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| ID | Type | Description | Link |
|---|---|---|---|
| R21AG069387 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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Fluctuations in alertness are very common in persons with Lewy body dementias and are a major source of disability. Changes in a chemical messenger molecule called acetylcholine within certain brain regions may play a role in these fluctuations. We propose to test this hypothesis and also determine whether a non-invasive way of stimulating affected brain regions may be of relevance for future management of these fluctuations.
The central premise of the research study was that cholinergic system changes in specific neural network regions underlie cognitive fluctuations in patients with LBD. The cingulo-opercular task control (COTC) neural network is believed to play a role in maintenance of alertness but this remains uncertain in LDB. This critical knowledge gap formed the basis of the study's first aim. The study proposed to use transcranial direct current stimulation (tDCS) to "excite" critical cholinergic denervation components of the COTC as an adjunct to cholinergic pharmacotherapy in a target engagement study. tDCS is an emerging non-invasive neurostimulation technology that may improve a range of neurological symptoms, including cognition. The study evaluated whether target engagement by tDCS excitation of cholinergic denervated COTC hubs may affect cognitive fluctuations in LBD subjects.
While the cingulo-opercular network was expected to be the primary site of cholinergic denervation based on preliminary evidence, and thus the focus of the stimulation intervention, the typical pattern of cholinergic denervation in our sample occurred at a temporal lobe region that is classified as a node of the ventral attention network in the Gordon atlas. Additional results from examining different networks have been added to reflect the unanticipated relocation of stimulation location.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental: HD-tDCS | Experimental | Maximum 4 milliAmp (mA) per channel of HD-tDCS treatment for 20 minutes, for 10 sessions. Total mA dose determined by individualized computational models. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HD-tDCS | Device | Participants will receive HD-tDCS at up to 4 mA per channel for 20 minutes for 10 sessions. Dose determined through individualized computational models. |
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| Measure | Description | Time Frame |
|---|---|---|
| Dementia Cognitive Fluctuations Scale | Score on a 4-item subscale of the 17-item Dementia Cognitive Fluctuation Scale (DCFS), developed to address limitations in prior scales and has good test-retest and inter-rater reliability; this subscale highly discriminates between dementia with Lewy bodies (DLB) and other dementia groups. The DCFS is a subjective report of cognitive fluctuation, the spontaneous change in cognitive ability which is a core diagnostic feature of DLB. Total subscale scores range from 4 to 20, with higher scores indicating greater cognitive fluctuations. A decrease in score between Baseline and Post-Testing indicates an improvement in cognitive fluctuation. | Baseline and Post-Testing (3-4 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Resting State fMRI | Functional connectivity measures whether activity in different brain regions show similar patterns of change over time. Graph theory metrics of resting-state fMRI can characterize functional connectivity among nodes (regions) of a brain network, and well as between nodes of different brain networks. Network segregation is the difference of within-network and between-network connectivity as a proportion of within-network connectivity, such that higher numbers reflect more segregation. Given that network segregation typically decreases with normal and pathological aging, higher network segregation is generally considered cognitively beneficial. Network segregation was examined for the ventral attention network (the actual focus of stimulation based on observed cholinergic denervation) and the original cingulo-opercular network, which was predicted at the time of grant proposal (but not supported by the observed cholinergic denervation). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Benjamin Hampstead, PhD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 4250 Plymouth Road (University of Michigan) | Ann Arbor | Michigan | 48105 | United States |
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Participants enrolled are those who consented to be in the study. They then underwent a screening process. Three participants did not continue after the screening process.
