APOEε4 Genotype and Hypertension Modify Eight-year Cortical Thinning: Five Occasion Evidence from the Seattle Longitudinal Study

We investigated individual differences in longitudinal trajectories of brain aging in cognitively-normal healthy adults from the Seattle Longitudinal Study covering 8-years of longitudinal change (across 5occasions) in cortical thickness in 249 midlife and older adults (52-95 years-old). We aimed to: understand true brain change; examine the influence of salient risk factors that modify an individual’s rate of cortical thinning; and compare cross-sectional age-related differences in cortical thickness to longitudinal within-person cortical thinning. We used Multivariate Multi-Level Modeling to simultaneously model dependencies among five lobar composites (Frontal, Parietal, Temporal, Occipital, Cingulate) and account for the longitudinal nature of the data. Results indicate 1) all five lobar composites significantly atrophied across 8-years, showing nonlinear longitudinal rate of cortical thinning decelerated over time, 2) longitudinal thinning was significantly altered by hypertension and APOEε4, varying by location: frontal and cingulate thinned more rapidly in APOEε4 carriers. Notably, thinning of parietal and occipital cortex showed synergistic effect of combined risk factors, where individuals who were both APOEε4 carriers and hypertensive had significantly greater 8-year thinning than those with either risk factor alone or neither risk factor, 3) longitudinal thinning was three-times greater than cross-sectional estimates of age-related differences in thickness in parietal and occipital cortices.

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