Odor identification and Alzheimer disease biomarkers in clinically normal elderly

Our objective was to investigate cross-sectional associations between odor identification ability and imaging biomarkers of neurodegeneration and amyloid deposition in clinically normal (CN) elderly individuals, specifically testing the hypothesis that there may be an interaction between amyloid deposition and neurodegeneration in predicting odor identification dysfunction.

Data were collected on 215 CN participants from the Harvard Aging Brain Study. Measurements included the 40-item University of Pennsylvania Smell Identification Test and neuropsychological testing, hippocampal volume (HV) and entorhinal cortex (EC) thickness from MRI, and amyloid burden using Pittsburgh compound B (PiB) PET. A linear regression model with backward elimination (p < 0.05 retention) evaluated the cross-sectional association between the University of Pennsylvania Smell Identification Test and amyloid burden, HV, and EC thickness, assessing for effect modification by PiB status. Covariates included age, sex, premorbid intelligence, APOE ε4 carrier status, and Boston Naming Test.

In unadjusted univariate analyses, worse olfaction was associated with decreased HV (p < 0.001), thinner EC (p = 0.003), worse episodic memory (p = 0.03), and marginally associated with greater amyloid burden (binary PiB status, p = 0.06). In the multivariate model, thinner EC in PiB-positive individuals (interaction term) was associated with worse olfaction (p = 0.02).

In CN elderly, worse odor identification was associated with markers of neurodegeneration. Furthermore, individuals with elevated cortical amyloid and thinner EC exhibited worse odor identification, elucidating the potential contribution of olfactory testing to detect preclinical AD in CN individuals.