Predicting Risk of Impending Cognitive Decline in Asymptomatic Individuals with Early Alzheimer’s Disease: Insights from Cortical Diffusion MRI

Neurodegeneration associated with Alzheimer’s disease (AD) can start at the microstructural level years before cognitive symptoms; yet, it has been difficult to definitively detect these early changes to plan effective treatments. Using a cortical column-based analysis of high-resolution diffusion magnetic resonance imaging data, we aim to identify early microstructural neurodegeneration in the gray matter across different cortical depths and regions. We compared four groups of participants across a spectrum of cognitive decline (n=60): cognitively normal amyloid-negative (normal controls), cognitively normal amyloid-positive (stage-1 AD), mild cognitive impairment (MCI), and AD dementia. Our results showed progressive increases in radial diffusivity across these groups in cortical regions associated with AD, and our analysis in individual asymptomatic stage-1 AD participants was able to differentiate such diffusivity increases to predict risk of impending cognitive decline in two participants who had cognitive decline and MCI diagnosis at their follow-up clinical exam and 11 participants who did not.