Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease.

OBJECTIVE

To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease.

DESIGN

Eighteen persons at risk for Huntington's disease had two positron emission tomographic glucose metabolic studies and two magnetic resonance imaging scans separated by 42 (+/- 9) months.

SETTING

Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology.

SUBJECTS

Seven of the individuals were Huntington' disease gene negative by testing at the polymorphic DNA loci D4S10, D4S43, and D4S125; the remainder were gene positive by genetic testing or onset of chorea after study entry.

INTERVENTIONS

None.

OUTCOME MEASURES

Onset of chorea and imaging results.

RESULTS

The gene-positive group demonstrated a significant 3.1% loss of glucose metabolic rate per year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48) compared with the gene-negative group. There was a 3.6% per year increase in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a linear measure of caudate atrophy. The rate of change in caudate size did not correlate with the rate of change in caudate metabolism, suggesting that metabolic loss and atrophy may develop independently.

CONCLUSIONS

The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism.