Olfactory Phenotypes Differentiate Cognitively Unimpaired Seniors from Alzheimer’s Disease and Mild Cognitive Impairment: A Combined Machine Learning and Traditional Statistical Approach

Background: Olfactory dysfunction (OD) is an early symptom of Alzheimer’s disease (AD). However, olfactory testing is not commonly performed to test OD in the setting of AD. Objective: This work investigates objective OD as a non-invasive biomarker for accurately classifying subjects as cognitively unimpaired (CU), mild cognitive impairment (MCI), and AD. Methods: Patients with MCI (n = 24) and AD (n = 24), and CU (n = 33) controls completed two objective tests of olfaction (Affordable, Rapid, Olfactory Measurement Array –AROMA; Sniffin’ Sticks Screening 12 Test –SST12). Demographic and subjective sinonasal and olfaction symptom information was also obtained. Analyses utilized traditional statistics and machine learning to determine olfactory variables, and combinations of variables, of importance for differentiating normal and disease states. Results: Inability to correctly identify a scent after detection was a hallmark of MCI/AD. AROMA was superior to SST12 for differentiating MCI from AD. Performance on the clove scent was significantly different between all three groups. AROMA regression modeling yielded six scents with AUC of the ROC of 0.890 (p