Publications (4)5.9 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.
- Neurotherapeutics. 01/2009; 6(1):209-209.
- Neurotherapeutics 6(1):202-212. · 5.90 Impact Factor
- Neurotherapeutics. 6(1):202-212.