People who carry a genetic variant that raises the risk of Alzheimer’s disease may start to lose their sense of smell before they experience any decline in cognitive function
By Soumya Sagar
28 July 2023
Losing the sense of smell may be an indicator of later cognitive decline in people who are genetically at-risk of Alzheimer’s
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People who are genetically predisposed to develop Alzheimer’s disease may experience a decline in their sense of smell before any change to their cognitive function. Testing for changes to someone’s sense of smell could therefore improve Alzheimer’s diagnoses and allow treatments to be started earlier.
“The sense of smell is one of the most ancient senses,” says Jayant Pinto at the University of Chicago, Illinois. “As the nervous system evolved, it remained closely connected to other brain functions like emotion, pleasure, memory etc. Because memory problems are a key feature of Alzheimer’s, we focused on the connection between smell and cognition.”
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A gene called APOE is highly expressed in parts of the sensory system that relate to smell. One of its variants, APOE4, has been linked with an increased risk of Alzheimer’s. People who carry a single copy of this variant are around three times more likely to develop Alzheimer’s than those without this variant, with the risk more than doubling among people who have two copies of the variant.
To understand any link between APOE4 and a person’s sense of smell, Pinto and his colleagues looked at data that was collected as part of the US National Social Life, Health, and Aging Project (NSHAP). In 2010, more than 800 of the project’s participants – aged 62 to 85 – were genetically screened to identify those with the APOE4 variant. That same year, they were tested on their cognition, namely their thinking and memory skills. None of the participants had dementia symptoms at the start of the study.
They also completed tests on their ability to differentiate between different concentrations of the same odour, known as odour sensitivity, and their ability to differentiate one odour from another, known as odour identification, which were ranked on a scale of zero to six. The cognition and smell tests were repeated in 2015.