MCR, characterized by slow gait speed and subjective cognitive complaints, has been associated with dementia risk; however, the degree to which WM hyperintensities (WMHs) and alterations in WM microstructure occur in individuals with MCR remains unclear. Whether MCR exhibits a pattern of neuropathological changes distinct from mild cognitive impairment (MCI) is also unknown.

Nondemented participants in the Atherosclerosis Risk in Communities study (N=1591) were classified as MCR+/- based on information from a memory questionnaire and 4-meter walk. MCI+/- status was classified by expert diagnosis using standardized criteria; MCR+ and MCI+ groups overlapped. Participants underwent a 3T brain MRI to quantify WMH volume (cm³); diffusion tensor imaging (DTI) sequences quantified WM microstructural measures using a WM atlas. Multivariable linear regression, adjusted for demographic variables, quantified differences in neuroimaging characteristics, comparing MCR+ and MCI+ groups to MCR- and MCI-, respectively, in separate models.

Among 1591 participants (mean age = 75.9 years; 60.1% women, 27.8% Black, 4.5% MCR+, 34.4% MCI+) both MCR+ and MCI+ statuses were independently associated with greater WMH volume compared to MCR- and MCI- groups, respectively. The MCR associated increase in WMHs (β=0.289, 95% CI: 0.116, 0.542) was over double (143% greater than) that associated with MCI (β=0.119; 95% CI: 0.026, 0.245). MCR+ and MCI+ were associated with WM alterations in commissural, association, and projection tracts. Although individuals with MCR and MCI exhibited similar WM microstructural alterations in the corpus callosum, increased WM abnormalities were observed in several association and projection tracts—including the superior fronto-occipital fasciculus and posterior limb of the internal capsule, respectively—among individuals with MCR.

MCR may represent a clinical manifestation of white matter dysfunction or other brain changes associated with cerebral small vessel disease.