African American Alzheimer's Progression Markers - CSF and Neuro-Imaging
African American Alzheimer's Progression Markers - CSF and Neuro-Imaging
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.
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.
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