APOE epsilon 4 Genotype and Hypertension Modify 8-year Cortical Thinning: Five Occasion Evidence from the Seattle Longitudinal Study

作者：Rast Philippe^*; Kennedy Kristen M; Rodrigue Karen M; Robinson Paul R A W; Gross Alden L; McLaren Donald G; Grabowski Tom; Schaie K Warner; Willis Sherry L

来源：Cerebral Cortex, 2018, 28(6): 1934-1945.

DOI：10.1093/cercor/bhx099

• aging
• APOE
• cortical thinning
• hypertension
• longitudinal modeling

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 5 occasions) 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 Multilevel Modeling to simultaneously model dependencies among 5 lobar composites (Frontal, Parietal, Temporal, Occipital, and Cingulate [CING]) and account for the longitudinal nature of the data. Results indicate (1) all 5 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 Apolipoprotein-E epsilon 4 (APOE epsilon 4), varying by location: Frontal and CING thinned more rapidly in APOEe4 carriers. Notably, thinning of parietal and occipital cortex showed synergistic effect of combined risk factors, where individuals who were both APOE epsilon 4 carriers and hypertensive had significantly greater 8-year thinning than those with either risk factor alone or neither risk factor, (3) longitudinal thinning was 3 times greater than cross-sectional estimates of age-related differences in thickness in parietal and occipital cortices.

• 出版日期2018-6