# Genome-wide Prediction of Dementia in Parkinson Disease

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $692,479

## Abstract

Genome-wide Prediction of Dementia in Parkinson's Disease
Progression, not susceptibility, is the major determinant of patients' well-being. Dementia is one of the most
debilitating manifestations of disease progression in patients with Parkinson's. It negatively impacts quality of
life, burdens caregivers and increases health costs. Existing therapies cannot prevent the decline from initial
motor symptoms to cognitive impairment. The pace of deterioration varies dramatically between patients for
reasons that are poorly understood. Limited evidence has been found for a proposed association between
prognosis and susceptibility variants. Our initial studies provide compelling evidence for distinct genome loci
predictive of memory loss.
 We hypothesize that novel prognosis loci will powerfully predict a patient's risk for developing Parkinson's
disease dementia. Previous genome-wide association studies were time-static, cross-sectional, case-control
studies that cannot address the time dimension critical for understanding progression. To systematically decode
the genetic architecture of cognitive progression in Parkinson's, here we will perform an unbiased, longitudinal
genome-wide survival study with deep imputation of nineteen cohorts from North America and Europe. More
than six thousand patients with Parkinson’s disease and over fifty thousand cognitive assessments will be
analyzed using Cox proportional hazards and mixed random and fixed effect models. In Aim 1, we will discover
novel loci associated with progression to Parkinson's disease dementia. In Aim 2, we will replicate and verify
forwarded genetic variants in an independent population. In Aim 3, we will build and test a versatile Polygenic
Hazard Score to accurately forecast risk of future cognitive decline.
 This study is poised to elucidate progression loci for Parkinson’s disease dementia, improve clinical
prognostication, and transform clinical trial design. The genetic drivers will point to a distinct biology of cognitive
decline that could inspire new therapeutic directions.

## Key facts

- **NIH application ID:** 10022178
- **Project number:** 5R01NS115144-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** CLEMENS R SCHERZER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $692,479
- **Award type:** 5
- **Project period:** 2019-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022178

## Citation

> US National Institutes of Health, RePORTER application 10022178, Genome-wide Prediction of Dementia in Parkinson Disease (5R01NS115144-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022178. Licensed CC0.

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