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

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. This study was supported by K01AG066971 (National Institute on Aging) and the Vanderbilt CTSA grant UL1TR002243 from NCATS/NIH. The funder played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.

Department of Neurology, Vanderbilt University Medical Center, Nashville, USA Mallory L. Tobias, Kian Pazira, Haley Kling, Leeza Kopaeva, Liliana Venditti, Han Nguyen, Owen Dong, Sheffield Sharp, Thomas L. Davis, David Charles & Ciaran Considine Department of Psychiatry, Rutgers University, New Brunswick, USA Department of Psychiatry, Vanderbilt University Medical Center, Nashville, USA Department of Physical Medicine and Rehabilitation, Vanderbilt University Medical Center, Nashville, TN, USA ET, KP, HK, HN, LV, OD, SS report no conflicts of interest relevant to the manuscript.

MH is a shareholder of and consultant for Arena Therapeutics, a company focused on advancing research of DBS for the treatment of patients recently diagnosed with PD and a consultant for AbbVie. TD is a consultant for AbbVie. DHZ receives royalties from Neumora Therapeutics and grants from NIH.