A decreased ability to identify odors might indicate the development of cognitive impairment and Alzheimer's disease, according to the results of two research trials reported at the Alzheimer's Association International Conference® 2014.  In the two studies, the decreased ability to identify odors was significantly associated with loss of brain cell function and progression to Alzheimer's disease.

"In the face of the growing worldwide Alzheimer's disease epidemic, there is a pressing need for simple, less invasive diagnostic tests that will identify the risk of Alzheimer's much earlier in the disease process," said Heather Snyder, Ph.D., Alzheimer's Association director of Medical and Scientific Operations. "This is especially true as Alzheimer's researchers move treatment and prevention trials earlier in the course of the disease."

There is growing evidence that the decreased ability to correctly identify odors is a predictor of cognitive impairment and an early clinical feature of Alzheimer's. As the disease begins to kill brain cells, this often includes cells that are important to the sense of smell.

In one study, Matthew E. Growdon, B.A., M.D./M.P.H. candidate at Harvard Medical School and Harvard School of Public Health, and colleagues investigated the associations between sense of smell, memory performance, biomarkers of loss of brain cell function, and amyloid deposition in 215 clinically normal elderly individuals enrolled in the Harvard Aging Brain Study at the Massachusetts General Hospital. The researchers administered the 40-item University of Pennsylvania Smell Identification Test (UPSIT) and a comprehensive battery of cognitive tests. They also measured the size of two brain structures deep in the temporal lobes – the entorhinal cortex and the hippocampus (which are important for memory) – and amyloid deposits in the brain.

At AAIC 2014, Growdon reported that, in this study population, a smaller hippocampus and a thinner entorhinal cortex were associated with worse smell identification and worse memory. The scientists also found that, in a subgroup of study participants with elevated levels of amyloid in their brain, greater brain cell death, as indicated by a thinner entorhinal cortex, was significantly associated with worse olfactory function after adjusting for variables including age, gender, and an estimate of cognitive reserve.

"Our research suggests that there may be a role for smell identification testing in clinically normal, older individuals who are at risk for Alzheimer's disease," said Growdon. "For example, it may prove useful to identify proper candidates for more expensive or invasive tests. Our findings are promising but must be interpreted with caution. These results reflect a snapshot in time; research conducted over time will give us a better idea of the utility of olfactory testing for early detection of Alzheimer's."

The Harvard Aging Brain Study is funded by the U.S. National Institute on Aging and the Alzheimer's Association.

In another study, Davangere Devanand, M.B.B.S., M.D., Professor of Psychiatry (in Neurology and in the Sergievsky Center) at Columbia University Medical Center and colleagues investigated a multi-ethnic (34% White, 30% African-American, 36% Hispanic) sample of 1037 non-demented elderly people in New York City, with an average age of 80.7, and assessed them in a variety of ways at three time periods – from 2004-2006, 2006-2008, and 2008-2010. UPSIT was administered in English and Spanish between 2004 and 2006. During follow-up 109 people transitioned to dementia (101=Alzheimer's). There were 270 deaths.

At AAIC 2014, Devanand reported that, in 757 subjects who were followed, lower odor identification scores on UPSIT were significantly associated with the transition to dementia and Alzheimer's disease, after controlling for demographic, cognitive, and functional measures, language of administration, and apolipoprotein E genotype. For each point lower that a person scored on the UPSIT, the risk of Alzheimer's increased by about 10%. Further, lower baseline UPSIT scores, but not measures of verbal memory, were significantly associated with cognitive decline in participants without baseline cognitive impairment.

"Odor identification deficits were associated with the transition to dementia and Alzheimer's disease, and with cognitive decline in cognitively intact participants, in our community sample. The test was effective in both English and Spanish," said Devanand. "If further large-scale studies reproduce these results, a relatively inexpensive test such as odor identification may be able to identify subjects at increased risk of dementia and Alzheimer's disease at a very early stage, and may be useful in identifying people at increased risk of cognitive decline more broadly."