Thalamic metabolism and symptom onset in preclinical Huntington's disease.
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.
Feigin
A
A
Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, USA.
Tang
C
C
Ma
Y
Y
Mattis
P
P
Zgaljardic
D
D
Guttman
M
M
Paulsen
J S
JS
Dhawan
V
V
Eidelberg
D
D
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*
D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D019788:Fluorodeoxyglucose F18; D020891:Raclopride