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Robert S. Wilson, PhD; Julie A. Schneider, MD; Steven E. Arnold, MD; Yuxiao Tang, PhD; Patricia A. Boyle, PhD; David A. Bennett, MD

Arch Gen Psychiatry. 2007;64(7):802-808.

Context  Mild cognitive impairment (MCI) is often a precursor to Alzheimer disease, but knowledge about factors that predict its development is limited.

Objective  To test the hypothesis that impaired odor identification is related to increased risk of incident MCI.

Design  Longitudinal cohort study.

Setting  Academic research.

Participants  Subjects were 589 community-dwelling older persons without cognitive impairment at study baseline, at which time odor identification was assessed using the 12-item Brief Smell Identification Test (mean ± SD score, 9.3 ± 1.9).

Main Outcome Measures  Incidence of MCI and rate of decline in cognitive function.

Results  During annual observation of up to 5 years, 177 subjects developed MCI. In a proportional hazards model adjusted for age, sex, and education, odor identification score predicted development of MCI (relative risk, 1.15; 95% confidence interval, 1.07-1.23), with risk increased by 50% in persons with below-average (score of 8 [25th percentile]) compared with above-average (score of 11 [75th percentile]) odor identification scores. Results were not substantially changed in subsequent analyses that controlled for level of cognitive function or disability, presence of stroke, or smoking status at baseline or that required MCI to persist for at least 1 year. Impaired odor identification was also associated with a lower level of global cognition at baseline and with more rapid decline in episodic memory, semantic memory, and perceptual speed.

Conclusion  Among older persons without manifest cognitive impairment, difficulty in identifying odors predicts subsequent development of MCI.

Author Affiliations: Rush Alzheimer's Disease Center (Drs Wilson, Schneider, Boyle, and Bennett), Rush Institute for Healthy Aging (Dr Tang), and Departments of Neurological Sciences (Drs Wilson, Schneider, and Bennett), Behavioral Sciences (Drs Wilson and Boyle), Pathology (Dr Schneider), and Internal Medicine (Dr Tang), Rush University Medical Center, Chicago, Illinois; and Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia (Dr Arnold).