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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG055389-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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Alzheimer's disease (AD) is the most common cause of dementia in adults 65 years and older. AD leads to a complete loss of memory and independent function, and presently there is no cure. Many studies suggest that lithium treatment may delay dementia onset or slow its progression. However, more research is needed to understand the extent of its anti-dementia properties if it will be deployed broadly in the general population. This study will examine whether lithium has anti-dementia properties in older adults who have mild cognitive impairment and are at risk of becoming demented.
Alzheimer's disease (AD) is the most common cause of dementia in adults 65 years and older. Unchecked, the disease will reach epidemic proportions in the United States and worldwide by 2050, and presently, there is no intervention that has shown a clear effect on AD progression. Over the past several years, there has been increasing interest in re-purposing the use of lithium for diseases involving neurodegeneration. Lithium treatment has been associated with neurogenesis in the hippocampus, up-regulation of important neurotrophic factors such as B-cell lymphoma 2 (Bcl-2) and brain-derived neurotrophic factor (BDNF), and inhibition of glycogen synthase kinase 3 (GSK-3) isoforms α and β. In particular, GSK-3α interacts with gamma-secretase playing a critical role in the conversion of amyloid precursor protein (APP) to amyloid-beta (Aβ); lithium has been shown to reduce Aβ production and memory deficits in AD transgenic mouse models. GSK-3β phosphorylates tau, a critical step in the formation of neurofibrillary tangles, and lithium has been shown to reduce tau phosphorylation in vivo and in vitro. That lithium may alter the AD trajectory is supported by numerous observational reports showing delay of dementia onset in those treated with it. However, the results of the few human lithium trials conducted have been mixed. Additional research is needed to determine whether lithium has a role as an anti-dementia agent. In contrast to previous studies, we will implement an Randomized Controlled Trial (RCT) with a more integrative, comprehensive approach than done before involving state-of-the-art ultra-high field (7T) human Magnetic Resonance Imaging (MRI), neurocognitive assessment, and blood- and Cerebrospinal Fluid (CSF)- based biomarker measurement to investigate the role of lithium as an anti-dementia agent. The specific aim of this pilot-feasibility study is to examine the potential disease modifying properties of lithium in individuals with mild cognitive impairment (MCI) in delaying conversion to dementia. The study will enroll and randomly assign 80 individuals 60 years and older with MCI to take lithium, titrated to a maximally tolerated blood level (0.5 to 0.8 meq/L), or placebo for two years to assess lithium's effects on preserving cognition and delaying conversion to dementia. Participants will receive annual neurocognitive assessment, blood- and CSF-based biomarker measurement, and 7T MRI of structural brain volumes (e.g., hippocampal, total cortical gray). At baseline, all subjects who are able will undergo Positron Emission Tomography (PET) imaging for Aβ. The following hypotheses will be tested: H1: a) Participants randomized to take lithium for two years, compared to placebo, will better maintain cognitive function, primarily in memory, which b) will be associated with changes in biomarkers (e.g., GSK-3β, BDNF). H2: a) Participants randomized to take lithium, compared to placebo, will have larger hippocampal volumes and lower total gray matter thinning, which b) will be associated with changes in biomarkers and c) better cognitive function, primarily in memory. The exploratory aim examines whether lithium is related to additional markers of enhanced brain integrity (e.g., lower level of microbleeds, higher white matter integrity, better network connectivity, or decreased CSF phospho tau levels).
