Worsening cognitive impairment linked with loss of smell in ALS
Association evident in language, verbal fluency, executive function
Losing the ability to smell with amyotrophic lateral sclerosis (ALS) is significantly associated with worsening cognitive function, a new study in China finds.
The association was particularly evident in ALS-related functions such as language, verbal fluency, and executive function, that is, a set of mental skills that helps people plan, focus, remember, and juggle multiple tasks. Memory and visuospatial function were not associated with the ability to smell.
The findings may indicate that a loss of smell is driven by a reduced ability to recognize and discriminate different smells due to cognitive impairment, rather than a decline in olfactory function itself, the study’s researchers said in “Smell loss is associated with cognitive impairment in amyotrophic lateral sclerosis patients,” which was published in CNS Neuroscience & Therapeutics.
ALS is a neurodegenerative disease that primarily affects the nerve cells that are essential for muscle movement, called motor neurons. As these cells deteriorate and die, it leads to muscle weakness that causes ALS symptoms such as trouble walking, speech difficulties, swallowing problems, and eventually breathing issues. Up to half of patients also show cognitive impairment and many also have symptoms such as pain, mental health issues, and loss of smell.
Loss of smell is common in several neurodegenerative diseases such as Parkinson’s and Alzheimer’s, and has been linked to cognitive impairment in some of them.
Cognition and the sense of smell
Here, researchers in China conducted smell and neuropsychological tests in 216 ALS patients (mean age, 50.8), who were screened at the Peking University Third Hospital from August 2022 to December 2023 to better understand the mechanisms that lead to smell loss in ALS. The study also included 90 healthy Chinese participants, who served as controls.
To measure cognition, researchers used the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), scores of which range from 0 to 136, with higher scores indicating better cognitive function. The test measures ALS-specific functions such as language, verbal fluency, and executive function, along with nonspecific functions such as memory and visuospatial skill.
The ability to identify different smells was assessed with the Chinese Smell Identification Test (CSIT), which is designed for the Chinese population. It involves smelling 40 different odors and then identifying them from among four options.
A significant relationship between smell function and cognitive tests scores was observed, with a better performance on the cognitive function tests tied to a greater ability to correctly identify each odor in the CSIT test.
This correlation remained significant when researchers took other factors that could influence the results into account, such as age, sex, body mass index (BMI), which is a measure of body fat, education level, hunger, eagerness for food, stress, smoking status, alcohol consumption, and upper respiratory tract infections (URTI) or rhinitis. In this analysis, the degree of hunger and age were also significantly associated with CSIT scores.
During the screening period, 60 ALS patients and 15 healthy participants reported URTI or rhinitis, which can negatively affect olfactory function. When these patients were excluded from the analyses, the previous results remained significant.
To determine which type of cognitive functions were associated with smell function, the researchers examined ALS-specific and nonspecific functions separately. In the total population, none of functions were individually related to CSIT scores. However, when data from people with URTI and rhinitis were once more excluded, ALS-specific functions were significantly associated with CSIT values.
A comparison of ALS patients and healthy volunteers also showed CSIT scores were significantly lower in patients, indicating a worse sense of smell.
“Our study found that smell loss was correlated with cognitive impairment in ALS patients, especially with ALS-specific ECAS scores. This result is consistent with previous theories,” wrote the researchers, who believe this might be related to damage in certain brain regions that impairs cognitive functions related to smell, namely the ability to recognize and discriminate odors.
The researchers acknowledged their study had limitations, namely that the ALS participants were recruited from a single center and that the control group wasn’t matched to the ALS group by sex, age, BMI, or education, meaning the results can’t be generalized. Further studies, including imaging and biological evaluations, are needed to describe the specific mechanisms behind loss of smell in ALS patients, they said.
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