Impaired Senses, Especially Smell, Linked to Dementia

Pauline Anderson

August 12, 2020

Dr Willa Brenowitz

A poor combined score on tests of hearing, vision, smell, and touch is associated with a higher risk for dementia and cognitive decline among older adults, new research suggests.

The study, which included almost 1800 participants, adds to emerging evidence that even mild levels of multisensory impairment are associated with accelerated cognitive aging, the researchers note.

Clinicians should be aware of this link between sensory impairment and dementia risk, lead author Willa Brenowitz, PhD, assistant professor, Department of Psychiatry and Behavioral Sciences, University of California at San Francisco, told Medscape Medical News.

"Many of these impairments are treatable, or at least physicians can monitor them; and this can improve quality of life, even if it doesn't improve dementia risk," Brenowitz said.

The findings were published online July 12 in Alzheimer's and Dementia.

Additive Effects

Previous research has focused on the link between dementia and individual senses, but this new work is unique in that it focuses on the additive effects of multiple impairments in sensory function, said Brenowitz.

The study included 1794 dementia-free participants in their 70s from Health, Aging and Body Composition (Health ABC), a prospective cohort study of healthy black and white men and women.

Researchers tested participants' hearing using a pure tone average without hearing aids and vision using contrast sensitivity with glasses permitted. They also measured vibrations in the big toe to assess touch and had participants identify distinctive odors such as paint thinner, roses, lemons, and onions to assess smell.

A score of 0 to 3 was assigned based on sample quartiles for each of the 4 sensory functions. Individuals with the best quartile were assigned a score of 0 and those with the worst were assigned a score of 3.

The investigators added scores across all senses to create a summary score of multisensory function (0 to 12) and classified the participants into tertiles of good, medium, and poor. Individuals with a score of 0 would have good function in all senses, whereas those with 12 would have poor function in all senses. Those with medium scores could have a mix of impairments.

Participants with good multisensory function were more likely to be healthier than those with poor function. They were also significantly more likely to have completed high school (85.0% vs 72.1%), were significantly less likely to have diabetes (16.9% vs 27.9%), and were marginally less likely to have cardiovascular disease, high blood pressure, and history of stroke.

Investigators measured cognition using the Modified Mini-Mental State (3MS) examination, a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a measure of cognitive processing speed. Cognitive testing was carried out at the beginning of the study and repeated every other year.

Dementia was defined as the use of dementia medication, being hospitalized with dementia as a primary or secondary diagnosis, or having a 3MS score 1.5 standard deviations lower than the race-stratified Health ABC study baseline mean.

Over an average follow-up of 6.3 years, 18% of participants developed dementia.

Dose-Response Increase

Results showed that with worsening multisensory function score, the risk for dementia increased in a dose-response manner.

In models adjusted for demographics and health conditions, participants with a poor multisensory function score were more than twice as likely to develop dementia than those with a good score (hazard ratio [HR], 2.05; 95% CI, 1.50 - 2.81; P < .001). Those with a middle multisensory function score were 1.45 times more likely to develop dementia (HR, 1.45; 95% CI, 1.09 - 1.91; P < .001).

Even a 1-point worse multisensory function score was associated with a 14% higher risk for dementia (95% CI, 8% - 21%), while a 4-point worse score was associated with 71% higher risk for dementia (95% CI, 38% - 211%).

Smell was the sensory function most strongly associated with dementia risk. Participants whose sense of smell declined by 10% had a 19% higher risk for dementia vs a 1% to 3% higher risk for declines in vision, hearing, and touch.

It is not clear why smell was a stronger determinant of dementia risk. However, loss of this sense is often considered to be a marker for Alzheimer's disease "because it's closely linked with brain regions that are affected" in that disease, said Brenowitz.

However, that doesn't necessarily mean smell is more important than vision or hearing, she added. "Even if hearing and vision have a smaller contribution to dementia, they have a stronger potential for intervention," she said.

The findings suggest "some additive or cumulative" effects for loss of the different senses, said Brenowitz. "There's an association above and beyond those which can be attributed to individual sensory domains."

