Please select the eligibility criteria that correspond to the clinical trial below.
Title: Exercise and Intensive Vascular Risk Reduction in Preventing Dementia
Brief Summary: 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.


Options:
A: Inclusion Criteria:

* 75 years of age or older
* Seated clinic systolic BP \>150 mmHg in the untreated state (see criterion D)
* At risk for cerebrovascular disease (history of smoking, dyslipidemia, type 2 diabetes, longstanding hypertension, family history). Patients must have visible (0.5% WMH or more)white-matter hypertensity lesions on screening magnetic resonance imaging
* To achieve success in maintaining a 24-hour systolic BP of \<140-145 mmHg in the standard treatment group or a systolic BP \<125-130 mmHg in the intensive treatment group, patients will be eligible for inclusion if (1) their clinic systolic BP is 150-170 mmHg, and they are taking 0 to 2 antihypertensives, (2) their systolic BP is \>170 mmHg and they are taking 0 to 1 antihypertensives

Exclusion Criteria:

* Uncontrolled diabetes mellitus (HBA1c \>10%)
* History of stroke, dementia or clinically impaired gait (Mini-mental status exam score (MMSE) \<24, Short Physical Performance Battery for gait (SPPB) \< 9,)
* Body Mass Index \> 45 kg/m2 and/or arm circumference \> 44 cm)
* Poor kidney function (defined as estimated GFR \<30 ml/minute)
* Active liver disease or serum transaminases \>3 times the upper limit of normal
* Major cardiovascular event (e.g. myocardial infarction) or procedure (e.g. cardiac bypass surgery) in past 3 months; stroke with residual gait abnormality
* Uncompensated congestive heart failure (NYHA class III or IV or documented ejection fraction \<30%)
* Chronic atrial fibrillation that disallows ambulatory BP monitoring to be successfully performed
* Medical conditions that limit survival to \< 3 years
* Non-dermatologic cancer diagnosed within 2 years
* Organ transplantation requiring anti-rejection drug therapy
* Severe and unexplained weight loss (\>15%) in past 6 months
* Medical need to undergo recurrent phlebotomy or blood transfusions
* Current participation in another investigational trial
* Unable to obtain informed consent
* Factors limiting adherence to the interventions
* MRI contraindications (including MRI-incompatible implants, severe claustrophobia).
B: Inclusion Criteria:

1. Age 60-85, all races/ethnicities, and both sexes are eligible.
2. a) A positive family history of dementia defined as having at least one first-degree relative with a history of AD or other type of dementia,or b) having subjective cognitive decline.
3. 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. a) Individuals treated for HTN with 110 ≤ SBP ≤ 130 mmHg; or b) Individuals with SBP \> 130 and SBP \< 180 (If an individual, not treated for HTN, has a SBP ≥ 125 mmHg, consider rescreening after 24 hours).
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 \> 12, 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; or presence of a major psychiatric disorder that in the investigator's opinion, could interfere with adherence to research assessments or procedures.
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. History of atrial fibrillation and evidence on ECG with any of the following: active symptoms of persistent palpitation, dizziness, history of syncope, chest pain, dyspnea, orthopnea, shortness of breath at rest, or paroxysmal nocturnal dyspnea within the past 6 months; resting heart rate of \< 30 or \> 110 bpm; taking class I or III anti-arrhythmic drugs including flecanide, propafenone, dronedarone, sotalol, dofetilide, and amiodarone; or clinical concerns for safely participating in exercise and lowering blood pressure.
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 rheumatic.
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 ≥ 45; clinical judgment should be applied in all cases to assess patient safety and anticipated compliance.
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.
C: Inclusion Criteria:

* essential hypertension
* 50-79 years old
* with at least one of the cardiovascular risk factor
* sign consent forms

Exclusion Criteria:

