# Dissecting Oligogenic Biomarkers in Ashkenazi Jews with Parkinson Disease

> **NIH NIH U01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $352,792

## Abstract

Lewy body dementias (LBD) are comprised of Dementia with Lewy Bodies (DLB) and Parkinson Disease (PD)
with Dementia (PDD). Most LBD are associated with sleep disorders that may predate or be concurrent with
cognitive symptoms. In PD there are decreased rest-activity rhythms and reduced melatonin amplitude, both
suggestive of circadian disruption, which can be the underlying cause of the sleep disturbances and cognitive
decline seen in this population. Light, the strongest stimulus for the circadian system, has been shown to improve
sleep and reduce fatigue and dementia in persons with Alzheimer’s disease and related dementias (ADRD) as
well as in cancer patients. We are proposing to 1) determine whether sleep disturbances commonly found in
persons with PD and PD and dementia, and specifically those with GBA and LRRK2 mutations, are related to
circadian disruption and 2) determine whether light can improve sleep and therefore improve cognition and
decrease fatigue in PD and dementia by promoting entrainment of their circadian rhythms. Using new
technologies, we propose to implement and test the efficacy of a practical but scientifically sophisticated day-
night lighting system (TLI) designed to deliver a robust light-dark pattern and improve sleep quality, reduce
fatigue, and improve mood in persons with PD and PD and dementia. Based on our preliminary studies
showing a positive impact of a TLI on sleep, mood, and behavior in ADRD, we propose to first
characterize sleep disturbances in 50 subjects from three genotype groups (LRRK2 mutation PD/PD
dementia, GBA mutation PD/PD and dementia and idiopathic [no LRRK2 or GBA mutation] PD/PD and
dementia) using actigraphy and sleep. Second, we will extend this work and investigate in a single arm,
within-subjects study the impact of short-term (4 weeks) exposures to a tailored lighting intervention
(TLI) on sleep (actigraphy and questionnaires), fatigue, urinary melatonin, and cognition in a subset. We
hypothesize that compared to baseline, TLI will improve objective and subjective sleep and increase amplitude
of nocturnal melatonin and clock gene expression, suggesting better circadian alignment, and 2) better circadian
alignment will lead to reduced fatigue, as assessed by the FACIT-F Scale, 7,8 reduce daytime sleepiness, as
measured by the ESS, and reduce symptoms of depression, anxiety and apathy, as measured by the Hamilton
depression Rating Scale, 9 Hamilton Anxiety Rating Scale, 10 and Apathy Scale. 11 In an exploratory aim, we
will correlate data from Supplement Aims 1 and 2 with the genomic and expression data from the parent grant
to look at the relationship between genomic and circadian gene expression changes, with particular focus on the
major pathways of neurodegeneration, immune, and lysosomal dysfunction. Taken together, these aims will
enable better understanding of how non-motor alterations affect the lives of people with PD and PD and dementia
and will allow us to perform simple, yet ef...

## Key facts

- **NIH application ID:** 10402022
- **Project number:** 3U01NS107016-03S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Laurie J. Ozelius
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $352,792
- **Award type:** 3
- **Project period:** 2021-09-29 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402022

## Citation

> US National Institutes of Health, RePORTER application 10402022, Dissecting Oligogenic Biomarkers in Ashkenazi Jews with Parkinson Disease (3U01NS107016-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10402022. Licensed CC0.

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