Dementia With Lewy Bodies - Infinitome

Connectomic Analysis in Dementia With Lewy Bodies: A Potential Diagnostic Imaging Biomarker

Dementia with Lewy bodies (DLB) is the second most common cause of dementia and is associated with parkinsonism, hallucinations, and cognitive fluctuations. Diagnosis is often either missed or delayed due to physician lack of familiarity with characteristic features, the inability of structural MRI to detect a pathological signature for this condition, and the lack of healthcare provider access to "indicative biomarkers" that are either unavailable at community clinics or costly due to lack of insurance coverage. The role of resting state function MRI (rs-fMRI) as a diagnostic biomarker has been underexplored in this disease. We propose using a novel cloud-based automated imaging software processing program that identifies abnormal brain networks or connectomes using resting state functional MRI (rs-fMRI) and data from the Human Connectome Project (HCP). Furthermore, the imaging protocol to capture this data is relatively short (15 minutes) and can be performed at most imaging centers, lending potential clinical applicability to this study. We intend to study dysfunctional large scale brain networks (LSBNs) in DLB by comparing rs-fMRI imaging data in this population with cognitively normal (CN) and mild Alzheimer's disease (AD) subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI)-2/3 database.

Study Overview

• Status: Completed
• Conditions: Dementia With Lewy Bodies
• Intervention / Treatment: Procedure: Infinitome

Detailed Description

Omniscient, a for-profit, Sydney, Australia-based company, created the cloud-based software Infinitome, a program that utilizes data from the Human Connectome Project (HCP) together with machine learning to analyze diffusion tensor and resting-state fMRI imaging data from remote sites. The foundation for this imaging tool is based upon the HCP atlas, which has also informed prior publications from our group, including the Connectomic Atlas of the Human Cerebrum (Baker, Burks, Briggs, Conner, et al. 2018). The Infinitome program creates a subject specific version of the Human Connectome Project Multimodal Parcellation (HCP-MMP1) atlas using diffusion tractography. Analytics are performed on both diffusion tensor imaging and rs-fMRI. Outlier detection using a tangent space connectivity matrix is performed by comparing results with a subset of 300 normal HCP subject fMRI samples to determine the range of normal correlations for each regions of interest in a large scale brain network which include:

1. Locus coeruleus vs. Nucleus basalis of Meynert
2. Locus coeruelus vs. Intralaminar nucleus of the thalamus
3. Nucleus basalis of Meynert vs. Intralaminar nuclei of the thalamus
4. FST in the vs. Area PH in the lateral occipital lobe
5. Substantia nigra vs. Caudate nucleus Clinical Measures will be correlated with functional connectivity scores to identify relationship between clinical symptoms and large scale brain networks in DLB

• Study Type: Observational
• Enrollment (Actual): 91

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55130
      • HealthPartners Neuroscience Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

HealthPartners Neurology Clinic in Saint Paul, MN undergoing care for DLB and subjects included in the ADNI database.

Description

Inclusion Criteria:

• Age 40-90 years
• Established DLB diagnosis
• Mini mental status exam (MMSE) >15

Exclusion Criteria:

• Other forms of dementia including, but not limited to Alzheimer's dementia, frontotemporal dementia, vascular dementia, normal pressure hydrocephalus (NPH), etc,
• Inability to tolerate brain function magnetic resonance imaging (fMRI)
• Risk of brain fMRI due to implants or metal.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with DLB; Patients diagnosed with DLB enrolled from the HealthPartners Neuroscience Center.	Procedure: Infinitome; All patients will have rs-FMRI images analyzed with the Infinitome cloud-based software processing program.
Patients with Alzheimer's disease (AD); Patients diagnosed with AD age and sex-matched, selected from the ADNI database.	Procedure: Infinitome; All patients will have rs-FMRI images analyzed with the Infinitome cloud-based software processing program.
Patients with normal cognition (CN); Patients diagnosed with normal cognition age and sex-matched, selected from the ADNI database.	Procedure: Infinitome; All patients will have rs-FMRI images analyzed with the Infinitome cloud-based software processing program.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.	Identify functional connectivity scores between pairs of large scale brain networks as determined by connectomic analysis using rs-fMRI Infinitome software in order to compare functional connectivity scores between groups. Eight parcellation pairs were chosen as primary pairs of interest. For each parcellation pair - Range [-1,1]. Higher positive score indicates greater connectivity.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of Clinical Measures and Functional Connectivity Scores	Clinical Measures will be correlated with functional connectivity scores to identify relationship between clinical symptoms and large scale brain networks in DLB . Range [-1,1]. Higher score indicates greater connectivity. Correlation of: Caudate R/Substantia Nigra R and Clock Drawing Test; Caudate R/Substantia Nigra R and ADAS Number Cancellation; PH R/FST R and ADAS Construction Praxis; PH R/FST R and Clock Drawing Test	Baseline

Collaborators and Investigators

• Sponsor: HealthPartners Institute
• Investigators: Principal Investigator: Michael H Rosenbloom, MD, HealthPartners Neurology

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2021
• Primary Completion (Actual): February 8, 2023
• Study Completion (Actual): June 19, 2023

Study Registration Dates

• First Submitted: February 22, 2021
• First Submitted That Met QC Criteria: February 23, 2021
• First Posted (Actual): February 26, 2021

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Dementia; Lewy Body Disease
• Other Study ID Numbers: A21-037

Drug and device information, study documents

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