Examining APOE ε4 and Longitudinal Vascular Brain Injury: The Strong Heart Study.

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• American Indians face high risks for cerebrovascular disease, vascular brain injury (VBI), and dementia.
• The apolipoprotein (APOE) ε4 allele is a known Alzheimer's disease risk factor, also linked to white matter hyperintensities (WMH) and VBI.

Purpose of the Study:

• To investigate the association between APOE ε4 allele carriage and longitudinal changes in WMH.
• To determine if the null effect of APOE ε4 on cross-sectional findings extends to longitudinal changes in American Indians.

Main Methods:

• Analysis of a population-based, longitudinal cohort of 395 American Indians (aged 64-95) from the Strong Heart Study.
• Assessment of magnetic resonance imaging markers including WMH, infarcts, lacunes, and hemorrhages.
• Dichotomized APOE genotype (ε4 carrier vs. non-carrier) and adjusted for covariates using Poisson, linear mixed-effects, and Cox regression models.

Main Results:

• No significant cross-sectional associations were found between APOE ε4 and lacunes, infarcts, or hemorrhages.
• Longitudinal analyses showed no significant association between APOE ε4 and changes in WMH volume.
• APOE ε4 was not significantly associated with overall VBI incidence in adjusted models.

Conclusions:

• APOE ε4 does not appear to be a specific risk factor for WMH in American Indians.
• Larger sample sizes and investigation into modifiable environmental factors are needed to validate these findings and understand their impact on brain aging.