# Investigations of Dementia in Parkinson Disease

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $1,574,996

## Abstract

ABSTRACT
This project focuses on dementia in Parkinson disease (PD), one of the Alzheimer Disease Related
Dementias. PD produces progressive motor and cognitive impairments leading to dementia in ~75% of
patients after 10 years. Development of therapies to slow PD progression requires validated biomarkers of
pathologic processes and that predict progression. Such biomarkers could reflect local, regional pathology or
disruption of widely distributed networks that cause behavioral deficits. This project focuses on cross-sectional
and longitudinal relationships among proteinopathy, cholinergic and noradrenergic deficits, disruption of
functional connectivity networks and behavior. We will build upon our findings in a single site (to maximize
rigorous quality control and retention of participants) longitudinal cohort of 299 people with PD and controls to
extend and expand a multimodal approach to determine the time course of biomarker changes that correspond
with and predict cognitive decline in PD. We have the potential to provide in vivo neuroimaging and CSF
biomarkers of pathology and pathophysiology that could independently, or in combination, predict clinical
manifestations in PD. We will combine PiB (an Aβ amyloid imaging agent), VAT (a vesicular cholinergic
transport ligand), and MRB (a norepinephrine transport ligand) PET, CSF protein levels and resting state
functional connectivity analyses (FC using advanced analysis methods) measures of pathophysiology with
sophisticated behavioral measures focusing on cognition and postmortem brain analyses including
quantification of pathologic proteins. We will determine the relationships between PET biomarkers and CSF
proteinopathy, and compare these to clinical manifestations. FC, as a measure of brain function, will link brain
pathology and neurochemistry with the associated clinical manifestations. In this manner, we will develop a
strong mechanistic understanding of changes in these neuroimaging and CSF biomarkers and how this relates
to cognitive decline and dementia onset in PD. This project holds great promise for identifying
pathophysiological biomarkers for prediction of PD progression, patient stratification for clinical trials, and
evaluation of new treatments.

## Key facts

- **NIH application ID:** 10365610
- **Project number:** 2R01NS075321-11
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** MEGHAN C CAMPBELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,574,996
- **Award type:** 2
- **Project period:** 2011-05-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10365610

## Citation

> US National Institutes of Health, RePORTER application 10365610, Investigations of Dementia in Parkinson Disease (2R01NS075321-11). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10365610. Licensed CC0.

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