Accelerated Non-Atherosclerotic Brain Arterial Aging Relationship to Alzheimer's Disease

Accelerated Non-Atherosclerotic Brain Arterial Aging Relationship to Alzheimer's Disease

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.

Inclusion Criteria:

• Age 50 and older
• Being part of the NOMAS MRI substudy
• Subjects unable to provide informed consent must have a surrogate decision maker
• Written and oral fluency in English or Spanish
• Able to participate in all scheduled evaluations and to complete all required tests and procedures.
• In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study.

Exclusion Criteria:

• Past or present history of certain brain disorders other than Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD) (self-reported brain tumor, dementia of Lewy body, frontotemporal dementia).
• Certain significant medical conditions, which make study procedures of the current study unsafe (liver cirrhosis, end-stage renal disease on dialysis, terminal cancer (death expected within 6 months)).
• Contraindication to MRI scanning
• Conditions precluding entry into the scanners (e.g., morbid obesity, claustrophobia, etc.).
• Exposure to research related radiation in the past year that, when combined with this study, would place subjects above the allowable limits.
• Participation in a clinical trial for a disease-modifying drug for AD the year prior to the date of the first PET scan.
• Inability to have a catheter in subject's vein for the injection of radioligand.
• Inability to have blood drawn from subject's veins.
• Subjects will not be included in the study if they have participated in the last year in a clinical trial for a disease-modifying drug for AD.