Differential WMH progression trajectories in progressive and stable mild cognitive impairment

Background Pathological brain changes such as white matter hyperintensities (WMHs) occur with increased age and contribute to cognitive decline. Current research is still unclear regarding the association of amyloid positivity with WMH burden and progression to dementia in people with mild cognitive impairment (MCI). Methods This study examined whether WMH burden increases differently in both amyloid-negative (Aβ-) and amyloid-positive (Aβ+) people with MCI who either remain stable or progress to dementia. We also examined regional WMHs differences in all groups: amyloid positive (Aβ+) progressor, amyloid negative (Aβ–) progressor, amyloid positive (Aβ+) stable, and amyloid negative (Aβ–) stable. MCI participants from the Alzheimer’s Disease Neuroimaging Initiative were included if they had APOE ɛ4 status and if they had amyloid measures to determine amyloid status (i.e., positive, or negative). A total of 820 MCI participants that had APOE ɛ4 status and amyloid measures were included in the study with 5054 follow-up time points over a maximum period of 13 years with an average of 5.7 follow-up timepoints per participant. Linear mixed-effects models were used to examine group differences in global and regional WMHs. Results People who were Aß– stable had lower baseline WMHs compared to both Aß+ progressors and Aß+ stable across all regions. When examining change over time, compared to Aß– stable, all groups had steeper change in WMH burden with Aß+ progressors having the largest change (largest increase in WMH burden over time). Conclusion These findings suggest that WMH progression is a contributing factor to conversion to dementia both in amyloid-positive and negative people with MCI.