Diffusion microstructure alterations in subcortical gray matter are associated with cognitive and motor performance...

The cholinergic basal forebrain and subcortical gray matter have previously been implicated in Parkinson's disease (PD), but the relationship between the symptomology of PD, including cognitive impairment, and specific patterns of damage remains unclear. Additionally, understanding the impact of fitness, including motor skills, on brain structure remains a knowledge gap. In this study, we examine a longitudinal cohort of PD patients using advanced microstructural analysis derived from diffusion MRI, alongside volumetric and connectivity components. These imaging metrics are compared to comprehensive cognitive and motor skill fitness metrics. Although the volumetric components well characterize change across the longitudinal timescale, the microstructural analysis was related to a number of composite cognitive scores, including attention, executive function, cognition, language, and the level of motor skill fitness. We further assess the connectivity of the cholinergic basal forebrain, particularly the nucleus basalis of Meynert in area 4 (CH4), and find that connectivity between CH4 and the thalamus is associated with motor skill fitness. The pattern of microstructural results suggests that increased cellularity may support reduced cognitive decline in individuals with PD and greater motor skill fitness.