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.
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BibTeX
@article{hacker2026cognitive,
title = {{Cognitive performance before and after a one-week medication washout in early-stage Parkinson’s disease}},
author = {Mallory L. Hacker and Ella R. Tobias and Kian Pazira and Haley Kling and Leeza Kopaeva and Liliana Venditti and Han Nguyen and Owen Dong and Sheffield Sharp and Thomas L. Davis and David H. Zald and David Charles and Ciaran Considine},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-73037-1},
url = {https://www.nature.com/articles/s41598-026-73037-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cognitive performance before and after a one-week medication washout in early-stage Parkinson’s disease
AU - Mallory L. Hacker
AU - Ella R. Tobias
AU - Kian Pazira
AU - Haley Kling
AU - Leeza Kopaeva
AU - Liliana Venditti
AU - Han Nguyen
AU - Owen Dong
AU - Sheffield Sharp
AU - Thomas L. Davis
AU - David H. Zald
AU - David Charles
AU - Ciaran Considine
PY - 2026
DA - 2026/10/05
JO - Scientific Reports
DO - 10.1038/s41598-026-73037-1
UR - https://www.nature.com/articles/s41598-026-73037-1
AB - 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.
SN - 2045-2322
ER -