The following amendments were made with entering the results to correct mistakes in the original registration:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lithium carbonate | Experimental | Lithium carbonate will be initiated at 150 mg per day and increased based on blood levels until a steady blood level between 0.6 and 0.8 meq/L is achieved. Participants will continue at the dose achieved for 2 years with quarterly monitoring. |
|
| placebo | Placebo Comparator | Matching placebo will be initiated and increased based on pretend blood levels. Participants will take placebo for 2 years with quarterly monitoring. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lithium Carbonate | Drug | See lithium carbonate arm |
| |
| Measure | Description | Time Frame |
|---|---|---|
| California Verbal Learning Test II | California Verbal Learning Test II. Long-delay free recall. Scores range from 0 - 16; higher means better. | Year 1 and Year 2 |
| Brief Visuospatial Memory Test - Revised | Brief Visuospatial Memory Test - Revised. Delayed Recall. Scores range from 0 - 12; higher means better. | Year 1 and Year 2 |
| Preclinical Alzheimer Cognitive Composite Composed of Memory and Other Cognitive Tests | Cognitive testing measures with a composite of memory, executive function, processing speed, activities of daily living, and general cognition tests. Values are Z-scores. Higher values mean better cognition. A Z-score of 0 represents the population mean, while Z-scores of ±1 capture approximately 68% of the data around the mean and Z-scores of ±2 capture approximately 95% of the data in a normal distribution. | Year 1 and Year 2 |
| Glycogen Synthase Kinase-3 Beta (GSK-3β) Activity | Values of blood-based biomarkers | Year 1 and Year 2 |
| Brain-derived Neurotrophic Factor | Brain-Derived Neurotrophic Factor (BDNF) supports neuron survival and growth; reduced levels linked to neurodegeneration. Nucleic Acid-Linked Immuno-Sorbent Assay (NULISA) measures BDNF using nucleic acid-tagged antibody pairs recognizing different BDNF epitopes. Sequential capture/purification via polyA/biotin tails, then ligation and next-generation sequencing quantification achieves attomolar sensitivity alongside hundreds of other proteins. | Year 1 and Year 2 |
| Cerebral Cortical Gray Matter Volume |
| Measure | Description | Time Frame |
|---|---|---|
| Cerebrospinal Fluid Phospho Tau Level (CSF) | Cerebrospinal fluid phospho tau levels | Year 1 and Year 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Brain Integrity as Measured by Structural Imaging (7T MRI) | Exploratory analyses of additional measures of brain integrity, such as lower level of microbleeds, higher white matter integrity, or better network connectivity | Year 1 and Year 2 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ariel Gildengers, MD | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41770546 | Derived | Gildengers AG, Ibrahim TS, Anderson SJ, Emanuel JE, Santini T, Diaz JL, Lopresti BJ, Royse SK, Lopez OL, Zeng X, de Almeida B, Alkhateeb SK, Chu C, Karikari TK, Lee L, Weinstein AM, Butters MA. Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. JAMA Neurol. 2026 Apr 1;83(4):310-319. doi: 10.1001/jamaneurol.2026.0072. | |
| 40501510 | Derived | Gildengers AG, Ibrahim TS, Zeng X, Aizenstein HJ, Alkhateeb SK, Anderson SJ, Chu C, Diaz JL, Emanuel JE, Karikari TK, Li J, Lopez OL, Lopresti BJ, Royse SK, Sajewski AN, Santini T, Weinstein AM, Wu M, Butters MA. The LATTICE Study: Design of a pilot feasibility randomized controlled trial of lithium to delay cognitive decline in mild cognitive impairment. Alzheimers Dement (N Y). 2025 Jun 11;11(2):e70112. doi: 10.1002/trc2.70112. eCollection 2025 Apr-Jun. |
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Deidentified participant data will be shared with the National Cell Repository for Alzheimer's Disease (NCRAD).
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Following Data and Safety Monitoring Board approval 9/1/2017, the first participant enrolled 2/2/2018, and last enrolled 8/29/2022. Recruitment involved senior centers, education classes, communities, housing, internet methods, University of Pittsburgh Alzheimer's Disease Research Center partnerships, primary care practices, former participants. During the pandemic, internet/print ads replaced in-person activities.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lithium Carbonate | Lithium carbonate will be initiated at 150 mg per day and increased based on blood levels to a steady blood level between 0.6 and 0.8 meq/L or the maximum tolerated dose based on side effects if lower. Participants will continue at the dose achieved for 2 years with quarterly monitoring. Lithium Carbonate: See lithium carbonate arm |
| FG001 | Placebo | Matching placebo will be initiated and increased based on pretend blood levels. Participants will take placebo for 2 years with quarterly monitoring. Placebo oral capsule: See placebo arm |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Three participants in the placebo arm withdrew consent after randomization, but prior to initiating the study medication and are excluded from the baseline sample.
