Publications (5)15.16 Total impact
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ABSTRACT: Transgenic HD mouse model studies have shown that raising mice in an enriched environment delays the onset of symptoms, leading us to consider whether pre-morbid lifestyle may affect age-at-onset in humans. Subjects with symptomatic HD were interviewed using a questionnaire to retrospectively ascertain pre-morbid lifestyle, including participation in a range of leisure activities and non-leisure activities (education, occupation, and domestic duties). Recorded activities were classified as physical, intellectual, or passive, and activity scores were generated under the headings leisure, non-leisure, and total lifestyle. Surveys were matched with the subject's age-at-onset and CAG repeat length. Analysis of age-at-onset data from 154 subjects in Australia and New Zealand showed a mean of 45.7 years (range 21-76), and a strong inverse correlation with CAG repeat length (r = −0.72, p < 0.001). Furthermore, a relationship between CAG repeat length and average pre-morbid lifestyle passivity was demonstrated (r = 0.34, p < 0.001), suggesting passivity to be a preclinical manifestation of disease. Upon this background, further analyses were undertaken. Multiple regression analyses that included CAG repeat length as one predictor variable showed passivity (both in leisure and non-leisure) to be a second, independent predictor of age-at-onset (b = −0.28, p = 0.04, and b = −0.27, p = 0.02, respectively), suggesting that a passive lifestyle also contributes to the early onset of symptoms. Leisure activity data covering three life stages (teens, 20s/30s, and 40s/50s) indicate that it is teenage passivity that correlates most strongly with age-at-onset (r = −0.38, p < 0.001). No relationships of significance were apparent involving age-at-onset and either intellectual or physical activity. The impact of passivity on age-at-onset is illustrated by comparing the mean age-at-onset in three groups based on lifestyle passivity score. A difference of 4.6 years (95% CI = 1.3 to 7.9) between high and low scoring groups (after adjusting for the impact of CAG repeat length) indicates a significant delay in the onset of symptoms in those who are less passive.Neurotherapeutics 01/2009; 6(1):202-202. DOI:10.1016/j.nurt.2008.09.005 · 5.05 Impact Factor
- Neurotherapeutics 01/2009; 6(1):209-209. DOI:10.1016/j.nurt.2008.10.018 · 5.05 Impact Factor
- Neurotherapeutics 01/2009; 6(1):202-212. DOI:10.1016/j.nurt.2008.09.004 · 5.05 Impact Factor
Article: A Metabolic Challenge on CD-ROM[Show abstract] [Hide abstract]
ABSTRACT: We have introduced a novel approach to the learning of metabolism by undergraduate students of biochemistry by providing them, on CD-ROM, with an intellectual challenge relating to 'real world' metabolic problems. The CD-ROM Biochemistry -A Metabolic Challenge is an integral component of our course curriculum but has been introduced with different emphasis into the different undergraduate Biochemistry courses. For science students, the programs are an adjunct to formal lectures and part of problem-solving sessions that are a component of the practical classes. For biomedical and medical students, who are high academic achievers, the CD-ROM is also used for self-directed learning and case studies whereby students are expected to take more responsibility for their own learning. The problem-solving exercises, entitled The Great Metabolic Race and The After Race Banquet, explore the metabolic changes that occur to an athlete during a long distance race, and the subsequent recovery phase. The exercises are question/problem based and interactive, requiring students to analyse the questions, think logically and respond by integrating information drawn from a variety of sources. A set of thirteen self-paced, interactive tutorials covering the fundamentals of metabolism are linked to these exercises to act as one resource. While the answers to the questions do not appear in the tutorials, the information required to formulate the answers does. The CD-ROM is used for self-directed learning to help students visualize pathways and the relationship between them, and to integrate the knowledge they have acquired from various sources. It also contains case studies to teach students how these pathways are affected in specific clinical cases. Surveys have shown that students respond particularly well to the participatory nature of this new resource and find the self-paced learning and testing very valuable. We also have preliminary indications that the use of these programs does translate into improved student comprehension as judged by examination performance.
Murdoch Childrens Research InstituteMelbourne, Victoria, Australia