Aerobic Exercise Training in Mild Cognitive Impairment Study

We plan to study 70 patients with amnestic MCI and 30 healthy older adults with similar age,
sex, and educational level in this research at the University of Texas Southwestern(UTSW)
Medical Center Dallas and Texas Health Presbyterian Hospital Dallas - Institute for Exercise
an Environmental Medicine (IEEM).

To help decide if you qualify to be in this study, the researchers may ask you questions
about your health, including medications you take and any surgical procedures you have had.
You may also have to fill out certain forms or have the following exams, tests or
procedures. The screening process usually takes 2-3 hours.

You will be required to come for 7-9 visits including the initial screening for eligibility
to participate in this study. The experiments will measure your brain perfusion, vascular
function and exercise capacity.

For the healthy controls, the expected length of this study will be about 2-3 months
including all the test visits. Your participation in this study will end following
completion of your testing.

For those with Mild Cognitive Impairment, the expected length of this study will be about 18
months including all the test visits and exercise training. Your participation in this study
will end following completion of your repeat testing after one-year exercise training or
control intervention. On occasion, training may be delayed due to injury, illness or
personal matters. If this is the case, your enrollment in the study may last longer than one
year as we attempt to complete the training and testing.

Inclusion Criteria:

1. Age 55-80 years old, Male or Female

2. Control Subjects: absence of cognitive complaints and normal performance in Uniform
Data Set (UDS) neuropsychological tests.

3. For patients: Diagnosis of amnestic MCI (single and multiple domains) by Petersen's
criteria (as modified for ADNI-GO study).

4. Stable medical condition for > 6 months

5. Sable medications for >2 months (use of cholinesterase inhibitors, or prior use of
multivitamins is allowed)

6. Caregiver/informant available to accompany patient for scheduled visits in case the
patient develops cognitive impairment that interferes with independent study
participation.

7. Fluency of patient and caregiver in English

8. Ability to return to clinic for additional visits over a 12 month period.

9. ≥ 10 years of education or enough work history to exclude mental retardation.

10. Adequate visual and auditory acuity to allow neuropsychological testing.

11. Screening laboratory tests and ECG without significant abnormalities that might
interfere with the study.

12. Physical ability to undergo endurance exercise training.

Exclusion Criteria:

1. Diagnosis of Alzheimer's Disease or other type of dementia.

2. Participant enrolled in any other investigational drug study within 2 months or
longer, depending on the investigational drug half-life.

3. Modified Hachinski Score ≥ 4.

4. Subject has history in the past 2 years of epileptic seizures, or DSM-IV criteria of
any major psychiatric disorders.

5. Past history or MRI evidence of brain damage including significant trauma, stroke,
hydrocephalus, mental retardation or serious neurological disorder.

6. Carotid stent or sever stenosis.

7. Significant history of active alcoholism or drug abuse.

8. History of myocardial infarction within the previous year. Unstable cardiac, renal,
lung, liver or other severe chronic diseases.

9. Uncontrolled hypertension (Systolic Blood Pressure (SBP) ≥160, Diastolic Blood
Pressure (DBP) ≥100)or hypotension (SBP <100 mmHg).

10. Currently diagnosed and being treated for Diabetes Mellitus (DM).

11. Obesity with Body Mass Index (BMI) ≥ 35.

12. History of familial early onset (<55 years old) dementia

13. Pacemaker or other medical device of metal that precludes performing MRI.

14. Subjects who have been engaged in moderate intensity aerobic exercise training for >
30 minutes, 3 times per week over the past 2 years.

15. History of a clinical diagnosis of B12 deficiency or hypothyroidism. (stable
treatment for at least 3 months is allowed).

16. Chronic inflammatory diseases including, lupus, rheumatoid arthritis and polymyalgia
rheumatica.

Prohibited Medications:

- narcotics

- anti-Parkinsonian medications

- anti-convulsants for treatment of seizure disorder

- drugs that can influence psychometric test results.

- Subjects on a statins or non-steroidal anti-inflammatory drug (NSAID) are
eligible but must be on a stable dose for at least 2 months.