OLFACTORY IMPAIRMENT IN OFFSPRING STUDY OF RACIAL DISPARITIES IN ALZHEIMER'S DISEASE

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We plan to test the 12-item BSIT, a short, standardized, cross-culturally validated subset of the 40-item University of Pennsylvania Smell Identification Test (UPSIT), in an add-on study to the recently funded project “Offspring study of mechanisms for racial disparities in Alzheimer's disease” (RF1 AG054070). Middle-aged offspring (age 40-64) of parents who participated in the Washington Heights Inwood Columbia Aging Project (WHICAP) are being studied with clinical and neuropsychological evaluation (n=3,000), high-resolution structural MRI (n=1,000), and Aβ PET (n=150). In the years 2004-2010, over one-third (n=1,369) of the intensively studied parent cohort had odor identification testing with the full 40-item UPSIT. Odor identification impairment distinguishes dementia from cognitively intact controls, predicts transition from mild cognitive impairment (MCI) to dementia, and predicts cognitive decline in older adults without dementia better than episodic verbal memory deficits. Further, odor identification impairment has been associated with increased mortality even after controlling for dementia and medical comorbidity in older adults, and in this offspring study, mortality will become an important outcome if longitudinal follow-up is instituted eventually. In the proposed cross-sectional study, we hypothesize that in the cohort of 3,000 offspring, lower BSIT scores (impaired odor identification) will be associated with increased age and the apolipoprotein E ε4 allele, and correlate with impaired cognitive ability in Whites (increased incipient AD pathology) to a greater extent than in African Americans or Hispanics (increased incipient cerebrovascular pathology). In the 1,000 offspring that get MRI brain scans, we expect that lower BSIT scores will be associated with smaller hippocampal volume and cortical thinning in Whites but not African Americans or Hispanics. In the 150 offspring that get amyloid PET scans, lower BSIT scores are anticipated to be associated with greater amyloid uptake among Whites, but not among African Americans or Hispanics. We will also evaluate BSIT in the offspring in relation to parental BSIT performance and risk of AD in the parents. We have begun pilot work in administering the BSIT to the first 300 offspring being studied, and expect to be able to assess all study participants with the BSIT, without loss of any BSIT data, if this proposal is funded. Our overarching goal is to identify priority biological or social factors for intervention during the preclinical stage of AD, and determine whether strategies to prevent AD should differ across race/ethnicity. Adding odor identification testing furthers these goals in the existing project and allows for the testing of specific hypotheses that will enhance our understanding of the associations and potential utility of this inexpensive early biomarker of AD.