Objective: Evaluate the neuropathological correlates and prospective incident cognitive and motor changes associated with odor identification (OI) in cognitively normal (CN) subjects.

Background: Hyposmia is a well-established prodromal feature of Parkinson’s disease (PD), which predates the onset of its motor symptoms by over a decade and is associated with the presence of Lewy-related pathology (LRP) at death. Previous studies have shown that hyposmia is associated with increased risk of developing mild cognitive impairment (MCI) and dementia.

Method: We included 721 subjects from the Rush Memory and Aging Project (MAP) with at least one pre-mortem OI test and post-mortem neuropathological evaluation. 65.6%, 25.8%, and 8.6% had a diagnosis of CN, MCI or dementia at baseline with a median follow-up of 6.5 years from their first OI test until death.

Results: To evaluate the association between OI and clinical and neuropathological findings, we selected the last OI testing (median 1.5 years before the subject’s death). MCI and dementia were strongly associated with lower OI scores. Hence, we studied the association of OI with neuropathological findings in CN subjects. LRP was associated with lower OI scores, whereas TDP-43 and AD pathology were not. This association was present in subjects who remained cognitively normal for 10 years and did not develop PD. Using a training set with an independent validation set, OI showed high specificity to predict the presence of LRP 5 years before the subjects’ death. Thresholds were affected by the cognitive function. When we evaluated the incidence of PD and cognitive symptoms using the OI scores obtained at baseline, lower OI scores were associated with increased risk of developing MCI or dementia; this association remained after controlling for the presence of LRP at autopsy. No significant association was found with incident PD risk.

Conclusion: Odor identification is a non-invasive test with high specificity to detect the presence of LRP, though it has a lower sensitivity. OI is independently affected by the presence of cognitive impairment leading to different cut-offs. In this population-based study of aging, it was associated with the incidence of MCI and dementia, but not of PD. It also was an independent predictor of cognitive impairment even after adjusting for the presence of PD, Alzheimer’s disease and TDP-43 pathology.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/odor-identification-as-a-biomarker-of-incident-cognitive-impairment-and-its-correlation-with-neuropathology-in-the-rush-map/