A retrospective study of the impact of lifestyle on age at onset of Huntington disease.
In transgenic mouse models of Huntington disease (HD) environmental enrichment significantly delays disease onset. A questionnaire-based survey of 154 adults with diagnosed HD (mean 4.2 years postdiagnosis) and a known IT15 CAG repeat length, explored whether premorbid lifestyle may relate to age-at-onset (AO). Participants were drawn from HD outpatient clinics in Australia and New Zealand. Premorbid physical, intellectual, and passive activity levels were used to generate scores in the categories of leisure, nonleisure (education, occupation and domestic duties) and total lifestyle. AO was associated with increased CAG repeat length as expected (r = -0.72, P < 0.001), but also with a lifestyle that included higher levels of passive activity (r = -0.38, P < 0.001). Multiple linear regression modeling showed lifestyle passivity to be a variable independent of CAG repeat length in predicting AO (R(2) = 0.54, b = -0.22, P = 0.005). Comparison of the mean AO across tertiles of lifestyle passivity scores showed onset 4.6 years (95% CI = 1.3-7.9) later in the least compared with the most passive tertile. CAG repeat length was also shown to predict lifestyle passivity (R(2) = 0.12, b = 1.08, P < 0.0005). Neither intellectual nor physical activity showed significant relationships to AO or CAG repeat length in this cohort. Our study leads to two conclusions: that a passive lifestyle may be a preclinical expression of HD, and that it actually contributes to the earlier onset of symptoms. Overcoming the tendency to be passive may substantially delay onset of HD. (c) 2010 Movement Disorder Society.
Trembath
M Kaye
MK
Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
Horton
Zoë A
ZA
Tippett
Lynette
L
Hogg
Virginia
V
Collins
Veronica R
VR
Churchyard
Andrew
A
Velakoulis
Dennis
D
Roxburgh
Richard
R
Delatycki
Martin B
MB
D000328:Adult; D017668:Age of Onset; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000453:epidemiology* / Q000235:genetics / Q000523:psychology*; D008019:Life Style; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009520:New Zealand / Q000453:epidemiology; D009687:Nuclear Proteins / Q000235:genetics; D012189:Retrospective Studies; D013223:Statistics as Topic; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D055815:Young Adult
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins