A Study of Brain Aging in Vietnam War Veterans

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.

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.

Eligibility 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.

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.