Olfaction, Cognitive Impairment, and PET Biomarkers in Community-Dwelling Older Adults

Abstract

Background: Olfactory deficits are early features of preclinical Alzheimer's disease (AD). Whether olfaction is associated with PET biomarkers among community-dwelling older adults is less clear.

Objective: Investigate cross-sectional and longitudinal associations of olfaction with mild cognitive impairment (MCI) and amyloid-β (Aβ) and tau deposition.

Methods: We analyzed 364 initially cognitively normal participants (58% women, 24% black) who had baseline olfaction data and subsequent cognitive assessments during an average 2.4-year. A subset of 129 had PET-PiB (Aβ) (n = 72 repeated) and 105 had 18F-flortaucipir (FTP)-PET (tau) (n = 44 repeated). Olfaction was measured using a 16-item Sniffin' Sticks Odor Identification Test. The association of olfaction with incident MCI was examined using Cox regression. Associations with PiB-distribution volume ratio (DVR) and FTP-standardized uptake value ratio (SUVR) were examined using partial correlation. We tested whether PiB+/-status modified these associations. Analyses were adjusted for demographics and olfactory test version.

Results: 17 (5%) participants developed MCI. Each unit lower odor identification score was associated with 22% higher risk of developing MCI (p = 0.04). In the PET subset, lower scores were associated with higher mean cortical DVR and DVR in orbitofrontal cortex (OFC), precuneus, and middle temporal gyrus (p≤0.04). The "olfaction*PiB+/-" interaction in OFC DVR was significant (p = 0.03), indicating the association was limited to PiB positive individuals. Greater decline in odor identification score was associated with greater increase in anterior OFC DVR and entorhinal tau SUVR (p≤0.03).

Conclusion: Among community-dwelling older adults, poorer olfaction predicts incident MCI and is associated with overall and regional Aβ. Greater olfaction decline is associated with faster Aβ and tau accumulation in olfaction-related regions. Whether olfaction predicts AD-related neurodegenerative changes warrants further investigations.

Keywords: Amyloid-β; PET biomarkers; olfaction; tau.

Figure 1.. Kaplan–Meier plot for baseline odor identification score associated with MCI survival.

Legend: Dashed line indicates anosmia defined as 10^th percentile (score ≤7) base on previous literature [1]; Solid line indicates free of anosmia (score >7). Covariate-adjusted hazard ratio of anosmia = 4.18 (95% CI=1.38–12.62, p=0.011).

Figure 2.. Scatter plots of odor identification score with regional orbitofrontal cortex (OFC) PiB DVR stratified by PiB+/− status.

Legend: Filled circle indicates PiB positive. Empty circle indicates PiB negative.

Figure 3.. Scatter plots of the annual rate of change in odor identification score with annual rates of change in amyloid-β (top) and tau (bottom) biomarkers identified in Table 3.