Neuroimaging Biomarkers and Impaired Olfaction in Cognitively Normal Individuals

Objective: There is a need for inexpensive noninvasive tests to identify older healthy persons at risk for Alzheimer disease (AD) for enrollment in AD prevention trials. Our objective was to examine whether abnormalities in neuroimaging measures of amyloid and neurodegeneration are correlated with odor identification (OI) in the population-based Mayo Clinic Study of Aging. Methods: Cognitively normal (CN) participants had olfactory function assessed using the Brief Smell Identification Test (B-SIT), underwent magnetic resonance imaging (n = 829) to assess a composite AD signature cortical thickness and hippocampal volume (HVa), and underwent C-11-Pittsburgh compound B (n = 306) and (18)fluorodeoxyglucose (n = 305) positron emission tomography scanning to assess amyloid accumulation and brain hypometabolism, respectively. The association of neuroimaging biomarkers with OI was examined using multinomial logistic regression and simple linear regression models adjusted for potential confounders. Results: Among 829 CN participants (mean age = 79.2 years; 51.5% men), 248 (29.9%) were normosmic and 78 (9.4%) had anosmia (B-SIT score < 6). Abnormal AD signature cortical thickness and reduced HVa were associated with decreased OI as a continuous measure (slope = -0.43, 95% confidence interval [CI] = -0.76 to -0.09, p = 0.01 and slope = -0.72, 95% CI = -1.15 to -0.28, p < 0.01, respectively). Reduced HVa, decreased AD signature cortical thickness, and increased amyloid accumulation were significantly associated with increased odds of anosmia. Interpretation: Our findings suggest that OI may be a noninvasive, inexpensive marker for risk stratification, for identifying participants at the preclinical stage of AD who may be at risk for cognitive impairment and eligible for inclusion in AD prevention clinical trials. These cross-sectional findings remain to be validated prospectively.