Heterogeneity of Brain Glucose Metabolism in Mild Cognitive Impairment and Clinical Progression to Alzheimer Disease

Abstract

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 (18 FDG-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 18 FDG-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 18 FDG-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 18 FDG-PET findings combined with memory scores may be useful in predicting short-term conversion to AD.

Clinical and biological predictors of Alzheimer's disease in patients with amnestic mild cognitive impairment

“…Other techniques with promising diagnostic support are longitudinal measurements of wholebrain and/or hippocampal atrophy with structural MRI, cerebral blood flow with SPECT, and cerebral metabolism or amyloid imaging with PET scans. 16,18,38 Additionally, the combination of these diagnostic strategies seems to increase the predictive power to identify AD patients at the prodromal stages of the disease. 39 According to a recent task-force that proposed the revised NINCDS-ADRDA diagnostic criteria for research, 40 the presence of AD-compatible pathological findings, as indicated by one or more of these biomarkers, endorses the diagnosis of incipient (pre-dementia) AD given the clinical characterization of episodic memory impairment.…”

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal

“…Prior research suggests that anosognosia in MCI portends a faster rate of conversion to AD (Tabert et al, 2002). Additionally, PCC resting glucose metabolism and perfusion have been cited as prognostic indices of faster progression to AD (Anchisi et al, 2005;Huang et al, 2002;Kogure et al, 2000). Longitudinal follow-up of the current findings is needed to address the hypothesis that attenuated activity in cortical midline structures associated with anosognosia is predictive of faster cognitive and functional decline in MCI.…”

“…Investigations of resting brain function indicate that medial parietal regions such as the posterior cingulate cortex (PCC) show metabolic decline in MCI (Nestor et al, 2003), and longitudinal studies indicate that PCC metabolism and regional blood flow discriminate between individuals with MCI who soon develop AD and those who do not (Anchisi et al, 2005;Chetelat et al, 2003;Huang et al, 2002;Kogure et al, 2000). Additionally, fMRI studies of episodic recognition indicate that MCI participants show less PCC activation than age-matched controls (Johnson et al, 2005;Ries et al, 2006).…”

A Cochrane review on brain [18F]FDG PET in dementia: limitations and future perspectives

“…However, both these values were higher than 80 % in about half of the studies included [15][16][17][18][19][20], an accuracy that compares better with previous studies in which confirmation of underlying neurodegenerative pathology was obtained at autopsy. In the latter case, [ 18 F]FDG PET identified patients with AD with a sensitivity of 94 % and a specificity of 73 % [21].…”