Periventricular White Matter Hyperintensities and Functional Decline

Background/Objectives: We previously showed that global brain white matter hyperintensity volume (WMHV) was associated with accelerated long-term functional decline. The objective of the current study was to determine whether WMHV in particular brain regions is more predictive of functional decline. Design: Prospective population-based study. Setting: Northern Manhattan magnetic resonance imaging (MRI) study. Participants: Individuals free of stroke at baseline (N = 1,195; mean age 71 ± 9; n = 460 (39%) male). Measurements: Participants had brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences. Volumetric WMHV distribution across 14 brain regions (brainstem; cerebellum; bilateral frontal, occipital, temporal, and parietal lobes; and bilateral anterior and posterior periventricular white matter (PVWM)) was determined using a combination of bimodal image intensity distribution and atlas-based methods. Participants had annual functional assessments using the Barthel Index (BI) (range 0–100) over a mean of 7.3 years and were followed for stroke, myocardial infarction (MI), and mortality. Because there were multiple collinear variables, least absolute shrinkage and selection operator (LASSO) regression–selected regional WMHV variables most associated with outcomes and adjusted generalized estimating equations models were used to estimate associations with baseline BI and change over time. Results: Using LASSO regularization, only right anterior PVWM was found to meet criteria for selection, and each standard deviation greater WMHV was associated with accelerated functional decline of 0.95 additional BI points per year (95% confidence interval (CI) = −1.20 to −0.70) in an unadjusted model, −0.92 points per year (95% CI = −1.18 to −0.67) with baseline covariate adjustment, and −0.87 points per year (95% CI = −1.12 to −0.62) after adjusting for incident stroke and MI. Conclusion: In this large population-based study with long-term repeated measures of function, periventricular WMHV was particularly associated with accelerated functional decline.