Topographical differences in white matter hyperintensity burden and cognition in aging, MCI, and AD

Abstract

AbstractBackgroundWhite matter hyperintensities (WMHs) are pathological changes that develop with increased age and are associated with cognitive decline. Most research on WMHs has neglected to examine regional differences and instead focuses on using a whole‐brain approach. This study examined regional WMH differences and their association with different cognition domains in normal controls (NCs), people with mild cognitive impairment (MCI), and Alzheimer’s disease (AD).Methods We included participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Few studies using ADNI data have examined the most recent cohort, ADNI‐3. Our study included datapoints from this recently released cohort. Participants were selected from ADNI and were included if they had at least one WMH measurement and cognitive scores examining global cognition (Alzheimer’s Disease Assessment Scale‐13), executive functioning (Trail Making Test‐Part B, and memory (Rey Auditory Verbal Learning Test). MCI and AD participants were included only if they were amyloid positive. A total of 1573 participants with 7381 follow‐ups met inclusion criteria. Linear mixed‐effects models were completed to examine group differences in WMH burden and the association between WMH burden and cognition in aging, MCI, and AD.ResultsPeople with MCI and AD had increased total and regional WMH burden compared to cognitively healthy older adults. An association between WMH and cognition was observed for global cognition, executive functioning, and memory in NCs in all regions of interest. A steeper decline (stronger association between WMH and cognition) was observed in MCI compared to NCs for all cognitive domains in all regions. A steeper decline was observed in AD compared to NCs for global cognition in only the temporal region.Conclusion Including ADNI‐3 data in this study is a novel strength to this study. These results suggest WMH burden increases from aging to AD. A strong association is observed between all cognitive domains of interest and WMH burden in healthy aging and MCI, while those with AD only had a few associations between and WMH and global cognition. These findings indicate that WMH burden is associated with changes in cognition in healthy aging and prodromal AD but not AD.