Rapid loss of smell predicts cognitive decline and small brain regions associated with Alzheimer’s

Summary: A new study suggests that loss of smell in older adults can predict not only cognitive decline but also structural changes in brain structures associated with Alzheimer’s disease.

A source: University of Chicago

Our sense of smell is often underestimated compared to our senses of sight and hearing, but our sense of smell provides important information to our brain, from detecting potential hazards like smoke to recognizing the sweet smell of cookies.

Researchers at the University of Chicago have found another reason to appreciate our sniffers. A decline in a person’s sense of smell over time not only predicts their loss of cognitive function, but can also predict structural changes in brain regions important in Alzheimer’s disease and dementia.

The findings are based on a longitudinal study of 515 older adults published on July 2 Alzheimer’s and Dementia: Journal of the Alzheimer’s Associationmay lead to the development of smell-test screening for early detection of cognitive impairment in patients.

“This study provides further evidence that rapid decline in olfactory sensitivity is a good indicator of what is happening structurally in specific brain regions,” said senior author Jayant M. Pinto, doctor of medical sciences, professor. An ENT specialist who studies surgery and olfaction and sinus disease at the University of Chicago.

More than 6 million Americans are estimated to be affected by Alzheimer’s disease every day, which is characterized by memory loss and other symptoms such as mood swings and difficulty completing tasks. There is no cure for Alzheimer’s, but some medications can temporarily slow its symptoms.

Memory plays an important role in our ability to recognize smell, and researchers have long known the link between smell and dementia. The plaques and wrinkles that characterize the tissue affected by Alzheimer’s disease often appear in areas associated with smell and memory before they appear in other parts of the brain. Whether this damage actually causes a person’s reduced sense of smell is not yet known.

Pinto and his team wanted to see if it would be possible to detect changes in the brain associated with the loss of smell and cognitive function in humans over time.

“We think that people who lose their sense of smell more rapidly over time are more likely to develop brain damage and even Alzheimer’s disease than people who lose their sense of smell more slowly or retain their normal sense of smell,” says Rachel Pacina. , a rising fourth-year medical student at the Chicago Pritzker School of Medicine and lead author of the study.

The team found anonymous patient data from Rush University’s Memory and Aging Project (MAP), a research group started in 1997 to study chronic conditions of aging and neurodegenerative diseases such as Alzheimer’s disease. MAP participants are seniors who live in retirement or senior housing communities in Northern Illinois and are tested annually on their ability to detect certain odors, cognitive function and symptoms of dementia, and other health parameters. Some participants also received an MRI scan.

Scientists at UChicago Medicine have found that rapid decline in a person’s sense of smell during periods of normal cognition predicts several features of Alzheimer’s disease, including smaller gray matter in brain regions associated with smell and memory, cognitive decline and risk of the disease. it is dementia in the elderly.

In fact, the risk of losing the sense of smell was similar to carrying the APOE-e4 gene, a known genetic risk factor for developing Alzheimer’s.

Changes were seen in key olfactory regions, including the amygdala, a major contributor to the hippocampus, and the entorhinal cortex, a site important in Alzheimer’s disease.

“We were able to show that people with rapid olfactory loss had smaller gray matter volume and shape in areas of the brain associated with smell and memory compared to people with less olfactory loss,” Pinto said.

An autopsy is the gold standard for confirming whether someone has Alzheimer’s disease, and Pinto hopes to eventually expand on these findings by examining brain tissue for Alzheimer’s markers.

The team also hopes to study the effectiveness of using smell tests in clinics – similar to how vision and hearing tests are used – as a means of screening and monitoring older adults for signs of early dementia and developing new treatments.

Smell tests are an inexpensive, easy-to-use tool that consists of a series of sticks similar to felt-tip pens. Each stick is filled with a different scent, which people must identify from a set of four choices.

“If we could identify people in their 40s, 50s and 60s earlier, we would have enough information to put them into clinical trials and develop better drugs,” Pakina said.

Memory plays an important role in our ability to recognize smell, and researchers have long known the link between smell and dementia. Image is in the public domain

The study was limited to participants receiving only one MRI scan, which the team lacked to determine when structural changes in the brain began or how quickly brain regions shrank.

“We have to take our study in the context of all the risk factors we know about Alzheimer’s, including the effects of diet and exercise,” Pinto said.

“Olfaction and olfactory changes must be an important component in the context of a number of factors believed to affect the brain in health and aging.

Also, because the majority of MAP participants were white, further research is needed to determine whether underrepresented populations are similarly affected. The team’s previous work showed differences by race, with African-Americans experiencing the most severe impairment of olfactory function.

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Pinto’s previous research has examined the sense of smell as an important marker of declining health in older adults. His 2014 work found that elderly people with no sense of smell were three times more likely to die within five years – a better predictor of death than a diagnosis of lung disease, heart failure or cancer.

Other scientists contributing to the “Rapid Decline of Smell in AD Brain Regions Cause Dementia and GMV Loss” include Kristen Wroblewski, PhD, and Martha McClintock, PhD, David Lee Shillinglow Professor Emerita of the Department of Psychology. of Comparative Human Development at the University of Chicago and Duke Hahn, PhD, Professor of Family Medicine, Neuroscience, Psychology, and Gerontology at the University of Southern California.

This is about research news on smell and Alzheimer’s disease

Author: Cassandra Gift
A source: University of Chicago
The connection: Cassandra Belek – University of Chicago
Photo: Image is in the public domain

Original research: Open access.
Jayant M. Pinto et al. Alzheimer’s and dementia


Rapid decline in olfactory sensitivity during aging predicts dementia and GMV loss in AD brain regions

Wrap up

Longitudinal multivariate analyzes are needed to determine whether the rate of smell decline during normal cognition predicts subsequent Alzheimer’s disease (AD) diagnoses and brain dysmorphology.


Older people (do not = 515) were assessed annually for olfaction, cognitive function, and clinical diagnosis of dementia (maximum follow-up 18 years). Regional gray matter volume (GMV) was quantified in a cross-sectional subsample (3T MRI) (do not = 121). Regression models were adjusted for APOE-ε4 genotype, dementia risk factors, and demographics.


A more rapid decline in olfactory function during normal cognition predicted a higher risk of subsequent MCI or dementia (OR 1.89, 95% CI: 1.26, 2.90, P < 0.01; comparable to carrying the APOE-ε4 allele) and smaller GMV in AD and olfactory regions (β = −0.11, 95% CI −0.21, −0.00).


Rapid decline in olfaction during normal cognition predicted subsequent cognitive impairment, dementia, and smaller GMVs by repeated olfactory measurements, highlighting its potential as a simple biomarker for early detection of AD.

Important moments

  • The rate of odor decline was greater than ≥3 time points from the olfactory test.
  • Rapid deterioration of the sense of smell is associated with a higher risk of cognitive decline and dementia.
  • Neurodegeneration on 3T magnetic resonance imaging was similar in people with olfactory impairment and Alzheimer’s disease.

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