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

J Alzheimers Dis. 2022;86(3):1275-1285. doi: 10.3233/JAD-210636.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Alzheimer Disease*
  • Amyloid beta-Peptides
  • Biomarkers
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / epidemiology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Independent Living
  • Male
  • Positron-Emission Tomography
  • Smell
  • tau Proteins


  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins