Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging

Abstract Objectives To explore whether the ability to recognize specific odorant items are differentially affected in aging versus Alzheimer's disease (AD); To refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. Design Prospective multicenter cross-sectional study with a longitudinal arm Setting Outpatient memory diagnostic clinics in New York and Texas Participants Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. Measurements Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. Results For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. Conclusions Non-overlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals.