Cerebral small vessel disease unveils a vascular pathway to motoric cognitive risk in aging

Background: Motoric cognitive risk (MCR) syndrome is characterized by subjective cognitive complaints and slow gait and confers a higher risk of dementia. Cerebral small vessel disease (CSVD) is associated with poor cognitive, functional, and survival outcomes in aging. Markers of CSVD seen on magnetic resonance imaging (MRI) include white matter hyperintensities (WMHs) and lacunes. Objective: To examine associations between imaging markers of CSVD and the MCR syndrome. Methods: Cross-sectional data from 4 cohorts in 4 countries were examined. WMHs and lacunes were quantified from brain MRIs manually, using a standardized grading scale. Regression models examined the associations between WMH and lacunes and MCR, gait speed, slow gait, and cognitive complaints. We also compared the prevalence of the outcomes of interest between participants with “confluent or diffuse” or “no or mild” WMH. Statistical models were adjusted for age, sex, study site, and vascular risk factors. Results: Data from 1772 participants (M Age = 71.1 years, 49.9% female) was analyzed. Higher global WMH scores were associated with MCR (aOR = 1.07, p = 0.015). Frontal and basal ganglia WMH scores were associated with MCR (aOR = 1.23, p = 0.007, aOR = 1.31, p = 0.023, respectively). Participants with “confluent-diffuse” WMH had significantly higher prevalence of MCR (30.2% versus 19.2%, p = 0.003). Basal ganglia lacunes were associated with MCR (aOR = 1.57, p = 0.018). Conclusions: In this multi-cohort study of older adults without cognitive impairment, we show that WMH and lacunes independently predict increased risk of MCR, after adjusting for key confounders. Our findings, based on a large multi-ethnic cohort, reveal region-specific CSVD patterns linked to MCR and related outcomes.