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| ID | Title | Description |
|---|---|---|
| FG000 | Experimental: HD-tDCS | HD-tDCS treatment for 20 minutes, repeated across 10 sessions (3-5 sessions/week). The pattern and dose of stimulation was individualized for each participant to generate electric field in regions of cholinergic denervation, as determined by reduced FEOBV binding. A maximum of 4 milliamps (mA) of current was delivered at each anode. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Baseline is considered to be the participants who were deemed eligible to receive the study intervention (tDCS)
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| ID | Title | Description |
|---|---|---|
| BG000 | Experimental: HD-tDCS | Maximum 4 milliAmp (mA) per channel of HD-tDCS treatment for 20 minutes, for 10 sessions. Total mA dose determined by individualized computational models. HD-tDCS: Participants will receive HD-tDCS at up to 4 mA per channel for 20 minutes for 10 sessions. Dose determined through individualized computational models. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age is reported on the number of participants who were eligible to receive study intervention |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dementia Cognitive Fluctuations Scale | Score on a 4-item subscale of the 17-item Dementia Cognitive Fluctuation Scale (DCFS), developed to address limitations in prior scales and has good test-retest and inter-rater reliability; this subscale highly discriminates between dementia with Lewy bodies (DLB) and other dementia groups. The DCFS is a subjective report of cognitive fluctuation, the spontaneous change in cognitive ability which is a core diagnostic feature of DLB. Total subscale scores range from 4 to 20, with higher scores indicating greater cognitive fluctuations. A decrease in score between Baseline and Post-Testing indicates an improvement in cognitive fluctuation. | Data is reported for participants who completed both baseline and week 3/4 measures. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Post-Testing (3-4 weeks) |
|
4 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Experimental: HD-tDCS | Maximum 4 milliAmp (mA) per channel of HD-tDCS treatment for 20 minutes, for 10 sessions. Total mA dose determined by individualized computational models. HD-tDCS: Participants will receive HD-tDCS at up to 4 mA per channel for 20 minutes for 10 sessions. Dose determined through individualized computational models. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Progression of preexisting delusions related to Lewy Body Dementia disease progression | Nervous system disorders | Systematic Assessment | Changes of environment are known to be potential causes of worsening dementia symptoms. Participant was relocated to participate in the study. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Benjamin Hampstead | University of Michigan | 734-936-6185 | bhampste@med.umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 5, 2022 | Jul 22, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Sep 21, 2023 | Jul 22, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D020961 | Lewy Body Disease |
| C565078 | Lewy Body Variant of Alzheimer Disease |
| D003704 | Dementia |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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Eligible participants receive individualized intervention/stimulation based on their fMRI and PET imaging.
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Investigator, Outcomes Assessor, and Participant/Care Provider will all know the participant is receiving intervention/stimulation. There is no placebo condition.
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| Baseline and Post-Testing (3-4 weeks) |
| Stroop Color Word Interference Test - Cognitive Control Performance | Outcome Measure Description: Interference score in time to complete the Color Word Interference Test version of the Stroop task from the Delis-Kaplan Executive Function System. Participants 1) identify a series of colors, 2) read color words (e.g. blue) all written in black ink, and 3) name the ink color of color words printed in incongruous colored inks (e.g. for the word "green" written in red ink, the correct response is "red"). Tasks are performed as quickly as possible. Time to complete each task is recorded. Interference score is calculated as the time to complete the color-word (interference) test (CWT), less the average of the time to complete the color task (CT) and word-reading task (WT): CWT - ((CT + WT)/2). The score has a theoretical valid range of 0 - 300; a lower score suggests better cognitive control. A negative change (decrease) in score between Baseline and Post-Testing indicates improvement in cognitive control performance. | Baseline, 3-4 weeks |
| Objective Measures of Working Memory (N-back Test) | The n-back test is a working memory task where a participant identify a stimulus that matches the stimulus experienced "n" steps back. Participants performed a 2-back test, in which they were asked to remember and press a button when presented with a stimulus that appeared two steps before the current one (e.g. square, circle, square). The number of correct and incorrect identifications are normalized (z-score). Total score is the z-score of correct button presses minus the z-score of incorrect button presses. Possible scores range from -4.85 to 4.85. A higher score (d') reflects better discrimination between target and non-target stimuli, and therefore better working memory performance. A positive change (increase) in 2-back score (d') between Baseline and Post-Testing indicates an improvement in working memory performance. | Baseline, 3-4 weeks |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Sex is reported on the number of participants who were eligible to receive study intervention | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Ethnicity is reported on the number of participants who were eligible to receive study intervention | Count of Participants | Participants |
|
| Race (NIH/OMB) | Race is reported on the number of participants who were eligible to receive study intervention | Count of Participants | Participants |
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| Region of Enrollment | Region of enrollment is reported on the number of participants who were eligible to receive study intervention | Number | participants |
|
HD-tDCS treatment for 20 minutes, repeated across 10 sessions (3-5 sessions/week). The pattern and dose of stimulation was individualized for each participant to generate electric field in regions of cholinergic denervation, as determined by reduced FEOBV binding. A maximum of 4 milliamps (mA) of current was delivered at each anode.
