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April 4, 2011

Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia

April 5, 2011 issue
76 (14) 1263-1269

Abstract

Background:

The prognostic implications of cognitive impairment in amyotrophic lateral sclerosis (ALS) are not established.

Objectives:

To investigate the survival effect of the comorbid frontotemporal dementia (FTD) and to determine whether, in the absence of dementia, impairment in different cognitive domains affects outcome.

Methods:

A prospective population-based study of incident cases of ALS in the Republic of Ireland included home-based neuropsychological assessments using age-, sex-, and education-matched controls. Four cognitive domains were evaluated: executive function, memory, language, and visuospatial skills.

Results:

Mean age of the participants (n = 139) was 63.3 years; 61.2% were male and 35.3% had bulbar-onset ALS. Factors associated with shorter survival included age more than 60, severe disability at baseline, shorter delay to diagnosis, and early respiratory involvement. Comorbid FTD was associated with significantly shorter survival time (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.04–6.85, p = 0.041). In patients with ALS without dementia, the presence of executive dysfunction was significantly associated with shorter survival. This was confirmed in a multivariate model that included age, delay to diagnosis, disease severity at baseline, education, and respiratory status (HR 3.44, 95% CI 1.45–8.18, p = 0.005). In the absence of executive dysfunction, single or multi-domain impairment in other cognitive domains had no significant effect on survival.

Conclusion:

Comorbid frontotemporal dementia is a negative prognostic indicator. In patients with ALS without dementia, executive dysfunction, but not impairment in other cognitive domains, is an important negative prognostic indicator.

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Supplementary Material

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Information & Authors

Information

Published In

Neurology®
Volume 76Number 14April 5, 2011
Pages: 1263-1269
PubMed: 21464431

Publication History

Received: September 16, 2010
Accepted: December 22, 2010
Published online: April 4, 2011
Published in print: April 5, 2011

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Disclosure

Dr. Elamin receives research support from the ALS Association, the Health Research Board, and Research Motor Neurone. Dr. Phukan, Dr. Bede, N. Jordan, Dr. Byrne, and Dr. Pender report no disclosures. Dr. Hardiman has served on scientific advisory boards for Novartis, Biogen Idec, Allergan, Inc., Sanofi-Aventis, Ono Pharmaceutical Co. Ltd., and the Health Research Board, Ireland; has received speaker honoraria from Janssen, Biogen Idec, Sanofi-Aventis, and Merck Serono; serves as Editor-in-Chief of Amyotrophic Lateral Sclerosis and on the editorial board of Journal of Neurology Neurosurgery & Psychiatry; has patents pending re: Treatment of central nervous system injury and treatment of neurodegenerative disease; and receives research support from the ALS Association, the Health Research Board, and Research Motor Neurone.

Authors

Affiliations & Disclosures

M. Elamin, MRCP
From the Trinity Institute of Neuroscience (M.E., J.P., P.B., S.B., O.H.), Dublin; and Department of Neuropsychology, Beaumont Hospital (N.J., N.P., O.H.), Dublin, Ireland.
J. Phukan, PhD
From the Trinity Institute of Neuroscience (M.E., J.P., P.B., S.B., O.H.), Dublin; and Department of Neuropsychology, Beaumont Hospital (N.J., N.P., O.H.), Dublin, Ireland.
P. Bede, MRCP
From the Trinity Institute of Neuroscience (M.E., J.P., P.B., S.B., O.H.), Dublin; and Department of Neuropsychology, Beaumont Hospital (N.J., N.P., O.H.), Dublin, Ireland.
N. Jordan, MSc
From the Trinity Institute of Neuroscience (M.E., J.P., P.B., S.B., O.H.), Dublin; and Department of Neuropsychology, Beaumont Hospital (N.J., N.P., O.H.), Dublin, Ireland.
S. Byrne, MRCP
From the Trinity Institute of Neuroscience (M.E., J.P., P.B., S.B., O.H.), Dublin; and Department of Neuropsychology, Beaumont Hospital (N.J., N.P., O.H.), Dublin, Ireland.
N. Pender, PhD
From the Trinity Institute of Neuroscience (M.E., J.P., P.B., S.B., O.H.), Dublin; and Department of Neuropsychology, Beaumont Hospital (N.J., N.P., O.H.), Dublin, Ireland.
O. Hardiman, FRCPI, FAAN
From the Trinity Institute of Neuroscience (M.E., J.P., P.B., S.B., O.H.), Dublin; and Department of Neuropsychology, Beaumont Hospital (N.J., N.P., O.H.), Dublin, Ireland.

Notes

Study funding: Supported by the ALS Association, the Health Research Board (Ireland), and Research Motor Neurone.
Address correspondence and reprint requests to Dr. Marwa Elamin, Trinity Institute of Neuroscience, Dublin, Ireland [email protected]

Author Contributions

Statistical analysis was conducted by Dr. Marwa Elamin.

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