# Enhancing Cognitive Resilience In Parkinson's Disease: Role Of Antiaging Protein Klotho

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $190,504

## Abstract

PROJECT SUMMARY
This is an application for a Mentored Patient-Oriented Research Career Development Award (K23) by Dr.
Nijee Luthra, a neurologist specializing in movement disorders. As the number of people with Parkinson’s
disease (PD) is expected to grow to pandemic proportions, cognitive deterioration associated with PD will
prevail in a majority of this population. The integrated career development and research plan proposed for this
K23 award is motivated by an increasing awareness of the urgent need to identify pathways that target
cognitive impairment in PD. Exercise has potent anti-aging effects and can influence cognitive outcomes in PD
but its underlying mechanisms remain unclear. Identifying biomarkers that respond to exercise, and how they
associate with cognition and underlying disease pathology may elucidate key mechanisms for countering
cognitive decline. This proposal focuses on longevity hormone klotho as a biomarker that may mediate
exercise-induced benefits and contribute to cognitive resilience. Klotho has been shown to enhance cognition,
synaptic plasticity, and brain volumes in mouse models of aging and neurodegeneration. Dr. Luthra and her
team have also recently shown that klotho associates with better cognitive function in PD patients. While klotho
levels decrease with aging and in PD, physical exercise robustly increases klotho levels in healthy adults.
Whether exercise increases klotho in PD and protects against cognitive decline is not yet known. To this end,
the aims of this research proposal are: 1) knowing its positive link with cognition, to now investigate whether
klotho modifies underlying markers of PD pathology, and 2) in parallel, design a pilot study to determine if
klotho increases in response to exercise in PD and correlates with improved cognitive abilities. Answers to
these questions would highlight the potential of klotho as an exercise-related biomarker and as a new pathway
for targeting cognitive dysfunction.
 The research plan is complemented by didactic and practical training in design and conduct of clinical
trials, advanced biostatistical methods, and analysis and interpretation of multimodal biomarkers and cognitive
assessments. To accomplish the goals of this research and training, the candidate has assembled a mentoring
team with decades of experience in clinical trials and exercise interventions, along with expertise in biomarkers
and cognitive impairment in PD. Completion of this research plan and training objectives will allow the
candidate to advance her career in becoming an independent clinical investigator focused on investigating
strategies such as exercise and multiple related biomarkers that mediate cognitive resilience in PD.

## Key facts

- **NIH application ID:** 10692781
- **Project number:** 5K23NS123506-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nijee Luthra
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $190,504
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10692781

## Citation

> US National Institutes of Health, RePORTER application 10692781, Enhancing Cognitive Resilience In Parkinson's Disease: Role Of Antiaging Protein Klotho (5K23NS123506-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10692781. Licensed CC0.

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