People At Risk for Alzheimer Disease May Lose Sense of Smell Faster

Those with the APOE e4 gene variant, which has been associated with having the strongest risk of Alzheimer disease, may lose their sense of smell sooner than those without the gene variant, according to a recent study published in Neurology.

“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, University of Chicago, in a news release from the American Academy of Neurology. “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.”

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Researchers conducted at-home studies with 865 participants and tested their ability to detect smells as well as their ability to identify what the smell is. Tests were administered every 5 years—in 2005, 2010, and 2015—and scores ranged from zero to six. Participants’ thinking and memory skills were also tested once in 2010 and again in 2015 using the Montreal Cognitive Assessment. DNA samples were used to identify which participants carried the APOE e4 gene.

Those carrying the APOE e4 gene variant were found to be 37% less likely to have good smell detection than those without the gene variant after stratifying for age, sex, and educational level. Odor sensitivity began to decline in APOE ε4 carriers at ages 65-69, while odor identification did not show decline until ages 75-79. Both groups showed similar cognition and memory levels at the beginning of the study, but those with the gene variant showed faster cognitive decline than those without the variant.

“Identifying the mechanisms underlying these relationships will help us understand the role of smell in neurodegeneration,” GoodSmith noted.

Authors noted that people with severe dementia were not included in the study, which could limit study results. 

References
GoodSmith MS, Wroblewski KE, Schumm LP, et al. Association of APOE ε4 status with long-term declines in odor sensitivity, odor identification, and cognition in older US adults. Neurology. Published online July 26, 2023. doi.org/10.1212/WNL.0000000000207659

People with increased genetic risk of Alzheimer’s may lose sense of smell first. News release. American Academy of Neurology. July 26, 2023. Accessed August 1, 2023.