Affiliations: [a] Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA
| [b] Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA
| [c] Department of Neurology and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Correspondence:
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Correspondence to: Qu Tian, PhD, 251 Bayview Blvd., Suite 100, RM04B316, Baltimore, MD 21224, USA. Tel.: +1 410 558 8232; E-mail: qu.tian@nih.gov.
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, olfaction, PET biomarkers, tau
