Study Sniffs Out Link Between Smaller Brain Volume and Poor Olfaction

Norra MacReady

March 26, 2010

March 26, 2010 (Anaheim, California) — Poor olfaction is associated with diminished left hippocampal volume in cognitively normal elderly men, according to findings presented here at the American Medical Student Association 60th Annual Convention.

Previous research has shown an association between left hippocampal volume loss and poor olfaction in people with Alzheimer's disease, and low scores on olfactory tests have been predictive of cognitive impairment, said Iris Kim, who presented the findings at a poster session. However, no one has studied this association in people who are still cognitively intact. "These findings may contribute to our understanding of the pathophysiology of Alzheimer's disease, and may help us develop future screening tests for it," said Ms. Kim, a second-year medical student at the University of Hawaii at Manoa.

The subjects were men participating in the longitudinal Honolulu-Asia Aging Study (HAAS), part of the Honolulu Heart Program (HHP), which has been running since 1965. The HAAS began in 1991, when cognitive screening was added to the periodic examinations that were part of the HHP.

The men in this study were screened from 1991 to 1993 (examination 4 of the HHP), and again from 1994 to 1996 (examination 5). To measure olfaction, the Brief Smell Identification Test (B-SIT), a validated scratch-and-sniff odor identification test, was administered during those exams.

In examination 5, a subset of 576 men underwent magnetic resonance imaging (MRI) scans of the brain. Men with evidence of cognitive impairment at examinations 4 or 5 or with invalid B-SIT results were excluded from this analysis, leaving a final sample of 276 participants. The average age was 81 years (range, 71 to 95 years) across the 2 examinations.

After adjustment for age, education, apoE4 allele, and prevalent stroke, men in the lowest olfaction quartile had an odds ratio of having significantly reduced left hippocampal volume of 3.0 (= .03). Poor olfaction also was associated with reduced right hippocampal volume, but the relation faded after adjustment for the covariates.

Different hemispheres govern different types of cognitive functions, with the left hemisphere controlling language and certain memory tasks. "The lateralization of our results may reflect the involvement of the left brain in the identification of smells," Ms. Kim wrote in the poster.

Alzheimer's disease is not the only neurologic disorder associated with declining olfaction, said Susan Bookheimer, PhD, Joaquin Fuster Professor of Cognitive Neuroscience at the University of California at Los Angeles Geffen School of Medicine. "Parkinson's disease, frontotemporal dementia, and even traumatic brain injury are associated with poor smell."

The olfactory bulb is especially vulnerable to insults because it contains relatively few neurons, so "it's a sensitive mark of neural loss, because it doesn't need to take a lot of hits before it goes," she explained.

"These results are interesting but not surprising," said Dr. Bookheimer, who was not involved in this research. "We know that in the pre-Alzheimer's stages there is both hippocampal loss and smell loss, but it's nice that they were able to show that these were related to one another in a preclinical population."

The significance, Dr. Bookheimer told Medscape Medical Med Students, is that "if you can screen someone with a smell test, it's a lot cheaper than having them in for an MRI scan to detect the possibility of developing more serious problems. These findings point toward potential studies that might help with the early detection of Alzheimer's disease."

American Medical Student Association (AMSA) 60th Annual Convention: Abstract 20. Presented March 11, 2010.

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