Diffusion-Cognitive Correlates of Cortical Cholinergic Pathways Denervation for Early Detection of Alzheimer's disease

Motivation: Denervation of nucleus basalis of Meynert (NBM) tracts may capture cognitive impairment that precedes grey matter loss in Alzheimer's disease(AD). Goal(s): To map the cholinergic pathways and establish diffusion-cognition correlates for early detection of AD. Approach: We mapped the NBM-cholinergic pathways exhibiting significant correlations with cognitive assessment in 11 early-dementia(ED) patients, 22 mild cognitive impairment(MCI) and 22 healthy controls(HC) using correlational tractography. Results: Quantitative anisotropy(QA) and restricted diffusion imaging(RDI) demonstrated significant correlations with cognitive assessment(MOCA) in the NBM-cholinergic pathways of all cohorts. Significantly reduced QA and RDI with MOCA were seen in ED but did not significantly differ between MCI and HC. Impact: The findings establish biological correlates to cognitive manifestation as objective biomarkers for early detection of AD by mapping the NBM-cholinergic tracts with strongest correlation. The surrogate markers aid development of modifying therapies, and potentially discriminate MCI subgroups for personalized management.