Difficulty Identifying Odors May Herald Mild Cognitive Impairment

July 9, 2007 — A study shows that among older individuals, difficulty recognizing familiar odors predicts the subsequent development of mild cognitive impairment (MCI). The results are published in the July 2007 issue of the Archives of General Psychiatry.
"We think this shows that difficulty identifying and recognizing familiar odors is a very early sign of Alzheimer's disease that can even precede the appearance of cognitive impairment that we think of as really the first sign of AD [Alzheimer's disease]," lead author Robert S. Wilson, PhD, from the Rush Alzheimer's Disease Center at Rush University Medical Center in Chicago, Illinois, told Medscape.
"We suggest this procedure could be used for early identification even before they've developed the terrible problems with memory and cognition that are associated with mild cognitive impairment and full-blown AD."
Early Warning Signal?
It has been known for some time that the brain regions first affected by AD are the olfactory centers, Dr. Wilson said. In this study, he and his colleagues tested the hypothesis that impaired odor identification may precede the development of MCI among subjects with normal cognitive scores at baseline.
Subjects for the study were 589 community-dwelling persons with an average age of 79.9 years, who were free of cognitive impairment in 1997. They underwent testing at this time using the Brief Smell Identification Test, a standardized and commercially available tool that assesses the individual's ability to recognize 12 familiar odors including lemon, rose, black pepper, and onion.
The mean score for the group was 9.3 (± 1.9). Dr. Wilson pointed out that younger individuals would be expected to score no more than 1 wrong on the test. "At the beginning of our study, the average score was about 2 to 3 errors, but about a quarter of people were making 0 or 1 errors like you would expect from younger people, but about a quarter were making 4 or more errors, suggestive of a problem," he said.
Subjects were then followed up for as many as 5 years with annual clinical evaluations. During follow-up, 177 (30.1%) subjects developed MCI.
After adjustment for age, sex, and education, odor identification score predicted development of MCI, with a relative risk of 1.15 (95% confidence interval [CI], 1.07 - 1.23). For those who scored below average — 8 correct of 12 (the 25th percentile) — the risk for MCI was increased by 50% compared with those who scored 11 of 12 (the 75th percentile).
Results were not substantially changed in further analyses that also controlled for level of cognitive function or disability, the presence of stroke, or smoking status at baseline or that required MCI to persist for at least 1 year, the authors add.
"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," they write.
Their findings build on previous research by showing that difficulty in identifying odors not only predicts the transition from MCI to AD but also the transition from normal cognition to MCI, they write.
This is important because new drugs now in development target amyloid, one of the abnormal proteins that accumulate in the brain and are the main constituent of neuritic plaques, Dr. Wilson concluded. "If these medications, as we hope, have a disease-altering effect and are able to slow the progression of the disease, it will be extremely important to identify people who are at risk for developing it but are not yet showing the crippling symptoms. We argue that olfactory testing will be important in identifying people in this very early stage."
However, the authors add, difficulty in identifying odors is associated with other neurologic disease, notably Parkinson's disease. "Further clinicopathological and clinicoradiological research on age-related olfactory dysfunction is needed."
The study was supported by grants from the National Institute on Aging and the Illinois Department of Public Health. The authors have disclosed no relevant financial relationships.
Arch Gen Psychiatry. 2007;64:802-808.