Dementia With Lewy Bodies
Conditions
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
All patients will have rs-FMRI images analyzed with the Infinitome cloud-based software processing program.
Sponsors
Study design
Eligibility
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
| Measure | Time frame | Description |
|---|---|---|
| Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | Baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Clinical Measures and Functional Connectivity Scores | Baseline | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Unable to data match | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Patients With DLB | Total | Patients With Normal Cognition (CN) | Patients With Alzheimer's Disease (AD) |
|---|---|---|---|---|
| Age, Continuous | 75 years STANDARD_DEVIATION 6.6 | 75 years STANDARD_DEVIATION 6.7 | 74 years STANDARD_DEVIATION 6.3 | 76 years STANDARD_DEVIATION 7.3 |
| Education years | 17 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 Participants | 5 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 85 Participants | 32 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 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 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 8 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 79 Participants | 29 Participants | 32 Participants |
| Sex: Female, Male Female | 15 Participants | 41 Participants | 11 Participants | 15 Participants |
| Sex: Female, Male Male | 3 Participants | 49 Participants | 25 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 18 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 18 | 0 / 0 | 0 / 0 |
Outcome results
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients With DLB | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_right and FST_left | 0.164 connectivity score | Standard Error 0.008 |
| Patients With DLB | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_right and FST_right | 0.340 connectivity score | Standard Error 0.01 |
| Patients With DLB | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_all and FST_left | 0.307 connectivity score | Standard Error 0.009 |
| Patients With DLB | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_all and FST_right | 0.359 connectivity score | Standard Error 0.011 |
| Patients With DLB | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_left and Caud_left | 0.124 connectivity score | Standard Error 0.012 |
| Patients With DLB | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_left and Caud_right | 0.134 connectivity score | Standard Error 0.006 |
| Patients With DLB | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_right and Caud_left | 0.088 connectivity score | Standard Error 0.012 |
| Patients With DLB | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_right and Caud_right | 0.063 connectivity score | Standard Error 0.01 |
| Patients With Alzheimer's Disease (AD) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_all and FST_left | 0.456 connectivity score | Standard Error 0.006 |
| Patients With Alzheimer's Disease (AD) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_right and Caud_left | 0.127 connectivity score | Standard Error 0.003 |
| Patients With Alzheimer's Disease (AD) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_all and FST_right | 0.530 connectivity score | Standard Error 0.005 |
| Patients With Alzheimer's Disease (AD) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_left and Caud_left | 0.122 connectivity score | Standard Error 0.005 |
| Patients With Alzheimer's Disease (AD) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_left and Caud_right | 0.112 connectivity score | Standard Error 0.005 |
| Patients With Alzheimer's Disease (AD) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_right and FST_left | 0.374 connectivity score | Standard Error 0.006 |
| Patients With Alzheimer's Disease (AD) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_right and FST_right | 0.517 connectivity score | Standard Error 0.006 |
| Patients With Alzheimer's Disease (AD) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_right and Caud_right | 0.123 connectivity score | Standard Error 0.004 |
| Patients With Normal Cognition (CN) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_all and FST_left | 0.433 connectivity score | Standard Error 0.006 |
| Patients With Normal Cognition (CN) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_right and FST_right | 0.442 connectivity score | Standard Error 0.005 |
| Patients With Normal Cognition (CN) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_right and FST_left | 0.344 connectivity score | Standard Error 0.006 |
| Patients With Normal Cognition (CN) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | PH_all and FST_right | 0.493 connectivity score | Standard Error 0.005 |
| Patients With Normal Cognition (CN) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_right and Caud_left | 0.130 connectivity score | Standard Error 0.004 |
| Patients With Normal Cognition (CN) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_left and Caud_right | 0.144 connectivity score | Standard Error 0.005 |
| Patients With Normal Cognition (CN) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_left and Caud_left | 0.132 connectivity score | Standard Error 0.004 |
| Patients With Normal Cognition (CN) | Functional Connectivity Scores Between Pairs of Large Scale Brain Networks. | SubNigComp_right and Caud_right | 0.123 connectivity score | Standard Error 0.004 |
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patients With DLB | Correlation of Clinical Measures and Functional Connectivity Scores | Caudate R/Substantia Nigra R and Clock Drawing Test | -0.50 correlation coefficient |
| Patients With DLB | Correlation of Clinical Measures and Functional Connectivity Scores | Caudate R/Substantia Nigra R and ADAS Number Cancellation | -0.65 correlation coefficient |
| Patients With DLB | Correlation of Clinical Measures and Functional Connectivity Scores | PH R/FST R and ADAS Construction Praxis | -0.31 correlation coefficient |
| Patients With DLB | Correlation of Clinical Measures and Functional Connectivity Scores | PH R/FST R and Clock Drawing Test | -0.17 correlation coefficient |
| Patients With Alzheimer's Disease (AD) | Correlation of Clinical Measures and Functional Connectivity Scores | PH R/FST R and Clock Drawing Test | 0.18 correlation coefficient |
| Patients With Alzheimer's Disease (AD) | Correlation of Clinical Measures and Functional Connectivity Scores | Caudate 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 Scores | PH R/FST R and ADAS Construction Praxis | -0.05 correlation coefficient |
| Patients With Alzheimer's Disease (AD) | Correlation of Clinical Measures and Functional Connectivity Scores | Caudate R/Substantia Nigra R and ADAS Number Cancellation | -0.01 correlation coefficient |
| Patients With Normal Cognition (CN) | Correlation of Clinical Measures and Functional Connectivity Scores | PH R/FST R and Clock Drawing Test | -0.03 correlation coefficient |
| Patients With Normal Cognition (CN) | Correlation of Clinical Measures and Functional Connectivity Scores | Caudate R/Substantia Nigra R and ADAS Number Cancellation | -0.06 correlation coefficient |
| Patients With Normal Cognition (CN) | Correlation of Clinical Measures and Functional Connectivity Scores | PH R/FST R and ADAS Construction Praxis | -0.02 correlation coefficient |
| Patients With Normal Cognition (CN) | Correlation of Clinical Measures and Functional Connectivity Scores | Caudate R/Substantia Nigra R and Clock Drawing Test | 0.26 correlation coefficient |