Integrity of callosal white matter moderates the relationship between white matter hyperintensities and executive function in older adults

Abstract

AbstractBackgroundWhite matter integrity (WMI) may contribute to brain and cognitive reserve in the face of cerebrovascular disease. We investigated WMI in the genu of the corpus callosum (GCC), an area associated with age‐related WMI and cerebrovascular health, and whether it moderates the relationship between WMH and executive functioning in older adults.MethodParticipants were dementia‐free older adults (N = 175; age range 55‐89 years, M = 72.78; SD = 0.52; 52% male) from the Alzheimer’s Disease Neuroimaging Initiative. Diffusion weighted imaging, T1, and FLAIR scans were used to calculate diffusion tensor imaging (DTI) measures (fractional anisotropy; FA and mean diffusivity; MD) and WMH. Participants were divided into high and low GCC integrity using a median split, stratified by hemisphere and measure (i.e., Right/Left; FA/MD) Neuropsychological tests included Trail Making Test B (TMT B) and Animals. Multiple linear regression determined moderating effects of GCC WMI on WMH and executive function. Education, age, and sex were included as covariates.ResultIn individuals with low GCC WMI, WMH correlated with TMT B (Right FA: p = 0.004, R2= .215; Left FA: p = .014, R2= .222; Right MD: p = .009, R2 = .122 ; Left MD: p = .018, R2= .216) and Animals (Right FA: p = .005; Left FA: p = .022; R2= .131; Right MD: p = .054 (trended); R2= .049). In contrast, WMH did not correlate with TMT B (Right FA: p = .219; Right MD: p = .064; Left MD: p = .095) or Animals (Right FA: p = .411; Left FA: p = .280; Right MD: p = .124; Left MD: p = .274) in older adults with high GCC WMI.ConclusionWe observed a differential effect of GCC WMI on the relationship between WMH and executive function, such that greater WMH predicted lower executive functioning only in individuals with low GCC WMI. No relationship between WMH and executive function was found in individuals with high GCC WMI. GCC WMI may thus be a source of cerebrovascular‐related brain reserve and contribute to cognitive resilience by mitigating the clinical consequences of WMH in individuals with cerebrovascular disease.