Murphy J, Factor-Litvak P, Goetz R, Lomen-Hoerth C, Nagy PL, Hupf J, Singleton J, Woolley S, Andrews H, Heitzman D, Bedlack RS, Katz JS, Barohn RJ, Sorenson EJ, Oskarsson B, Fernandes Filho JA, Kasarskis EJ, Mozaffar T, Rollins YD, Nations SP, Swenson AJ, Koczon-Jaremko BA, Mitsumoto H, ALS COSMOS. Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort. Neurology. 2016 Mar 1;86(9):813-20. Epub 2016 Jan 22 PubMed.
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Institute of Psychiatry, Psychology and Neurosciencei
The COSMOS study definitely adds to the understanding of the likely prevalence of cognitive and behavioural involvement in ALS. It has been undertaken by a number of the key professionals in this field and highlights the importance of screening for impairment in patients at an early stage. There are a number of screening batteries designed for this purpose but it is really helpful to have data on the use of the ALS CBS-cog, ALS CBS-behaviour subscale and other measures in such a large sample. The authors are to be congratulated on their study.
View all comments by Laura GoldsteinMassachusetts General Hospital
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily affecting the motor neurons and leading to progressive muscular weakness and ultimately to death within approximately three to five years from symptom onset. ALS was long believed to spare cognition and behavior; however, based on recent clinical studies, it has been acknowledged that a large proportion of patients suffering from ALS can also experience variable degrees of cognitive impairment and behavioral changes. These manifest particularly as executive dysfunction, apathy, disinhibition and social cognition deficits. In addition, 5 to 15 percent of ALS patients meet the diagnostic criteria for frontotemporal dementia (FTD), a common cause of pre-senile dementia, characterized by behavioral and/or language disturbances. This clinical continuum between ALS and FTD is further supported by common pathology, in the form of accumulation of TDP-43 protein, and by common genetics, such as mutations in the C9orf72 gene.
This compelling association between two neurodegenerative diseases presenting with very different clinical manifestations that deeply affect patients and their caregivers poses the challenge of appropriately identifying, evaluating, managing, and monitoring the overlapping symptoms in the clinical as well as in the research settings.
In this context, the study presented by Dr. Murphy on behalf of the ALS COSMOS study group, focusing on evaluation of cognitive-behavioral impairment in a large cohort of people with ALS, represents an important contribution to the field.
This study utilizes a combination of a selection of previously validated measures of cognition, behavior, and ALS-related symptoms to further characterize how motor, cognitive, and behavioral deficits are intertwined in early ALS (within 18 months from symptom onset).
While the cognitive and behavioral measures utilized are screening rather than diagnostic tools, they have the advantage of not only being easy and fast to administer but they are also specific for ALS. In fact, they have been developed and/or adapted for people with motor neuron disease: They are based on known ALS-related cognitive/behavioral profiles and account for the possible motor deficits, hence their relevance in ALS clinical and research practices, and the importance of screening cognitive/behavioral disturbances typical of motor neuron disease. Along these lines, when assessing C9orf72 mutation carriers, it would be important to also evaluate for delusions and psychotic symptoms that are often present in this population.
The study confirms the remarkable frequency and clinical relevance of cognitive/behavioral symptoms in ALS and it also highlights the significant impact of behavioral changes on functional status that can also greatly affect caregivers’ burden.
The remarkable value of this research resides in the large number of the study participants (n=274) and in the demonstration that, with appropriate training, the implementation of these cognitive/behavioral screening tools is not only possible but valid across different ALS centers on a large scale. This supports the concept that these instruments can be efficiently utilized not only in clinical practice, but also in clinical research and therapeutics development.
The confirmation of the significant overlap between motor and cognitive/behavioral deficits in a large ALS cohort further supports the need to integrate the evaluation of cognitive/behavioral symptoms with motor measures in routine ALS clinical assessments/medical practice as well as in ALS research. To this purpose, a number of screening instruments have been developed.
Furthermore, building on the recent knowledge, the detailed characterization of the pattern and relationships of the cognitive and behavioral changes occurring in ALS described in the study offers invaluable information for effective education of patients and caregivers.
Potential next steps may include studies evaluating the performance of different measures of cognitive/behavioral changes in a large cohort of people with ALS followed over time. Longitudinal studies can provide important information regarding progression of cognitive/behavioral symptoms in ALS and allow more accurate prognostication and inform the potential development of novel clinical endpoints.
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