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Signs of Alzheimer’s: Loss of Smell in At-Risk Individuals

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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Individuals who have a genetic predisposition to develop Alzheimer’s disease may experience a decline in their sense of smell even before any noticeable cognitive changes occur. Therefore, evaluating changes in a person’s sense of smell could potentially improve the accuracy of Alzheimer’s diagnoses and allow for early intervention and treatment.

The sense of smell has ancient origins and maintains close connections with various brain functions, including emotion, pleasure, and memory. Given that memory problems are a key characteristic of Alzheimer’s disease, researchers have focused on the relationship between smell and cognition.

A specific gene known as APOE is highly expressed in parts of the sensory system associated with smell. One of its variants, APOE4, is linked to an increased risk of developing Alzheimer’s. Individuals who carry a single copy of this variant are three times more likely to develop the disease compared to those without the variant. The risk more than doubles for individuals who have two copies of the APOE4 variant.

In order to explore the connection between APOE4 and a person’s sense of smell, Jayant Pinto from the University of Chicago and his colleagues analyzed data from the US National Social Life, Health, and Aging Project (NSHAP). The study included over 800 participants aged 62 to 85 who underwent genetic screening to identify those with the APOE4 variant. These participants were also tested for cognition, thinking, and memory skills.

The researchers conducted tests to measure the participants’ ability to differentiate between different concentrations of an odor (odor sensitivity) and to identify different odors (odor identification). These tests were ranked on a scale of zero to six. The same tests were repeated in 2015.

Among the 323 participants who carried one or two APOE4 variants, the results indicated a decline in odor sensitivity starting between the ages of 65 and 69. The average score for individuals with the APOE4 variant was 3.2, compared to 3.9 for non-carriers. Although the difference may seem small, statistical analysis suggests it is significant and not a chance finding.

The decline in odor identification abilities among APOE4 carriers occurred at an older age range, between 75 and 79, compared to the decline in odor sensitivity.

At the beginning of the study, the cognitive abilities of carriers and non-carriers were similar. However, cognitive decline occurred more rapidly in individuals with the APOE4 variant.

Considering that the decline in odor sensitivity preceded any cognitive differences between the two groups, assessing this sense of smell could potentially be a valuable method for predicting the development of Alzheimer’s symptoms within the next five years for genetically susceptible individuals.

Matthew GoodSmith, a member of the research team from the University of Chicago, acknowledges the study’s limitations in terms of tracking participants who went on to develop Alzheimer’s or show signs of the disease in the brain. Nevertheless, the results shed light on the relationship between smell loss and cognitive decline in individuals at high genetic risk for Alzheimer’s.

The next step is to determine if evaluating a person’s odor sensitivity could aid in the early diagnosis of Alzheimer’s and promote early intervention. Pinto states that smell testing should be as widely available for older individuals as vision and hearing tests.

Mark Albers from Massachusetts General Hospital emphasizes the importance of early detection of brain health abnormalities and the implementation of therapies as soon as possible in the disease course. The earlier the treatment, the greater the potential impact. Therefore, olfactory screening may play a crucial role in annual wellness visits for Alzheimer’s disease.


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