Cognitive Performance in Prodromal Neuronal α Synuclein Disease

Prodromal neuronal α-synuclein disease shows modestly lower baseline verbal-memory performance than healthy controls, with an adjusted difference of -0.20 SD (95% CI, -0.34 to -0.07).

• Why it matters: Cognitive abnormalities in prodromal neuronal α-synuclein disease may appear before diagnosis, but which cognitive domains are affected and how they change over time are unclear.
• What they did: In a multicenter longitudinal PPMI cohort (n=3031; up to 4 years), cognition was tracked across verbal memory, executive function, processing speed, language, and visuospatial function, with models adjusted for age, sex, education, and APOE ε4.
• The result: Verbal-memory trajectory differed from healthy controls over 4 years (P=.009) but not in an age-matched subset through year 3 (P=.62), while baseline MCI probability rose from 10.2% to 15.1% versus 8.4% to 5.0% in controls.

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