The impact of cognitive and behavioral impairment in amyotrophic lateral sclerosis

ABSTRACT

Introduction: A spectrum of non-motor manifestations in amyotrophic lateral sclerosis (ALS) patients has been increasingly recognized, with cognitive and behavioral impairments the most prominent. Evidence suggests that ALS overlaps on a pathological, genetic, and clinical level with frontotemporal dementia (FTD), thereby suggesting a frontotemporal spectrum disorder (ALS-FTSD). Cognitive impairment has been reported in up to 75% of ALS patients, whilst the rate of behavioral dysfunction ranges up to 50%.

Areas covered: The present review explores the current understanding of cognitive and behavioral changes in ALS with a particular emphasis on its implications on prognosis and survival.

Expert commentary: Further longitudinal studies are needed to clarify the evolution of cognitive impairment in ALS and how this may ultimately influence survival. Improving understanding of cognitive changes has important implications toward the capacity of patients in making critical medical decisions. There is a need to develop a universally accepted and validated cognitive assessment tool to be administered in a multidisciplinary clinic that is efficient and sensitive, as well as being integrated into the design and analysis of future ALS drug trials. In addition, revision of the ALS diagnostic criteria is critically needed that should accommodate cognitive and behavioral symptoms in addition to motor manifestations.

KEYWORDS:

• Amyotrophic lateral sclerosis
• motor neuron disease
• cognition
• behavior
• prognosis
• survival

Article Highlights

• 30–50% of ALS patients develop cognitive and/or behavioral impairment during the course of their disease.

• Executive dysfunction represents the key feature with the most striking and consistently reported deficit being in letter fluency.

• The most commonly reported behavioral changes include apathy, irritability, inflexibility, restlessness, and disinhibition with the most consistent abnormality being apathy.

• The neuropathological correlate of cognitive impairment in ALS is frontal and temporal lobar ubiquitinated inclusions containing TDP-43 deposits.

• Cognitive impairment and in particular, executive dysfunction is associated with faster motor progression and poorer survival.

• There is a need to observe and assess for cognitive and behavioral dysfunction in ALS patients to improve quality of life, compliance to treatment, and patient survival.

Declaration of interest

W Huynh was supported by the Beryl-Bayley Post-doctorate Fellowship, Motor Neuron Disease Research Institute of Australia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

W Huynh was supported by the Beryl-Bayley Post-doctorate Fellowship, Motor Neuron Disease Research Institute of Australia.