Olfaction, Cognition, and Early Signs of Neurodegenerative Disease in a Community-Based Sample of Older Adults

Introduction: We investigated associations of impaired odor identification with signs of early Alzheimer disease (AD) and Lewy Body disease (LBD). Methods: In 787 community-sampled adults aged ≥65 without dementia or Parkinson disease, we evaluated cross-sectional associations of olfaction (Brief Smell Identification Test, BSIT) with 5 cognitive domain scores, gait, tone, tremor, REM sleep behavior disorder (RBD) symptoms, and plasma biomarkers of neurodegeneration. Results: In adjusted regression models, worse BSIT scores were associated with lower cognitive scores in all domains, slowed gait, resting tremor, and RBD-like symptoms. The association between BSIT and memory was stronger in APOE4 carriers. In cognitively unimpaired participants (Clinical Dementia Rating=0), most associations remained significant. BSIT scores were associated with plasma p-tau217 and NfL in exploratory analyses. Conclusion: Odor identification is associated with cognition in an undifferentiated pattern and with Parkinsonian signs in older adults, even among those with normal cognition. The stronger association in APOE4 carriers potentially suggests an emerging AD-like pathway, consistent with exploratory plasma biomarker analyses. In sum, evidence points to olfactory dysfunction as relevant for both AD and LBD-associated future risk.