K. Trembath

Murdoch Childrens Research Institute, Melbourne, Victoria, Australia

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Publications (6)21.97 Total impact

  • M. Delatycki · K. Trembath
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    ABSTRACT: Background A study of pre-morbid lifestyle in 154 individuals in Australasia published in 2010 made two findings. Firstly, a passive lifestyle can be a preclinical expression of HD. Secondly, and more importantly, the higher levels of lifestyle passivity associated with those showing an earlier age at onset (AO) is in part independent of the HD mutation, suggesting that overcoming the tendency to be passive may delay onset. Aims To undertake a replication study in a European cohort through EHDN. Methods The Australian questionnaire was modified to reflect cultural differences and translated into Czech, French, German, Italian, Norwegian, Polish, Spanish and Swedish. Trained interviewers in 30 centres gathered data from 194 individuals with early symptomatic HD to ascertain pre-morbid lifestyle, including participation in leisure and non-leisure activities (education, occupation and domestic duties). Activities were classified as physical, intellectual or passive, and scores were generated under the categories leisure, non-leisure and total lifestyle, and data were matched with the individual’s AO and HTT CAG repeat length. Results The mean AO was 44.4 years (range 16–71) There were strong inverse correlations between AO and both CAG repeat length (r=-0.68, p < 0.001) and a lifestyle that includes higher levels of passive activity (r = -0.22, p < 0.001), though not with higher levels of intellectual or physical activity. CAG repeat length and average pre-morbid lifestyle passivity were also strongly associated (r= + 0.32, p < 0.001). Details of the breakdown into leisure and non-leisure aspects of lifestyle and into activity data for various life stages (teens, 20s/30s and 40s/50s) will be presented. Conclusions The data support the contention that passivity can be a pre-clinical manifestation of disease and that there may be a considerable impact of lifestyle on the age of onset.
    No preview · Article · Sep 2014 · Journal of Neurology Neurosurgery & Psychiatry
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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.
    No preview · Article · Jan 2009 · Neurotherapeutics
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    ABSTRACT: Please see Platform Presentation above for abstract body.
    No preview · Article · Jan 2009 · Neurotherapeutics
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    Full-text · Article · Jan 2009 · Neurotherapeutics
  • K. Trembath · Z. Horton · L. Tippett · V. Hogg · V. Collins

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