroundLatent dementia index (LDI) variables are increasingly popular, mainly because they make it possible to quantify a continuous measure of dementia risk using cognitive and functional ability variables when no clinical gold standard is available. Validation studies of LDI variables tend to include clinical gold standard outcomes and demographic variables (e.g., age and gender). No studies to date, however, have validated LDI variables using APOE ε4 allele status. To the extent that effects are similar, we can claim greater convergent validity of the LDI. The purpose of this study is evaluate whether effects of APOE ε4 allele status on LDI is similar to effects of e4 status on clinical gold standard.MethodThe study included 856 participants from the 2001‐2003 Aging, Demographics, and Memory Study (ADAMS), a subsample from the United States Health and Retirement Study. Respondents completed a comprehensive neuropsychological battery, including tests evaluating cognitive ability across multiple cognitive domains (such as memory, executive function, orientation, attention, spatial ability, and language). Informants provided data on functional ability. The LDI was modeled as a latent variable indicated by task specific cognitive scores and functional ability tasks. Lower LDI scores indicate greater risk of dementia. APOE status was an ordinal variable to indicate the absence (0 alleles) or presence (1 or 2 alleles) of ε4 allele status. Clinical gold standard was determined by neuropsychological assessment, which included medical, functioning, cognitive, and physical exams. Regression analyses were performed to test the correlation between APOE ε4 allele status and both measures of dementia.ResultAPOE ε4 allele status significantly predicted clinical gold standard (OR: 1.44 [.95CI: 1.23, 1.69]). APOE ε4 allele status also significantly predicted LDI (β = ‐0.15, SE =0.04, p < .001). APOE ε4 allele status accounted for approximately half the amount of the variance in LDI (2%) as in clinical gold standard (3.6%).ConclusionBased on the similarity of the effects of APOE ε4 allele status on LDI and clinical gold standard, the LDI appears to be a valid continuous proxy measure of dementia.