To examine how cholinergic basal forebrain volume changes over time in early Parkinson disease (PD) and which baseline clinical features predict this change.

Mean baseline Ch4 density was 0.473 (SD=0.050) and mean change between baseline and 4 years was -0.025 (SD=0.031) or -5.2% (SD=6.6%). Mean change in Ch4 density was -2.4% between baseline and 2 years and -2.3% between 2 years and 4 years. Baseline Ch4 density was not significantly correlated with change in Ch4 density between baseline and 4 years (r=-0.151, p=0.14). In univariate analyses, the following variables were significantly correlated with change in Ch4 density between baseline and 4 years at p<0.05: age (r=-0.351, p=0.0004), Movement Disorders Society – Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part 1 score (r=-0.306, p=0.002), MDS-UPDRS Part 2 score (r=-0.22, p=0.03), and University of Pennsylvania Smell Identification Test (UPSIT) total score (r=0.359, p=0.0003). In a multivariate linear regression model adjusted for baseline Ch4 density, greater age (p=0.003) and MDS-UPDRS Part 1 score (p=0.003) were significantly associated with greater decline in Ch4 between baseline and 4 years; higher UPSIT score was associated with less decline in Ch4 between baseline and 4 years (p=0.01).

Ch4 density linearly declines in early PD. Among many considered demographic variables, clinical symptoms, and molecular biomarkers, greater age, greater burden of non-motor symptoms, and impaired olfaction at baseline are associated with more rapid decline in Ch4 density over 4 years in early PD.