Alzheimer's Disease, Mild Cognitive Impairment, Post Traumatic Stress Disorder, Traumatic Brain Injury
Conditions
Keywords
traumatic brain injury (TBI), post traumatic stress disorder (PTSD), Alzheimer's disease (AD), mild cognitive impairment (MCI), dementia, biomarkers, amyloid, neuroimaging, cognition disorder, tau
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.
Interventions
None listed
Sponsors
United States Department of Defense
Telemedicine & Advanced Technology Research Center
Northern California Institute of Research and Education
San Francisco Veterans Affairs Medical Center
Alzheimer's Therapeutic Research Institute
University of Southern California
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
Participants will be classified as either controls, TBI, or PTSD. General Inclusion/
Exclusion criteria
will apply to all groups, with specific criteria for each group as described below. 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, * Post-traumatic amnesia \>24 hours, OR * Alteration of consciousness or mental state \>24 hours Specific Inclusion Criteria for PTSD: * Subjects who meet the Structured Clinical Interview 1 of the Diagnositic and Statistical Manual of Mental Disorders, Version IV, (Axis 1) - Text Revision \[SCID-I of the DSM-IV-TR\] criteria for current/chronic PTSD (identified by records, and verified by our telephone assessments); * In addition to meeting DSM-IV-TR criteria for current/chronic PTSD, subjects must have a minimum current Clinician Administered PTSD Scale (CAPS) score of 50 as determined by telephone assessment; * The PTSD symptoms contributing to the PTSD Diagnosis and Current CAPS score must be related to a Vietnam War related trauma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rates of change in brain regions based on neuroimaging | 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 | 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 |
| Rates of change in neuropsychological measures of memory and general cognitive performance | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Rate of change of tau deposition as measured by 18F-AV-1451 | 1 year | Rates of change in brain regions based on Tau PET neuroimaging to show that those with TBI and/or PTSD have increased evidence for AD compared to Veteran controls |
| Group differences in the patterns of amyloid deposition (from Florbetapir F 18) and brain atrophy | 1 year | Group differences may give insight into whether TBI or PTSD is associated with reduced brain reserve causing greater cognitive impairments as indicated by neuropsychological test performance. |
| Group differences in white matter integrity as assessed with Diffusion Tension Imaging (DTI) | 1 year | Group differences in axonal damage as indicated by white matter integrity measured with DTI to determine if axonal injury resulting from TBI is associated with greater amyloid accumulation or whether brain regions with axonal damage have less amyloid accumulation due to disconnection and reduced brain activity. |
Countries
United States
Outcome results
None listed