Body Mass Index, White Matter Hyperintensities, and Cognitive Performance in American Indians: Data from the Strong...

Previous studies report that obesity can be a risk and a protective factor for cognitive health. However, they have not examined whether white matter hyperintensities (WMH) mediate the association between mid- or late-life body mass index (BMI) and late-life cognitive performance. We examined this question in American Indians, a population underrepresented in neuropsychological research.

We used longitudinal data from the cerebrovascular disease and its consequences in American Indians (n = 817), with BMI data collected at midlife (1989-91) and lat-life (2010-13). Cognitive data were collected in late life, with tests for general cognition, processing speed, verbal fluency, and memory. Neuroradiologist-scored WMH severity and volume using standard analysis pipelines. We examined associations among BMI, WMH severity and volume, and cognitive scores using linear regression and the Baron and Kenny method to estimate mediation.

High BMI in late life was associated with a 1.79-point higher score in general cognition (95% CI 0.63-2.95, p-value = 0.002), but not the other tests. Mediated by WMH severity, high late-life BMI was associated with a 1.53-point higher score in general cognition (95% CI 0.37-2.69) and, by WMH volume, 1.63 points higher (95% CI 0.49-2.77). The association between late-life obesity and cognitive performance is stronger for females (β = 1.74, 95% CI 0.35-3.13, p-value = 0.014) than for males (β = 1.66, 95% CI -0.63-3.95, p-value = 0.158).

In American Indians, high late-life BMI was positively associated with cognitive performance, with a stronger association for females. WMH severity and volume partly attenuate these associations.