Literature Review

Cognitive and Behavioral Problems Increase With ALS Disease Stage

Data raise the question of whether cognitive and behavioral change should be included in ALS diagnostic criteria.


Cognitive deficits and behavioral symptoms that are specific to amyotrophic lateral sclerosis (ALS) occur more frequently as the disease progresses, according to research published online ahead of print September 12 in Neurology. Few patients are free of neuropsychologic impairment when they reach the final stage of the disease. It might be appropriate to include cognitive and behavioral change in the diagnostic criteria and future staging systems for ALS, said the authors.

In 2013, Elamin et al suggested that cognitive change in ALS may be associated with indirect measures of disease progression, such as total score on the ALS Functional Rating Scale-Revised. Christopher Crockford, PhD, a researcher at the University of Edinburgh, and colleagues sought to determine whether the cognitive and behavioral symptoms in ALS were more prevalent at more advanced stages of disease.

Christopher Crockford, PhD

The Role of Letter Fluency Impairment

They conducted a multicenter, cross-sectional, observational study that included 161 patients from Edinburgh, Dublin, and London with possible, probable, or definite ALS, according to revised El Escorial diagnostic criteria. The researchers also recruited 80 healthy, matched controls. Through interviews, Dr. Crockford and colleagues elicited demographic and clinical data. They measured participants’ clinical staging with the King’s Clinical Staging System and neuropsychologic status with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS).

The investigators did not observe significant differences between the patient and control groups in background variables. Approximately 67% of patients with ALS were male, compared with 60% of controls. Mean age at testing was approximately 61 in both groups. Among patients with ALS, 40 were in Stage 1, 45 were in Stage 2, 22 were in Stage 3, and 54 were in Stage 4.

Compared with controls, patients with ALS had significantly worse cognitive performance on all domains of the ECAS except visuospatial functioning. Dr. Crockford’s group found a significant cross-sectional effect across disease stages for ALS-specific functions (eg, executive, language, and letter fluency) and ECAS total score. They did not find a similar effect for ALS-nonspecific functions (eg, memory and visuospatial). In addition, rates of ALS-specific impairment and behavioral change increased with increasing disease stage.

Letter fluency impairment may explain the relationship between cognitive function and disease stage, said the authors. They observed higher rates of all behavioral problems in later King’s stages. Bulbar signs were significantly related to ALS-specific scores, ECAS total score, and behavioral scores. Site of onset was not related to these scores, however.

Intervention programs to alleviate the effect of patients’ neuropsychologic impairment on caregivers may be appropriate, said the authors. “Furthermore, clinicians should be cognizant of current neuropsychologic status when prescribing life-prolonging interventions to patients and implement support structures for those with a neuropsychologic impairment,” they added.

Informing Patients and Caregivers

Although Dr. Crockford and colleagues focused on the behavioral and cognitive effects of ALS, the disease may affect mental health as well, said Paul Wicks, PhD, Vice President of Innovation at PatientsLikeMe in Cambridge, Massachusetts, and Steven M. Albert, PhD, Professor and Chair of Behavioral and Community Health Sciences at the University of Pittsburgh, in an accompanying editorial. The data show that the rates of major depression and depressed mood increase with increasing disease stage.

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