A Study of Brain Aging in Vietnam War Veterans

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.

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.