15 Sep 2018

When Stephen Hawking died after a 55-year battle with amyotrophic lateral sclerosis—his body paralyzed but his mind apparently intact—his celebrity helped spread a misconception that ALS spares the mind. Just how unusual Hawking was is reinforced by a paper in the September 12 Neurology. Sharon Abrahams, University of Edinburgh, and colleagues correlated ALS disease stage with cognitive and behavioral symptoms and detected deficits even in patients newly diagnosed. By late stages, 80 percent of patients in Abrahams’ cohort had one or multiple cognitive or behavioral problems. The authors suggest that cognitive impairment is more common in ALS than previously realized and argue for routine, early screening.

“These deficits are found at the very earliest stages of disease and are even more common later,” Abrahams said. “We have to move away from the idea that ALS is a disease just of the motor system,” a belief that Abrahams says persists among clinicians and the public. “ALS involves changes in people’s thinking and behavior that are an integral part of the disease.”

It has long been known that some people with ALS have a degree of cognitive or behavioral impairment (Strong et al., 1996). Small studies have estimated that cognitive symptoms arise in up to 40 percent of patients and that 15 percent have frontotemporal dementia, as well (Goldstein et al., 2013; Phukan et al., 2012). More recently, a larger multicenter study of 274 patients found that cognitive problems are even more common, affecting 60 percent of patients, while 30 percent have behavioral deficits (Jan 2016 news). However, whether the number of cognitive and behavioral symptoms matches the severity of disease, and which early clinical variables might best predict impairment, have not been examined in depth.

Impaired Cognitive Domains. Patients at all stages of ALS have some form of cognitive impairment. [Courtesy of Crockford et al., 2018.]

First author Christopher Crockford and colleagues correlated assessments of disease stage and cognitive impairment in a cohort of 161 ALS patients and 80 controls recruited from centers in London, Edinburgh, and Dublin. They used a staging system developed by researchers at King’s College London, whereby stages 1 through 3 are assigned according to the number of body areas affected (upper limbs, lower limbs, and bulbar), and stage 4 is marked by respiratory or nutritional insufficiency.

For cognitive and behavioral change, the researchers used the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Its 15 items span five domains: language function, executive function, and letter fluency, which are combined into an ALS-specific score; and memory and visuospatial function, which comprise an ALS-nonspecific score. This test is especially suitable for ALS, because it controls for motor deficits that would confound other cognitive tests. ECAS also includes an interview with caregivers, in which they rate behavioral disinhibition, loss of sympathy/empathy, apathy, or other behavioral changes in the patient.

The researchers found that at all stages of disease, patients were, on average, more cognitively impaired than controls. Coming up with words beginning with a specific letter, i.e., letter fluency, posed the most common problem, with executive and language problems close behind. Behavioral symptoms predominated in 55 percent of patients, with apathy, loss of sympathy/empathy, and changes in eating behavior being most common. According to the King’s Clinical Staging System, cognitive and behavioral problems arose in 18 percent of patients at stage 1, but had affected 39 and 65 percent of patients, respectively, by stage 4. Patients with bulbar involvement, meaning problems with swallowing and speech, were especially prone to have worse scores all round. At King’s stage 4, only 19.6 percent of patients remained cognitively and behaviorally normal.

The results suggest that few patients with ALS escape cognitive or behavioral impacts, and that later stages of disease bring worse problems. “Educating patients and caregivers that cognitive change is a part of ALS should be no different from similar discussions to be had in multiple sclerosis, Parkinson disease, and a range of other conditions,” wrote Paul Wicks of the Cambridge, Massachusetts-based PatientsLikeMe and Steven Albert, University of Pittsburgh, in an accompanying editorial. “In our experience, colleagues report keeping the information from patients in order to spare them further distress.” However, informing patients and caregivers of the likelihood of behavioral impairment allows them to prepare for symptoms that do arise and to more easily report them at checkups, Wicks and Albert wrote.

Abrahams cautioned that these patients were assessed at a single time point, so she cannot say how cognitive impairment progresses over the course of disease. She is following up these patients to map longitudinal changes in their cognition and behavior.—Gwyneth Dickey Zakaib

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References

News Citations

1. Confirmed: ALS Attacks Cognition and Behavior 29 Jan 2016

Paper Citations

1. Strong MJ, Grace GM, Orange JB, Leeper HA. Cognition, language, and speech in amyotrophic lateral sclerosis: a review. J Clin Exp Neuropsychol. 1996 Apr;18(2):291-303. PubMed.
2. Goldstein LH, Abrahams S. Changes in cognition and behaviour in amyotrophic lateral sclerosis: nature of impairment and implications for assessment. Lancet Neurol. 2013 Apr;12(4):368-80. PubMed.
3. Phukan J, Elamin M, Bede P, Jordan N, Gallagher L, Byrne S, Lynch C, Pender N, Hardiman O. The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):102-8. PubMed.

Further Reading

Papers

1. Lulé D, Böhm S, Müller HP, Aho-Özhan H, Keller J, Gorges M, Loose M, Weishaupt JH, Uttner I, Pinkhardt E, Kassubek J, Del Tredici K, Braak H, Abrahams S, Ludolph AC. Cognitive phenotypes of sequential staging in amyotrophic lateral sclerosis. Cortex. 2018 Apr;101:163-171. Epub 2018 Jan 31 PubMed.
2. Xu Z, Alruwaili AR, Henderson RD, McCombe PA. Screening for cognitive and behavioural impairment in amyotrophic lateral sclerosis: Frequency of abnormality and effect on survival. J Neurol Sci. 2017 May 15;376:16-23. Epub 2017 Feb 27 PubMed.

News

1. Does Cognition Change With the Seasons? 13 Sep 2018
2. Before 40, Brain Atrophy in ALS Mutation Carriers? 8 Dec 2017