Effects of Traumatic Brain Injury and Post Traumatic Stress Disorder on Alzheimer's Disease (AD) in Veterans Using Alzheimer's Disease Neuroimaging Initiative (ADNI)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Traumatic Brain Injury
- Sponsor
- University of Southern California
- Enrollment
- 289
- Locations
- 19
- Primary Endpoint
- Rates of change in neuropsychological measures of memory and general cognitive performance
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
Traumatic brain injury (TBI) and post traumatic stress disorder (PTSD) are common combat related problems and may be associated with a greater risk of Alzheimer's disease (AD). The purpose of this study is to examine the possible connections between TBI and PTSD, and the signs and symptoms of AD on Veterans as they age.
The information collected will help to learn more about how these injuries may affect Veterans of the Vietnam War as they grow older, as well as Veterans of the current wars in Iraq and Afghanistan, who also have these types of combat related injuries.
Detailed Description
The overall long-term goal of this project is to prevent AD, which affects almost 50% of the US population over 85 years of age, and is the most common cause of dementia. Clinical signs and symptoms of AD include cognitive impairments, especially memory and emotional disturbances. In order to accomplish this goal of prevention, a population at risk must be identified. Evidence suggests that both TBI and PTSD increase risk for cognitive decline, AD, and dementia. TBI and PTSD are common problems resulting from military service. Thus far, there have been no prospective studies using imaging and biomarkers, which directly measure changes in the brain and AD pathology to study the effects of TBI and PTSD. This proposed study will provide novel data to test these hypotheses. The results will have major implications for identifying, subjects at increased risk for AD, a possible need for early detection of AD in military Veterans with histories of TBI and PTSD, and a possible need to employ prevention and treatment measures to avoid accelerated development of AD in US military Veterans. This study is a first step toward a larger, more comprehensive study of dementia risk factors in Veterans. The results will lead to a design and statistical powering of a prevention trial. Therefore, this project could be the first step toward the prevention of AD in Veterans, and in the general population.
Investigators
Paul Aisen
Professor
University of Southern California
Eligibility Criteria
Inclusion Criteria
- •General (applies to each cohort):
- •Subjects must be Veterans of the Vietnam War, 50-90 years of age. (Subjects 60-80 years of age will be selected first, while subjects \<60 or \>80 years of age will be added if recruitment numbers are too low in the 60-80 age range);
- •Must live within 150 miles of the closest ADNI clinic in subject's area.
- •Specific Inclusion Criteria for Controls:
- •Comparable in age, gender, and education with TBI and PTSD groups;
- •May be receiving Veterans Affairs (VA) disability payments for something other than TBI or PTSD - or no disability at all.
- •Specific Inclusion Criteria for TBI:
- •Subjects must have a documented history of moderate-severe non-penetrating TBI, which occurred during military service in Vietnam (identified from the Department of Defense or VA records);
- •TBI will be defined as:
- •Loss of consciousness,
Exclusion Criteria
- •General (applies to each cohort):
- •MCI/dementia;
- •History of psychosis or bipolar affective disorder;
- •History of alcohol or substance abuse/dependence within the past 5 years (by DSM-IV-TR criteria) or a prior prolonged history of abuse;
- •MRI-related exclusions: aneurysm clips, metal implants that are determined to be unsafe for MRI; and/or claustrophobia;
- •Contraindications for lumbar puncture, PET scan, or other procedures in this study;
- •Any major medical condition must be stable for at least 4 months prior to enrollment. These include but are not limited to clinically significant hepatic, renal, pulmonary, metabolic or endocrine disease, cancer, HIV infection and AIDS, as well as cardiovascular disease, including:
- •cardiac surgery or myocardial infarction within the last 4 weeks;
- •unstable angina;
- •acute decompensated congestive heart failure or class IV heart failures;
Outcomes
Primary Outcomes
Rates of change in neuropsychological measures of memory and general cognitive performance
Time Frame: 1 Year
Rates of change in neuropsychological measures of memory and general cognitive performance based on cognitive measures to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls
Rates of change in brain regions based on neuroimaging
Time Frame: 1 year
Rates of change in brain regions based on neuroimaging (magnetic resonance imaging \[MRI\] and amyloid positron-emission tomography \[PET\]) to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls
Rates of change in CSF amyloid beta and CSF tau/P tau levels based on biomarkers
Time Frame: 1 year
Rates of change in CSF amyloid beta and CSF tau/P tau levels based on biomarkers such as cerebrospinal fluid (CSF) to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls
Secondary Outcomes
- Group differences in white matter integrity as assessed with Diffusion Tension Imaging (DTI)(1 year)
- Correlations within each group (TBI and PTSD) to assess whether baseline levels or rates of atrophy or cognitive decline are associated with severity of TBI or PTSD(1 year)
- Group differences in the patterns of amyloid deposition (from Florbetapir F 18) and brain atrophy(1 year)
- Rate of change of tau deposition as measured by 18F-AV-1451(1 year)