Researchers of a longitudinal Parkinson’s Progression Markers Initiative (PPMI) analysis followed 392 people with Parkinson’s disease for up to 4 years, classifying them as with (PDP) or without psychosis (PDnP). Striatal presynaptic dopamine function was indexed by striatal dopamine transporter (DAT) striatal binding ratio (SBR). Cognition was tracked with multiple tests at each visit while adjusting for sociodemographics, neuropsychiatric features, and PD-specific symptoms. Across all timepoints—and after adjusting for age, sex, and ethnicity—PDP showed lower DAT SBR than PDnP (b=−0.092, p=0.035). PDP also exhibited worse cognitive trajectories on the Mini-Mental State Examination, the Montreal Cognitive Assessment (MoCA) (b=−0.238, p=0.001), and the Symbol Digit Modalities Test (SDMT; b=−0.534, p=0.016).
Critically, decline in SDMT performance was differentially linked to decline in DAT SBR over time (Group×Time×DAT SBR: b=0.683, p=0.028), whereas MoCA decline, although greater in PDP (Group×Time: b=−0.284, p=0.016), was not directly tied to DAT loss. This pattern points to a selective dependence of processing speed/working memory (SDMT) on striatal dopaminergic integrity, with more global cognition (MoCA) likely reflecting additional non-dopaminergic or network factors. Clinically, serial SDMT alongside DAT imaging may help flag PDP patients at risk for faster cognitive slowing, while MoCA changes could prompt broader evaluation beyond dopamine-centered mechanisms.
Reference: Pisani S, Velayudhan L, Aarsland D, et al. Decline in striatal binding ratio associated with accelerated decline in performance on symbol digit modality but not MoCA in Parkinson’s Disease Psychosis. BMJ Ment Health. 2025;28(1):e301430. doi: 10.1136/bmjment-2024-301430.
