Clinical and neuroimaging correlates of motoric cognitive risk syndrome in cerebral small vessel disease: a cross-sectional study

Introduction – Cerebral small vessel disease (CSVD) and motoric cognitive risk syndrome (MCR) are both associated with adverse outcomes in older adults. Factors associated with MCR in CSVD remain poorly understood. We aimed to explore factors associated with MCR and its components (slow gait and subjective cognitive complaints [SCCs]) in CSVD, and to evaluate exploratory association-based multivariable models. Methods – This cross-sectional study included CSVD patients aged ≥55 years without possible dementia based on education-adjusted MoCA screening from the cognitive subgroup of a national registry. Demographics, clinical variables, physical activity, and CSVD neuroimaging markers were assessed. MCR was defined as co-existing slow gait (age- and sex-adjusted) and SCCs (single-item memory complaint from the 15-item Geriatric Depression Scale). Logistic regression and receiver operating characteristic analyses were performed to identify associated factors and evaluate models. Firth penalized logistic regression and bootstrap internal validation were additionally performed to assess sparse-data bias and optimism in model discrimination. Results – Among 225 patients (mean age 65.4 years, 54.2% male), MCR prevalence was 16.4%. In multivariable models, MCR was associated with lower average systolic blood pressure and high total CSVD burden, while physical inactivity showed a positive but imprecise association because of sparse exposure. SCCs were associated with greater juxtacortical white matter hyperintensity volume and higher total CSVD burden. Slow gait was associated with dyslipidemia, poorer functional status, and higher basal ganglia perivascular spaces. The comprehensive exploratory model integrating demographic, clinical, and neuroimaging factors achieved areas under the curve of 0.732 for MCR, 0.733 for SCCs, and 0.770 for slow gait; the corresponding optimism-corrected AUCs were 0.691, 0.696, and 0.725, respectively. Conclusion – In this exploratory cross-sectional analysis, MCR in CSVD patients showed associations with vascular, lifestyle-related, and neuroimaging markers. However, given the small number of MCR events, the single-item SCC assessment, the lack of temporality, and the limited persistence of associations after FDR correction, these findings should be interpreted as hypothesis-generating.