1. Are Cognitive Changes in Amyotrophic Lateral Sclerosis
Markers for Distinct Disease Subtypes?
A Population-Based Longitudinal Study
Elamin M, Bede P, Byrne S, Jordan N, MSc, Gallagher L, Lynch C,
O'Brien C, Wynne B, Pender N, Hardiman O
Trinity College Institute of Neuroscience, Dublin, Beaumont Hospital, Dublin
• Objective: To determine whether the presence of cognitive impairment is indicative of a distinct subgroup of
Amyotrophic Lateral Sclerosis (ALS).
Background: ALS is associated with a spectrum of frontotemporal syndromes, ranging from frank dementia to more
subtle cognitive changes. However, it remains unclear as to whether cognitive change is an integral part of the
disorder, or whether they represent a phenotypic marker of a subgroup of ALS.
Design/Methods: The setting is a population-based, case-control longitudinal study of incident cases of ALS. Home-
visits were undertaken at baseline and at six-monthly intervals. A detailed neuropsychological was designed to assess
executive function, language, visuo-spatial and memory. ALS patients were compared to age, sex, and education
matched healthy controls who were also assessed longitudinally.
Results: 192 ALS patients have been recruited. Mean age is 62.8 years, 59.1% are males, and 32.4% had bulbar-
onset ALS. At baseline, cognitive changes were identified in 46.2% of the cohort. A second, and third assessment
have been carried out in 94, and 35 ALS patients respectively. Assessment at six months revealed that (i) patients
with executive impairment at baseline had reduced survival. In those who survived, 15.3% developed frank
frontotemporal dementia. (ii)) 80% of those with normal cognitive at baseline remained normal at six months. (iii) All
patients who developed new-onset executive impairment at six months had subtle executive changes at baseline.
Conclusions: In ALS, distinct and non-overlapping cognitive subgroups can be identified. Cognitive stratification
persists on longitudinal analysis. Cognition is a useful clinical biomarker in ALS.
• Research Supported by the Health Seventh Framework Programme, ALSA (the ALS Association), HRB (the Health
Research Board), and Research Motor Neuron (previously named Motor Neuron Disease Research Foundation.