African American Alzheimer's Progression Markers - CSF and Neuro-Imaging
Condition: Mild Cognitive Impairment; Alzheimer's Disease
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Study type: Observational

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.
    

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.
    

Intervention name(s): Lumbar puncture; Blood draw; Magnetic Resonance Imaging (MRI)
Intervention type(s): Procedure; Procedure; Procedure
Intervention description(s): 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.; One tube of blood will be collected in an ethylenediaminetetraacetic acid (EDTA)-K2 plasma tube for DNA analysis.; 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.
Other intervention name(s): Spinal tap
Observational model: Case-Control
Time perspective: Prospective
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.
      
Biospecimen description: 
      Cerebrospinal fluid, plasma, and DNA will be saved.