Odor identification and Alzheimer disease biomarkers in clinically normal elderly

Abstract

Objectives: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Figure 1. UPSIT identifies a subset of the cohort with normal episodic memory performance that is putatively at risk

Venn diagram depicting overlap of groups defined by lower 25th percentile of episodic memory and odor identification testing (n = 91 in the low performer groups). Blue depicts low performers on UPSIT (n = 59), red depicts low performance on memory testing (n = 54), and purple depicts participants who had low performance on both tests (n = 22). Note the relatively small overlap between low-performing groups, and the fact that a slightly greater number of participants had low performance on the odor identification test compared with those who had low performance on the episodic memory tests. UPSIT = 40-item University of Pennsylvania Smell Identification Test.

Figure 2. Depiction of the associations among UPSIT, EC thickness, and amyloid

In the multivariate model with UPSIT-40 as the dependent variable (n = 165), in PiB-positive individuals, thinner EC was significantly associated with worse odor identification (interaction term, p = 0.02). The slope for the PiB-positive individuals was significant (β = 2.6, 95% confidence interval: 0.88, 4.4; p = 0.004), while the slope for PiB-negative individuals was not (β = 0.038, 95% confidence interval: −1.3, 1.4; p = 0.96). EC = entorhinal cortex; PiB = Pittsburgh compound B (PiB status 1.20 distribution volume ratio positivity cutoff); UPSIT = 40-item University of Pennsylvania Smell Identification Test.