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| ID | Title | Description |
|---|---|---|
| BG000 | Lithium Carbonate | Lithium carbonate will be initiated at 150 mg per day and increased based on blood levels until a steady blood level between 0.6 and 0.8 meq/L is achieved. Participants will continue at the dose achieved for 2 years with quarterly monitoring. Lithium Carbonate: See lithium carbonate arm |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Pooled mean and pooled standard deviation. |
| 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 | California Verbal Learning Test II | California Verbal Learning Test II. Long-delay free recall. Scores range from 0 - 16; higher means better. | Intention-to-treat analysis; all randomized participants were included regardless of study completion or protocol adherence. | Posted | Mean | Standard Deviation | units on a scale | Year 1 and Year 2 |
|
At weekly titration visits until participants achieved a steady dose within target range or the maximum tolerated dose, then at monthly/quarterly/annual visits thereafter during their 2 year treatment period. Additional data was collected if participants contacted study staff outside of these visits and reported adverse events, if an extra visit was necessary for added clinical monitoring, or if study staff identified serious adverse events when reviewing medical records.
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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 | Lithium Carbonate | Lithium carbonate will be initiated at 150 mg per day and increased based on blood levels until a steady blood level between 0.6 and 0.8 meq/L is achieved. Participants will continue at the dose achieved for 2 years with quarterly monitoring. Lithium Carbonate: See lithium carbonate arm |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Congestive heart failure | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Increased creatinine | Renal and urinary disorders | Systematic Assessment |
The results presented are preliminary.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ariel Gildengers, M.D. | University of Pittsburgh | 412-246-6002 | ariel.gildengers@pitt.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 | Mar 12, 2025 | Jul 21, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D003704 | Dementia |
| D000544 | Alzheimer Disease |
| D020774 | Pick Disease of the Brain |
| D058225 | Plaque, Amyloid |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| D016651 | Lithium Carbonate |
| ID | Term |
|---|---|
| D002254 | Carbonates |
| D000468 | Alkalies |
| D007287 | Inorganic Chemicals |
| D002255 | Carbonic Acid |
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Longitudinal, randomized, double-blind, placebo-controlled experimental trial
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Participants, investigators (who will also be prescribers/care providers), and both clinical and cognitive raters will be blind to treatment. A non-blind physician not providing care or ratings will receive real and generate false blood levels to communicate to other investigators for the purpose of titration of the lithium/placebo. Measures for emergency unblinding will be available as well for safety.
| Placebo oral capsule |
| Drug |
See placebo arm |
|
Cerebral cortical gray matter volume as measured by structural imaging (7T MRI) corrected for age, sex, and intracranial volume
| Year 1 and Year 2 |
| Hippocampal Volume | Hippocampal volume values as measured by structural imaging (7T MRI) corrected for age, sex, and intracranial volume | Year 1 and Year 2 |
| Placebo |
Matching placebo will be initiated and increased based on pretend blood levels. Participants will take placebo for 2 years with quarterly monitoring. Placebo oral capsule: See placebo arm |
| BG002 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Education (years) | Mean | Standard Deviation | years |
|
| Amyloid-beta | Positron Emission Tomography (PET)-amyloid imaging classification amyloid-beta positive or negative. PET-amyloid imaging is a specialized brain scan that can detect abnormal protein deposits called amyloid-beta plaques, which are a hallmark of Alzheimer's disease. Amyloid-positive: Significant amyloid plaques are present in the brain. Amyloid-negative: Little to no amyloid plaques are detected. | Count of Participants | Participants |
|
| Mild Cognitive Impairment | Mild Cognitive Impairment (MCI) means having memory or thinking problems that are more than normal aging but not severe enough to be dementia. Amnestic MCI - primarily affects memory. Non-amnestic MCI - affects thinking skills other than memory. | Count of Participants | Participants |