|
|
|
| Secondary | Resting State fMRI | Functional connectivity measures whether activity in different brain regions show similar patterns of change over time. Graph theory metrics of resting-state fMRI can characterize functional connectivity among nodes (regions) of a brain network, and well as between nodes of different brain networks. Network segregation is the difference of within-network and between-network connectivity as a proportion of within-network connectivity, such that higher numbers reflect more segregation. Given that network segregation typically decreases with normal and pathological aging, higher network segregation is generally considered cognitively beneficial. Network segregation was examined for the ventral attention network (the actual focus of stimulation based on observed cholinergic denervation) and the original cingulo-opercular network, which was predicted at the time of grant proposal (but not supported by the observed cholinergic denervation). | Ten participants completed resting-State fMRI at Baseline and Post-Testing. Two participants were not eligible for MRI. | Posted | Mean | Standard Deviation | ratio of network segregation | Baseline and Post-Testing (3-4 weeks) |
|
|
|
|
| Secondary | Stroop Color Word Interference Test - Cognitive Control Performance | Outcome Measure Description: Interference score in time to complete the Color Word Interference Test version of the Stroop task from the Delis-Kaplan Executive Function System. Participants 1) identify a series of colors, 2) read color words (e.g. blue) all written in black ink, and 3) name the ink color of color words printed in incongruous colored inks (e.g. for the word "green" written in red ink, the correct response is "red"). Tasks are performed as quickly as possible. Time to complete each task is recorded. Interference score is calculated as the time to complete the color-word (interference) test (CWT), less the average of the time to complete the color task (CT) and word-reading task (WT): CWT - ((CT + WT)/2). The score has a theoretical valid range of 0 - 300; a lower score suggests better cognitive control. A negative change (decrease) in score between Baseline and Post-Testing indicates improvement in cognitive control performance. | 8 participants completed the Color Word Interference Test at Baseline and Post-Testing. 4 participants did not complete the test. Negative scores are technically possible, but given the known robust and reliable cognitive effort required in color word interference, a negative interference score would call into question the validity of the administration and be excluded. No participants' scores were negative and therefore none were excluded for this reason.. | Posted | Mean | Standard Deviation | calculated score | Baseline, 3-4 weeks |
|
|
|
|
| Secondary | Objective Measures of Working Memory (N-back Test) | The n-back test is a working memory task where a participant identify a stimulus that matches the stimulus experienced "n" steps back. Participants performed a 2-back test, in which they were asked to remember and press a button when presented with a stimulus that appeared two steps before the current one (e.g. square, circle, square). The number of correct and incorrect identifications are normalized (z-score). Total score is the z-score of correct button presses minus the z-score of incorrect button presses. Possible scores range from -4.85 to 4.85. A higher score (d') reflects better discrimination between target and non-target stimuli, and therefore better working memory performance. A positive change (increase) in 2-back score (d') between Baseline and Post-Testing indicates an improvement in working memory performance. | 12 participants completed the n-back working memory task at both Baseline and Post-Testing, however one participant used an incorrect button to make responses at Baseline, so these responses were not recorded, leaving 11 participants with recorded data at Baseline and Post-Testing. Of these 11, 5 performed below chance (<50% hit rate) on the control task at one or both timepoints and were excluded from analysis. | Posted | Mean | Standard Deviation | calculated score | Baseline, 3-4 weeks |
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| 0 |
| 13 |
| 0 |
| 13 |
| 13 |
| 13 |
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| Itching | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Worsening of dizziness upon standing post treatment | General disorders | Systematic Assessment |
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| Burning sensation | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Tingling | General disorders | Systematic Assessment |
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| Scalp Pain | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Trouble Concentrating | General disorders | Systematic Assessment |
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| Sleepiness | General disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| Acute Mood Change | General disorders | Systematic Assessment |
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| Neck Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Skin Redness | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| 3/4 weeks - Cingulo-opercular network |
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p value for the Cingulo Opercular Network (network segregation) |
| Superiority |