Researchers from Johns Hopkins Medicine found a link between a decreased sense of smell and a heightened risk of late-life depression in a study that followed over 2,000 older adults for eight years. While not proving causation, the findings suggest a diminished sense of smell could indicate overall health and well-being concerns.
Hyposmia has historically been linked to Alzheimer’s disease and other dementias in the elderly; recent research further supports its connection to other age-related conditions.
In a research spanning eight years that involved over 2,000 older adults residing in communities, Johns Hopkins Medicine scientists have uncovered compelling evidence suggesting a connection between a reduced sense of smell and an increased likelihood of experiencing late-life depression.
While the results, which were recently published in the Journal of Gerontology: Medical Sciences, don’t prove that a diminished sense of smell directly leads to depression, they hint at its potential as a strong marker of overall health and wellness.
“We’ve seen repeatedly that a poor sense of smell can be an early warning sign of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, as well as a mortality risk. This study underscores its association with depressive symptoms,” says Vidya Kamath, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “Additionally, this study explores factors that might influence the relationship between olfaction and depression, including poor cognition and inflammation.”
The study used data gathered from 2,125 participants in a federal government study known as the Health, Aging, and Body Composition Study (Health ABC). This cohort was composed of a group of healthy older adults ages 70–73 at the start of the eight-year study period in 1997–98. Participants showed no difficulties in walking 0.25 miles, climbing 10 steps, or performing normal activities at the start of the study, and were assessed in person annually and by phone every six months. Tests included those for the ability to detect certain odors, depression, and mobility assessments.
In 1999, when smell was first measured, 48% of participants displayed a normal sense of smell, 28% showed a decreased sense of smell, known as hyposmia, and 24% had a profound loss of the sense, known as anosmia. Participants with a better sense of smell tended to be younger than those reporting significant loss or hyposmia. Over follow-up, 25% of participants developed significant depressive symptoms.
When analyzed further, researchers found that individuals with decreased or significant loss of smell had an increased risk of developing significant depressive symptoms at longitudinal follow-up than those in the normal olfaction group. Participants with a better sense of smell tended to be younger than those reporting significant loss or hyposomia.
Researchers also identified three depressive symptoms “trajectories” in the study group: stable low, stable moderate, and stable high depressive symptoms. A poorer sense of smell was associated with an increased chance of a participant falling into the moderate or high depressive symptoms groups, meaning that the worse a person’s sense of smell, the higher their depressive symptoms. These findings persisted after adjusting for age, income, lifestyle, health factors, and use of antidepressant medication.
“Losing your sense of smell influences many aspects of our health and behavior, such as sensing spoiled food or noxious gas, and eating enjoyment. Now we can see that it may also be an important vulnerability indicator of something in your health gone awry,” says Kamath. “Smell is an important way to engage with the world around us, and this study shows it may be a warning sign for late-life depression.”
Humans’ sense of smell is one of two chemical senses. It works through specialized sensory cells, called olfactory neurons, which are found in the nose. These neurons have one odor receptor; it picks up molecules released by substances around us, which are then relayed to the brain for interpretation. The higher the concentration of these smell molecules the stronger the smell, and different combinations of molecules result in different sensations.
Smell is processed in the brain’s olfactory bulb, which is believed to interact closely with the amygdala, hippocampus, and other brain structures that regulate and enable memory, decision-making, and emotional responses.
The Johns Hopkins researchers say their study suggests that olfaction and depression may be linked through both biological (e.g., altered serotonin levels, brain volume changes) and behavioral (e.g., reduced social function and appetite) mechanisms.
The researchers plan to replicate their findings from this study in more groups of older adults and examine changes to individuals’ olfactory bulbs to determine if this system is in fact altered in those diagnosed with depression. They also plan to examine if smell can be used in intervention strategies to mitigate the risk of late-life depression.
Reference: “Olfactory Dysfunction and Depression Trajectories in Community-Dwelling Older Adults” by Vidyulata Kamath, Kening Jiang, Kevin J Manning, R Scott Mackin, Keenan A Walker, Danielle Powell, Frank R Lin, Honglei Chen, Willa D Brenowitz, Kristine Yaffe, Eleanor M Simonsick and Jennifer A Deal, 26 June 2023, The Journals of Gerontology: Series A.
DOI: 10.1093/gerona/glad139
Other scientists who contributed to this research are Kening Jiang, Danielle Powell, Frank Lin, and Jennifer Deal of the Johns Hopkins University School of Medicine and Bloomberg School of Public Health; Kevin Manning of the University of Connecticut; R. Scott Mackin, Willa Brenowitz and Kristine Yaffe of the University of California, San Francisco; Keenan Walker and Eleanor Simonsick of the National Institute on Aging; and Honglei Chen of Michigan State University.
No authors declared conflicts of interest related to this research under Johns Hopkins University School of Medicine policies.
This work was supported by the National Institute on Aging, the National Institute of Nursing Research and the Intramural Research Program of the National Institutes of Health: National Institute on Aging.
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