Impaired olfaction is associated with cognitive decline and neurodegeneration in the brain

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.

Figure 1. Flowchart of study participants

D = died; FU = follow-up; M = missing.

Figure 2. Predicted trajectory of global cognitive decline by olfaction categories

Lines represent β coefficients from linear mixed-effects model adjusted for age, sex, education, practice effects, and APOE ε4 allele, with normal olfaction as reference group. Green line: normal olfaction (B-SIT score men 10.25–12, women 10.5–12); red line: hyposmia (B-SIT score men 6–10, women 6–10.25); and blue line: anosmia (B-SIT <6). B-SIT = Brief Smell Identification Test.

Figure 3. β Coefficients and 95% CIs of olfactory function in relation to regional brain volumes from linear regression (adjusted for age, sex, education, APOE ε4, baseline global cognition, and scanning site)

Olfaction categories were defined based on baseline Brief Smell Identification Test scores as follows: anosmia (score <6), hyposmia (6–10 men, women 6–10.25), and normal olfaction (10.25–12 men, women 10.5–12). Volumes are expressed as tenths of percentages of intracranial volume. CI = confidence interval.