The aging of the United States (US) population will lead to a steep rise in Alzheimer disease (AD). There is an urgent need for novel therapies that may tackle this looming societal problem. People with Alzheimer disease have frequently evidence of vascular disease in the brain, and vascular disease can increase the risk of Alzheimer disease. Based on this finding, the investigators plan to expand the understanding of how vascular disease contributes to Alzheimer disease, hoping to identify novel target to modify the natural progression of the disease. The investigators will accomplish this goal by inviting 300 participants (with and without dementia) of the Northern Manhattan Study (NOMAS) to undergo a brain magnetic resonance imaging (MRI) and donate blood. Of the 300 participants enrolled, 60 participants will be randomly selected to undergo Aβ and tau positron emission tomography (PET) imaging. From the brain MRI, the investigators will obtain measurements of cerebrovascular disease and relate the to the risk of Alzheimer disease. With the blood, the investigators hope to identify measures of aging and inflammation that may predict changes noted in brain scan and identify people at a higher risk of dementia. The investigators will examine PET markers of inflammation and aging in the brain and how the markers relate to dementia.
Research about non-atherosclerotic BAA and its effects on cognition has been hampered by the lack of high-resolution arterial wall imaging, the preponderance of research focused on intracranial large artery atherosclerosis (ILAA) and the lack of mechanistic studies. This study aims to address these shortcomings. By using high-resolution brain arterial wall imaging in participants in the NOMAS cohort, the investigators will derive a wall-based measure of non-atherosclerotic BAA and relate it to pre-MRI cognitive trajectories, AD risk, and ipsilateral markers of neurodegeneration including Aβ/tau PET imaging.
Study Type
OBSERVATIONAL
Enrollment
238
PET imaging to measure 18kDa translocator protein; target imaging dose of up to 20 millicurie (mCi)
PET imaging to measure tau; target imaging dose of 4 to 5 mCi
PET radioligand that binds to amyloid plaques; target-imaging dose of up to 8.1 mCi
Brain MRI
Columbia University Medical Center
New York, New York, United States
Standardized Uptake Values (SUVRs) of Florbetaben
Concentration of radioactivity of Florbetaben (to mark amyloid deposition) in each target region of interest (prefrontal cortex, superior temporal gyrus, combined middle/inferior temporal gyri, medial temporal cortex, superior parietal lobule, inferior parietal lobule, posterior cingulate cortex, and occipital cortex) will be divided by that in cerebellar gray matter to calculate standardized uptake values (SUVRs).
Time frame: Up to 1 month
Standardized Uptake Values (SUVRs) of 18F-MK- 6240
Concentration of radioactivity of 18F-MK- 6240 (to mark tau deposition) in each target region of interest (prefrontal cortex, superior temporal gyrus, combined middle/inferior temporal gyri, medial temporal cortex, superior parietal lobule, inferior parietal lobule, posterior cingulate cortex, and occipital cortex) will be divided by that in cerebellar gray matter to calculate standardized uptake values (SUVRs).
Time frame: Up to 1 month
Association Between Non-Atherosclerotic Brain Arterial Aging (BAA) and Prevalent Alzheimer's' Disease
Calculation of the effect size (estimated beta=0.024 +/- 0.0008) of the association between non-atherosclerotic brain arterial aging (BAA) and prevalent Alzheimer's' disease. Each artery forming the circle of Willis and the vertebral arteries will be rated for measuring wall thickness, lumen diameter, lumen-to-wall ratio, and pattern of thickness. The investigators will use spline regression plots to inform the best cutoff to define "thickened arterial wall" and "dilated artery" (based on time of flight MRA). The BAA score will be the sum of three variables: presence of thickened wall, dilated artery, and concentric wall thickening.
Time frame: Up to 1 month
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