The relationship between disease stage and behavior is important given the strength of the relationship relative to cognition and its negative impact on patients and caregivers.
Sharon Abrahams, PhD
A new study found that amyotrophic lateral sclerosis (ALS)-specific cognitive deficits and behavioral impairment are more frequent with an advancing disease stage and by end-stage, only a small percentage of patients no longer have neuropsychological impairment.
Researchers sought to determine, in a large observational cohort, the relationship between disease stage in ALS, measured with the King’s Clinical Staging System, and cognitive and behavioral change, measured with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Specifically, the objective was to examine which domains of cognition and behavior are specifically related to disease stage, and which, if any, clinical variables relate to cognition and behavior in ALS.
“Unfortunately, we found that people with ALS have problems with thinking skills as well as behavioral problems such as apathy, changes in eating behaviors and lack of inhibition even at the earliest stages of the disease,” study author Sharon Abrahams, PhD, Professor of Neuropsychology, University of Edinburgh, told the American Academy of Neurology. “By the last stage of the disease, only a small percentage of people are free of these cognitive and behavioral problems.”
The study, which included 161 cross-sectional participants with ALS and 80 healthy match controls, were administered ECAS and categorized into groups based on their clinical disease stage at the time of testing. Stages are determined by the number of regions involved in the disease: stage 1 involves 1 region, stage 2 involves 2 regions, stage 3 involves 3 regions, and stage 4 is when breathing or eating is affected enough that interventions like breathing or feeding tubes are needed. Of the participants with ALS, 149 primary caregivers provided behavioral data.
Among the participants, 64% (n=103) had classic ALS with symptom onset in the upper or lower limbs, 26% (n=41) had bulbar onset, 9% (n=15) had mixed onset, and 1% (n=2) had respiratory onset.
Significant differences were observed in participants with ALS compared to the control group for letter fluency—most commonly observed at 30.4%— executive functions (22.5%), language dysfunction (21.3%), and memory (16.8%), but no significant difference was observed for visuospatial function (9.4%), which is not known to be affected by ALS.
Of the behavioral data available, 45% had no behavioral features, 21.5% had 1 symptom, 14.1% had 2 symptoms, and 19.5% had ≥3 symptoms. Impairment was found in 39.6% of participants. The most commonly reported symptom was apathy (30.9%), followed by a loss of sympathy/empathy (27.5%), changes in eating behaviors (24.8%), preservation (24.8%), and disinhibition (15.4%). Researchers found that impairment in cognitive domains was most strongly associated with other cognitive domains as opposed to behavioral features and vice versa.
Participants were found to have a greater number of behavioral symptoms and cognitive impairment at more advanced disease stages. At stages 1, 2, 3, and 4, 20%, 21%, 33%, and 40% reported cognitive impairment, respectively, and at stages 1, 2, 3, and 4, 18%, 27%, 36%, and 65%, respectively, reported behavioral problems.
The findings significantly demonstrate that cognitive domains typically affected in ALS, the ECAS total performance, and the number of reported behavioral features are significantly related to the King’s Clinical Staging System and are present in all stages of the disease. There was association observed for cognitive functions not typically affected by ALS. Behavioral impairment was also related to disease stage. There was no significant relationship observed between cognition or behavior and site of onset, diagnostic delay, riluzole use, weight, upper limb involvement, lower limb involvement or levels of anxiety. Those whose disease affected the bulbar region were more likely to report problems with cognitive impairment and behavior than those whose disease did not affect that region—not relative to the area of the body first affected.
Researchers note that it may be necessary to consider intervention programs for caregivers to alleviate the impact of neuropsychological impairment, preferably early in the disease course. Clinicians should be conscious of current neuropsychological status when prescribing life-prolonging interventions, as well as implementing support structures. The relationship between disease stage and behavior, according to researchers, is particularly important because it’s relative to cognition and its negative impact on both patients and caregivers. Monitoring cognitive and behavioral symptoms across the disease course is vital in order to provide appropriate and timely care. Measures of cognitive and behavioral change should be incorporated in the diagnostic criteria for ALS and in future staging systems.
“People with ALS and their caregivers should also be informed that changes in thinking skills and behavior can be a part of ALS so they can plan for and watch for these issues and know that they are related to the disease itself,” Abrahams said.
Crockford C, Newtown J, Lonergan K, et al. ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS. Neurology. 2018;91:1-11.