Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to alzheimer disease

Background: Subjects with amnesic mild cognitive impairment (aMCI) may include patients at high risk for progression to Alzheimer disease (AD) and a population with different underlying pathologic conditions. Objective: To evaluate the potential roles of positron emission tomography with fluodeoxyglucose F 18 (¹⁸FDG-PET) and memory scores in identifying subjects with aMCI and in predicting progression to dementia. Design, Setting, and Patients: Sixty-seven patients at European centers for neurologic and AD care who were diagnosed as having aMCI each underwent an extensive clinical and neuropsychological examination and an ¹⁸FDG-PET study. Forty-eight subjects were followed up periodically for at least 1 year, and progression to dementia was evaluated. Main Outcome Measures: Brain glucose metabolism and memory scores. Results: Fourteen subjects with aMCI who converted to AD within 1 year showed bilateral hypometabolism in the inferior parietal, posterior cingulate, and medial temporal cortex. Subjects with "stable" aMCI presented with hypometabolism in the dorsolateral frontal cortex. The severity of memory impairment, as evaluated by the California Verbal Learning Test-Long Delay Free Recall scores, correlated with the following brain metabolic patterns: scores less than 7 were associated with a typical ¹⁸FDG-PET AD pattern, and scores of 7 or higher were associated with hypometabolism in the dorsolateral frontal cortex and no progression to AD. Conclusion: These data provide evidence for clinical and functional heterogeneity among subjects with aMCI and suggest that ¹⁸FDG-PET findings combined with memory scores may be useful in predicting short-term conversion to AD.