Multidimensional apathy: evidence from neurodegenerative disease

Apathy is a demotivation syndrome common in neurodegenerative diseases and is fundamentally multidimensional in nature. Different methodologies have been used to identify and quantify these dimensions, which has resulted in multifarious concepts, ranging in the number and characteristics of apathy subtypes. This has created an ambiguity over the fundamental substructure of apathy. Here we review the multidimensional concepts of apathy and demonstrate that overlapping elements exist, pointing towards commonalities in apathy subtypes. These can be subsumed under a unified Dimensional Apathy Framework: a triadic structure of Initiation, Executive and Emotional apathy. Distinct cognitive processes may underlie these domains, while self-awareness interplays with all subtypes. Evidence from neurodegenerative diseases supports this distinction with differing apathy profiles in amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease

Clinicians' attitudes towards cognitive and behavioural screening in motor neurone disease

Amyotrophic lateral sclerosis (ALS), the most common variant of motor neurone disease (MND), is a fatal neurodegenerative condition marked by progressive motor disability. Cognitive and behavioural changes occur in approximately 50% of patients, which may impact caregiver burden, adherence to life-prolonging interventions and care planning. The aim of this study was to explore the attitudes and practices of health professionals working with ALS patients in Scotland towards cognitive and behavioural screening. Structured interviews with ALS health professionals were conducted and subjected to thematic analysis. While 93% of clinicians in this study believed that cognitive and behavioural screening should be routinely applied for all patients, it is not common practice, nor are formalised screening tools widely used. Participants noted that barriers to screening include other members of staff, limited resources, and issues concerning patients and their families. Participants suggested that increased education and training, making screening a standardised protocol to all patients and increased psychology input may help overcome these barriers. </jats:p

The response of staff to the design of the CSIRO's Discovery building

There is an increasing demand for scientists to make the results of their research available for scrutiny by members of the public, and for scientists to demystify science. In response to this pressure, research organisations are adopting a variety of methods to communicate with the public. One approach taken by CSIRO in the mid 1990s was to build a multipurpose building, the Discovery Centre, which incorporated an exhibition, an education centre, and laboratories that featured floor to ceiling glass walls so visitors could view researchers at work. This sub-thesis documents the design phase of the Discovery building and looks at how the researchers feel about working in a ‘lab-in-view’ laboratory. It also addresses some aspects of internal communication between researchers in Discovery laboratories. The impact of being more or less in view of the public was identified as well as the role of increased contact for informal communication opportunities afforded by the convenient location of the cafe. Opportunities for further research are also identified

Multidimensional apathy in ALS:validation of the Dimensional Apathy Scale

AIM: Apathy is a prominent symptom of amyotrophic lateral sclerosis (ALS), but measurement is confounded by physical disability. Furthermore, it has been traditionally measured as a unidimensional symptom despite research demonstrating a multifaceted construct. The new Dimensional Apathy Scale (DAS) has been specifically designed for patients with motor disability to measure 3 neurologically based subtypes of apathy: Executive, Emotional and Initiation. We aimed to explore this behavioural symptom by examining the substructure of apathy in ALS and to determine the reliability and validity of the DAS in patients and their carers.  METHOD: Patients and carers were recruited through the national Scottish Motor Neurone Disease Register and were asked to complete the DAS, the standardised Apathy Evaluation Scale, and the Geriatric Depression Scale-Short Form. 83 patients with ALS, 75 carers and 83 sex-matched, age-matched and education-matched controls participated.  RESULTS: When compared with healthy controls, patients showed a significant increase in apathy on the Initiation subscale, and were significantly less apathetic on the Emotional subscale. Scores on the DAS patient and carer versions did not significantly differ. Internal consistency reliability, convergent and discriminant validity were found to be good for the DAS subscales. There was no association between the DAS and functional disability using the ALS Functional Rating Scale.  CONCLUSIONS: Apathy in ALS is characterised by a specific profile of increased initiation apathy and reduced emotional apathy. The DAS is a reliable and valid measure for the assessment of multidimensional apathy in ALS

UV-mediated Regulation of the anti-senescence factor Tbx2

Several lines of evidence have implicated members of the developmentally important T-box gene family in cell cycle regulation and in cancer. Importantly, the highly related T-box factors Tbx2 and Tbx3 can suppress senescence through repressing the cyclin-dependent kinase inhibitors p19(ARF) and p21(WAF1/CIP1/SDII). Furthermore, Tbx2 is up-regulated in several cancers, including melanomas where it was shown to function as an anti-senescence factor, suggesting that this may be one of the mechanisms by which T-box proteins contribute to the oncogenic process. However, very little is known about whether Tbx2 is regulated by p21-mediated stress-induced senescence signaling pathways. In this study, using the MCF-7 breast cancer cell line known to overexpress Tbx2, we show that in response to stress induced by ultraviolet irradiation the Tbx2 protein is specifically phosphorylated by the p38 mitogen-activated protein kinase. Using site-directed mutagenesis and in vitro kinase assays, we have identified serine residues 336, 623, and 675 in the Tbx2 protein as the p38 target sites and show that these sites are phosphorylated in vivo. Importantly, we show by Western blotting, immunofluorescence, and reporter assays that this phosphorylation leads to increased Tbx2 protein levels, predominant nuclear localization of the protein, and an increase in the ability of Tbx2 to repress the p21(WAF1/CIP1/SDII) promoter. These results show for the first time that the ability of Tbx2 to repress the p21 gene is enhanced in response to a stress-induced senescence pathway, which leads to a better understanding of the regulation of the anti-senescence function of Tbx2