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Rapid Loss of Smell May Be Alzheimer's Precursor

Rapid Loss of Smell May Be Alzheimer's Precursor

Could the future of dementia screening include a test of a person's sense of smell?

It may, suggests a new study that found the decline in a person's sense of smell could predict their loss of mental function and warn of structural changes in the brain that are important in Alzheimer's disease.

"This study provides another clue to how a rapid decline in the sense of smell is a really good indicator of what's going to end up structurally occurring in specific regions of the brain,"said co-author Dr. Jayant Pinto, a professor of surgery at the University of Chicago and an ear, nose and throat specialist.

That there is a link between sense of smell and dementia isn't new information. Plaques and tangles that happen in Alzheimer's disease often appear in smell- and memory-associated areas of the brain before they show up in other parts of the brain, the study authors noted. Researchers do not know if this damage causes the decline in sense of smell.

For this study, the investigators worked to see if it was possible to identify alterations in the brain that correlated with loss of smell and mental, or cognitive, function over time.

"Our idea was that people with a rapidly declining sense of smell over time would be in worse shape -- and more likely to have brain problems and even Alzheimer's itself -- than people who were slowly declining or maintaining a normal sense of smell,"said Rachel Pacyna, a rising fourth-year medical student at the University of Chicago School of Medicine and lead author of the study.

The research team used data on 515 older adults from Rush University's Memory and Aging Project (MAP).

Researchers test MAP volunteers annually for their ability to identify certain smells, for mental function and for signs of dementia. Some participants have also received an MRI scan.

The study team found that the rapid decline in sense of smell during a period of normalcy predicted smaller gray matter volume in the areas of the brain related to smell and memory. It also predicted worse mental functioning and higher risk of dementia in these older adults.

The risk was similar to carrying the APOE-e4 gene, which is already a known genetic risk factor for developing Alzheimer's, the team explained in a university news release.

The researchers also found that the changes were most noticeable in the primary olfactory regions -- regions related to the sense of smell -- including the amygdala and entorhinal cortex. This is a major input to the hippocampus, which is a critical site in Alzheimer's disease.

"We were able to show that the volume and shape of gray matter in olfactory and memory-associated areas of the brains of people with rapid decline in their sense of smell were smaller compared to people who had less severe olfactory decline,"Pinto said.

The study was limited in that participants received only one MRI scan, so the team could not pinpoint when structural changes in these brains began.

"We have to take our study in the context of all of the risk factors that we know about Alzheimer's, including the effects of diet and exercise,"said Pinto. "Sense of smell and change in the sense of smell should be one important component in the context of an array of factors that we believe affect the brain in health and aging."

Another limitation is that participants were only white adults. Prior work by the team had shown marked disparities by race.

More than 6 million Americans have Alzheimer's disease, for which there is no cure. Some medications can temporarily slow symptoms.

The findings were published online July 28 in Alzheimer's & Dementia.

More information

The U.S. National Institute on Aging has more on Alzheimer's disease.

SOURCE: University of Chicago Medical Center, news release, July 28, 2022

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