Platform Presentation—Lifestyle Activity and the Age of Onset of Huntington Disease

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 p 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 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.