title: Basal ganglia atrophy in prodromal Huntington's disease is detectable over one year using automated segmentation.
abstract: Future clinical trials of neuroprotection in prodromal Huntington's (known as preHD) will require sensitive in vivo imaging biomarkers to track disease progression over the shortest period. Since basal ganglia atrophy is the most prominent structural characteristic of Huntington's pathology, systematic assessment of longitudinal subcortical atrophy holds great potential for future biomarker development. We studied 36 preHD and 22 age-matched controls using a novel method to quantify regional change from T(1) -weighted structural images acquired 1 year apart. We assessed cross-sectional volume differences and longitudinal volumetric change in 7 subcortical structures-the accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. At baseline, accumbens, caudate, pallidum, and putamen volumes were reduced in preHD versus controls (all P < .01). Longitudinally, atrophy was greater in preHD than controls in the caudate, pallidum, and putamen (all P < .01). Each structure showed a large between-group effect size, especially the pallidum where Cohen's d was 1.21. Using pallidal atrophy as a biomarker, we estimate that a hypothetical 1-year neuroprotection study would require only 35 preHD per arm to detect a 50% slowing in atrophy and only 138 preHD per arm to detect a 25% slowing in atrophy. The effect sizes calculated for preHD basal ganglia atrophy over 1 year are some of the largest reported to date. Consequently, this translates to strikingly small sample size estimates that will greatly facilitate any future neuroprotection study. This underscores the utility of this automatic image segmentation and longitudinal nonlinear registration method for upcoming studies of preHD and other neurodegenerative disorders.
authors.affiliation: Department of Psychology, University of California, San Diego, San Diego, California 92093-0841, USA.
authors.forename: D S Adnan
authors.initials: DS
authors.lastname: Majid
authors.forename: Adam R
authors.initials: AR
authors.lastname: Aron
authors.forename: Wesley
authors.initials: W
authors.lastname: Thompson
authors.forename: Sarah
authors.initials: S
authors.lastname: Sheldon
authors.forename: Samar
authors.initials: S
authors.lastname: Hamza
authors.forename: Diederick
authors.initials: D
authors.lastname: Stoffers
authors.forename: Dominic
authors.initials: D
authors.lastname: Holland
authors.forename: Jody
authors.initials: J
authors.lastname: Goldstein
authors.forename: Jody
authors.initials: J
authors.lastname: Corey-Bloom
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D001479:Basal Ganglia / Q000473:pathology*; D001480:Basal Ganglia Diseases / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009714:Nucleus Accumbens / Q000473:pathology; D013788:Thalamus / Q000473:pathology