Aerobic Exercise Training in Mild Cognitive Impairment Study

This study is being done to find out whether regulation of brain blood flow is altered in patents with mild cognitive impairment (those who have memory problems but otherwise healthy) when compared with healthy elderly individuals. In addition, this study will determine whether exercise training improves brain blood flow, brain structure, and brain function in patients with mild cognitive impairment (MCI).

This is a research study because at present the investigators know little about brain blood flow regulation in patients with mild cognitive impairment. The investigators also know little about whether exercise training improves brain blood flow, brain structure, and brain function in patients with mild cognitive impairment.

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.

Eligibility Criteria:
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.