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

NCT05419453 | Recruiting

• 1 other identifier: SC3NS124906
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease

Keywords

Parkinson Disease; Cognition

Outcome Measures

Primary Outcomes (1)

• Cognitive Impairment

  Cognitive functioning as measured by a composite measure (average) of all neuropsychological tests

  4 hours

Study Arms (1)

Parkinson's

Those with Parkinson's Disease

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

primary care clinic, community sample

You may qualify if:

• Parkinson's Disease

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

California State University San Bernardino

San Bernardino, California, 92407, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Whole blood, fecal matter

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Central Study Contacts

Kenya Luna, B.A.

CONTACT

9094543135; gutbrainstudy1@gmail.com

Alejandra Pawlak

CONTACT

9094543135; gutbrainstudy1@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Psychologist

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: June 15, 2022
• Study Start: April 30, 2021
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

US (1)