Growth of White Matter Signal Aberrations and Cortical Changes in Men and Women: A 9-Year Multiple-Time-Point Longitudinal MRI Study in Older Adults.

In aging, white matter hyperintensities (WMH) or white matter signal aberrations (WMSA), a proxy for cerebral small vessel disease, are the most common age-related finding on brain MRI scans, with women reported to have a greater burden. Previous studies found that WMH/WMSA were linked to lower cortical volume and thickness. However, no study has investigated the connection between WMSA and both cortical thickness and area using multiple assessments over 9 years. We hypothesized that increasing WMSA was associated with a decrease in both cortical thickness and area over time, compounding the age-typical decrease, and that the effect was more pronounced in women than men. Our cohort consisted of 104 older adults from the general population, born between 1936 and 1942, scanned at the same 3T scanner at baseline (mean age 72.4 years), and followed up at 1-, 3-, 5, and 9 years. We analyzed the 3D MPRAGE scans in FreeSurfer's longitudinal pipeline and extracted the volume of WMSA, cortical thickness and area, grey matter-white matter intensity ratio, plus hippocampal and intracranial volume. Linear mixed-effects models included the interaction between sex and WMSA on cortical thickness and area, and hippocampal volume. We also performed sex-specific analyses. Finally, complete case and sensitivity analyses with known confounders were run. In both men and women, baseline WMSA volume was 3.6 cm