Association of the Brain White Matter Hyperintensity with the Cognitive Performance in Middle-Aged Population

White matter hyperintensity (WMH) is typically classified into periventricular and deep WMH (PVWMH and DWMH) based on its proximity to the ventricles. While WMH volume has been associated with the cognitive performance and decline in patients with cerebral small vessel disease, the relative contributions of PVWMH and DWMH to the cognitive profile of these patients remain unclear. Therefore, we aimed to determine the differences in association of PVWMH and DWMH with a battery of cognitive tests in a group of middle-aged population at risk for cardiovascular disease.

Participants in the Genetic Study for Atherosclerosis Risk (GeneSTAR) who had a brain magnetic resonance imaging, a cognitive battery, and were older than 50 years of age were studied. The relative association of PVWMH and DWMH with each of the cognitive measures was tested using multilevel linear regression models adjusting for age, intracranial volume, and cardiovascular risk factors. Adjustment for multiple comparisons was completed by using Benjamini-Hochberg procedure for the primary outcome and q-value of <0.1 was considered significant. Maximal likelihood estimation analysis was used to explore whether age moderated the difference in association of PVWMH and DWMH with the cognitive tests.

A total of 435 participants (age 58.9 ± 6.14 years, 58.38% women, and 39.54% black) were studied. We identified a greater association of PVWMH than DWMH with a worse performance on the grooved peg board test (q-value = 0.06) including the dominant (q-value = 0.098) and nondominant hand (q-value = 0.098) performance as well as the delayed word recall test in its short form (q-value = 0.098). Age did not moderate the differences in the association of PVWMH and DWMH with these cognitive tests.

Our findings indicate a greater effect of PVWMH than DWHM on manipulative manual dexterity and delayed word recall functions suggesting potential injury of the white matter tracts that are relevant to these function by PVWMH. These findings need to be confirmed in future large prospective studies.