Back to Search
Start Over
Frailty and Associated Environmental Factors Only Have Small Effects on Age of Onset in Huntington's Disease.
- Source :
-
Journal of Huntington's disease [J Huntingtons Dis] 2023; Vol. 12 (4), pp. 355-361. - Publication Year :
- 2023
-
Abstract
- Background: Over one third of age of onset variation in Huntington's disease is unexplained by CAG repeat length. In Alzheimer's disease, frailty partly modulates the relationship between neuropathology and dementia.<br />Objective: We investigated whether a multi-domain frailty index, reflecting non-genetic factors in Huntington's disease, similarly modulates the relationship between CAG repeat length and age of onset.<br />Methods: We created a frailty index assessing comorbidities, substance abuse, polypharmacy, and education. We applied multiple linear regression models to 2,741 subjects with manifest Huntington's disease from the Enroll-HD cohort study, including 729 subjects with late-onset (post-60 years) disease, using frailty index or constituent item scores and CAG repeat length as independent variables. We used actual and "residual" ages of onset (difference between actual and CAG-based predicted onset) as dependent variables, the latter offsetting the increased time available to accumulate comorbidities in older subjects.<br />Results: Higher frailty index scores were associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.03), though the effect was small (R2 = 0.27 with frailty as a predictor vs. 0.26 without). Number of comorbidities was also associated with significantly lower residual ages of onset in the late-onset subgroup (p = 0.04). Drug abuse and smoking were associated with significantly earlier ages of onset in the whole cohort (p < 0.01, p = 0.02) and late-onset subgroup (p < 0.01, p = 0.03).<br />Conclusions: The impact of non-genetic factors on age of onset, assessed using a frailty index or separately, in Huntington's disease is limited.
Details
- Language :
- English
- ISSN :
- 1879-6400
- Volume :
- 12
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of Huntington's disease
- Publication Type :
- Academic Journal
- Accession number :
- 38007671
- Full Text :
- https://doi.org/10.3233/JHD-230572