Neuropsychological functioning across the ALS disease course and its assessment
Item statusRestricted Access
Embargo end date28/11/2019
Crockford, Christopher James
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Amyotrophic Lateral Sclerosis (ALS) is a rapid and fatal neurodegenerative disease marked by progressive muscle weakness and wasting. Approximately 50% of people with ALS experience changes in cognition and behaviour. Previous research has been mixed as to whether cognition declines over the course of ALS, or whether it is related to proxies of disease progression (e.g., functional disability scales). However, this research has suffered from limitations including the use of inappropriate measures of cognition, imprecise measures of disease progression, high attrition, practice effects, and biased analytic approaches. Fortunately, recent advances in clinical assessment have provided accurate measures of neuropsychological functioning and disease progression, namely, the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the King’s Clinical Disease Staging. The present study aims to utilise recent advances in ALS disease metrics to overcome previous limitations and explore the evolution of cognitive and behavioural dysfunction over the course of ALS. Specifically, the aims of the present project are to 1) develop alternate forms of the ECAS to accommodate repeated longitudinal assessment; 2) examine how cognition and behaviour relate to clinical disease stages in ALS; 3) evaluate how cognitive and behavioural symptoms evolve over the course of the disease in ALS; and 4) explore clinicians’ attitudes toward cognitive and behavioural screening in ALS. To achieve Aim 1, two new versions of the ECAS (ECAS-B and ECAS-C) were developed and administered to a group of age, education, and gender matched controls to that of the original ECAS-A validation study. Results demonstrate that the alternate forms of the ECAS (B and C) were equivalent to the original ECAS-A, reducing practice effects and possessing excellent inter-rater reliability. The ECAS forms were administered longitudinally to a separate group of healthy controls. Over an interval of 4 months, the ECAS-A-B-C showed no evidence of practice effects and excellent test-retest reliability validating their utility in the longitudinal monitoring of cognition in ALS. The ECAS forms were then used in an international multi-centre clinical sample of 161 ALS patients and 80 matched controls to achieve Aim 2. Patients were grouped into their King’s Clinical Disease Stage at time of testing. Analysis revealed a significant cross-sectional relationship between disease stage and ALS-Specific cognitive functions, driven by a decline in verbal fluency performance. A significant relationship was also observed between disease stage and behavioural features. By end-stage disease 80% of patients demonstrated neuropsychological impairment. Participants were followed up longitudinally to explore the progression of cognitive and behavioural symptoms. Latent Growth Curve models of the ECAS subdomains (utilising the alternate versions) demonstrated a significant decline in ALS Specific cognitive, but not behavioural, functioning over time. This decline was explained by advancing disease stage, the presence of the C9orf72 repeat expansion, and years of education. Rate of change in ALS Non-Specific functions was dependent on baseline performance. Visuospatial functions and perseveration declined at similar rates and were distinct from language, fluency, apathy, and disinhibited behaviour. Cluster analysis of patients revealed a three-cluster solution with one group demonstrating no significant decline, a second group with mild cognitive and behavioural decline, and a third group with more severe neuropsychological decline. When data was restructured by diseases stage, rather than time, longitudinal results were similar to cross-sectional findings. To examine clinician’s attitudes to cognitive and behavioural screening. Fourteen Health Care Professionals (HCP) working in ALS (Neurologists, Psychologists, and Clinical Care Specialists) were interviewed. Thematic analysis revealed that HCPs recognised the importance of cognitive and behavioural screening in ALS, but that it is not common practice. Important barriers to screening were reported including other members of staff, a lack of resources, and issues concerning patients and their families. Participants suggested increasing training and psychology input, and making screening a standardised protocol to all patients may alleviate these barriers. Cognition and behaviour are critically related to advancing disease stage, both cross-sectionally and longitudinally. Declining cognitive and behavioural symptoms has important implications for clinical practice, caregiver impact, and end-of-life decision making. However, clinicians report that cognitive and behavioural screening is not common practice and that significant barriers exist. The newly developed alternate forms of the ECAS provide an accurate, effective, and clinically useful means of monitoring cognitive function over the course of the disease in ALS.