Why losing your sense of smell can be an early sign of illness

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A new study shows that a poor sense of smell may be an early sign of Alzheimer’s among people with a genetic risk of developing the disease. Nadine Brandt/Stocksy
  • Alzheimer’s disease is the most common form of dementia and affects more than 6 million people in the United States.
  • Early diagnosis is key to managing the disease, but initial symptoms, such as memory problems, are often dismissed as normal signs of aging.
  • A new study has found that carriers of the APOE ε4 gene, who are at higher risk of developing Alzheimer’s disease, may lose their ability to identify smells earlier than those who do not carry the gene variant.
  • Since this impaired sense of smell can be an early sign of future cognitive problems, testing people’s sense of smell can help identify those at greater risk of Alzheimer’s.

According to Alzheimer’s Association1 in 9 people over the age of 65 have Alzheimer’s disease (AD) in the United States, a total of 6.7 million people. With an aging population, experts expect this number to exceed 12 million by 2050.

Alzheimer’s is an incurable, progressive disease, but it is not inevitable in aging. If a person begins to experience memory problems and cognitive deficits, these should not be dismissed as normal signs of aging, as early diagnosis allows treatment that can alleviate symptoms.

About 13.7% of people worldwide carry a gene variant, APOE ε4, which increases the risk of Alzheimer’s disease. This gene is found in 40% of people diagnosed with the condition.

A new study published in Neurology found that people who carry this gene variant may experience an impaired sense of smell before symptoms of Alzheimer’s disease, such as mild cognitive impairment, appear.

The researchers suggest that testing a person’s ability to detect odors may be useful in identifying those at risk.

“This is an interesting study that assesses the relationship between declines in olfactory sensitivity and odor identification in APOE ε4 carriers and the risk of future cognitive decline.”

Dr. Emily D. Clark, DOassistant professor of psychiatry and associate director of the Alzheimer’s Disease Care, Research and Education Program (AD-CARE) at the University of Rochester.

The study participants came from National Social Life, Health and Aging Project (NSHAP) — a study of the social life and health of older adults conducted by the University of Chicago.

For this study, over 865 people took an at-home survey that included testing their sense of smell. The tests were repeated at 5-year intervals, with odor identification assessed in 2005, 2010 and 2015, and olfactory sensitivity tested in 2010 and 2015. In 2010 and 2015, participants also completed thinking and memory tests. In 2010, the average age of the participants was 72.3 (range 62-95)

The study aimed to determine whether APOE ε4 is associated with a decline in the sense of smell and cognition, and if so how. The researchers took DNA samples to determine which of the respondents carried the gene variant.

Study author Dr. Matthew S. GoodSmithfrom the University of Chicago, told Medical News Today: “In our cross-sectional analysis, about 25% of participants carried the APOE ε4 gene (of this, 1% were homozygous, 24% were heterozygous).”

Odor tests included olfactory sensitivity—the ability to detect odors at different concentrations—and odor identification, which assessed people’s ability to determine what the odor was.

Throughout the study, those with the gene were 37% less likely to have good odor detection than those without the gene.

At age 65, people with the APOE ε4 variant could detect fewer odors than those without the gene, suggesting that their ability to detect odors had already declined at this age. However, non-carriers, who started with a better ability to detect smells, showed a faster decline after 65 years.

In contrast, in odor identification there was no difference between carriers and non-carriers at 65, but carriers’ ability declined more rapidly, especially from age 75. Cognition showed a similar pattern with faster decline in cognition in those with the APOE ε4 variant.

Although they found no correlation between odor detection and cognition, the researchers’ findings suggest that odor identification and cognition are linked.

Dr. Clark, who was not involved in the investigation, said MNT: “The authors found impairments in olfactory sensitivity in APOE ε4 carriers presented earlier in life (65-69 years) than impairments in odor identification (75-79 years). Furthermore, deficits in olfactory sensitivity preceded cognitive decline in APOE ε4 carriers.”

“This suggests that decreased olfactory sensitivity may be an early marker of future cognitive impairment in APOE ε4 carriers,” she added.

The study found that olfactory sensitivity is impaired before problems with odor identification develop, and that the initial olfactory impairment is independent of cognitive problems.

“Many structures involved in smelling (including the olfactory epithelium and the olfactory bulb) have been shown to express high levels of APOE.

– Dr. GoodSmith.

The researchers suggest that olfactory epithelium (nerve cells and supporting cells in the nose) are first affected in APOE ε4 carriers and damage to olfactory cortex in the brain occurs later. However, they stress that further study is needed to confirm their findings.

Dr. Clark commented, “It is possible that the APOE ε4 allele is responsible for disruptions in otherwise normal functioning activity in these structures, leading to reduced olfactory sensitivity and identification.”

“It is important to note that in our study we had no way of keeping track of which patients would eventually develop Alzheimer’s,” said Dr. GoodSmith us. “And since our data were derived from survey data collected from adults living at home who were able to tolerate a lengthy interview process, respondents with severe dementia were unable to participate.”

“That said,” he added, “our findings highlight the interplay between smell loss and cognitive decline in patients at high genetic risk of developing Alzheimer’s. We hope that with further research, testing the sense of smell may develop into a useful screening or diagnostic tool in the future.

So while these are early findings, Dr. Clark agrees that they can point to new methods of detecting early Alzheimer’s disease:

“These findings, if further validated, provide a new opportunity for the use of smell testing as an early screening marker in clinical research studies. As the clinical research field focuses more on intervention in early symptomatic and prodromal Alzheimer’s disease, the ability to use something like olfactory performance as an early biomarker make the identification of suitable populations easier and possibly more cost-effective.”

However, she added a caveat: “Further validation of these results and a better understanding of the underlying mechanisms behind these changes are needed before this can be accepted as a screening test in clinical practice.”

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