The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) in the assessment of early onset dementia

Early onset dementia is the gradual cognitive decline that interferes with independence in everyday activities, when it occurs in people younger than 65 years old (Fadil et al., 2009; American Psychiatric Association, 2013). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was originally developed to assess cognitive and behavioural changes observed in amyotrophic lateral sclerosis (ALS) (Abrahams et al. 2014); as between 10- 15% of ALS patients develop frontotemporal dementia, and an additional 35% develop a milder cognitive impairment of frontotemporal dysfunction (Goldstein and Abrahams, 2013; Strong et al., 2017). The ECAS includes the domains of language, fluency, and executive functions for the assessment of ALS, but it also includes the domains of memory and visuospatial abilities to differentiate changes from other pathologies, such as Alzheimer's Disease (AD) (Abrahams et al. 2014). In addition, the ECAS includes a behavioural interview. In this thesis I explore whether the ECAS is a sensitive test to the types of cognitive and behavioural changes in people with early onset dementia without Amyotrophic Lateral Sclerosis (ALS). In the first study my objectives were: to investigate the relationship between the ECAS and the Addenbrooke's Cognitive Examination (ACE-III); to investigate the effects of age, education, and IQ on the ECAS, and create appropriate cut-off scores to determine abnormality. I assessed 80 healthy participants divided into four groups according to age and education. The ECAS and the ACE-III had a significant correlation indicating good convergent validity. IQ, followed by age, were the strongest predictors of the total ECAS score. While IQ predicted 46% of the ACE-III variance, it only predicted 24% of the ECAS variance. I created abnormality cut-off scores adjusted for age and education. This research was published in De Icaza Valenzuela et al. (2018). In the second study my aim was to determine the sensitivity of the ECAS to behavioural variant frontotemporal dementia (bvFTD) without ALS, AD, primary progressive aphasia (PPA) without ALS, posterior cortical atrophy (PCA) and mild cognitive impairment (MCI). I also validated the ECAS against a comprehensive neuropsychological assessment, and compared it with the ACE-III, for each diagnosis. We additionally performed a qualitative thematic analysis of the ECAS behavioural interviews to determine the differences in themes between the diagnoses of bvFTD and AD. The study included 16 people with bvFTD (without ALS), 32 with AD, 12 with MCI, 13 with PPA, 6 with PCA and 48 healthy controls. The ECAS was more sensitive than the ACE-III to detect bvFTD, AD, MCI and PPA; with equal sensitivity to detect PCA. The anterior functions (comprising executive, fluency and language scores) composite score was sensitive to bvFTD; while the posterior functions (comprising memory and visuospatial scores) composite score was sensitive to AD. The ECAS was able to detect cognitive impairment as determined by a comprehensive neuropsychological assessment in most of the patients. A cut-off of 4 or more behavioural domains affected differentiated well between bvFTD and AD, while different themes emerged between the groups in the qualitative analysis of the behavioural interview. Finally, for the third study my objectives were: to investigate the relationship between the ECAS and functional severity of dementia; to validate the behavioural interview of the ECAS with other behavioural screens used to assess FTD; and to determine whether the ECAS scores changed over time in bvFTD, AD, MCI, PPA, and PCA. For this purpose, I did a longitudinal study and analysed the correlations between the ECAS with the Clinical Dementia Rating Scale (CDR-FTLD), the Frontal Behavioural Inventory (FBI), and the Frontotemporal Dementia Rating Scale (FRS). I assessed 56 patients on the first assessment, 29 on the second assessment and 13 on the third assessment. The ECAS total score had good convergent validity with the CDR-FTLD severity classification, while the ECAS behavioural screen had convergent validity with the FBI, FRS and CDR-FTLD. I created an impairment cut-off score of 96 to differentiate the groups of questionable versus mild dementia based on the CDR-FTLD. The CDR-FTLD, FIQ, FBI, and FRS predicted 71.3% of the variance of the ECAS Total Score. The variance of the ECAS behavioural score was predicted 74.7% by the FBI, FIQ and age. FRS was the single variable to predict attrition by 20.4%. In our study there was no significant difference of ECAS scores between assessments. The ECAS proved to be a valid test to assess the cognitive and behavioural impairments in people with early onset dementia without ALS. It was more sensitive than the ACE-III at detecting dementia in most of the patient groups, with the exception of the PCA group where they had equal sensitivity. The ECAS had also equal sensitivity to detect bvFTD, PPA and PCA as an extensive neuropsychological assessment. It could therefore be used as a first assessment in early onset dementia clinics.