ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02089555
Recruitment Status : Completed
First Posted : March 18, 2014
Last Update Posted : June 23, 2016
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
William Hu MD/PhD, Emory University

Brief Summary:
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.

Condition or disease Intervention/treatment
Mild Cognitive Impairment Alzheimer's Disease Procedure: Lumbar puncture Procedure: Blood draw Procedure: Magnetic Resonance Imaging (MRI)

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
Actual Enrollment : 135 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Biomarkers for Alzheimer's Disease and Mild Cognitive Impairment in African Americans and Caucasians
Study Start Date : September 2013
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016


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 Name: 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 Name: 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.




Primary Outcome Measures :
  1. CSF endothelial marker levels [ Time Frame: one time only ]
  2. CSF Alzheimer's biomarker levels [ Time Frame: one time only ]

Secondary Outcome Measures :
  1. MRI evidence of small vessel disease [ Time Frame: one time only ]
  2. MRI evidence of brain atrophy [ Time Frame: one time only ]

Biospecimen Retention:   Samples With DNA
Cerebrospinal fluid, plasma, and DNA will be saved.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   60 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02089555


Locations
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
National Institute on Aging (NIA)
Investigators
Principal Investigator: William Hu, MD, PhD Emory University

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: William Hu MD/PhD, Assistant Professor of Neurology, Emory University
ClinicalTrials.gov Identifier: NCT02089555     History of Changes
Other Study ID Numbers: IRB00066145
R21AG043885 ( U.S. NIH Grant/Contract )
First Posted: March 18, 2014    Key Record Dates
Last Update Posted: June 23, 2016
Last Verified: June 2016

Additional relevant MeSH terms:
Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders