Summary: New research shows that loss of smell in older adults can predict not only future cognitive decline but also shrinkage in brain regions associated with Alzheimer’s disease.
Source: University of Chicago
Although we often take our sense of smell for granted compared with vision or hearing, olfaction supplies the brain with vital information—from detecting danger to evoking memories and emotions.
Researchers at the University of Chicago Medicine report that a rapid decline in the ability to identify odors over time predicts later cognitive impairment and structural changes in brain areas tied to Alzheimer’s disease and dementia.
The results come from a longitudinal analysis of 515 older adults and were published July 2 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. The findings suggest that routine smell testing could become a low-cost screening tool to detect early cognitive decline.
“Our data show that a fast drop in olfactory ability is a strong indicator of subsequent structural changes in specific brain regions,” said senior author Jayant M. Pinto, MD, a professor of surgery and ENT specialist at the University of Chicago who studies smell and sinus disorders.
More than 6 million Americans currently live with Alzheimer’s disease, which causes memory loss and other difficulties such as mood shifts and trouble performing daily tasks. While treatments can sometimes slow symptoms, there is no cure. Because smell and memory systems are closely linked, early olfactory changes may provide an accessible signal of emerging Alzheimer’s-related damage.
Memory and olfaction share neural circuitry, and previous work has shown that the plaques and tangles characteristic of Alzheimer’s often appear early in olfactory and memory-associated brain regions. What remained unclear was whether declining smell ability over time predicted later structural brain changes and clinical cognitive decline.
To answer that question, Pinto and colleagues analyzed anonymized data from Rush University’s Memory and Aging Project (MAP), a long-running cohort study of older adults living in retirement and senior housing communities in northern Illinois. MAP participants undergo annual testing for odor identification, cognitive performance, dementia diagnosis, and other health measures; a subset also received MRI scans.
The investigators found that participants who experienced a rapid decline in odor identification while still cognitively normal were more likely to develop mild cognitive impairment or dementia later. That faster olfactory decline also correlated with smaller gray matter volumes in regions linked to smell and memory, such as the amygdala and entorhinal cortex—areas that feed into the hippocampus, a key site of Alzheimer’s pathology.
Importantly, the risk associated with rapid smell loss was comparable to carrying an APOE-ε4 allele, a well-known genetic risk factor for Alzheimer’s disease.
“We measured both the volume and shape of gray matter and found that people with a rapid drop in smell ability had reduced size in olfactory and memory-related brain regions compared with those whose smell declined slowly or remained stable,” Pinto said.
The research team views smell testing as an inexpensive, easy-to-administer screen: test kits look like felt-tip pens, each containing a distinct scent that the test-taker must identify from multiple choices. Used routinely in clinics—much like vision or hearing checks—olfactory tests could help identify people at higher risk earlier, enabling enrollment in prevention trials or monitoring over time.
“If we can detect elevated risk in people in their 40s, 50s and 60s, we may be better positioned to offer them clinical trials or interventions before significant decline occurs,” said Rachel Pacyna, lead author and a medical student at the University of Chicago Pritzker School of Medicine.
The study did have limitations. Most participants received only one MRI, so the researchers could not track exactly when brain volume changes began or the rate at which specific regions shrank. The MAP cohort is also predominantly white, highlighting the need for research across more diverse populations; previous work by the team showed racial disparities in smell function, with African American participants often showing the most severe impairment.
Pinto plans to extend these findings by correlating olfactory decline with tissue markers from brain autopsies, the definitive method for confirming Alzheimer’s disease. Meanwhile, the group aims to evaluate smell testing as a routine clinical screen and to explore whether early detection can improve enrollment in prevention trials and the development of new treatments.
Pinto’s earlier research has linked severe olfactory loss in older adults with higher short-term mortality: a 2014 study found that older adults with no sense of smell had a greater risk of dying within five years than those with other serious diagnoses. That body of work underscores olfaction’s broader role as a marker of aging and health.
Other contributors to the paper “Rapid olfactory decline during aging predicts dementia and GMV loss in AD brain regions” include Kristen Wroblewski, MS; Martha McClintock, PhD; and Duke Han, PhD, among others.
About this olfaction and Alzheimer’s disease research news
Author: Cassandra Belek
Source: University of Chicago
Contact: Cassandra Belek – University of Chicago
Image: The image is in the public domain
Original Research: Open access.
“Rapid olfactory decline during aging predicts dementia and GMV loss in AD brain regions” by Jayant M. Pinto et al. Alzheimer’s & Dementia
Abstract
Rapid olfactory decline during aging predicts dementia and GMV loss in AD brain regions
Introduction
Longitudinal, multivariable analyses are necessary to determine whether the rate of olfactory decline during periods of normal cognition predicts subsequent Alzheimer’s disease diagnoses and related brain atrophy.
Methods
Older adults (n = 515) were assessed annually for odor identification, cognitive function and clinical diagnosis of dementia over a follow-up period up to 18 years. Regional gray matter volumes (GMV) were measured with 3T MRI in a cross-sectional subsample (n = 121). Regression models adjusted for APOE-ε4 status, demographic variables and other dementia risk factors.
Results
A faster decline in odor identification during periods of normal cognition predicted higher incidence of later mild cognitive impairment or dementia (OR 1.89, 95% CI: 1.26–2.90, p < 0.01), with an effect size comparable to carrying an APOE-ε4 allele. Faster olfactory decline also predicted smaller GMV in Alzheimer’s-related and olfactory brain regions (β = −0.11, 95% CI −0.21 to −0.00).
Discussion
Repeated measures of olfactory function during normal cognition identified individuals at higher risk for later cognitive impairment, dementia, and reduced gray matter in Alzheimer’s-associated regions, supporting the potential of olfactory testing as a simple biomarker for early detection.
Highlights
- Olfactory decline rates were derived from testing across three or more time points.
- Rapid olfactory decline predicted impaired cognition and higher dementia risk.
- Neurodegeneration seen on 3T MRI in those with rapid smell loss mirrored changes observed in Alzheimer’s disease.