Approaches to timescale choice in cognitive aging research and potential implications for estimated exposure effects: coordinated analyses in ten cohorts of older adults.

Abstract

Background: Cognitive change is an important factor in understanding dementia. Estimating effects of exposures on cognitive change requires choosing an analytical timescale, typically time on study or current age. There is limited consensus regarding timescale choice in epidemiologic cognitive aging research.

Methods: Using a coordinated analytic approach in ten cohorts of older adults, we evaluated whether estimated effects of two exposures on memory change differed depending on timescale (time on study or current age). We modeled effects of APOE ε4 genotype (a time-invariant exposure) and diabetes (a potentially time-varying/acquired exposure evaluated at baseline) using mixed-effects models with linear and non-linear time specifications for both timescales.

Results: Among APOE ε4 carriers, model-estimated memory scores at baseline (time on study timescale) or at each cohort's median baseline age (current age timescale) were lower and average rate of decline was faster than among APOE ε4 noncarriers. Model-estimated memory scores at baseline or at median baseline age were generally similar across baseline diabetes status, with variability across cohorts in the diabetes-memory change association. In some cohorts, trends in diabetes-memory change associations differed in direction across timescales.

Conclusions: Timescale was largely inconsequential for estimated effects of APOE genotype, but yielded differences in estimated diabetes effects, raising questions about the appropriate scale. Current age scale may be problematic because diabetes was measured heterogeneously in age across individuals, a common issue in aging cohorts. Our work demonstrates approaches to evaluate alternative timescales, including in multi-cohort analyses, and highlights potential implications for estimated exposure effects on cognitive change.