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Dementia With Lewy Bodies - Infinitome

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

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT04773041
Enrollment
91
Registered
2021-02-26
Start date
2021-04-27
Completion date
2023-06-19
Last updated
2024-11-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dementia With Lewy Bodies

Brief summary

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.

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

Interventions

PROCEDUREInfinitome

All patients will have rs-FMRI images analyzed with the Infinitome cloud-based software processing program.

Sponsors

HealthPartners Institute
Lead SponsorOTHER

Study design

Observational model
COHORT
Time perspective
CROSS_SECTIONAL

Eligibility

Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frameDescription
Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.BaselineIdentify 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.

Secondary

MeasureTime frameDescription
Correlation of Clinical Measures and Functional Connectivity ScoresBaselineClinical 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: 1. Caudate R/Substantia Nigra R and Clock Drawing Test 2. Caudate R/Substantia Nigra R and ADAS Number Cancellation 3. PH R/FST R and ADAS Construction Praxis 4. PH R/FST R and Clock Drawing Test

Countries

United States

Participant flow

Participants by arm

ArmCount
Patients With DLB
Patients diagnosed with DLB enrolled from the HealthPartners Neuroscience Center. Infinitome: All patients will have rs-FMRI images analyzed with the Infinitome cloud-based software processing program.
18
Patients With Alzheimer's Disease (AD)
Patients diagnosed with AD age and MMSE-matched, selected from the ADNI database. Infinitome: All patients will have rs-FMRI images analyzed with the Infinitome cloud-based software processing program.
36
Patients With Normal Cognition (CN)
Patients diagnosed with normal cognition age-matched, selected from the ADNI database. Infinitome: All patients will have rs-FMRI images analyzed with the Infinitome cloud-based software processing program.
36
Total90

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyUnable to data match100

Baseline characteristics

CharacteristicPatients With DLBTotalPatients With Normal Cognition (CN)Patients With Alzheimer's Disease (AD)
Age, Continuous75 years
STANDARD_DEVIATION 6.6
75 years
STANDARD_DEVIATION 6.7
74 years
STANDARD_DEVIATION 6.3
76 years
STANDARD_DEVIATION 7.3
Education years17 years
STANDARD_DEVIATION 4
16 years
STANDARD_DEVIATION 4.1
16 years
STANDARD_DEVIATION 0.99
16 years
STANDARD_DEVIATION 3.6
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants5 Participants4 Participants1 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
18 Participants85 Participants32 Participants35 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Mini-Mental State Examination (MMSE)23 units on a scale
STANDARD_DEVIATION 2.2
26 units on a scale
STANDARD_DEVIATION 2.5
29 units on a scale
STANDARD_DEVIATION 2.6
23 units on a scale
STANDARD_DEVIATION 2.6
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants8 Participants6 Participants2 Participants
Race (NIH/OMB)
More than one race
0 Participants3 Participants1 Participants2 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
18 Participants79 Participants29 Participants32 Participants
Sex: Female, Male
Female
15 Participants41 Participants11 Participants15 Participants
Sex: Female, Male
Male
3 Participants49 Participants25 Participants21 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 180 / 00 / 0
other
Total, other adverse events
0 / 180 / 00 / 0
serious
Total, serious adverse events
0 / 180 / 00 / 0

Outcome results

Primary

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.

