African American Alzheimer's Progression Markers - CSF and Neuro-Imaging (A3PM)

June 21, 2016 updated by: William Hu MD/PhD, Emory University

Biomarkers for Alzheimer's Disease and Mild Cognitive Impairment in African Americans and Caucasians

African Americans are twice as likely to develop Alzheimer's disease as white Americans, but few African Americans are enrolled in large Alzheimer's biomarker studies. The current proposal aims to determine the influence of Alzheimer's disease and vascular disease on memory and aging in African Americans through modern biomarkers (spinal fluid, MRI, and amyloid imaging), and how these may differ between African Americans and white Americans in preparation for a large multi-center study of aging in African American.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

African Americans represent about 10% of the population in the US, but are under-represented in biomarker-related aging studies such as the Alzheimer's Disease Neuro-imaging Initiative (ADNI) and World Wide ADNI. Epidemiologic studies show that, compared to non-Hispanic white (NHW) Americans, African Americans (AA) are more likely to develop mild cognitive impairment (MCI) and Alzheimer's disease (AD), have different genetic risks of developing AD, and experience different rates of cognitive decline after cognitive symptoms develop. All these point to the existence of an MCI/AD endophenotype for AA, although few of these epidemiological studies involve modern chemical or imaging biomarkers associated with AD pathology and progression. Preliminary studies using AA subjects who have undergone CSF analysis (n=36) show that AA MCI subjects are more likely to have normal CSF AD biomarkers than NHW MCI subjects, yet at the same time greater hippocampal atrophy on MRI. The investigators hypothesize that endothelial dysfunction is an alternate mechanism which independently contributes to cognitive impairment in AA subjects with sub-threshold AD pathology in a race-independent fashion, and endothelia dysfunction further enhances the neurotoxicity of AD-associated brain changes in a race-dependent fashion. The investigators propose to build on their success in recruiting AA volunteers into memory and aging studies at the Emory's Registry for Remembrance to recruit a cross-sectional cohort of 75 AA subjects along with 75 NHW subjects with normal cognition, MCI, or mild AD. They will test this hypothesis through two aims. In Aim 1, they will determine whether endothelial dysfunctions independently contribute to cognitive decline in AA and NHW subjects by measuring cerebrospinal fluid (CSF) levels of AD, endothelial, and inflammatory markers. Each subject will also undergo MRI analysis for total area of white matter hyperintensities as an imaging marker of endothelial dysfunction. Based on the hypothesis, they predict that AA MCI/AD subjects are more likely than NHW MCI subjects to have normal CSF AD biomarkers, abnormal CSF endothelial markers, and greater number and area of white matter hyperintensities on MRI. In Aim 2, the investigators will determine if an endothelial marker - intercellular adhesion molecule 1 or ICAM-1 - gene variant unique to AA enhances AD neurotoxicity to explain the greater hippocampal atrophy among AA MCI subjects. The Lys56Met ICAM1 gene variant associated with low ICAM-1 levels is uniquely found in 16-20% of AA, and these subjects may have impaired downstream activation of neprilysin, an Abeta-degrading enzyme. If the hypothesis is true, AA subjects with the Lys56Met gene variant will be more likely to have hippocampal atrophy, temporal-parietal cerebral hypoperfusion, and cerebral amyloid deposition than AA subjects and NHW subjects without the gene variant. This may occur in the setting of CSF Abeta2 pseudo-normalization if low neprilysin levels lead to increased Abeta42 levels. Successful completion of the current proposal will confirm the preliminary finding of a unique AA endophenotype within the broader AD-spectrum disorders, directly examine whether endothelial dysfunctions additively and synergistically lead to cognitive decline in AD among AA in a cross-sectional cohort, and help power and design a future a multi-center, multi-racial longitudinal biomarker study to validate these cross-sectional findings.

Study Type

Observational

Enrollment (Actual)

135

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

African American and non-Hispanic white seniors with normal cognition, mild cognitive impairment (MCI), or mild Alzheimer's disease.

Description

Inclusion Criteria:

  • Ages 60-85.
  • Has normal cognition, a diagnosis of mild cognitive impairment, or a diagnosis of Alzheimer's disease or mild cognitive impairment.
  • Self-reported race of African American or non-Hispanic white.
  • Able to undergo neuropsychological testing, lumbar puncture, and MRI.
  • English speaking.

