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Impaired olfaction as a marker for cognitive decline

Interaction with apolipoprotein E 4 status

From the Department of Epidemiology and Biostatistics (Dr. Borenstein Graves and L. Rajaram), University of South Florida, Tampa, FL; the Departments of Neurology (Dr. Bowen), Medicine (Drs. McCormick and Larson), and Psychiatry and Behavioral Sciences (Dr. McCurry), University of Washington, Seattle, WA; and the Division of Gerontology and Geriatric Medicine (Dr. Schellenberg), Veterans Affairs Medical Center, GRECC, Seattle, WA.

Address correspondence and reprint requests to Dr. Amy Borenstein Graves, Department of Epidemiology and Biostatistics, College of Public Health, MDC-56, University of South Florida, 13201 Bruce B. Downs Boulevard, Tampa, FL 33612-3805; e-mail: agraves{at}hsc.usf.edu

OBJECTIVE: To determine whether olfactory status predicts cognitive decline (CD) over a 2-year follow-up period.

METHODS: The authors enrolled individuals in a community-based longitudinal study of memory and aging in the Japanese–American community in King County, WA, between 1992 and 1994. At baseline they screened 1,985 persons using the Cognitive Abilities Screening Instrument (CASI) and the 12-item Cross-Cultural Smell Identification Test (CC-SIT). Of these 1,985 people, 1,836 were found not to be demented. Two years later the authors rescreened 1,604 participants with the CASI. They defined CD as a 2-year loss of 5.15 points/100 on the CASI. They genotyped 69% of the 1,604 people completing both examinations for apolipoprotein E (apoE).

RESULTS: After adjusting for age, CASI score at baseline, education, smoking, sex, and follow-up time, the authors determined an odds ratio (OR) for CD of 0.90 (95% CI, 0.84 to 0.97) for an increase in each correct point on the CC-SIT (range, 0 to 12). Compared with normosmics, the OR for persons with impaired olfaction (microsmics) was 1.25 (95% CI, 0.83 to 1.89) and for anosmics the OR was 1.92 (95% CI, 1.06 to 3.47). Persons who were anosmic at baseline and who had at least one APOE-4 allele had 4.9 times the risk of CD (95% CI, 1.6 to 14.9) compared with normosmics without the 4 allele. The estimated relative risk among women was 9.7 (95% CI, 1.3 to 70.4), and for men the risk was 3.2 (95% CI, 0.8 to 12.6). Receiver operating characteristic (ROC) curves showed that although the area under the curve (AUC) for baseline CASI was only 0.51, the AUC for CC-SIT alone was 0.62. Adding CC-SIT to the ROC model with CASI improved the AUC curve from 0.51 to 0.62.

CONCLUSIONS: Unexplained olfactory dysfunction in the presence of one or more APOE-4 alleles is associated with a high risk of cognitive decline. Cross-Cultural Smell Identification Test classifies people with cognitive decline correctly to a greater degree than a global cognitive test.

Key words: Olfaction—Apolipoprotein E—Cognitive decline.

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