Time frame: Baseline

ArmMeasureGroupValue (MEAN)Dispersion
Patients With DLBFunctional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_right and FST_left0.164 connectivity scoreStandard Error 0.008
Patients With DLBFunctional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_right and FST_right0.340 connectivity scoreStandard Error 0.01
Patients With DLBFunctional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_all and FST_left0.307 connectivity scoreStandard Error 0.009
Patients With DLBFunctional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_all and FST_right0.359 connectivity scoreStandard Error 0.011
Patients With DLBFunctional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_left and Caud_left0.124 connectivity scoreStandard Error 0.012
Patients With DLBFunctional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_left and Caud_right0.134 connectivity scoreStandard Error 0.006
Patients With DLBFunctional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_right and Caud_left0.088 connectivity scoreStandard Error 0.012
Patients With DLBFunctional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_right and Caud_right0.063 connectivity scoreStandard Error 0.01
Patients With Alzheimer's Disease (AD)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_all and FST_left0.456 connectivity scoreStandard Error 0.006
Patients With Alzheimer's Disease (AD)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_right and Caud_left0.127 connectivity scoreStandard Error 0.003
Patients With Alzheimer's Disease (AD)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_all and FST_right0.530 connectivity scoreStandard Error 0.005
Patients With Alzheimer's Disease (AD)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_left and Caud_left0.122 connectivity scoreStandard Error 0.005
Patients With Alzheimer's Disease (AD)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_left and Caud_right0.112 connectivity scoreStandard Error 0.005
Patients With Alzheimer's Disease (AD)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_right and FST_left0.374 connectivity scoreStandard Error 0.006
Patients With Alzheimer's Disease (AD)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_right and FST_right0.517 connectivity scoreStandard Error 0.006
Patients With Alzheimer's Disease (AD)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_right and Caud_right0.123 connectivity scoreStandard Error 0.004
Patients With Normal Cognition (CN)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_all and FST_left0.433 connectivity scoreStandard Error 0.006
Patients With Normal Cognition (CN)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_right and FST_right0.442 connectivity scoreStandard Error 0.005
Patients With Normal Cognition (CN)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_right and FST_left0.344 connectivity scoreStandard Error 0.006
Patients With Normal Cognition (CN)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.PH_all and FST_right0.493 connectivity scoreStandard Error 0.005
Patients With Normal Cognition (CN)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_right and Caud_left0.130 connectivity scoreStandard Error 0.004
Patients With Normal Cognition (CN)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_left and Caud_right0.144 connectivity scoreStandard Error 0.005
Patients With Normal Cognition (CN)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_left and Caud_left0.132 connectivity scoreStandard Error 0.004
Patients With Normal Cognition (CN)Functional Connectivity Scores Between Pairs of Large Scale Brain Networks.SubNigComp_right and Caud_right0.123 connectivity scoreStandard Error 0.004
Secondary

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: 1. Caudate R/Substantia Nigra R and Clock Drawing Test 2. Caudate R/Substantia Nigra R and ADAS Number Cancellation 3. PH R/FST R and ADAS Construction Praxis 4. PH R/FST R and Clock Drawing Test

Time frame: Baseline

ArmMeasureGroupValue (NUMBER)
Patients With DLBCorrelation of Clinical Measures and Functional Connectivity ScoresCaudate R/Substantia Nigra R and Clock Drawing Test-0.50 correlation coefficient
Patients With DLBCorrelation of Clinical Measures and Functional Connectivity ScoresCaudate R/Substantia Nigra R and ADAS Number Cancellation-0.65 correlation coefficient
Patients With DLBCorrelation of Clinical Measures and Functional Connectivity ScoresPH R/FST R and ADAS Construction Praxis-0.31 correlation coefficient
Patients With DLBCorrelation of Clinical Measures and Functional Connectivity ScoresPH R/FST R and Clock Drawing Test-0.17 correlation coefficient
Patients With Alzheimer's Disease (AD)Correlation of Clinical Measures and Functional Connectivity ScoresPH R/FST R and Clock Drawing Test0.18 correlation coefficient
Patients With Alzheimer's Disease (AD)Correlation of Clinical Measures and Functional Connectivity ScoresCaudate R/Substantia Nigra R and Clock Drawing Test-0.23 correlation coefficient
Patients With Alzheimer's Disease (AD)Correlation of Clinical Measures and Functional Connectivity ScoresPH R/FST R and ADAS Construction Praxis-0.05 correlation coefficient
Patients With Alzheimer's Disease (AD)Correlation of Clinical Measures and Functional Connectivity ScoresCaudate R/Substantia Nigra R and ADAS Number Cancellation-0.01 correlation coefficient
Patients With Normal Cognition (CN)Correlation of Clinical Measures and Functional Connectivity ScoresPH R/FST R and Clock Drawing Test-0.03 correlation coefficient
Patients With Normal Cognition (CN)Correlation of Clinical Measures and Functional Connectivity ScoresCaudate R/Substantia Nigra R and ADAS Number Cancellation-0.06 correlation coefficient
Patients With Normal Cognition (CN)Correlation of Clinical Measures and Functional Connectivity ScoresPH R/FST R and ADAS Construction Praxis-0.02 correlation coefficient
Patients With Normal Cognition (CN)Correlation of Clinical Measures and Functional Connectivity ScoresCaudate R/Substantia Nigra R and Clock Drawing Test0.26 correlation coefficient

Source: ClinicalTrials.gov · Data processed: Feb 6, 2026