Cognitive impairment is a core feature of neuronal synuclein disease (NSD) across the Parkinson's disease (PD) continuum, emerging in prodromal states and progressing variably after diagnosis. Leveraging Parkinson's Progression Markers Initiative (PPMI) findings, we highlight that dementia risk in PD appears lower and later than historically estimated (approximately 10% at 10 years), whereas cognition is shaped by converging factors including age, education, affective symptoms, dopaminergic deficit, diffuse cortical atrophy, reduced cerebrospinal fluid (CSF) Aβ1-42, and genetic variants. These insights inform clinical research-encouraging prodromal-stage enrollment, cognition-linked functional endpoints, and platform designs-whereas myPPMI enables scalable remote phenotyping to accelerate mechanistic discovery and biologically-targeted trials of cognitive decline. ANN NEUROL 2026.
Weintraub et al. (Wed,) studied this question.