|
| APOE e4 allele | The Apolipoprotein E (APOE) e4 allele is a specific version of the APOE gene that significantly increases your risk of developing Alzheimer's disease. Carrier means that the participant has at least one copy of the gene. | Count of Participants | Participants |
|
| Framingham Stroke Risk Profile | The Framingham Stroke Risk Profile (FSRP) estimates 10-year stroke probability using age, sex, blood pressure, diabetes, smoking, cardiovascular disease, and atrial fibrillation. Scores range from 0.50% to 95.71%. Higher scores indicate greater stroke risk, helping guide prevention strategies and treatment decisions. | Mean | Standard Deviation | percentage |
|
| Cumulative Illness Rating Scale-Geriatric | The Cumulative Illness Rating Scale-Geriatric (CIRS-G) measures medical illness burden across 14 organ systems, each scored 0-4 (none to extremely severe). Total scores range from 0 to 56. Higher scores indicate greater comorbidity burden and illness severity, predicting mortality and healthcare outcomes in older adults. | Mean | Standard Deviation | units on a scale |
|
| Creatinine | Serum creatinine is a blood test measuring creatinine. Normal levels are roughly 0.6-1.2 mg/dL for adults. Higher levels indicate decreased kidney function or kidney disease. It is used to assess kidney health and calculate estimated glomerular filtration rate (eGFR). | Mean | Standard Deviation | mg/dL |
|
| Glomerular Filtration Rate (GFR) | Glomerular filtration rate (GFR) measures how well kidneys filter blood, indicating kidney function. Normal GFR is 90+ mL/min/1.73m². Values 60-89 suggest mild decrease, 30-59 moderate decrease, 15-29 severe decrease, and <15 kidney failure. Estimated GFR (eGFR) is calculated from serum creatinine. | Mean | Standard Deviation | mL/min/1.73m^2 |
|
| Medication count | Total number of medications prescribed to the participant. | Mean | Standard Deviation | Number of medications |
|
| Anticholinergic Burden | Anticholinergic burden measures cumulative effects of medications blocking acetylcholine. The scale ranges from 0 (no burden) to 5+ (high burden), with each medication contributing 0-3 points based on anticholinergic activity. Scores ≥3 are clinically significant, warranting medication review due to increased risk of cognitive impairment, falls, and other anticholinergic side effects. Total score is the sum of individual medication scores (0-3 each). No maximum total score exists. | Mean | Standard Deviation | units on a scale |
|
| Physical Activity Scale for the Elderly (PASE) | The Physical Activity Scale for the Elderly (PASE) measures self-reported physical activity in adults 65+ across leisure, household, and occupational activities over 7 days. Scores range from 0 to 793 with typical scores ranging 0 to 400+. Higher scores indicate greater physical activity levels and better health outcomes. | Mean | Standard Deviation | units on a scale |
|
| Patient Health Questionnaire-9 item (PHQ-9) | The Patient Health Questionnaire-9 (PHQ-9) is a 9-item depression screening tool. Scores range from 0-27, with each item rated 0-3. Higher scores indicate more severe depression: 0-4 minimal, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe depression. | Mean | Standard Deviation | units on a scale |
|
| Brief Visual Memory Test Revised (BVMT-R) | The Brief Visuospatial Memory Test-Revised (BVMT-R) assesses visual memory using 6 geometric figures learned over 3 trials, then delayed recall after 25 minutes. Each trial has a maximum of 12 points, with Total Recall scores ranging 0-36 and Delayed Recall 0-12. Higher scores indicate better visual memory and learning ability. Delayed Recall score is presented. | One participant in Group lithium did not receive the BVMT-R and CVLT-II because she had substantial familiarity with those tests. | Mean | Standard Deviation | units on a scale |
|
| California Verbal Learning Test 2nd edition (CVLT-II) | The California Verbal Learning Test 2nd Edition (CVLT-II) assesses verbal learning and memory using a 16-word list learned over 5 trials, plus delayed recall and recognition. Total Learning scores range 0-80 (16 words × 5 trials), delayed recall 0-16. Higher scores indicate better verbal learning and memory performance. Delayed recall score is presented. | One participant in Group lithium did not receive the BVMT-R and CVLT-II because she had substantial familiarity with those tests. | Mean | Standard Deviation | units on a scale |
|
