# Molecular Imaging of the Nicotinic Cholinergic Receptor in Parkinson's disease (PD): Implication of for understanding the neurobiology of cognitive impairment

> **NIH NIH K23** · JOHNS HOPKINS UNIVERSITY · 2020 · $199,980

## Abstract

Project Summary/Abstract
This resubmission for a Mentored Patient-Oriented Research Career Development Award (K23) is from a
neurologist specializing in movement disorders. The integrated career development and research plan are
focused on the development of markers of vulnerability to cognitive decline in Parkinson’s disease (PD) and
use their use to predict cognitive decline following Deep Brain Stimulation (DBS) in PD, using cognitive
performance combined with PET imaging of the α4β2-nicotinic acetylcholine receptor (α4β2-AChR). The
overarching hypothesis is that cognitive dysfunction localizing to specific cortical regions, and decreased α4β2-
AChR availability in these regions, will predict cognitive impairment following DBS surgery. The research
project is motivated by the increasing awareness of cognitive impairment as a disabling symptom of PD as
motor symptoms are treated earlier with advances in therapies. The lack of reliable clinical markers for
impending cognitive impairment in surgical decision-making exposes some patients to excessive “cognitive
risk” by undergoing DBS surgery while allowing other good candidates to go untreated with DBS. To this end,
the aims are to 1) measure α4β2-AChR in PD patients and controls in regions involved in PD-related cognitive
impairment, 2) measure associations between α4β2-AChR and cognitive impairment in PD, and 3) measure
associations between baseline α4β2-AChR and subsequent cognitive decline following DBS surgery.
 The research plan is complemented by a career development plan with the following specific short-term
training goals focused on: 1) the application, analysis and interpretation of PET imaging, 2) selection, analysis,
and interpretation of cognitive evaluations, 3) a comprehensive understanding of cognitive changes related to
DBS, 4) advanced training in biostatics, and 5) developing multidisciplinary collaboration as a translational
researcher. The candidate will be mentored directly by senior faculty with expertise in pathophysiology
research in PD, molecular imaging and cognition in neurodegenerative disease and PD, motor and non-motor
effects of DBS in PD and biostatistics and will participate in complementary formal coursework and external
training programs.
 Completion of the research and training objectives will advance the career of a junior investigator toward
developing an independent research program focused on developing neuropsychological and molecular
imaging risk factors for cognitive decline following functional neurosurgery in PD patients, an increasingly
common procedure and prevalent disease. Understanding the mechanistic role of the nicotinic cholinergic
system in rapid changes in cognitive function following invasive brain procedures will inform the design of an
R01 proposal to validate the use of these markers in the prediction of impending cognitive decline in PD
following invasive brain procedures. The results will also have implications for the development of ...

## Key facts

- **NIH application ID:** 10001607
- **Project number:** 5K23NS101096-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Kelly Alexander Mills
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,980
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001607

## Citation

> US National Institutes of Health, RePORTER application 10001607, Molecular Imaging of the Nicotinic Cholinergic Receptor in Parkinson's disease (PD): Implication of for understanding the neurobiology of cognitive impairment (5K23NS101096-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001607. Licensed CC0.

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