People with familial amyotrophic lateral sclerosis (ALS) related to the gene VAPB — known as ALS type 8 — can show subtle cognitive deficits and obvious behavioral changes, which may lead to clinically significant depression and anxiety, a Brazilian study shows.
This data supports prior studies of sporadic ALS, the disorder’s most common form, that showed the disease can affect other neurological functions beyond motor control — findings that should be considered for patient care, the researchers said.
ALS is a neurodegenerative disease that causes the death of motor neurons, the nerve cells that transmit impulses from the brain and spinal cord to muscles, controlling their contraction. Upper motor neurons send messages from the brain to the spinal cord, while lower motor neurons send signals from the spinal cord to the muscles.
Over time, the loss of motor neurons prevents the brain from commanding movement, and as a result, muscles become smaller and weaker.
While the progression of symptoms is slower in ALS8 compared with typical forms of ALS, the degradation of lower motor neurons is more evident. Deterioration starts in the lower limbs, with prominent muscle twitching (fasciculations), cramps, and muscle wasting or atrophy.
In the past, sporadic ALS was considered solely a motor disorder, but more recent research has challenged this idea showing that patients also may experience cognitive and behavioral changes.
Researchers now sought to determine whether ALS8 also could affect the cognitive capacity and behavior of patients, which has not been investigated so far.
Cognitive problems affect approximately half of the people with sporadic ALS and up to 15% of them also can show signs of frontotemporal dementia (FTD). Deficits in verbal memory, language, and social cognition have been reported in some patients, along with behavioral changes such as inhibition loss and apathy.
Given the predominance of lower motor neuron involvement in ALS8, researchers believed that patients would have mild to moderate cognitive deficits, especially in executive function, similar to those in sporadic ALS.
To investigate this, researchers examined the cognitive profile of 22 ALS8 patients, with a median age of 48 years, and screened for possible behavioral changes.
They compared the data to that of 33 healthy controls, matched to age, sex, and educational level.
All patients had typical symptoms of the disease, with a history of progressive worsening, and were recruited at two hospitals from University of Minas Gerais and Federal University of Juiz de Fora, in Brazil.
A battery of tests were given to all participants to determine cognitive executive function (the ability to organize and regulate thoughts and actions), emotional recognition, and visual memory. Participants also were assessed for anxiety or depression, and behavioral changes in self-care and everyday life.
The data showed that, in general, no major cognitive decline was observed in the ALS8 patients, when compared with the controls.
However, ALS8 patients had subtle deficits in executive functions, particularly in cognitive flexibility — the brain’s ability to switch from thinking about one concept to another, and to adapt to a changing environment — and inhibitory control, which is the ability to block or control impulsive or automatic responses, including the capacity to self-control and pay selective attention.
Researchers noted that some participants also showed clinically relevant signs of anxiety, affecting 36.4% of the entire patient population, and depression, which affected 27.3%.
Behavioral disorders, including stereotypic and abnormal motor behaviors, also were present in over 30% of the patients. The most frequent stereotypic behaviors were mental rigidity, checking time repeatedly, lack of motivation, and alterations in eating habits. Abnormal behaviors included disinhibition, impulsivity, and loss of decorum.
The study found those with ALS8 were equally good as healthy subjects in recognizing facial emotions, in contrast to patients with other ALS forms.
“Contrary to the original report [describing ALS8], our findings suggest that ALS8 is not a pure motor disease and is associated with cognitive and behavioural disorders. These results should be taken into account in the assistance and management of patients,” the researchers said.
“For instance, mood disorders should be investigated and treated. Caregivers should be informed about possible cognitive and behavioural manifestations of the disease, as these may be the cause of relevant carer burden,” they added.
Further studies with a larger sample of patients, and with follow-ups over time, are warranted to better understand these non-motor symptoms of ALS8, the investigators said.
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