# Cerebellar cholinergic connections as a biomarker of dementia and gait impairment in Parkinson disease

> **NIH NIH K23** · WASHINGTON UNIVERSITY · 2022 · $184,728

## Abstract

Parkinson disease (PD) is the second most common progressive neurodegenerative disorder characterized by
tremendous clinical heterogeneity. PD with dementia is considered one of the Alzheimer disease related
dementias. Dementia, afflicting up to 80% of PD patients and gait impairment cause significant morbidity and
mortality, and tremendously amplify the socioeconomic burden as effective treatments are lacking. Both these
impairments are refractory to dopaminergics suggesting involvement of other neurotransmitter systems or brain
regions beyond nigrostriatal pathways. Most neuroimaging studies have focused on striatal dopaminergic deficits
and fail to adequately explain gait and cognitive impairments in PD. The midbrain pedunculopontine nucleus
(PPN) sends cholinergic input to the cerebellar vermis, which has much greater cholinergic innervation in
humans than the cerebellar hemispheres. Degeneration of PPN, known to occur in PD could lead to cholinergic
denervation of vermis. Vermis modulates gait and cognition, but little is known about its role in PD. Recent
cerebellar resting-state functional connectivity (FC) analysis demonstrates altered vermal FC with sensorimotor
and association cortices in PD and their respective gait and cognitive correlates. This proposed study utilizing a
multimodal approach will extend the prior work and investigate whether longitudinal changes in vermal FC reflect
decline in gait and cognition in PD and whether cholinergic denervation of the vermis, as measured by vesicular
cholinergic transporter activity (VAChT) PET imaging, underlie these deficits in FC and behavior. The long term
goal is to investigate whether vermal FC and cholinergic PET measures can serve as antecedent markers of
dementia and falls in PD. The proposed study serves three major objectives. The first objective is to investigate
cholinergic denervation of vermis and two important aspects of vermal FC in PD: its ability to objectively reflect
progression of gait and cognitive impairment and its ties to underlying cholinergic pathology as measured by
VAChT PET, the two key attributes of a reliable imaging biomarker. The second objective is to leverage the
highly conducive and supportive environment, access to wealth of cross-sectional and longitudinal multimodal
imaging data and comprehensive, sophisticated behavioral measures, and an excellent diverse team of mentors
to provide the candidate with training in a) PET analysis and b) conducting longitudinal studies with special
emphasis on multivariate, longitudinal statistics to ensure a timely transition to independence. The final objective
for the candidate is to continue to author manuscripts especially involving PET and generate preliminary data
towards a R01 application. Although with independent research aims, this study is privileged to use the data
collected as a part of large scale longitudinal study with established funding. The proposed study could have
substantial clinical impact by eluc...

## Key facts

- **NIH application ID:** 10351813
- **Project number:** 1K23NS125107-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Baijayanta Maiti
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $184,728
- **Award type:** 1
- **Project period:** 2022-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10351813

## Citation

> US National Institutes of Health, RePORTER application 10351813, Cerebellar cholinergic connections as a biomarker of dementia and gait impairment in Parkinson disease (1K23NS125107-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10351813. Licensed CC0.

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