The purpose of this study is to determine if intensive lowering of systolic blood pressure (SBP), using FDA approved medications (antihypertensive), reduces Alzheimer's Disease pathology (i.e., excessive brain amyloid and tau protein deposition) in older adults at high risk for memory decline or dementia.
Age 60-85, all races/ethnicities, and both sexes are eligible;
Mini-Mental State Exam (MMSE) ≥ 26 to exclude gross dementia; based on clinical judgment, may be rescreened in ≥ 7 days;
Individuals with SBP ≥ 130 and SBP ≤ 180 if on 0 or 1 antihypertensive medications; ≥130 and ≤170 on up to 2 medications; ≥130 and ≤160 on up to 3 medications; ≥130 and ≤150 on up to 4 medications. Those on antihypertensives are eligible. If an individual, not treated for hypertension (HTN), has a SBP ≥ 125 mmHg, consider rescreening after 24 hours;
Willingness to be randomized into the treatment groups and ability to return to clinic for follow-up visits over 24 months;
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;
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;
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.
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;
Parallel
Angiotensin II Receptor Blockers (ARBs, losartan) and Calcium Channel Blockers (CCB, amlodipine)
DrugAngiotensin II Receptor Blockers (ARBs, losartan) and Calcium Channel Blockers (CCB, amlodipine) will be used to treat high blood pressure. Additional antihypertensive medications may be used if needed.
PCP
Other interventionParticipants will follow their PCP's recommendations for BP control.
Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ)
Brain Aβ will be measured by annual change of amyloid mean cortical standardized uptake value ratio (SUVR) with positron emission tomography (PET).
Change From Baseline in Brain Tau Deposition
Brain Tau Deposition will be measured by tau temporal meta-ROI composite with positron emission tomography (PET).
Change From Baseline in regional Cerebral Blood Flow (CBF)
Regional CBF will be measured by MRI using arterial spin labeling.
Change From Baseline in global Cerebral Blood Flow (CBF)
Global CBF will be measured by PC-MRI and 2D color-coded duplex ultrasonography.
Change From Baseline in Arterial Stiffness
Central arterial stiffness (pulse wave velocity and carotid β-stiffness index) will be measured by artery applanation tonometry.
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Rong Zhang
Lead sponsor
University of Texas Southwestern Medical Center
Sponsor institution
National Institute on Aging (NIA)
Collaborator
Texas Health Resources
Collaborator
Michigan State University
Collaborator
