Olfactory Deficit in Alzheimer's Disease?

To the Editor: D.P. Devanand, M.D., and colleagues (1) reported that a deficit in identifying odors, as measured by the Pennsylvania Smell Identification Test, predicted later development of Alzheimer’s disease in subjects who were unaware of their olfactory deficit. However, it remains unclear whether the observed deficit was a result of an impairment in olfactory discrimination or of a more general semantic categorization impairment (naming odors or recognizing their names). The few studies of olfactory evoked potentials in Alzheimer’s disease have contradictory results. In the study by Sakuma et al. (2) of patients with Alzheimer’s disease, olfactory evoked potentials had fewer components despite the patients’ having no olfactory dysfunction. By contrast, Hawkes and Shephard (3) found that scores on the Pennsylvania Smell Identification Test were abnormal in eight patients with Alzheimer’s disease, although olfactory evoked potentials were normal in the four who could be tested.

Dr. Devanand et al. found that olfactory difficulties, along with the lack of awareness of olfactory dysfunction, together predicted development of Alzheimer’s disease. Sixteen of their 19 patients who developed Alzheimer’s disease were aware of their declining cognitive function but reported having no problem identifying smells. However, explicit and implicit categorization is disrupted in patients with Alzheimer’s disease. Patients with Alzheimer’s disease are impaired in learning prototype categories (4) and in recognizing semantic categories (5). The Pennsylvania Smell Identification Test requires patients to recognize and select the name of the previously smelled odor from a list, which requires semantic categorization. Thus, impaired categorization could contribute to impairment on the Pennsylvania Smell Identification Test.

Because the prevalence of Alzheimer’s disease is 3% in individuals above age 40 in the population, the study by Dr. Devanand et al. is potentially of great significance; it could lead to the development of an easy, inexpensive olfaction/categorization screening test for Alzheimer’s disease. If impaired categorization is responsible for the findings of impaired odor identification in patients with Alzheimer’s disease, several other tests of categorization could be suggested for screening. On the other hand, if the olfactory impairment is found to be specific to Alzheimer’s disease, the use of the Pennsylvania Smell Identification Test and other olfactory measurements will be necessary. Further studies using complex behavioral, psychophysiological, and electrophysiological measures of olfaction could solve this problem.