Association between Age and Striatal Volume Stratified by CAG Repeat Length in Prodromal Huntington Disease

Elizabeth Aylward,Jane S Paulsen,Dawei Liu,Christopher A Ross,Peggy Nopoulos,James Mills,Ronald Pierson

doi:10.1371/currents.rrn1235

Elizabeth Aylward, Jane S Paulsen + Show 5 more

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https://doi.org/10.1371/currents.rrn1235

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Abstract

Background: Longer CAG repeat length is associated with faster clinical progression in Huntington disease, although the effect of higher repeat length on brain atrophy is not well documented. Method: Striatal volumes were obtained from MRI scans of 720 individuals with prodromal Huntington disease. Striatal volume was plotted against age separately for groups with CAG repeat lengths of 38–39, 40, 41, 42, 43, 44, 45, 46, and 47–54. Results: Slopes representing the association between age and striatal volume were significantly steeper as CAG repeat length increased. Discussion: Although cross-sectional, these data suggest that striatal atrophy, like clinical progression, may occur faster with higher CAG repeat lengths.

Highlights

It has long been known that greater CAG repeat lengths are associated with earlier onset of illness, especially for individuals with high repeat number
Based on cross-sectional data, our analyses suggest that increased CAG repeat length is associated with faster progression of striatal atrophy in prodromal HD, at least up through CAG = 44
It is clearly established that CAG repeat length has an effect on age at onset of HD [1] [11],few studies have examined the effect of CAG repeat length on rate of brain atrophy, and these have all been done on relatively small samples and most have examined brain regions other than the striatum

Summary

Introduction

It has long been known that greater CAG repeat lengths are associated with earlier onset of illness, especially for individuals with high repeat number. More recent evidence demonstrates that higher CAG repeat lengths are associated with faster clinical progression. Evidence for faster progression of striatal atrophy with higher CAG repeat length is not as clear. Cross-sectional and longitudinal studies have yielded conflicting results, with some suggesting that brain atrophy progresses more rapidly for individuals with higher CAG repeat length and others showing no relationship [2] [3] [4] [5] [6] [7] [8]. Longer CAG repeat length is associated with faster clinical progression in Huntington disease, the effect of higher repeat length on brain atrophy is not well documented. Discussion: cross-sectional, these data suggest that striatal atrophy, like clinical progression, may occur faster with higher CAG repeat lengths

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Conclusion