| Preclinical Alzheimer's Cognitive Composite (PACC) | The Preclinical Alzheimer's Cognitive Composite (PACC) combines tests assessing episodic memory, executive function, and global cognition to detect early cognitive decline before clinical symptoms appear. Higher scores indicate better cognitive performance. A Z-score of 0 represents the population mean, while Z-scores of ±1 capture approximately 68% of the data around the mean and Z-scores of ±2 capture approximately 95% of the data in a normal distribution. | Three Group placebo participants had missing data, preventing calculation of their PACC scores. | Mean | Standard Deviation | Z-score |
|
| Hippocampal volume | Hippocampal volume measures the size of the hippocampus, a brain region crucial for memory formation and learning. Smaller volumes indicate atrophy and are associated with memory impairment, Alzheimer's disease, depression, and aging. These values are not corrected for age, sex, and intracranial volume. | 18 participants were unable to complete neuroimaging or images were not analyzable. | Mean | Standard Deviation | mm^3 |
|
| Cerebral Cortical Gray Matter | Cerebral cortical gray matter volume measures the total amount of gray matter (neuron cell bodies, dendrites, synapses) in the brain's outer cortex. Reduced volumes are associated with aging, neurodegeneration, and cognitive decline. These values are not corrected for age, sex, and intracranial volume. | 18 participants were unable to complete neuroimaging or images were not analyzable. | Mean | Standard Deviation | mm^3 |
|
| Brain derived neurotrophic factor | Brain-Derived Neurotrophic Factor (BDNF) supports neuron survival and growth; reduced levels linked to neurodegeneration. Nucleic Acid-Linked Immuno-Sorbent Assay (NULISA) measures BDNF using nucleic acid-tagged antibody pairs recognizing different BDNF epitopes. Sequential capture/purification via polyA/biotin tails, then ligation and next-generation sequencing quantification achieves attomolar sensitivity alongside hundreds of other proteins. | Seven participants had missing BDNF values at baseline due to insufficient blood samples or for failing quality control. | Mean | Standard Deviation | Log transformed number of molecules |
|
Matching placebo will be initiated and increased based on pretend blood levels. Participants will take placebo for 2 years with quarterly monitoring.
Placebo oral capsule: See placebo arm
|
|
|
| Primary | Brief Visuospatial Memory Test - Revised | Brief Visuospatial Memory Test - Revised. Delayed Recall. Scores range from 0 - 12; higher means better. | Intention-to-treat analysis; all randomized participants were included regardless of study completion or protocol adherence. | Posted | Mean | Standard Deviation | units on a scale | Year 1 and Year 2 |
|
|
|
|
| Primary | Preclinical Alzheimer Cognitive Composite Composed of Memory and Other Cognitive Tests | Cognitive testing measures with a composite of memory, executive function, processing speed, activities of daily living, and general cognition tests. Values are Z-scores. Higher values mean better cognition. A Z-score of 0 represents the population mean, while Z-scores of ±1 capture approximately 68% of the data around the mean and Z-scores of ±2 capture approximately 95% of the data in a normal distribution. | Intention-to-treat analysis; all randomized participants were included regardless of study completion or protocol adherence. | Posted | Mean | Standard Deviation | Z-score | Year 1 and Year 2 |
|
|
|
|
| Primary | Glycogen Synthase Kinase-3 Beta (GSK-3β) Activity | Values of blood-based biomarkers | The researchers could not evaluate GSK-3β as commercial assays failed to reliably measure its activity in plasma. | Posted | Year 1 and Year 2 |
|
|
| Primary | Brain-derived Neurotrophic Factor | Brain-Derived Neurotrophic Factor (BDNF) supports neuron survival and growth; reduced levels linked to neurodegeneration. Nucleic Acid-Linked Immuno-Sorbent Assay (NULISA) measures BDNF using nucleic acid-tagged antibody pairs recognizing different BDNF epitopes. Sequential capture/purification via polyA/biotin tails, then ligation and next-generation sequencing quantification achieves attomolar sensitivity alongside hundreds of other proteins. | Intention-to-treat analysis; all randomized participants were included regardless of study completion or protocol adherence. | Posted | Mean | Standard Deviation | Log transformed number of molecules | Year 1 and Year 2 |
|
|
|
|
| Primary | Cerebral Cortical Gray Matter Volume | Cerebral cortical gray matter volume as measured by structural imaging (7T MRI) corrected for age, sex, and intracranial volume | Intention-to-treat analysis; all randomized participants were included regardless of study completion or protocol adherence. | Posted | Mean | Standard Deviation | mm^3 | Year 1 and Year 2 |
|
|
|
|
