Observational Study

. 2018 Oct 9;91(15):e1370-e1380.

doi: 10.1212/WNL.0000000000006317. Epub 2018 Sep 12.

ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS

Christopher Crockford¹, Judith Newton¹, Katie Lonergan¹, Theresa Chiwera¹, Tom Booth¹, Siddharthan Chandran¹, Shuna Colville¹, Mark Heverin¹, Iain Mays¹, Suvankar Pal¹, Niall Pender¹, Marta Pinto-Grau¹, Ratko Radakovic¹, Christopher E Shaw¹, Laura Stephenson¹, Robert Swingler¹, Alice Vajda¹, Ammar Al-Chalabi¹, Orla Hardiman¹, Sharon Abrahams²

Affiliations

¹ From Human Cognitive Neuroscience (C.C., J.N., T.B., R.R., S.A.), Psychology, Philosophy, Psychology and Language Sciences, Euan MacDonald Centre for Motor Neurone Disease Research (C.C., S.A.), and Alzheimer Scotland Dementia Research Centre (R.R.), University of Edinburgh; Anne Rowling Regenerative Neurology Clinic (J.N., S.C., S.P., R.R., L.S., R.S., S.A.), Royal Infirmary of Edinburgh, UK; Academic Unit of Neurology (K.L., M.H., I.M., M.P.-G., A.V., O.H.), Trinity College Dublin; Departments of Psychology (K.L., I.M., N.P., M.P.-G.) and Neurology (O.H.), Beaumont Hospital, Dublin, Ireland; and Maurice Wohl Clinical Neuroscience Institute (T.C., C.E.S., A.A.-C.), Department of Basic and Clinical Neuroscience, King's College London, UK.
² From Human Cognitive Neuroscience (C.C., J.N., T.B., R.R., S.A.), Psychology, Philosophy, Psychology and Language Sciences, Euan MacDonald Centre for Motor Neurone Disease Research (C.C., S.A.), and Alzheimer Scotland Dementia Research Centre (R.R.), University of Edinburgh; Anne Rowling Regenerative Neurology Clinic (J.N., S.C., S.P., R.R., L.S., R.S., S.A.), Royal Infirmary of Edinburgh, UK; Academic Unit of Neurology (K.L., M.H., I.M., M.P.-G., A.V., O.H.), Trinity College Dublin; Departments of Psychology (K.L., I.M., N.P., M.P.-G.) and Neurology (O.H.), Beaumont Hospital, Dublin, Ireland; and Maurice Wohl Clinical Neuroscience Institute (T.C., C.E.S., A.A.-C.), Department of Basic and Clinical Neuroscience, King's College London, UK. s.abrahams@ed.ac.uk.

PMID: 30209236
PMCID: PMC6177274
DOI: 10.1212/WNL.0000000000006317

Observational Study

ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS

Christopher Crockford et al. Neurology. 2018.

. 2018 Oct 9;91(15):e1370-e1380.

doi: 10.1212/WNL.0000000000006317. Epub 2018 Sep 12.

Authors

Affiliations

¹ From Human Cognitive Neuroscience (C.C., J.N., T.B., R.R., S.A.), Psychology, Philosophy, Psychology and Language Sciences, Euan MacDonald Centre for Motor Neurone Disease Research (C.C., S.A.), and Alzheimer Scotland Dementia Research Centre (R.R.), University of Edinburgh; Anne Rowling Regenerative Neurology Clinic (J.N., S.C., S.P., R.R., L.S., R.S., S.A.), Royal Infirmary of Edinburgh, UK; Academic Unit of Neurology (K.L., M.H., I.M., M.P.-G., A.V., O.H.), Trinity College Dublin; Departments of Psychology (K.L., I.M., N.P., M.P.-G.) and Neurology (O.H.), Beaumont Hospital, Dublin, Ireland; and Maurice Wohl Clinical Neuroscience Institute (T.C., C.E.S., A.A.-C.), Department of Basic and Clinical Neuroscience, King's College London, UK.
² From Human Cognitive Neuroscience (C.C., J.N., T.B., R.R., S.A.), Psychology, Philosophy, Psychology and Language Sciences, Euan MacDonald Centre for Motor Neurone Disease Research (C.C., S.A.), and Alzheimer Scotland Dementia Research Centre (R.R.), University of Edinburgh; Anne Rowling Regenerative Neurology Clinic (J.N., S.C., S.P., R.R., L.S., R.S., S.A.), Royal Infirmary of Edinburgh, UK; Academic Unit of Neurology (K.L., M.H., I.M., M.P.-G., A.V., O.H.), Trinity College Dublin; Departments of Psychology (K.L., I.M., N.P., M.P.-G.) and Neurology (O.H.), Beaumont Hospital, Dublin, Ireland; and Maurice Wohl Clinical Neuroscience Institute (T.C., C.E.S., A.A.-C.), Department of Basic and Clinical Neuroscience, King's College London, UK. s.abrahams@ed.ac.uk.

