Abstract
OBJECTIVE: We aimed to examine whether impaired olfaction is associated with cognitive decline and indicators of neurodegeneration in the brain of dementia-free older adults. METHODS: Within the Rush Memory and Aging Project, 380 dementia-free participants (mean age = 78 years) were followed for up to 15 years, and underwent MRI scans. Olfactory function was assessed using the Brief Smell Identification Test (B-SIT) at baseline, and categorized as anosmia (B-SIT <6), hyposmia (B-SIT 6-10 in men and 6-10.25 in women), and normal (B-SIT 10.25-12 in men and 10.5-12 in women). Cognitive function was annually assessed with a battery of 21 tests, from which composite scores were derived. Structural total and regional brain volumes were estimated. Data were analyzed using linear regression and mixed-effects models. RESULTS: At study entry, 138 (36.3%) had normal olfactory function, 213 (56.1%) had hyposmia, and 29 (7.6%) had anosmia. In multiadjusted mixed-effects models, hyposmia (β = -0.03, 95% confidence interval [CI] -0.05 to -0.02) and anosmia (β = -0.13, 95% CI -0.16 to -0.09) were associated with faster rate of cognitive decline compared to normal olfaction. On MRI, impaired olfaction (hyposmia or anosmia) was related to smaller volumes of the hippocampus (β = -0.19, 95% CI -0.33 to -0.05), and in the entorhinal (β = -0.16, 95% CI -0.24 to -0.08), fusiform (β = -0.45, 95% CI -0.78 to -0.14), and middle temporal (β = -0.38, 95% CI -0.72 to -0.01) cortices. CONCLUSION: Impaired olfaction predicts faster cognitive decline and might indicate neurodegeneration in the brain among dementia-free older adults.