| Primary | Hippocampal Volume | Hippocampal volume values as measured by structural imaging (7T MRI) corrected for age, sex, and intracranial volume | Intention-to-treat analysis; all randomized participants were included regardless of study completion or protocol adherence. | Posted | Mean | Standard Deviation | mm^3 | Year 1 and Year 2 |
|
|
|
|
| Secondary | Cerebrospinal Fluid Phospho Tau Level (CSF) | Cerebrospinal fluid phospho tau levels | CSF collection was not performed due to insufficient participant consent for lumbar puncture procedures. | Posted | Year 1 and Year 2 |
|
|
| Other Pre-specified | Brain Integrity as Measured by Structural Imaging (7T MRI) | Exploratory analyses of additional measures of brain integrity, such as lower level of microbleeds, higher white matter integrity, or better network connectivity | Not Posted | Year 1 and Year 2 | Participants |
| Post-Hoc | NIH Toolbox | NIH Toolbox performance | Valid NIH Toolbox cognitive composite scores were available for only one participant at baseline and 2-year follow-up due to two factors: 1) Coronavirus Disease 2019 (COVID-19) protocol changes required remote administration, for which composite scores are not provided due to unknown validity effects, and 2) composite scores are not available for participants aged 86+. The pandemic timing caused additional missing data, leaving only one participant with complete data across timepoints. | Posted | Year 1 and Year 2 |
|
|
| 0 |
| 41 |
| 12 |
| 41 |
| 41 |
| 41 |
| EG001 | Placebo | Matching placebo will be initiated and increased based on pretend blood levels. Participants will take placebo for 2 years with quarterly monitoring. Placebo oral capsule: See placebo arm | 1 | 39 | 9 | 39 | 37 | 39 |
| Motor Vehicle Accident | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Subdural Hemorrhage | Nervous system disorders | Systematic Assessment |
|
| Vasovagal Episode | Vascular disorders | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Total knee replacement | Surgical and medical procedures | Systematic Assessment |
|
| Community acquired pneumonia | Infections and infestations | Systematic Assessment |
|
| Rheumatoid lung disease | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Includes flare up and respiratory failure |
|
| Nausea and left arm pain | Gastrointestinal disorders | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Dislocation of right hip | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Recurrence of atrial flutter | Cardiac disorders | Systematic Assessment |
|
| Shortness of breath | Cardiac disorders | Systematic Assessment |
|
| Acute Kidney Injury | Renal and urinary disorders | Systematic Assessment | Include acute kidney injury and weakness |
|
| Fever and shortness of breath | Infections and infestations | Systematic Assessment |
|
| Leg pain and swelling | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Leg wounds | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Acute hypoxemia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Stroke | Nervous system disorders | Systematic Assessment |
|
| Lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| COVID-19 | Infections and infestations | Systematic Assessment |
|
| Etadolac related ischemic colitis | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Infectious aortitis | Infections and infestations | Systematic Assessment |
|
| Bleeding stomach ulcer | Gastrointestinal disorders | Systematic Assessment | Includes recurrence |
|
| Neck surgery | Surgical and medical procedures | Systematic Assessment |
|
| Fall, fracture of right hip | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Shortness of breath, pedal edema, pulmonary embolism, acute atrial flutter with RVR on chronic CHF | Cardiac disorders | Systematic Assessment | Shortness of breath, pedal edema, pulmonary embolism, acute atrial flutter with rapid ventricular response on chronic congestive heart failure. |
|
| Frequent falls | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Bilateral hip and leg pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Confusion and shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Radiation treatment of malignant skin neoplasm and osteomyelitis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Total knee athroscopy | Musculoskeletal and connective tissue disorders | Systematic Assessment | Left or right |
|
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Tremor | Nervous system disorders | Systematic Assessment |
|
| Sleepiness | General disorders | Systematic Assessment |
|
| Tiredness | General disorders | Systematic Assessment |
|
| Increased urinary frequency | Renal and urinary disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Dizziness | General disorders | Systematic Assessment |
