Correlations between white matter hyperintensities, magnetic resonance imaging findings, and cognition in the oldest old: a multimodal cross-sectional study.

Small vessel disease and brain atrophy are linked to cognition in later life, but whether these associations persist in the oldest old is unclear, as lesion burden and survivorship may change effect sizes. We analyzed 249 adults aged 89-94 years from the Kawasaki Aging and Wellbeing Project. White matter hyperintensities (WMHs) were segmented on fluid-attenuated inversion recovery; gray and white matter volumes were derived from T1-weighted magnetic resonance imaging; and peak width of skeletonized mean diffusivity (PSMD) indexed diffuse white matter damage. Global cognition was assessed with the Mini-Mental State Examination (MMSE). Robust multivariable regression related MMSE to age, education, sex, apolipoprotein E ε4 status, WMH burden, volumetric measures, PSMD, and a PSMD × education interaction. Voxel-wise lesion-symptom mapping and tract-based spatial statistics evaluated tract-level effects. Older age and higher WMH burden were associated with lower MMSE, whereas higher education was associated with higher MMSE. PSMD showed no independent main effect after covariate adjustment. An exploratory PSMD × education interaction was nominally significant in the primary model but attenuated in sensitivity analyses. Exploratory spatial analyses suggested that WMHs in the inferior fronto-occipital fasciculus (IFOF) and inferior longitudinal fasciculus, as well as higher axial diffusivity in the left IFOF, were associated with lower MMSE. Overall, the principal contribution of this study is confirmatory evidence, in a rare oldest-old cohort, that WMH burden and education remain associated with global cognition; spatial and interaction findings are hypothesis-generating and should not be interpreted as confirmatory evidence of tract-specific mechanisms.