title: Thalamic metabolism and symptom onset in preclinical Huntington's disease.
abstract: The neural basis for the transition from preclinical to symptomatic Huntington's disease (HD) is unknown. We used serial positron emission tomography (PET) imaging in preclinical HD gene carriers (p-HD) to assess the metabolic changes that occur during this period. Twelve p-HD subjects were followed longitudinally with [11C]-raclopride and [18F]-fluorodeoxyglucose PET imaging, with scans at baseline, 18 and 44 months. Progressive declines in striatal D2-receptor binding were correlated with concurrent changes in regional metabolism and in the activity of an HD-related metabolic network. We found that striatal D2 binding declined over time (P < 0.005). The activity of a reproducible HD-related metabolic covariance pattern increased between baseline and 18 months (P < 0.003) but declined at 44 months (P < 0.04). These network changes coincided with progressive declines in striatal and thalamic metabolic activity (P < 0.01). Striatal metabolism was abnormally low at all time points (P < 0.005). By contrast, thalamic metabolism was elevated at baseline (P < 0.01), but fell to subnormal levels in the p-HD subjects who developed symptoms. These findings were confirmed with an MRI-based atrophy correction for each individual PET scan. Increases in network expression and thalamic glucose metabolism may be compensatory for early neuronal losses in p-HD. Declines in these measures may herald the onset of symptoms in gene carriers.
authors: Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA.
authors: A
authors: A
authors: Feigin
authors: C
authors: C
authors: Tang
authors: Y
authors: Y
authors: Ma
authors: P
authors: P
authors: Mattis
authors: D
authors: D
authors: Zgaljardic
authors: M
authors: M
authors: Guttman
authors: J S
authors: JS
authors: Paulsen
authors: V
authors: V
authors: Dhawan
authors: D
authors: D
authors: Eidelberg
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D018450:Disease Progression; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D009483:Neuropsychological Tests; D009778:Occipital Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D011485:Protein Binding; D020891:Raclopride / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D019788:Fluorodeoxyglucose F18; D020891:Raclopride