# Impact of Anticholinergic and Dopamine Receptor Blocking Drug Exposure on Parkinson Disease Trajectory and Outcomes

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $530,531

## Abstract

Project Summary/Abstract
Cognitive impairment and falls leading to hip fracture are leading causes of institutionalization and mortality
in Parkinson disease (PD), a neurological disorder which predominantly affects the most rapidly growing
segment of the U.S. population (older adults). Preventing falls or delaying the onset of dementia in PD would
have a substantial public health impact. Drugs with anticholinergic (ACH) effects or dopamine receptor
blocking (DRB) activity have been demonstrated to impair gait, cause cognitive dysfunction, hasten the
progression of dementia and increase mortality. Parkinson disease patients are particularly vulnerable to
adverse effects of ACH and DRB drugs due to PD-related disruption of central dopaminergic and cholinergic
pathways. Furthermore, PD pharmacotherapy trials use gait and cognition as markers of disease progression
without considering ACH or DRB burden. Yet, no clinical guidelines limiting the use of ACH or DRB drugs
exist, representing a fundamental gap in knowledge this revised proposal will address.
We plan to use Medicare prescription, clinical, and utilization data and rich clinical research data from a
longitudinal cohort study of individuals with PD to identify the pharmacological determinants of preventable
adverse health outcomes and unreliable clinical trial endpoints in PD. This study will 1) produce highly useful
benchmark data on variation in prescribing in PD and 2) address a crucial clinical issue—comparative safety
among therapeutic alternatives for medications with ACH and DRB potential in PD. We expect to
fundamentally advance the field of clinical neurology by providing a strong evidence base for clinical guidelines
and care quality indicators related to ACH and DRB burden in PD. Our results will also have a positive
translational impact because defining the impact of ACH drugs on research measurements of disease trajectory
and clinical outcomes will alter data collection and analysis strategies for future PD neuroprotective drug trials,
improving the ability of such trials to identify effective drugs. We also directly address a priority
recommendation from the 2014 NINDS Parkinson's Disease Research Agenda: `to determine factors that
facilitate health services interventions'- by combining qualitative and quantitative data to produce new insights
into potentially preventable outcomes in PD that directly translate into policy initiatives.

## Key facts

- **NIH application ID:** 10225511
- **Project number:** 5R01NS099129-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Allison Willis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $530,531
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225511

## Citation

> US National Institutes of Health, RePORTER application 10225511, Impact of Anticholinergic and Dopamine Receptor Blocking Drug Exposure on Parkinson Disease Trajectory and Outcomes (5R01NS099129-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225511. Licensed CC0.

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