Cognitive performance before and after a one-week medication washout in early-stage Parkinson’s disease

Abstract Cognitive deficits are often present in early-stage Parkinson’s disease (PD) and may be differentially affected by dopaminergic therapy. Prior studies have relied on overnight OFF states, which may incompletely remove residual medication effects. Early-stage PD participants (dopaminergic treatment 1–4 years; aged 50–75 years; without motor fluctuations/dyskinesia) completed a comprehensive neuropsychological battery ON dopaminergic medication and after a one-week OFF-medication washout. Outcomes spanned executive function, attention/working memory, processing speed, memory, language, visuospatial function, and motor dexterity. Mean ON–OFF differences were estimated with 2,000-iteration bootstrap 95% CIs; paired tests were FDR-corrected. Nineteen of 20 participants (95%) completed the washout (mean age 65.8 ± 6.8 years; 75% male; LEDD = 490 ± 414 mg). OFF-medication scores were better for executive planning on D-KEFS Tower Total Achievement raw score (ON-OFF − 2.8; 95% CI − 4.3 to − 1.3; q = 0.027) and for processing speed on SDMT–Oral (− 6.2; 95% CI − 9.4 to − 3.1; q = 0.027). No FDR-significant ON–OFF differences were observed in attention/working memory, memory, or visuospatial measures. Effects were confined to the more cognitively demanding measures of executive planning and processing speed. These results are hypothesis-generating and require confirmation in counterbalanced designs.