Impact of disease, cognitive and behavioural factors on caregiver outcome in amyotrophic lateral sclerosis.

Up to 50% of patients with amyotrophic lateral sclerosis (ALS) show mild to moderate cognitive-behavioural change alongside their progressive functional impairment. This study examines the relative impact of patients' disease symptoms, behavioural change and current executive function and social cognition abilities on psychosocial outcomes in spouse caregivers of people with ALS. Thirty-five spouse caregivers rated their own levels of depression and anxiety, subjective burden and marital satisfaction. Caregivers also rated their partner's everyday behaviour. The patients were assessed for disease severity and cognitive function, with composite scores derived for executive function and social cognition. Regression analyses revealed that caregiver burden was predicted by the severity of patients' limb involvement and behavioural problems. Depression was predicted by patients' limb involvement, while behavioural problems and patient age predicted caregiver anxiety. Current marital satisfaction was predicted by patient behavioural problems beyond the level of pre-illness marital satisfaction. In conclusion, the study highlights the potential impact of ALS patients' functional impairment and behavioural change on ALS caregivers' psychosocial functioning. Clinical communication with ALS families should emphasise both physical and psychological challenges presented by the disease.

Executive dysfunction predicts social cognition impairment in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the motor system with recognised extra-motor and cognitive involvement. This cross-sectional study examined ALS patients' performance on measures requiring social inference, and determined the relationship between such changes and variations in mood, behaviour, personality, empathy and executive function. Fifty-five ALS patients and 49 healthy controls were compared on tasks measuring social cognition and executive function. ALS patients also completed measures examining mood, behaviour and personality. Regression analyses explored the contribution of executive function, mood, behaviour and personality to social cognition scores within the ALS sample. A between-group MANOVA revealed that, the ALS group was impaired relative to controls on two composite scores for social cognition and executive function. Patients also performed worse on individual tests of executive function measuring cognitive flexibility, response inhibition and concept formation, and on individual aspects of social cognition assessing the attribution of emotional and mental states. Regression analyses indicated that ALS-related executive dysfunction was the main predictor of social cognition performance, above and beyond demographic variables, behaviour, mood and personality. On at least some aspects of social cognition, impaired performance in ALS appears to be secondary to executive dysfunction. The profile of cognitive impairment in ALS supports a cognitive continuum between ALS and frontotemporal dementia.

Molecular classification of sporadic Creutzfeldt-Jakob disease.

According to the protein-only hypothesis of prion propagation, an abnormal isoform (designated PrP(Sc)) of the cellular prion protein (PrP(C)) is the principal or sole component of transmissible prions. However, the existence of multiple prion strains has been difficult to accommodate within this hypothesis. We have previously reported the identification of four types of human PrP(Sc) associated with sporadic and acquired human prion diseases. These PrP(Sc) types are distinguished by differing molecular mass of fragments following limited proteinase K digestion and by differing ratios of di-, mono- and unglycosylated PrP(Sc). That these discrete biochemical features of PrP(Sc) are serially transmissible to human PrP in transgenic mice following experimental transmission suggests that they may be responsible for encoding prion strain diversity. Here we present detailed clinical, pathological and molecular data from a large number of sporadic Creutzfeldt-Jakob disease (CJD) cases. We show that PrP(Sc) types are associated with codon 129 status, duration of illness and neuropathological phenotype. A novel PrP(Sc) type is presented, illustrating further heterogeneity in CJD, and suggesting that further molecular subtypes of CJD may exist at lower frequencies. A molecular classification of sporadic CJD is proposed.