A study found that individuals with the APOE e4 gene experience early loss of smell detection, followed by cognitive decline, suggesting a potential early marker for Alzheimer’s.
According to a study recently published in Neurology, the medical journal of the American Academy of Neurology, individuals carrying the APOE e4 gene variant, which is associated with the strongest risk for Alzheimer’s disease, may experience an early loss in their ability to perceive smells. This diminished ability to detect odors may serve as an early warning of future cognitive and memory difficulties.
“Testing a person’s ability to detect odors may be a useful way to predict future problems with cognition,” said study author Matthew S. GoodSmith, MD, of the University of Chicago. “While more research is needed to confirm these findings and determine what level of smell loss would predict future risk, these results could be promising, especially in studies aiming to identify people at risk for dementia early in the disease.”
The study involved an at-home survey that included testing the sense of smell of over 865 people—both their ability to detect an odor at all and their ability to identify what odor they were smelling. Tests were given at five-year intervals. People’s thinking and memory skills were also tested twice, five years apart. DNA samples gave researchers information about who carried the gene associated with an increased risk of Alzheimer’s.
For the test to see if people could detect odors, scores ranged from zero to six based on how many of the different concentrations of odors they could smell.
People who carried the gene variant were 37% less likely to have good odor detection than people without the gene at a single time point. Researchers accounted for other factors that could affect the results, such as age, sex, and educational level. The gene carriers started experiencing reduced smell detection at age 65 to 69. At that age, the gene carriers could detect an average of about 3.2 of the smells, compared to about 3.9 smells for the people who did not carry the gene.
The people carrying the gene variant did not show a difference in their ability to identify what odor they were smelling until they reached age 75 to 79. Once they started to lose their ability to identify odors, the gene carriers’ ability declined more quickly than those who did not carry the gene.
Thinking and memory skills were similar among the two groups at the start of the study. But as expected, those carrying the gene variant experienced more rapid declines in their thinking skills over time than those without the gene.
“Identifying the mechanisms underlying these relationships will help us understand the role of smell in neurodegeneration,” GoodSmith said.
Reference: “Association of APOE ε4 Status With Long-term Declines in Odor Sensitivity, Odor Identification, and Cognition in Older US Adults” by Matthew S. GoodSmith, Kristen E. Wroblewski, L. Philip Schumm, Martha K. McClintock and Jayant M. Pinto, 26 July 2023, Neurology.
DOI: 10.1212/WNL.0000000000207659
A limitation of the study is that people with severe dementia were not included.
The study was supported by the National Institutes of Health, National Institute on Aging and National Institute of Diabetes and Digestive and Kidney Diseases.
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