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Completed

NCT Number: NCT04510168

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.

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Key information

Conditions

Alzheimer Disease Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies Vascular Diseases

Age range

50 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Columbia University Medical Center

New York, 10032, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

11C-ER176

Drug

PET imaging to measure 18kDa translocator protein; target imaging dose of up to 20 millicurie (mCi)

[F-18]MK-6240

Drug

PET imaging to measure tau; target imaging dose of 4 to 5 mCi

Florbetaben

Drug

PET radioligand that binds to amyloid plaques; target-imaging dose of up to 8.1 mCi

Other names: NeuraCeq

Magnetic Resonance Imaging

Other

Brain MRI

Primary outcomes

  1. Standardized Uptake Values (SUVRs) of Florbetaben

    Time frame: Up to 1 month

    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).

  2. Standardized Uptake Values (SUVRs) of 18F-MK- 6240

    Time frame: Up to 1 month

    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).

Secondary outcomes

  1. Association Between Non-Atherosclerotic Brain Arterial Aging (BAA) and Prevalent Alzheimer's' Disease

    Time frame: Up to 1 month

    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.

Sponsors and collaborators

Lead sponsor

Jose Gutierrez, MD, MPH

Other

Registry information

Important dates

Study start
2020
Primary completion
2024
Study completion
2024
First posted
Aug 12, 2020
Registry last updated
Jul 16, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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