* secondary hypertension
* attack of cerebrovascular events or myocardial infarction within recent 3 months
* coexistence of severe cardiomyopathy, rheumatic or congenital heart diseases
* unstable angina
* severe hepatopathy or nephropathy (ALT elevation \> 2 fold or serum creatinine \> 2.5mg/dl)
* malignant tumor
* gout
* women taking contraceptives or with pregnancy
* allergic history to the research drugs
* validated contradiction to the research drugs
* participating in other clinical trials
* unable for long-term follow-up or poor compliance
* unsuitable for clinical trial at the discretion of doctors in charge
D: Inclusion Criteria:

Coronary Artery Disease: Previous Myocardial infarction(\> 2 days prior to informed consent), or stable or previous unstable angina (\> 30 days prior to informed consent) with documented multivessel coronary artery disease or a positive stress test, or multivessel Percutaneous Transluminal Coronary Angioplasty (\> 30 days prior to informed consent), or previous multivessel Coronary Artery Bypass Grafting without angina (if surgery performed \> 4 years prior to informed consent) or with recurrent angina after surgery.

Other High Risk:

1. Peripheral Arterial Disease: Previous limb bypass surgery or angioplasty or amputation, intermittent claudication on history with ankle/arm Blood Pressure ratio \< 0.8 on at least one side, or significant stenosis by angiography or non-invasive testing
2. Previous stroke
3. Transient ischemic Attack \> 7 days and \< 1 year prior to informed consent
4. Diabetes Mellitus (types I or II): with evidence of end-organ damage (retinopathy, Left ventricular hypertrophy, micro or macro albuminuria), or any evidence of previous cardiac or vascular disease.

No definite and specific indication or contraindication for any of the study treatments. Written informed consent.

Exclusion Criteria:

A. Medication use:

1. Inability to discontinue Angiotension Converting Enzyme (ACE) inhibitors or Angiotension 2 receptor antagonists (AIIAs).
2. Patients with known hypersensitivity or intolerance to Angiotension 2 receptor antagonists (AIIAs) or Angiotension Converting Enzyme (ACE)inhibitors.

NOTE: Patients with known intolerance to Angiotension Converting Enzyme inhibitor intolerance ( ACE-I) can be enrolled in the TRANSCEND study.

B. Cardiovascular disease:

1. Symptomatic congestive heart failure.
2. Hemodynamically significant primary valvular or outflow tract obstruction (e.g. aortic or mitral valve stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve).
3. Constrictive pericarditis.
4. Complex congenital heart disease.
5. Syncopal episodes of unknown etiology \< 3 months before informed consent.
6. Planned cardiac surgery or angioplasty within three months.
7. Uncontrolled hypertension on treatment (i.e.Blood pressure ( BP) \> 160/100).
8. Heart transplant recipient.
9. Strokes due to subarachnoid hemorrhage

C. Other conditions:

1. Significant renal disease defined as:

   1. Renal artery stenosis;
   2. Creatinine clearance \< 0.6 ml/min or serum creatinine \> 265 umol/L (\> 3.0 mg/dL);
   3. Hyperkalemia: potassium \> 5.5 mmol/L.
   4. Proteinuria\* (for TRANSCEND only).
2. Hepatic dysfunction as defined by the following laboratory parameters: Serum Glutamate Pyruvate Transaminase( SGPT) Alaninaminotransferase (ALT) or Serum Glutamic Oxaloacetic Transaminase (SGOT) Aspartate aminotransferase (AST) \> than 4 times upper limit of normal or additional criteria for hepatic impairment the upper limit of normal range, total Bilirubin \> 20 umol/L, biliary obstructive disorders.
3. Uncorrected volume depletion or sodium depletion.
4. Primary aldosteronism.
5. Hereditary fructose intolerance.
6. Any other major non-cardiac illness expected to reduce life expectancy or interfere with study participation.
7. Patient is simultaneously taking another experimental drug.
8. Patient with significant disability that precludes regular attendance at clinic for follow-up.
9. Patient has sufficient disability or other incapacity that precludes regular attendance at clinic for follow-up.
10. Unable or unwilling to provide written informed consent.

Answer: B