Frailty Link

After including mobility, which is a potential mediator, estimates for the multisensory function score were slightly lower. "Walking speed is pretty strongly associated with dementia risk," Brenowitz noted.

Physical frailty might help explain the link between sensory impairment and dementia risk, she added. "It's not clear if that's because people with dementia are declining or because people with frailty are especially vulnerable to dementia," she said.

The researchers also assessed the role of social support, another potential mechanism by which sensory decline, especially in hearing and vision, could influence dementia risk.

Although the study did not find substantial differences in social support measures, the investigators note that questions assessing social support were limited in scope.

Interactions between multisensory function score and race, APOE ε4 allele status, and sex were not significant.

Worsening multisensory function was also linked to faster annual rates of cognitive decline as measured by both the 3MS and DSST. Each 1-point worse score was associated with faster decline (P < .05), even after adjustment for demographics and health conditions.

Possible Mechanisms

A number of possible mechanisms may explain the link between poor sensory function and dementia. It could be that neurodegeneration underlying dementia affects the senses, or vision and/or hearing loss leads to social isolation and poor mental health, which in turn could affect dementia risk, the researchers write.

It is also possible that cardiovascular disease or diabetes affect both dementia risk and sensory impairment.

Brenowitz noted that because cognitive tests rely on a certain degree of vision and hearing, impairment of these senses may complicate such tests.

Still to be determined is whether correcting sensory impairments, such as wearing corrective lenses or hearing aids, affects dementia risk.

Meanwhile, it might be a good idea to more regularly check sensory function, especially vision and hearing. These functions affect various aspects of health and can be assessed rather easily, said Brenowitz.

However, because smell is so strongly associated with dementia risk, Brenowitz said she would like to see it also become "part of a screening tool."

A possible study limitation cited was that the researchers checked sensory function only once. "Most likely, some of these would change over time, but at least it captured sensory function at one point," Brenowitz said.

"Sheds Further Light"

Commenting on the study for Medscape Medical News, Jo V. Rushworth, PhD, associate professor and national teaching fellow, De Montfort University Leicester, UK, said it "sheds further light on the emerging links" between multisensory impairment and cognitive decline leading to dementia.

"The authors show that people with even mild loss of function in various senses are more likely to develop cognitive impairment," she noted.

Rushworth was not involved with the study but has done research in the area.

The current results suggest that measuring patients' hearing, vision, sense of smell, and touch might "flag at-risk groups" who could be targeted for dementia prevention strategies, Rushworth noted.

Such tests are noninvasive and potentially less distressing than other methods of diagnosing dementia, she added. "Importantly, the relatively low cost and simplicity of sensory tests offer the potential for more frequent testing and the use of these methods in areas of the world where medical facilities and resources are limited."

This new study raises the question of whether the observed sensory impairments are a cause or an effect of dementia, Rushworth noted. 

"As the authors suggest, decreased sensory function can lead to a decrease in social engagement, mobility, and other factors which would usually contribute to counteracting cognitive decline," she said.

The study raises other questions, too, said Rushworth. She noted that the participants who experienced more severe sensory impairments were, on average, 2 years older than those with the least impairments.

"To what degree were the observed sensory deficits linked to normal aging rather than dementia?" she asked.

As well, Rushworth pointed out that the molecular mechanisms that "kick-start" dementia are believed to occur in midlife — so possibly at an age younger than the study participants. "Do younger people of a 'pre-dementia' age range display multisensory impairments?" she mused. 

Because study participants could wear glasses during vision tests but were not allowed to wear hearing aids for the hearing tests, further standardization of sensory impairment is required, Rushworth said.

"Future studies will be essential in determining the value of clinical measurement of multisensory impairment as a possible dementia indicator and prevention strategy," she concluded.

The study was funded by the National Institute on Aging, the National Institute of Nursing Research, and the Alzheimer's Association. Brenowitz and Rushworth have reported no relevant financial relationships.

Alzheimers Dement. Published online July 12, 2020. Abstract

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