Losing sense of smell predicts dementia risk

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A long-term study of nearly 3,000 adults, aged 57 to 85, found that those who could not identify at least four out of five common odors were more than twice as likely as those with a normal sense of smell to develop dementia within five years

Although 78% of those tested were normal – correctly identifying at least four out of five scents – about 14% could name just three out of five, 5% could identify only two scents, 2% could name just one, and 1% of the study subjects were not able to identify a single smell.

Five years after the initial test, almost all of the study subjects who were unable to name a single scent had been diagnosed with dementia. Nearly 80% of those who provided only one or two correct answers also had dementia, with a dose-dependent relationship between degree of smell loss and incidence of dementia.

“These results show that the sense of smell is closely connected with brain function and health,” said the study’s lead author, Dr Jayant M Pinto, a professor of surgery at the University of Chicago and ENT specialist who studies the genetics and treatment of olfactory and sinus disease. “We think smell ability specifically, but also sensory function more broadly, may be an important early sign, marking people at greater risk for dementia.”

“We need to understand the underlying mechanisms,” Pinto added, “so we can understand neurodegenerative disease and hopefully develop new treatments and preventative interventions.”

“Loss of the sense of smell is a strong signal that something has gone wrong and significant damage has been done,” Pinto said. “This simple smell test could provide a quick and inexpensive way to identify those who are already at high risk.”

The study follows a related 2014 paper, in which olfactory dysfunction was associated with increased risk of death within five years. In that study, loss of the sense of smell was a better predictor of death than a diagnosis of heart failure, cancer or lung disease.
For both studies, the researchers used a well-validated tool, known as “Sniffin’Sticks”. These look like a felt-tip pen, but instead of ink, they are infused with distinct scents. Study subjects smell each item and are asked to identify that odor, one at a time, from a set of four choices. The five odors, in order of increasing difficulty, were peppermint, fish, orange, rose and leather.

78.1% of those examined had a normal sense of smell; 48.7% correctly identified five out of five odors and 29.4% identified four out of five. 18.7%, considered “hyposmic,” got two or three out of five correct. The remaining 3.2%, labelled “anosmic,” could identify just one of the five scents (2.2%), or none (1%).

The olfactory nerve is the only cranial nerve directly exposed to the environment. The cells that detect smells connect directly with the olfactory bulb at the base of the brain, potentially exposing the central nervous system to environmental hazards such as pollution or pathogens. Olfactory deficits are often an early sign of Parkinson’s or Alzheimer’s disease. They get worse with disease progression.

Losing the ability to smell can have a substantial impact on lifestyle and wellbeing, said Pinto, a specialist in sinus and nasal diseases and a member of the section of otolaryngology-head and neck surgery at University of Chicago Medicine. “Smells influence nutrition and mental health,” Pinto said. People who can’t smell face everyday problems such as knowing whether food is spoiled, detecting smoke during a fire, or assessing the need a shower after a workout. Being unable to smell is closely associated with depression as people don’t get as much pleasure in life.”

“This evolutionarily ancient special sense may signal a key mechanism that also underlies human cognition,” noted study co-author Dr Martha K McClintock, the David Lee Shillinglaw distinguished service professor of psychology at the University of Chicago, who has studied olfactory and pheromonal communication throughout her career.

McClintock noted that the olfactory system also has stem cells which self-regenerate, so “a decrease in the ability to smell may signal a decrease in the brain’s ability to rebuild key components that are declining with age, leading to the pathological changes of many different dementias.”

In an accompanying editorial, Dr Stephen Thielke, a member of the Geriatric Research, Education and Clinical Centre at Puget Sound Veterans Affairs Medical Centre and the psychiatry and behavioral sciences faculty at the University of Washington, wrote: “Olfactory dysfunction may be easier to quantify across time than global cognition, which could allow for more-systematic or earlier assessment of neurodegenerative changes, but none of this supports that smell testing would be a useful tool for predicting the onset of dementia.”

“Our test simply marks someone for closer attention,” Pinto explained. “Much more work would need to be done to make it a clinical test. But it could help find people who are at risk. Then we could enroll them in early-stage prevention trials.” “Of all human senses,” Pinto added, “smell is the most undervalued and underappreciated – until it’s gone.”

Both studies were part of the National Social Life, Health and Aging Project (NSHAP), the first in-home study of social relationships and health in a large, nationally representative sample of men and women ages 57 to 85. The study was funded by the National Institutes of Health – including the National Institute on Aging and the National Institute of Allergy and Infectious Disease – the Institute of Translational Medicine at the University of Chicago, and the McHugh Otolaryngology Research Fund.

Objectives: To investigate the relationship between olfactory dysfunction and subsequent diagnosis of dementia.
Design: Longitudinal study of a population representative of U.S. older adults.
Setting: Home interviews (National Social Life, Health, and Aging Project).
Participants: Men and women aged 57 to 85 (N = 2,906).
Measurements: Objective odor identification ability was measured at baseline using a validated five-item test. Five years later, the respondent, or a proxy if the respondent was too sick to interview or had died, reported physician diagnosis of dementia. The association between baseline olfactory dysfunction and an interval dementia diagnosis was tested using multivariate logistic regression, controlling for age, sex, race and ethnicity, education, comorbidities (modified Charlson Comorbidity Index), and cognition at baseline (Short Portable Mental Status Questionnaire).
Results: Older adults with olfactory dysfunction had more than twice the odds of having developed dementia 5 years later (odds ratio = 2.13, 95% confidence interval = 1.32–3.43), controlling for the above covariates. Having more odor identification errors was associated with greater probability of an interval dementia diagnosis (P = .04, 1-degree of freedom linear-trend test).
Conclusion: We show for the first time in a nationally representative sample that home-dwelling older adults with normal cognition and difficulty identifying odors face higher odds of being diagnosed with dementia 5 years later, independent of other significant risk factors. This validated five-item odor identification test is an efficient, low-cost component of the physical examination that can provide useful information while assessing individuals’ risk of dementia. Use of such testing may provide an opportunity for early interventions to reduce the attendant morbidity and public health burden of dementia.

Dara R Adams, David W Kern, Kristen E Wroblewski, Martha K McClintock, William Dale, Jayant M Pinto

University of Chicago Medical Centre material
American Journal of Geriatrics Society abstract

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