Cerebral small vessel disease is associated with concurrent physical and cognitive impairments at preclinical stage

Background: Physio-cognitive decline syndrome (PCDS) is a clinical construct of concurrent physical mobility and cognitive impairments in non-demented functional preserved elderly who are at risk of dementia and disable. The present study aimed to evaluate whether cerebral small vessel disease (SVD) is associated with this phenotype of accelerated aging. Methods: We stratified a non-demented non-stroke community-based population aged 50 or older into four groups: robust, isolated cognitive impairment no dementia (CIND), isolated physical mobility impairment no disable (MIND) and PCDS groups. SVD burden (SVD score) was defined by the presence of severe white matter hyperintensities (WMH), lacune(s) and cerebral microbleed (CMB). Univariate and multivariate analyses were performed to evaluate the cross-sectional relationships between SVD and PCDS. Results: Seven hundred and nine eligible participants were included. There were 317 (44.7%) classified as robust group, 212 (29.9%) as CIND group, 117 (16.5%) as MIND group and 63 (8.9%) as PCDS group. SVD (SVD score ≥ 2) was significantly associated with PCDS, concurrent mobility physical and cognitive impairments (odds-ratio, OR = 2.3; 95% confidence interval, 95% CI = 1.3-4.0; p = 0.003) but not with MIND or CIND, which was independent of age, sex and vascular risk factors. Among three SVD markers, the presence of severe WMH (OR = 1.9; 95% CI = 1.1-3.2; p = 0.023) and lacune (OR = 2.5; 95% CI = 1.3-4.8; p = 0.005) were significantly and mixed CMB (OR = 2.0; 95% CI = 1.0-4.1; p = 0.058) was borderline-significantly associated with PCDS independent of age, sex and vascular risk factors. Conclusion: SVD was associated with PCDS, a phenotype with concurrent physical mobility and cognitive impairments in the non-demented non-disable elderly population. The present study revealed the clinical features of SVD at early, preclinical stage and has provided insights into the pathophysiology and future management strategy of accelerated functional declines in the elderly.