Contributions of mTBI to Neurodegeneration Due to Chronic Traumatic Encephalopathy (CTE) and Alzheimer's Disease (AD)

NCT04124029 | Recruiting

• 2 other identifiers: NURD-011-19FI01-CX-19-008-CDA
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study that aims to examine whether Veterans with mild Traumatic Brain Injuries are at risk for dementia by studying their memory, brain wave activity, brain structure and proteins that can be elevated after brain injury and in dementia.

Conditions

Mild Traumatic Brain Injury; Moderate Traumatic Brain Injury; Mild Cognitive Impairment

Keywords

Mild Traumatic Brain Injury; Moderate Traumatic Brain Injury; Alzheimer's Disease; Chronic Traumatic Encephalopathy; Neurodegeneration

Outcome Measures

Primary Outcomes (1)

• To better understand the contribution of mild Traumatic Brain Injury (mTBI) to neurodegeneration with the intent of detecting early behavioral, physiologic, anatomic, and protein evidence of neurodegeneration due to AD and CTE

  The work proposed will allow exploration of the relationships between behavioral, event-related potential (ERP), MRI, and cerebrospinal fluid (CSF) measures at a variety of points along the disease continuum and will allow for future longitudinal studies in this cohort

  5 years

Secondary Outcomes (4)

• Recognition Memory

  5 Years

• EEG peak amplitude and latency

  5 years

• Cortical, quantitative MRI volume measurements

  5 years

• CSF Proteinopathy

  5 years

Study Arms (6)

Younger mild Traumatic Brain Injury

mTBI subjects aged 30-59 yo will be recruited who have a physician diagnosis of 1 or more mTBI episodes without concomitant moderate or severe TBI diagnosis (loss of consciousness greater than 30 minutes, posttraumatic amnesia greater than 24 hours, or altered mental status greater than 24 hours). mTBI subjects must pass effort measures on the Test of Memory Malingering (TOMM) and have intact color vision and visual acuity of 20/30 or better in order to be included in the study.

Device: No Intervention is used for this study but all subjects will be asked to complete EEG testing and an MRI scan.; Procedure: No intervention is used for this study but all subjects will be asked to complete a venous blood draw procedure and a lumbar puncture procedure.

Older mild Traumatic Brain Injury

mTBI subjects aged 60- 90 yo will be recruited who have a physician diagnosis of 1 or more mTBI episodes without concomitant moderate or severe TBI diagnosis (loss of consciousness greater than 30 minutes, posttraumatic amnesia greater than 24 hours, or altered mental status greater than 24 hours). mTBI subjects must pass effort measures on the TOMM and have intact color vision and visual acuity of 20/30 or better in order to be included in the study.

Device: No Intervention is used for this study but all subjects will be asked to complete EEG testing and an MRI scan.; Procedure: No intervention is used for this study but all subjects will be asked to complete a venous blood draw procedure and a lumbar puncture procedure.

moderate Traumatic Brain Injury

TBI control subjects, age-, education- and sex-matched with mTBI subjects (aged 30-90) will be recruited who have a physician diagnosis of 1 or more moderate TBI episodes (loss of consciousness greater than 30 minutes, posttraumatic amnesia greater than 24 hours, or altered mental status greater than 24 hours). Moderate TBI subjects must pass effort measures on the TOMM and have intact color vision and visual acuity of 20/30 or better in order to be included in the study.

Device: No Intervention is used for this study but all subjects will be asked to complete EEG testing and an MRI scan.; Procedure: No intervention is used for this study but all subjects will be asked to complete a venous blood draw procedure and a lumbar puncture procedure.

Mild Cognitive Impairment (MCI)

MCI control subjects, age-, education- and sex-matched with older mTBI subjects (aged 60-90) will be recruited if they meet diagnostic criteria for MCI (without a history of TBI) based on the judgement of a behavioral neurologist following the 2011 MCI criteria. Specifically, subjects will test in the impaired range on one or more cognitive domains on neuropsychological testing and will not have impairments in function (i.e. will not meet diagnostic criteria for dementia). MCI subjects will be matched for their Montreal Cognitive Assessment (MoCA) score with older mTBI subjects. Of note, subjects with MCI may or may not meet diagnostic criteria for MCI due to AD. The intent of this control group is to recruit a broad range of MCI subjects without TBI as controls for subjects with cognitive impairment who have a history of mTBI.

