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. 2025 Jul;38(4):254-263.
doi: 10.1177/08919887241313376. Epub 2025 Jan 7.

Impact of Anticholinergic Burden and Clinical-Demographic Characteristics on Incident Dementia in Parkinson Disease

Thanh Phuong Pham Nguyen  1   2   3   4 , Dylan Thibault  2   3   5 , Shelly L Gray  6 , Daniel Weintraub  7   8 , Allison W Willis  1   2   3   4   5   9
Affiliations

Impact of Anticholinergic Burden and Clinical-Demographic Characteristics on Incident Dementia in Parkinson Disease

Thanh Phuong Pham Nguyen et al. J Geriatr Psychiatry Neurol. 2025 Jul.

Abstract

PurposeAnticholinergic medication use measured via the Anticholinergic Cognitive Burden (ACB) scale has been associated with an increased dementia incidence in older adults but has not been explored specifically for Parkinson disease dementia (PDD). We used adjusted Cox models to estimate the risk of incident PDD associated with demographic factors, clinical characteristics, and time-varying total ACB in a longitudinal, deeply-phenotyped prospective PD cohort.Major findings56.5% of study participants were taking ACB-scale drugs at enrollment. Increasing age, motor symptom burden and psychosis were associated with PDD risk. Female sex and educational achievement were protective against PDD. ACB categories were not associated with PDD overall, but depression and impulse control disorder were strongly associated with PDD in a subsample with high baseline ACB.ConclusionsPatient and clinical factors modify PDD risk. PD drug safety and drug-disease interaction studies may require considering multiple mechanisms and including dose-based, prospectively acquired medication exposure measures.

Keywords: Parkinson disease; anticholinergic burden; cognitive impairment; dementia.

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Conflict of interest statement

Declaration of Conflicting InterestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Pham Nguyen was a member of the Junior Investigator Intensive Program of the 2022-2023 U.S. Deprescribing Research Network, which was funded by the National Institute on Aging (Grant #R24AG064025) and receives support from the National Institute of Health (Grants #1RF1NS132673-01, #R01NS099129, #R01AG02515215, #R01AG06458903) and Acadia Pharmaceuticals Inc, unrelated to this project. Dr Weintraub receives support from the National Institutes of Health (Grant #R01NS099129) and has also received research funding or support from Michael J. Fox Foundation for Parkinson’s Research, Alzheimer’s Therapeutic Research Initiative (ATRI), Alzheimer’s Disease Cooperative Study (ADCS), the International Parkinson and Movement Disorder Society (IPMDS); honoraria for consultancy from Acadia Pharmaceuticals Inc, Aptinyx, Biogen, Bracket, CHDI Foundation, Clintrex LLC, Enterin, F. Hoffmann-La Roche Ltd, Ferring, Promentis, Sunovion, and Takeda; and license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS. Dr Willis receives financial support from the National Institutes of Health (Grants #1RF1NS132673-01, #R01NS099129, #K24AG075234, #RF1NS132673), the Parkinson’s Foundation, Acadia Pharmaceuticals Inc, and the University of Pennsylvania. All other authors declared no competing interests in this work.

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