Olfactory impairment is associated with incident amnestic mild cognitive impairment (aMCI) and progression from aMCI to Alzheimer’s disease dementia, according to research published online ahead of print November 16 in JAMA Neurology. The results are consistent with previous data that indicate an association between olfactory impairment and cognitive impairment in late life. Olfactory tests thus may aid neurologists in screening for MCI and MCI that is likely to progress, said the authors.

A Population-Based Study

Rosebud O. Roberts, MB, ChB, Professor of Epidemiology and Neurology at Mayo Clinic in Rochester, Minnesota, and colleagues examined data for participants who were enrolled in the Mayo Clinic Study of Aging between 2004 and 2010 and were evaluated in person. At baseline, investigators asked each participant and an informant questions about memory and administered the Beck Depression Inventory, Beck Anxiety Inventory, the Clinical Dementia Rating scale, Functional Activities Questionnaire, and Neuropsychiatric Inventory Questionnaire. Physicians obtained medical histories from the participants, who underwent a neurologic exam and neuropsychologic testing that assessed memory, executive function, language, and visuospatial skills.

Researchers reviewed participants’ data for a diagnosis of MCI, dementia, or normal cognition. Patients were followed up at 15-month intervals for incident diagnoses of MCI or dementia. The investigators assessed participants’ olfaction using the Brief Smell Identification Test (B-SIT).

B-SIT Score Predicted MCI

A total of 1,430 cognitively normal participants were included in the study. Their mean age was 79.5, 49.4% were men, and their mean duration of education was 14.3 years. Approximately 25% of the cognitively normal participants were APOE ε4 carriers. During a mean 3.5 years of follow-up, 250 cognitively normal participants developed incident MCI. The researchers noted an association between decreasing olfactory identification, as measured by a decrease in the number of correct responses on the B-SIT, and an increased risk of MCI.

Dr. Roberts and colleagues found that the risk of MCI increased with decreasing B-SIT scores. They observed a significant dose-response association across worsening olfaction categories. The associations remained significant after the researchers adjusted for stroke or excluded participants with a history of stroke.

Although the investigators found no significant interaction of smell with sex or with APOE ε4 allele, the hazard ratio (HR) for MCI in men with B-SIT scores less than 9 (compared with men with scores of 9 or higher) was higher (HR, 2.35) than that for women with scores less than 9 (HR, 1.54). Also, the HR in APOE ε4 carriers with B-SIT scores less than 9 was higher (HR, 2.09) than that for noncarriers with scores less than 9 (HR, 1.72).

Impaired olfaction was associated with any MCI and with aMCI. After the researchers adjusted the data for other factors that could affect smell or MCI, the risk of aMCI for the worst B-SIT categories remained significantly elevated for quartile 1 versus quartile 4 (HR, 1.67) and for B-SIT score less than 9, compared with a score of 9 or greater. The B-SIT score was not associated with nonamnestic MCI (naMCI).

Each unit decrease in baseline B-SIT score was significantly associated with a decline in performance in memory, executive function, and language. The investigators noted similar cross-sectional and longitudinal association patterns for the individual test scores, except for Picture Completion.

In all, 221 participants with prevalent MCI were included in the study. Of these people, 36 had naMCI. The frequency of MCI decreased with increasing B-SIT score. During a mean follow-up of 3.1 years, 64 of these participants developed incident dementia. The frequency of any dementia or Alzheimer’s disease dementia decreased, and cognitive performance increased, with increasing B-SIT scores.

Among the 221 participants with prevalent MCI, the risk of dementia increased with decreasing B-SIT score, with a significant dose response across B-SIT categories. The worst B-SIT categories strongly predicted progression from aMCI to Alzheimer’s disease dementia.

Test May Spur Early Intervention

“Odor-identification tests may have use for early detection of persons at risk of cognitive outcomes,” said Dr. Roberts. “The B-SIT could be beneficial for screening to identify cognitively normal persons and persons with MCI who could benefit from early interventions to prevent or modulate risk for progression.” Combining the B-SIT with other predictors of Alzheimer’s disease dementia may help identify patients who should undergo expensive or invasive diagnostic testing to detect Alzheimer’s disease dementia pathology, she added, although the technique requires further investigation.

One weakness of the study is that the investigators could not identify and exclude people with a history of head trauma, allergies, nasal condition, or nasal diseases that could impair olfaction. Also, because of the predominance of northern European ancestry among study participants, the generalizability of the results is directly applicable to persons with similar ancestry. The authors note, however, that studies in multiethnic cohorts have reported similar findings. Because the study was population-based, the potential for selection bias was reduced. Furthermore, the study included a large cohort of cognitively normal participants and participants with MCI, and both sexes were equally represented. Reliable and valid information on covariates was abstracted from community medical records rather than by self-report.

—Erik Greb

Olfactory Impairment Is Associated With Amnestic MCI