Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults

Background For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis remain nonetheless scarce. Methods In this study, we applied regional and global bivariate latent growth curve modelling (BLGCM) to longitudinal data from 436 cognitively unimpaired participants (DELCODE cohort; median age 69.70 [IQR 65.44, 74.49] years; 52.98% female) to examine the extent to which WMH and cortical thickness were interrelated over a four-year period. Results Our findings were three-fold. First, at baseline, individuals with larger WMH volumes had lower mean cortical thicknesses over the entire brain. Second, individuals who experienced a steeper thinning of their cingulate and temporal cortices over time had larger baseline WMH volumes in the frontal, parietal, and occipital lobes. Third, individuals with thinner cortices at baseline tended to undergo faster WMH progression over four years, particularly in the occipital and parietal lobes. Conclusions Our study suggests that cortical thinning and WMH progression could be mutually reinforcing rather than parallel, unrelated processes, which become entangled before cognitive deficits are detectable.