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

NCT04510168 | Completed FDA Drug

• 2 other identifiers: AAAS7441R01 AG06616201
• Study Type: observational
• Target: 238
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease; Dementia

Keywords

Vascular Disease; Non-Atherosclerotic Brain Arterial Aging

Outcome Measures

Primary Outcomes (2)

• 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).

  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).

  Up to 1 month

Secondary Outcomes (1)

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

  Up to 1 month

Study Arms (2)

MRI Only

The investigators will acquire de-novo brain MRI and time-of-flight MRA in randomly selected surviving Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project (NOMAS) participants. The investigators aim to include at least 50-60 people with dementia (as determined by the ongoing NOMAS procedures).

Other: Magnetic Resonance Imaging

MRI and PET

The investigators will acquire de-novo brain MRI and time-of-flight MRA in randomly selected surviving Northern Manhattan Study (NOMAS) participants. The investigators aim to include at 20 participants with dementia and 40 participants without (as determined by the ongoing NOMAS procedures). In addition to MRI, participants in this group will have three PET studies.

Drug: 11C-ER176; Drug: [F-18]MK-6240; Drug: Florbetaben; Other: Magnetic Resonance Imaging

Interventions

11C-ER176 DRUG

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

MRI and PET

[F-18]MK-6240 DRUG

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

MRI and PET

Florbetaben DRUG

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

Also known as: NeuraCeq

MRI and PET

Magnetic Resonance Imaging OTHER

Brain MRI

MRI Only; MRI and PET

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The population targeted in this aim comes from the long-established NOMAS study, an ongoing, prospective, population-based cohort of 3,298 stroke-free participants. Cohort recruitment occurred from 1993 to 2001. Initial eligibility for the cohort included those aged \> 40 years who were permanent residents of Northern Manhattan, lived in a house with a telephone, and had no history of clinical stroke. NOMAS participants were recruited during annual follow-ups to undergo a brain MRI if they met the following criteria: free of clinical stroke, aged \>50 years, and could have an MRI.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jose Gutierrez, MD, MPH: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Vascular Diseases

Interventions

4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Jose Gutierrez, MD, MPH

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Florence Irving Assistant Professor of Neurology

Study Record Dates

• First Submitted: August 10, 2020
• First Posted: August 12, 2020
• Study Start: September 18, 2020
• Primary Completion: April 16, 2024
• Study Completion: April 17, 2024
• Last Updated: July 16, 2024

Record last verified: 2024-07

Locations

US (1)