Device: No Intervention is used for this study but all subjects will be asked to complete EEG testing and an MRI scan.; Procedure: No intervention is used for this study but all subjects will be asked to complete a venous blood draw procedure and a lumbar puncture procedure.

Younger Healthy Controls

Cognitively normal control subjects, age-, education- and sex-matched with younger mTBI subjects, but lacking and mTBI history. All subjects must be within 1 standard deviation of normal on all neuropsychologic testing in order to be enrolled.

Device: No Intervention is used for this study but all subjects will be asked to complete EEG testing and an MRI scan.; Procedure: No intervention is used for this study but all subjects will be asked to complete a venous blood draw procedure and a lumbar puncture procedure.

Older Healthy Controls

Cognitively normal control subjects, age-, education- and sex-matched with older mTBI subjects, but lacking and mTBI history. All subjects must be within 1 standard deviation of normal on all neuropsychologic testing in order to be enrolled.

Device: No Intervention is used for this study but all subjects will be asked to complete EEG testing and an MRI scan.; Procedure: No intervention is used for this study but all subjects will be asked to complete a venous blood draw procedure and a lumbar puncture procedure.

Interventions

No Intervention is used for this study but all subjects will be asked to complete EEG testing and an MRI scan. DEVICE

No intervention will be used.

Mild Cognitive Impairment (MCI); Older Healthy Controls; Older mild Traumatic Brain Injury; Younger Healthy Controls; Younger mild Traumatic Brain Injury; moderate Traumatic Brain Injury

No intervention is used for this study but all subjects will be asked to complete a venous blood draw procedure and a lumbar puncture procedure. PROCEDURE

No intervention will be used.

Mild Cognitive Impairment (MCI); Older Healthy Controls; Older mild Traumatic Brain Injury; Younger Healthy Controls; Younger mild Traumatic Brain Injury; moderate Traumatic Brain Injury

Eligibility Criteria

• Age: 30 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients from the memory disorders clinic will be recruited if they have a (1) history of mild TBI, (2) history of moderate TBI, or (3) mild cognitive impairment. In addition, the investigators will be recruiting healthy controls that meet satisfy the inclusion and exclusion criteria of the study.

You may qualify if:

• All Subjects:
• Intact color vision
• Visual acuity of 20/30 (or better)
• Patients must pass effort measures on the TOMM
• Patients must have intact decision-making capacity
• Patients must have no contraindications to lumbar puncture including:
• Being on a blood thinner
• Aspirin or Plavix
• Have no space occupying lesion on magnetic resonance imaging (MRI)
• An International Normalized Ratio (INR) value \< 1.4 and platelet count \>50,000
• No epidural infection or overlying cellulitis over the lumbar spine
• PTSD will be accounted for as a potential confounder and its presence will be included as a covariate in all analyses
• Mild TBI Subjects:
• Subjects will be recruited who have a physician diagnosis of 1 or more mTBI episodes without concomitant moderate or severe TBI diagnosis
• Mild TBI: Loss of consciousness greater than 30 minutes, posttraumatic amnesia greater than 24 hours, and/or altered mental status greater than 24 hours

You may not qualify if:

• All Subjects:
• If the primary language is not English
• Are unable to understand the informed consent process
• Have a clinically significant problem with any of the following conditions:
• A history of TBI within 1 year of study
• Suicidal or homicidal ideation requiring intervention
• Schizophrenia
• Bipolar disorder
• Active alcohol or drug abuse
• Impaired decision-making ability
• Patients will be excluded if there are contraindications to MRI including:
• Implants
• Shrapnel
• Aneurysm clips
• Pacemaker

Sponsors & Collaborators

• VA Office of Research and Development: lead
• VA Boston Healthcare System: collaborator

Study Sites (1)

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130-4817, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

The investigators will be obtaining whole blood samples and cerebrospinal fluid samples from subjects. Whole blood samples will be used to test for the e4 variant of the Apolipoprotein E (APOE) gene. Cerebrospinal fluid will be extracted to examine the proteinopathy associated with each groups.

MeSH Terms

Conditions

Brain Concussion; Cognitive Dysfunction; Alzheimer Disease; Chronic Traumatic Encephalopathy; Nerve Degeneration

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Brain Injury, Chronic; Brain Damage, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Katherine Turk, MD

  VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristina Morreale, BA

CONTACT

(857) 364-2139; Kristina.Morreale@va.gov

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 11, 2019
• Study Start: July 1, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)