The association between white matter hyperintensities of presumed vascular origin and disability is mediated by age: a population-based study in stroke-free older adults

Background: Information on the association between disability and severity of white matter hyperintensities (WMH) among stroke-free individuals is limited. We aimed to assess this association in apparently healthy older adults. Methods: Following a population-based cross-sectional design, community-dwelling older adults received a brain MRI to grade WMH severity and the Functional Activities Questionnaire to assess the ability to perform activities of daily living. Demographics, clinical risk factors and other markers of cerebral small vessel disease were taken into consideration for analysis. Results: Unadjusted analysis showed a significant association between moderate-to-severe WMH and disability (p= 0.003) that was tempered by the effect of age. Causal mediation analysis showed that age took away 65.9% of the effect of WMH severity on disability. An interaction model showed that disability was higher only among subjects with moderate-to-severe WMH above the median age. Conclusions: Increasing age mediates the probability of WMH-related disability in stroke-free individuals.