Cognitive, Emotional and Psychological Manifestations in Amyotrophic Lateral Sclerosis at Baseline and Overtime: A Review

Abstract

It is now well recognized that, in addition to motor impairment, amyotrophic lateral sclerosis (ALS) may cause extra-motor clinical signs and symptoms. These can include the alteration of certain cognitive functions, impaired social cognition, and changes in the perception and processing of emotions. Where these extra-motor manifestations occur in ALS, they usually do so from disease onset. In about 10% of cases, the cognitive and behavioral changes meet the diagnostic criteria for frontotemporal dementia. The timecourse of behavioral and cognitive involvement in ALS is unclear. Whereas longitudinal studies have failed to show cognitive decline over time, some cross-sectional studies have demonstrated poorer cognitive performances in the advanced stages of the disease. Neuroimaging studies show that in ALS, extra-motor signs and symptoms are associated with specific brain lesions, but little is known about how they change over time. Finally, patients with ALS appear less depressed than might be expected, given the prognosis. Moreover, many patients achieve satisfactory psychosocial adjustment throughout the course of the disease, regardless of their degree of motor disability. There are scant longitudinal data on extra-motor impairment in ALS, and to our knowledge, no systematic review on this subject has yet been published. Even so, a better understanding of patients’ clinical trajectory is essential if they are to be provided with tailored care and given the best possible support. We therefore undertook to review the evidence for extra-motor changes and their time course in ALS, in both the cognitive, emotional and psychological domains, with a view to identifying mechanisms that may help these patients cope with their disease.

A systematic review of neuropsychiatric and cognitive assessments used in clinical trials for amyotrophic lateral sclerosis

“…Only one trial assessed the impact of the candidate drug on both neuropsychiatric symptoms and cognitive impairment. This is despite overwhelming evidence that these extramotor features are prevalent across, and impactful upon, people with ALS [5,9,20]. Whilst the impact on physical functioning and survival justifiably remain the primary objectives for clinical trials of ALS, the importance of additional assessments for neuropsychiatric and cognitive functioning needs to be addressed.…”

Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Against Cognitive Decline in Neurodegenerative Diseases

“…ALS is marked by progressive degeneration of upper and lower motor neurons while MS is characterized by demyelination due to an autoimmune response. Although ALS and MS have been traditionally viewed as diseases of the motor system, cognitive impairment also occurs in these pathologies (Chiaravalloti and DeLuca, 2008 ; Benbrika et al, 2019 ). It has been suggested that VIP and PACAP may contribute to ALS and MS non-motor symptomatology (Staines, 2008 ).…”

Cognitive and Behavioral Manifestations in ALS: Beyond Motor System Involvement

“…The disease timeline is still a matter of debate. Longitudinal studies on the cognitive decline over time in ALS are still missing to the best of our knowledge; however, some cross-sectional studies have suggested poorer cognitive performance in the advanced stages of the disease [ 12 ]. It is not clear whether cognitive impairment in ALS (if it occurs) worsens in line with a physical disability.…”