Risk Reduction for Alzheimer's Disease

Physical inactivity, high blood pressure and dyslipidemia are risk factors for Alzheimer's
disease (AD) and vascular dementia. Importantly, these risk factors are modifiable with
lifestyle changes, pharmacological treatment, or both. The rrAD study will determine effects
of aerobic exercise training and intensive vascular risk reduction on cognitive performance
in older adults who have high risk for AD.

Eligibility Criteria

Inclusion Criteria:

1. Age 60-85, all races/ethnicities, and both sexes are eligible

2. A positive family history of dementia defined as a) having at least one first-degree
relative with a history of AD or other type of dementia,or b) having subjective
cognitive decline

3. AD8 <2, and Mini-Mental State Exam (MMSE) ≥ 26 to exclude gross dementia

4. Must lead a sedentary lifestyle defined by not having an "active" rating on Rapid
Assessment of Physical Activity (RAPA), i.e., score below 6 on RAPA

5. Hypertension defined as SBP ≥140 mmHg

6. Willingness to be randomized into the treatment groups and ability to return to
clinic for follow-up visits over 24 months

7. Fluency in English, adequate visual and auditory acuity to allow neuropsychological
testing

8. Participants must have a regular healthcare provider

9. Physical ability to undergo exercise training; able to walk 10 minutes without pain

Exclusion Criteria:

1. Clinically documented history of stroke, focal neurological signs or other major
cerebrovascular diseases based on clinical judgment or MRI/CT scans such as evidence
of infection, infarction or other brain lesions;

2. Diagnosis of AD or other type of dementia, or significant neurologic diseases such as
Parkinson's disease, seizure disorder, multiple sclerosis, history of severe head
trauma or normal pressure hydrocephalus;

3. Evidence of severe major depression (GDS > 6, may be rescreened after 12 weeks or
longer if evidence of reactive depression or temporary mood disturbances) or
clinically significant psychopathology(e.g. psychosis and schizophrenia); if
hospitalized in past year, can be rescreened in 6 months;

4. Unstable heart disease based on clinical judgment (e.g., heart attack/cardiac arrest,
cardiac bypass procedures within previous 6 months and congestive heart failure),or
other severe medical conditions;

5. Evidence of atrial fibrillation on ECG;

6. Systolic BP equal or greater than 180 mmHg and/or diastolic BP equal or greater than
110 mmHg, may be rescreened in 1 week;

7. Orthostatic hypotension, defined as the third standing SBP < 100mmHg, may be
rescreened after 2 weeks;

8. History of significant autoimmune disorders such as systemic lupus erythematosus,
rheumatoid arthritis or polymyalgia rheumatica;

9. Significant history of alcoholism or drug abuse within the last five years;

10. Uncontrolled diabetes mellitus, defined as hemoglobin A1C > 7.5%, or requiring
insulin treatment;

11. Regularly smoking cigarette within the past year;

12. Women with a potential for pregnancy, lactation/child bearing (2 year post-
menopausal or surgically sterile to be considered not child bearing potential);

13. Participant enrolled in another investigational drug or device study, either
currently or within the past 2 months;

14. Severe obesity with BMI ≥ 40;

15. Allergy to angiotensin receptor blockers (ARBs), i.e., drugs that have a suffix
"sartan";

16. Allergy to other study drugs or their ingredients; for example, clinical history or
self- reported allergy or intolerance to atorvastatin;

17. Abnormal screening laboratory tests (e.g., liver ALT and AST > 3 x ULN, CK > 3 x ULN,
GFR < 30 or Hct < 28%); may be rescreened after 2 weeks or longer;

18. A medical condition likely to limit survival to less than 3 years;

19. Participant has any condition(s) judged by the study investigator to be medically
inappropriate, risky or likely to cause poor study compliance. For example:

1. Plans to move outside the clinic catchment area in the next 2 years;

2. Significant concerns about participation in the study from spouse, significant
other, or family members;

3. Lack of support from primary health care provider;

4. Residence too far from the study clinic site such that transportation is a
barrier including persons who require transportation assistance provided by the
study clinic funds for screening or randomization visits;

5. Residence in a nursing home; persons residing in an assisted living or
retirement community are eligible if they meet the other criteria;

6. Other medical, psychiatric, or behavioral factors that, in the judgment of the
site PI or clinician, may interfere with study participation or the ability to
follow the study Protocol.

7. Couples or significant partners who live together cannot be enrolled or
participate simultaneously in the study.

20. Lack of approval from participant's regular healthcare providers, i.e. a signed
letter of agreement for the participants to be enrolled in rrAD.

Principal Investigator

Jeffrey Burns, MD

Study Contact

Angela VanSciver 913-945-5029 avansciver@kumc.edu

Estimated Completion Date

Wednesday, September 1, 2021

ClinicalTrials.gov #

NCT02913664
09/25/2016