A comprehensive exploration of longitudinal white matter microstructure and cognitive trajectories

COEX 

The primary clinical manifestation of Alzheimer's disease (AD) is cognitive impairment and longitudinal cognitive decline, and several prior diffusion MRI studies have investigated the association between white matter microstructure and cognitive decline in normal aging and AD^1–7. Recent work from our group explored the free-water (FW)-corrected associations with longitudinal scores of memory and executive function and found that medial temporal lobe tracts were significantly associated with both domains⁸. One interesting finding from this prior study is that the FW component, which is a separate 3D map which is created in the FW-correction pipeline, is particularly sensitive to cognitive impairment and decline. This is in line with several prior studies which have demonstrated similar findings in other neurodegenerative diseases. While these studies have been foundational to our understanding of white matter contributions to cognitive impairment and decline, large-scale studies using harmonized scores of cognitive function would drastically enhance our understanding by elucidating which white matter tracts are most vulnerable in individuals with cognitive decline.