Microbiome Composition and Function Contributes to Cognitive Impairment and Neuroinflammation in Parkinson's Disease

Cognitive impairment is a common non-motor symptom among individuals living with Parkinson's disease (PD). Traditionally, cognitive impairment is thought to reflect disruptions in dopaminergic frontal-striatal systems. However, the current conceptualization does not thoroughly explain the heterogeneous profiles or trajectories of cognitive impairment in PD; suggesting that alternative mechanisms may contribute to cognitive impairments. Identification of alternative mechanisms of cognitive impairment may lead to better prognostic prediction and yield novel treatment targets. The gut is implicated as a site of early pathology in PD. Early signs of PD pathology (alpha synuclein and Lewy body aggregates) are detected in the gastrointestinal tract years before motor symptoms manifest. Recent studies provide evidence that individuals with PD have an altered gut-bacterial composition (termed dysbiosis) relative to controls. To date, dysbiosis is linked to more severe motor symptoms and certain non-motor symptoms (constipation, REM behavioral sleep disorder) in PD, but the relationship between dysbiosis and cognitive impairment remains unknown. Animal studies support the hypothesis that microbiota composition play a direct role in cognitive impairment. Germ free (GF) mice demonstrate deficits in cognition. Specifically, findings suggest that a disrupted gut- microbial environment in conjunction with elevated stress hormones may create an imbalance of pro- inflammatory vs. anti-inflammatory cytokines that induces potentially reversible cognitive impairments. In human studies among individuals with PD, neuroinflammatory markers are associated with cognitive impairment. However, the relationship between dysbiosis, neural inflammation and cognitive functioning remains unknown. This model has incredible clinical implications, as microbiota dysbiosis may represent a reversible risk factor for cognitive impairment. The proposed study will examine the hypothesis that dysbiosis contributes to increased neuroinflammation and cognitive impairment. Microbiota composition/function, neuroinflammatory markers and cognitive functioning will be examined in 100 participants with PD. Analyses of microbiota composition/function will examine abundance of amplicon sequence variants (ASVs; 16s), bacterial species/strains (metagenomics), microbial genes, and functional pathways. The investigators hypothesize that microbiota composition/function will be associated with inflammatory markers (e.g. interleukin-6, tumor necrosis factor-alpha, c-reactive protein) and cognitive impairment.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease

Detailed Description

Removed personal pronouns

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Kenya Luna, B.A.; Phone Number: 9094543135; Email: gutbrainstudy1@gmail.com
• Study Contact Backup: Name: Alejandra Pawlak; Phone Number: 9094543135; Email: gutbrainstudy1@gmail.com

Study Locations

• United States
  • California
    • San Bernardino, California, United States, 92407
      • Recruiting
      • California State University San Bernardino
      • Contact: Jacob Jones, PhD; Phone Number: 909-537-5590; Email: jacob.jones@csusb.edu
      • Contact: Kenya Luna; Phone Number: 9094543135

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

primary care clinic, community sample

Description

Inclusion Criteria:

• Parkinson's Disease

Exclusion Criteria:

• Use of antibiotics or immunosuppressant medications within the last 3 months, history of psychiatric hospitalizations, stroke, epilepsy, head injury resulting in a loss of consciousness for more than 30 minutes, Alzheimer's disease or other significant brain injury or neurologic event, history of inflammatory gastrointestinal diseases such as Crohn's, Celiac's disease or irritable bowel syndrome

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Parkinson's; Those with Parkinson's Disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Impairment	Cognitive functioning as measured by a composite measure (average) of all neuropsychological tests	4 hours

Collaborators and Investigators

• Sponsor: California State University, San Bernardino
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 10, 2022
• First Posted (Actual): June 15, 2022

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Cognition; Parkinson Disease
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Inflammation; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Parkinson Disease; Cognitive Dysfunction; Neuroinflammatory Diseases
• Other Study ID Numbers: SC3NS124906 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No