APOEϵ4 Genotype and Hypertension Modify 8-year Cortical Thinning: Five Occasion Evidence from the Seattle Longitudinal Study

Philippe Rast, Kristen M. Kennedy, Karen M. Rodrigue, Paul R.A.W. Robinson, Alden L. Gross, Donald G. Mclaren, Tom Grabowski, K. Warner Schaie, Sherry L. Willis

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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 ϵ4 (APOEϵ4), varying by location: Frontal and CING 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 3 times greater than cross-sectional estimates of age-related differences in thickness in parietal and occipital cortices.

Original languageEnglish (US)
Pages (from-to)1934-1945
Number of pages12
JournalCerebral Cortex
Issue number6
StatePublished - Jun 1 2018


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

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'APOEϵ4 Genotype and Hypertension Modify 8-year Cortical Thinning: Five Occasion Evidence from the Seattle Longitudinal Study'. Together they form a unique fingerprint.

Cite this