Exclusion Criteria:

  • History of stroke.
  • Diagnosis of Parkinson's disease, amyotrophic lateral sclerosis, or another progressive neurological disorder which may spare cognition.
  • Mini-Mental State Examination (MMSE) < 17

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
African Americans
This group consists of African American (AA) individuals aged 65-80 who are part of the Emory Alzheimer's Disease Research Center (ADRC) (a multi-racial cohort of subjects with normal cognition, Mild Cognitive Impairment (MCI) or mild Alzheimer's Disease (AD)) or the Registry for Remembrance (RfR) (a community of AA individuals who are interested in studies of memory and aging). AA and Non-Hispanic White (NHW) participants will be frequency-matched for age, gender, and education within each cognitive category (35 with normal cognition, 30 with MCI, and 10 with mild AD for each race).
Procedure: Lumbar puncture
Cerebrospinal fluid (CSF) will be collected via lumbar puncture. During lumbar puncture, a needle is inserted between two lumbar bones (vertebrae) to remove a sample of cerebrospinal fluid. The procedure involves inserting a thin, hollow needle between the two lower vertebrae (lumbar region), through the spinal membrane (dura) and into the spinal canal and extracting a small amount of fluid. The procedure takes about 45 minutes.
Other Names:
  • Spinal tap
Procedure: Blood draw
One tube of blood will be collected in an ethylenediaminetetraacetic acid (EDTA)-K2 plasma tube for DNA analysis.
Procedure: Magnetic Resonance Imaging (MRI)
Each participant will undergo Magnetic Resonance Imaging (MRI) analysis using a modified Alzheimer's Disease Neuroimaging Initiative (ADNI) protocol with a 3 Tesla (3T) MRI Scan. The exam takes approximately 20 minutes.
Non-Hispanic Whites
This group consists of Non-Hispanic White (NHW) individuals aged 65-80 who are part of the Emory Alzheimer's Disease Research Center (ADRC) (a multi-racial cohort of subjects with normal cognition, Mild Cognitive Impairment (MCI) or mild Alzheimer's Disease (AD)). African American (AA) and Non-Hispanic White (NHW) participants will be frequency-matched for age, gender, and education within each cognitive category (35 with normal cognition, 30 with MCI, and 10 with mild AD for each race).
Procedure: Lumbar puncture
Cerebrospinal fluid (CSF) will be collected via lumbar puncture. During lumbar puncture, a needle is inserted between two lumbar bones (vertebrae) to remove a sample of cerebrospinal fluid. The procedure involves inserting a thin, hollow needle between the two lower vertebrae (lumbar region), through the spinal membrane (dura) and into the spinal canal and extracting a small amount of fluid. The procedure takes about 45 minutes.
Other Names:
  • Spinal tap
Procedure: Blood draw
One tube of blood will be collected in an ethylenediaminetetraacetic acid (EDTA)-K2 plasma tube for DNA analysis.
Procedure: Magnetic Resonance Imaging (MRI)
Each participant will undergo Magnetic Resonance Imaging (MRI) analysis using a modified Alzheimer's Disease Neuroimaging Initiative (ADNI) protocol with a 3 Tesla (3T) MRI Scan. The exam takes approximately 20 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
CSF endothelial marker levels
Time Frame: one time only
one time only
CSF Alzheimer's biomarker levels
Time Frame: one time only
one time only

Secondary Outcome Measures

Outcome Measure
Time Frame
MRI evidence of small vessel disease
Time Frame: one time only
one time only
MRI evidence of brain atrophy
Time Frame: one time only
one time only

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: William Hu, MD, PhD, Emory University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

June 1, 2016

Study Completion (Actual)

June 1, 2016

Study Registration Dates

First Submitted

March 14, 2014

First Submitted That Met QC Criteria

March 17, 2014

First Posted (Estimate)

March 18, 2014

Study Record Updates

Last Update Posted (Estimate)

June 23, 2016

Last Update Submitted That Met QC Criteria

June 21, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00066145
  • R21AG043885 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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