PMID: 30209236
PMCID: PMC6177274
DOI: 10.1212/WNL.0000000000006317

Abstract

Objective: To elucidate the relationship between disease stage in amyotrophic lateral sclerosis (ALS), as measured with the King's Clinical Staging System, and cognitive and behavioral change, measured with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).

Methods: A large multicenter observational cohort of 161 cross-sectional patients with ALS and 80 healthy matched controls were recruited across 3 research sites (Dublin, Edinburgh, and London). Participants were administered the ECAS and categorized into independent groups based on their King's clinical disease stage at time of testing.

Results: Significant differences were observed between patients and controls on all subtests of the ECAS except for visuospatial functioning. A significant cross-sectional effect was observed across disease stages for ALS-specific functions (executive, language, letter fluency) and ECAS total score but not for ALS-nonspecific functions (memory, visuospatial). Rates of ALS-specific impairment and behavioral change were also related to disease stage. The relationship between cognitive function and disease stage may be due to letter fluency impairment, whereas higher rates of all behavioral domains were seen in later King's stage. The presence of bulbar signs, but not site of onset, was significantly related to ALS-specific, ECAS total, and behavioral scores.

Conclusion: ALS-specific cognitive deficits and behavioral impairment are more frequent with more severe disease stage. By end-stage disease, only a small percentage of patients are free of neuropsychological impairment. The presence of bulbar symptoms exaggerates the differences observed between disease stages. These findings suggest that cognitive and behavioral change should be incorporated into ALS diagnostic criteria and should be included in future staging systems.

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Figures

**Figure 1. Cognitive performance across King’s clinical disease stages**
Patient performance is scaled to a standardized score (z score) on the basis of the mean and SD of local UK and Irish control groups. ALS = amyotrophic lateral sclerosis; ECAS = Edinburgh Cognitive and Behavioural ALS Screen.

**Figure 2. Frequency of behavioral impairment across King's clinical disease stages**

**Figure 3. Frequencies of impairment across King's clinical disease stage for Edinburgh Cognitive and Behavioural ALS Screen cognitive domains**

See this image and copyright information in PMC

Comment in

It's time to stop saying "the mind is unaffected" in ALS.
Wicks P, Albert SM. Wicks P, et al. Neurology. 2018 Oct 9;91(15):679-681. doi: 10.1212/WNL.0000000000006303. Epub 2018 Sep 12. Neurology. 2018. PMID: 30209233 No abstract available.
Amyotrophic lateral sclerosis - a multisystem neurodegenerative disorder.
Grossman M. Grossman M. Nat Rev Neurol. 2019 Jan;15(1):5-6. doi: 10.1038/s41582-018-0103-y. Nat Rev Neurol. 2019. PMID: 30446736 No abstract available.
Reader response: ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS.
Raaphorst J, Beeldman E, Govaarts R, Schmand B, de Visser M. Raaphorst J, et al. Neurology. 2019 Jul 9;93(2):85-86. doi: 10.1212/WNL.0000000000007761. Neurology. 2019. PMID: 31285404 No abstract available.
Author response: ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS.
Abrahams S, Crockford C. Abrahams S, et al. Neurology. 2019 Jul 9;93(2):86. doi: 10.1212/WNL.0000000000007760. Neurology. 2019. PMID: 31285405 No abstract available.

References

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1. Goldstein LH, Abrahams S. Changes in cognition and behaviour in amyotrophic lateral sclerosis: nature of impairment and implications for assessment. Lancet Neurol 2013;12:368–380. - PubMed
1. Phukan J, Elamin M, Bede P, et al. The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry 2012;83:102–108. - PubMed
1. Abrahams S, Leigh PN, Harvey A, Vythelingum GN, Grise D, Goldstein LH. Verbal fluency and executive dysfunction in amyotrophic lateral sclerosis (ALS). Neuropsychologia 2000;38:734–747. - PubMed
1. Abrahams S, Goldstein LH, Simmons A, et al. Word retrieval in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study. Brain 2004;127:1507–1517. - PubMed

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ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS

Affiliations

ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS

Authors

Affiliations

Abstract

Figures

Comment in

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous