Background:
Apolipoprotein E (APOE) is a prominent genetic risk factor for Alzheimer’s
disease (AD) and a frequent target for associations with non-demented and cognitively impaired aging.
APOE offers a unique opportunity to evaluate two dichotomous comparisons and selected gradations of
APOE risk. Some evidence suggests that APOE effects may differ by sex and emerge especially in
interaction with other AD-related biomarkers (e.g., vascular health).
Methods:
Longitudinal trajectories of non-demented adults (n = 632, 67% female, Mage = 68.9) populated
a 40-year band of aging. Focusing on memory performance and individualized memory trajectories,
a sequence of latent growth models was tested for predictions of (moderation between) APOE and
pulse pressure (PP) as stratified by sex. The analyses (1) established robust benchmark PP effects on
memory trajectories, (2) compared predictions of alternative dichotomous groupings (ε4- vs ε4+, ε2- vs
ε2+), and (3) examined precision-based predictions by disaggregated APOE genotypes.
Results:
Healthier (lower) PP was associated with better memory performance and less decline. Therefore,
all subsequent analyses were conducted in the interactive context of PP effects and sex stratification.
The ε4-based dichotomization produced no differential genetic predictions. The ε2-based analyses
showed sex differences, including selective protection for ε2-positive females. Exploratory follow-up
disaggregated APOE genotype analyses suggested selective ε2 protection effects for both homozygotic
and heterozygotic females.
Conclusion:
Precision analyses of AD genetic risk will advance the understanding of underlying
mechanisms and improve personalized implementation of interventions.
Disappearing metabolic youthfulness in the cognitively impaired female brain
