DOD-ADNI: A Study of Brain Aging in Vietnam War Veterans

Sponsor

University of Southern California (Other)

Overall Status

Completed

CT.gov ID

NCT01687153

Collaborator

United States Department of Defense (U.S. Fed), Telemedicine & Advanced Technology Research Center (Other), Northern California Institute of Research and Education (Other), San Francisco Veterans Affairs Medical Center (U.S. Fed), Alzheimer's Therapeutic Research Institute (Other)

289

Enrollment

Locations

107.7

Duration (Months)

15.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury Post Traumatic Stress Disorder Alzheimer's Disease Mild Cognitive Impairment

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.

Study Design

Study Type:

Observational

Actual Enrollment :

289 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Effects of Traumatic Brain Injury and Post Traumatic Stress Disorder on Alzheimer's Disease (AD) in Veterans Using Alzheimer's Disease Neuroimaging Initiative (ADNI)

Study Start Date :

Oct 1, 2012

Actual Primary Completion Date :

Sep 21, 2021

Actual Study Completion Date :

Sep 21, 2021

Arms and Interventions

Arm	Intervention/Treatment
Traumatic Brain Injury (TBI) 65-100 Vietnam Veterans with Traumatic Brain Injury (TBI), but without PTSD, mild cognitive impairment (MCI)/dementia
Post Traumatic Stress Disorder (PTSD) 65-100 Vietnam Veterans with PTSD, but without TBI, MCI/dementia
Controls 65-100 Vietnam Veteran Controls without TBI or PTSD and comparable in age, gender, and education to the other cohorts
TBI w/ MCI 65-100 Vietnam Veterans with TBI but without PTSD who meet the criteria for MCI but not dementia
PTSD w/ MCI 65-100 Vietnam Veterans with PTSD but without TBI who meet the criteria for MCI but not dementia
Controls w/ MCI 65-100 Vietnam Veteran Controls without TBI or PTSD who meet the criteria for MCI but not dementia, and are comparable in age, gender, and education to the other cohorts

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
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.
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

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;
current significant cardiac arrhythmia or conduction disturbance particularly those resulting in ventricular fibrillation, or causing syncope, or near syncope;
Uncontrolled high blood pressure
Seizure disorder or any systemic illness affecting brain function during the past 5 years will be exclusionary;
Clinical evidence of stroke;
Have a history of relevant severe drug allergy or hypersensitivity;
Subjects with current clinically significant unstable medical comorbidities, as indicated by history or physical exam, that pose a potential safety risk to the subject.

Specific Exclusion Criteria for Controls:

• Exclusionary criteria applied to TBI/PTSD (outlined below) will be applied to controls.

Specific Exclusion Criteria for TBI:

• Presence of PTSD by SCID-I for DSM-IV-TR criteria, or a CAPS score of >30 (Both current and/or a history of PTSD will be excluded).

Specific Exclusion Criteria for PTSD:

Documented or self report history of mild/moderate severe TBI;
Any history of head trauma associated with injury onset cognitive complaints; or
Loss of consciousness for >5 minutes.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Sun Health Research Institute	Sun City	Arizona	United States	85351
2	University of California, Irvine	Irvine	California	United States	92697
3	University of California, San Diego	La Jolla	California	United States	92093
4	University of Southern California	Los Angeles	California	United States	90033
5	VA Palo Alto HSC / Stanford School of Medicine	Palo Alto	California	United States	94304
6	University of California, San Francisco	San Francisco	California	United States	94117
7	Georgetown University	Washington	District of Columbia	United States	20057
8	Howard University	Washington	District of Columbia	United States	20060
9	Wien Center for Clinical Research	Miami Beach	Florida	United States	33140
10	Premiere Research Institute	West Palm Beach	Florida	United States	33407
11	Rush University Medical Center	Chicago	Illinois	United States	60612
12	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
13	Cornell Medical Center	New York	New York	United States	10021
14	Columbia University	New York	New York	United States	10032
15	University of Rochester Medical Center	Rochester	New York	United States	14620
16	Duke University Medical Center	Durham	North Carolina	United States	27710
17	Roper St Francis Healthcare	Charleston	South Carolina	United States	29401
18	U of WA / VA Puget Sound Alzheimer's Disease Research Center	Seattle	Washington	United States	98108
19	University of Wisconsin	Madison	Wisconsin	United States	53705

Sponsors and Collaborators

University of Southern California
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

Investigators

Study Director: Michael W. Weiner, MD, University of California, San Francisco
Principal Investigator: Paul Aisen, MD, USC Alzheimer's Therapeutic Research Institute (ATRI)
Principal Investigator: Ronald Petersen, MD, PhD, Mayo Clinic