Accelerated brain ageing in participants with higher cerebrovascular lesion load across aging, cognitive impairment, and mixed presentation

Abstract

AbstractBackgroundWe aimed to investigate the association between cortical brain age and white matter hyperintensities (WMH) in diverse forms of clinically‐defined vascular conditions. Our hypothesis was that a higher WMH burden would be associated with higher cortical brain age in all clinical subtypes.MethodWe used standardized MRI data obtained from participants in the COMPASS‐ND cohort of the CCNA. We used a standard linear support vector regression algorithm to estimate brain age, matching chronological age to cortical anatomical measurements obtained with the FreeSurfer toolbox on T1‐weighted MRI, sex, and intracranial volume. We calculated brain‐PAD (i.e., predicted brain age minus real age) and applied bias adjustment to remove age‐dependency in the estimates. A validated automated technique utilizing T2‐weighted and fluid attenuated inversion recovery MRIs was used to compute WMH loads.ResultParticipants included 107 CIE, 240 mild cognitive impairment (MCI), 115 vascular‐MCI (V‐MCI), 81 probable Alzheimer’s disease (AD), and 50 V‐AD. There was a significant difference in brain‐PAD [ F (4,599) = 56, P < 0.001, ANCOVA test] among groups, whilst adjusting for sex and chronological age. All four categories of patients exhibited a significantly higher mean brain‐PAD than CIE (P < 0.001), with the AD cohort having the highest brain‐PAD. There was a significant difference in WMH loads [ F (4,586) = 48, P < 0.001, ANCOVA test] between groups, whilst adjusting for sex and age. All cohorts showed a positive correlation between brain‐PAD and WMH, indicating accelerated ageing in people with higher WMHs. We observed moderate and significant correlations between brain‐PAD and WMH loads for V‐MCI (r = 0.34, P < 0.001) and V‐AD (r = 0.36, P = 0.001) but weaker, while significant correlations in CIE (r = 0.20, P = 0.035) and AD cohorts (r = 0.24, P = 0.025).ConclusionWe observed a positive and significant link between brain‐PAD and WMH in all categories. This finding indicates on the importance of treatment and prevention strategies for vascular risk factors, which might be able to slow down the progression of cerebrovascular lesions and delay the effect on cortical thickness.