Gait, Gray Matter Predict Mortality in Cerebral Small Vessel Disease

brain blood vessels
brain blood vessels
Compared to cognition, gait speed may be more predictive of mortality due to its relationship with other organ systems.

Age, gait speed, and gray matter volume are among the factors that predict mortality in people with cerebral small vessel disease (SVD), according to a prospective, single-center study published in JAMA Neurology.

SVD is a common imaging finding in older adults characterized by white matter hyperintensities, lacunes, microbleeds, and subcortical and cortical atrophy. Long-term prognosis may include cognitive and motor impairment and mood disturbances, which may lead to death; however it is unknown which patients are at highest risk for these outcomes.

In order to identify potential clinical and imaging factors associated with mortality in SVD, Helena M. van der Holst, MD, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues assessed cognition, motor skills, and cerebral MRI in 503 older adults with SVD over a follow-up of 8 years or until death. The final analysis included 494 participants (mean [SD] age, 65.7 [8.8] years; range, 50-85 years), of whom 78 died during follow-up.

The authors reported that gait speed, cognitive index, MRI markers of SVD, and diffusion measures of white matter were associated with an 8-year risk of mortality independent of age, sex, and vascular risk factors. Older age (1.05 per 1-year increase [1.01-1.08]), slower gait (1.15 per 0.1-m/s slower gait [1.06-1.24]), lower gray matter volume (0.72 per 1-SD increase [0.55-0.95]), and greater global mean diffusivity of white matter (1.51 per 1-SD increase [1.19-1.92]) were found to be the main factors linked to mortality. After adjustments, cognitive index and MRI markers of SVD did not remain significant factors.

In reasoning why gait remained significant while cognition did not, the authors stated “…gait relies not only on intact cerebral networks but also on the functioning of several organ systems, including respiratory, circulatory, musculoskeletal, and peripheral nerve systems. As a result, slower gait might not be primarily caused by dysfunction of one system (eg, the brain) but is probably due to accumulation of pathology among several organ systems…” 

They continued, “Because cognition is less affected by damage to other organ systems compared with the brain, it could be that the association between cognitive performance and mortality is mediated by SVD.”


van der Holst HM, van Uden IM, Tuladhar AM, et al. Factors Associated With 8-Year Mortality in Older Patients With Cerebral Small Vessel Disease: The Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) Study. JAMA Neurol. 2016. doi:10.1001/jamaneurol.2015.4560.