|
| Dry mouth | General disorders | Systematic Assessment |
|
| Weight gain | Metabolism and nutrition disorders | Systematic Assessment |
|
| Increase TSH value | Endocrine disorders | Systematic Assessment |
|
| Unsteadiness | General disorders | Systematic Assessment |
|
| Edema | Vascular disorders | Systematic Assessment |
|
| Hair loss | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Increased calcium value | Blood and lymphatic system disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Indigestion | Gastrointestinal disorders | Systematic Assessment |
|
| Pedal edema | Blood and lymphatic system disorders | Systematic Assessment |
|
| Concentration difficulties | General disorders | Systematic Assessment |
|
| Memory difficulties | Nervous system disorders | Systematic Assessment |
|
| Increased thirst | Metabolism and nutrition disorders | Systematic Assessment |
|
| Stomach pain | Gastrointestinal disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Mouth ulcers | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Metallic taste | General disorders | Systematic Assessment |
|
| Electrolyte abnormality | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hypnogogic hallucination | Nervous system disorders | Systematic Assessment |
|
| Stomach discomfort | Gastrointestinal disorders | Systematic Assessment |
|
| Falls, recurrent | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Accommodation Disturbance | Eye disorders | Systematic Assessment |
|
| Akathisia | Nervous system disorders | Systematic Assessment |
|
| Blurred vision | Eye disorders | Systematic Assessment |
|
| Body aches | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Congestive heart failure | Cardiac disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Depression | Psychiatric disorders | Systematic Assessment |
|
| Disorientation | General disorders | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | Systematic Assessment |
|
| Facial nerve palsy | Nervous system disorders | Systematic Assessment |
|
| Facial pain | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Flu-like symptoms | General disorders | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Heaviness in limbs | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Heel pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Hives | General disorders | Systematic Assessment |
|
| Hot flashes | General disorders | Systematic Assessment |
|
| Hungriness | General disorders | Systematic Assessment |
|
| Increased dream activity | Psychiatric disorders | Systematic Assessment |
|
| Increased sleep duration | Psychiatric disorders | Systematic Assessment |
|
| Inner unrest | General disorders | Systematic Assessment |
|
| Insomnia | General disorders | Systematic Assessment |
|
| Irritability | Psychiatric disorders | Systematic Assessment |
|
| Itchiness | General disorders | Systematic Assessment |
|
| Leg cramps | General disorders | Systematic Assessment |
|
| Lower back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Lung inflammation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Lyme disease | Infections and infestations | Systematic Assessment |
|
| Mechanical fall | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Micturation difficulty | Renal and urinary disorders | Systematic Assessment |
|
| Muscle aches | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscle cramps | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscle fatigue | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Night sweats | General disorders | Systematic Assessment |
|
| Palpitations | General disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Reduced emotional flattening | Psychiatric disorders | Systematic Assessment |
|
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sinusitis | Infections and infestations | Systematic Assessment |
|
| Somniloquy | General disorders | Systematic Assessment |
|
| Stomach ache | Gastrointestinal disorders | Systematic Assessment |
|
| Stuttering | Psychiatric disorders | Systematic Assessment |
|
| Twitching in sleep | Psychiatric disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Weight loss | General disorders | Systematic Assessment |
|
Not provided
Not provided
| D002493 |
| Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D057180 | Frontotemporal Dementia |
| D057174 | Frontotemporal Lobar Degeneration |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017554 |
| Carbon Compounds, Inorganic |
| D018020 | Lithium Compounds |
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Amyloid-beta unknown |
|
| Year 2 |
|
|
| Year 2 |
|
|
| Year 2 |
|
|
| Year 2 |
|
|
| Year 2 |
|
|