Metabolic network abnormalities in early Huntington's disease: an [(18)F]FDG PET study

The identification of discrete patterns of altered functional brain circuitry in preclinical Huntington's disease (HD) gene carriers is important to understanding the pathophysiology of this disorder and could be useful as a biologic disease marker. The purpose of this study was to use PET imaging of regional cerebral glucose metabolism to identify abnormal networks of brain regions that are specifically related to the preclinical phase of HD.

Eighteen presymptomatic HD gene carriers, 13 early-stage HD patients, and 8 age-matched gene-negative relatives were scanned using PET with [(18)F]FDG to quantify regional glucose utilization. A network modeling strategy was applied to the FDG PET data to identify disease-related regional metabolic covariance patterns in the preclinical HD cohort. The outcome measures were the region weights defining the metabolic topography of the HD gene carriers and the subject scores quantifying the expression of the pattern in individual subjects.

Network analysis of the presymptomatic carriers and the gene-negative control subjects revealed a significant metabolic covariance pattern characterized by caudate and putamenal hypometabolism but also included mediotemporal metabolic reductions as well as relative metabolic increases in the occipital cortex. Subject scores for this pattern were abnormally elevated in the preclinical group compared with those of the control group (P < 0.005) and in the early symptomatic group compared with those of the presymptomatic group (P < 0.005).

These findings show that FDG PET with network analysis can be used to identify specific patterns of abnormal brain function in preclinical HD. The presence of discrete patterns of metabolic abnormality in preclinical HD carriers may provide a useful means of quantifying the rate of disease progression during the earliest phases of this illness.