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.
The IPAT study is a 2-arm open-label randomized controlled trial to assess the effects of intensive pharmacological reduction of high blood pressure (SBP) on brain amyloid and tau protein deposition (Alzheimer's Disease pathology) in older adults who are at high risk for AD and related dementias, that is, those who have high blood pressure, family history of dementia, or subjective memory complaints. Furthermore, IPAT will examine effects of intensive blood pressure lowering on brain volume, perfusion, and neural network connectivity using magnetic resonance imaging (MRI) and cognitive performance.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
180
Angiotensin 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.
Participants will follow their PCP's recommendations for BP control.
University of Texas Southwestern Medical Center
Dallas, Texas, United States
RECRUITINGChange 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).
Time frame: Baseline, 24 months
Change From Baseline in Brain Tau Deposition
Brain Tau Deposition will be measured by tau temporal meta-ROI composite with positron emission tomography (PET).
Time frame: Baseline, 24 months
Change From Baseline in regional Cerebral Blood Flow (CBF)
Regional CBF will be measured by MRI using arterial spin labeling.
Time frame: Baseline, 12 months, 24 months
Change From Baseline in global Cerebral Blood Flow (CBF)
Global CBF will be measured by PC-MRI and 2D color-coded duplex ultrasonography.
Time frame: Baseline, 12 months, 24 months
Change From Baseline in Arterial Stiffness
Central arterial stiffness (pulse wave velocity and carotid β-stiffness index) will be measured by artery applanation tonometry.
Time frame: Baseline, 12months, 4 months
Change From Baseline in Amplitude of Low Frequency Fluctuations of Blood-Oxygen-Level-Dependent Signal (BOLD ALFF)
BOLD ALFF will be measured by resting state functional MRI (rs-fMRI).
Time frame: Baseline, 12 months, 24 months
Change From Baseline in White Matter Hyperintensity Volume
White matter hyperintensity volume will be measured by MRI using 3D T2 FLAIR sequence .
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Time frame: Baseline, 12 months, 24 months
Change From Baseline in Brain Neural Network Connectivity
Brain neural network connectivity will be measured by rs-fMRI.
Time frame: Baseline, 12 months, 24 months
Change From Baseline in Neurocognitive Function
A composite z score will be obtained by conversion of individual test scores of the Preclinical Alzheimer Cognitive Composite (PACC) and the NIH Toolbox Cognition Battery to standardized z scores, then averaged to assess changes in global cognitive function. Domain-specific z scores will be used to assess specific domains of cognitive function (i.e., memory, executive function, language etc.).
Time frame: Baseline, 12 months, 24 months