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

The specific aim of this project is 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.

This study will recruit patients with a history of mild-moderate traumatic brain injury, mild cognitive impairment, as well as healthy controls in order to better understand how single or repetitive mild Traumatic brain injuries may contribute to the development of dementia. It will be prospective in nature. Participants will be asked to complete a series of 3 study sessions. During the first study session, each subject will be asked to complete a neuropsychological assessment. If the subject's testing scores fall under the study criteria, they will also be asked to complete a computer task. In the second study session, the investigators will measure the subjects brain waves using an EEG while they complete a computer task. During the computer task, subjects will be asked to study a list of words and the investigators will test the subjects on their memory for those words. During the final study session, the investigators will ask subjects to complete (1) an MRI scan, (2) a standard blood draw procedure, and (3) a lumbar puncture procedure.

Clinical Implications: These studies will provide a better understanding of which individuals with Traumatic Brain Injury will develop dementia, and how many years in the future dementia may occur.

Inclusion criteria

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

Moderate TBI Subjects:

• Subjects will be recruited who have a physician diagnosis of 1 or more moderate TBI episodes
• Moderate TBI: loss of consciousness greater than 30 minutes, posttraumatic amnesia greater than 24 hours, and altered mental status greater than 24 hours

MCI Subjects:

• Subjects will be recruited that 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
• Subjects with MCI may or may not meet diagnostic criteria for MCI due to AD
• MCI subjects will be matched for their MoCA score with older TBI subjects

Healthy Controls:

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

The investigators will recruit all subjects without regard to gender, race, ethnicity, socioeconomic status, or other factors to allow results of this research to yield the greatest generalizability

Exclusion criteria

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
• Clinically significant neurological disease other than those stated in the inclusion criteria
• Impaired decision-making ability
• Patients will be excluded if there are contraindications to MRI including:
• Implants
• Shrapnel
• Aneurysm clips
• Pacemaker
• Pregnancy
• Non-TBI subjects must not have had an TBI
• No contraindication to lumbar puncture or blood draw including:
• Being on a blood thinner
• Aspirin or Plavix
• No space occupying lesion on MRI that makes lumbar puncture contraindicated