On the occasion of World Amyotrophic Lateral Sclerosis (ALS) Day, celebrated every year on June 21st, we interviewed Dr. Elisa Canu, of the Unit of Neurology led by Prof. Massimo Filippi and researcher at the Neuroimaging of Neurodegenerative Diseases laboratory led by Prof. Federica Agosta at IRCCS San Raffaele Hospital, to explore the cognitive aspects of a disease often thought to affect only motor skills.

What is ALS?

Amyotrophic Lateral Sclerosis, abbreviated as ALS, is a neurodegenerative disease that primarily affects motor neurons, the nerve cells responsible for muscle control. ALS is characterized by the progressive degeneration of nerve pathways in the lateral regions of the spinal cord (hence the term 'lateral') and the subsequent formation of scar tissue (sclerosis). The loss of nerve stimulation causes muscle atrophy, meaning a reduction in muscle trophism ('amyotrophic').
"Almost all patients who come for their first visit with suspected ALS actually present a motor disorder: they typically experience weakness, stiffness, or muscle atrophy (loss of muscle mass), but also – in the more aggressive forms of the disease – difficulties with breathing, swallowing, and dysarthria, which is the difficulty in articulating words clearly and understandably," explains Dr. Canu.
This disease affects, in Italy alone, between one and three new individuals per 100,000 people each year. "Currently, there are no treatments that slow down or halt the disease’s devastating progression, which has an average duration of only 3-4 years," Dr. Canu states.

The Silent Symptoms of ALS

Despite the disease’s onset being characterized by movement disorders, ALS can also present cognitive-behavioral symptoms, occurring in 30-50% of patients.
These cognitive impairments usually appear gradually and often go unnoticed both by the ALS patient and by their caregivers, which is why research has historically focused less on these non-motor symptoms.
However, in-depth study of this disease has progressively allowed researchers and specialists to recognize clinical, pathological, and genetic features shared within the spectrum of frontotemporal diseases—a group of neurodegenerative conditions causing progressive deterioration of cognitive and behavioral functions.
Thorough neuropsychological evaluation of these patients in cognitive and behavioral domains has revealed subtle and silent alterations that often go unrecognized by both the patient and the caregiver.
Moreover, cognitive changes in ALS patients are frequently associated with anosognosia (from Greek, meaning lack of awareness of the disease), a condition where the person is unaware of their impairments, complicating their detection and identification.
When present, cognitive disorders in ALS patients are linked to alterations in the frontotemporal circuitry, particularly the prefrontal cortex—the brain area that normally regulates social cognition, planning, and complex thought.
"As a result, these individuals may experience difficulties in executive functions, such as planning or ideation, and/or behavioral problems, such as apathy or impulsivity," Dr. Canu explains.
In some ALS patients suffering from cognitive-behavioral disorders, there is also a general difficulty recognizing facial emotions, especially negative ones like sadness, anger, and disgust, as well as an impairment in understanding others’ cognitive states, such as desires and intentions.
The ability to recognize others' emotions and cognitive states is studied within the field known as "social cognition," a relatively new branch of neuropsychology. "However, the few studies conducted on social cognition so far have involved very small samples of ALS patients," the doctor adds.

Measuring Social Cognition in ALS

In this context, a study conducted by Dr. Canu together with Dr. Veronica Castelnovo and colleagues investigated emotional recognition in ALS patients using tests that measure the ability to recognize the universal expressions of basic emotions such as joy, sadness, anger, surprise, fear, and disgust. These emotions are represented by standardized images of faces, known as the “Ekman faces.”
Participants undergoing the tests are, for example, asked to indicate which Ekman face, among several options, expresses a certain emotion. The study by the San Raffaele researchers showed that these tests not only help differentiate healthy individuals from those with ALS, but also help identify which patients among those affected present cognitive impairments and which do not.
“However, it should be noted that some of these tests are not always optimal for detecting patients with early signs of cognitive impairment. For this reason, a comprehensive neuropsychological assessment that investigates the integrity of all the patient’s cognitive and behavioral functions remains necessary,” Dr. Canu explains.

More Than Just Movement

ALS is a devastating disease, both for those who suffer from it and for their caregivers, in which severe motor symptoms appear very early, requiring prompt assistance.
Often, these individuals must make important decisions, not only regarding the type of treatment to undergo but also in their daily lives.
Making such decisions requires that patients maintain their cognitive abilities of discernment and awareness, which is why “it is essential to continue research on the cognitive and behavioral aspects of the disease so that we can support and assist patients in the best possible way,” concludes Dr. Canu.

 

Written by: Andrea Iotti

Published on: 23 June 2025