P2-037: Categorical and correlational analyses of baseline fluorodeoxyglucose positron emission tomography images from the Alzheimer's disease neuroimaging initiative

Abstract

Alzheimer's disease (AD) is characterized by regional reductions in fluorodeoxyglucose positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl), which are correlated with clinical severity, progressive and apparent before the onset of dementia or mild cognitive impairment (MCI). We have been using statistical parametric mapping (SPM) to analyze PET data from probable AD patients, amnestic MCI (aMCI) patients and normal controls (NC) from the AD Neuroimaging Initiative (ADNI). Our objective was to characterize patterns of cerebral hypometabolism in probable AD and aMCI, and correlate lower Mini-Mental State Examination (MMSE) scores with lower regional CMRgl in both the overall cohort of probable AD, aMCI and NC subjects and the probable AD group. Baseline PET images from 298 subjects, including 74 probable AD (age 70±10, MMSE 23.5±2.2), 142 aMCI (age 67±12, MMSE 27.1±1.7) and 82 NC (69±10 years old, MMSE 28.9±1.1), were analyzed on a voxel-by-voxel basis using SPM5. ANOVA with pair-wise comparisons contrasted regional CMRgl in the three subject groups. Linear regression correlated lower MMSE scores with lower CMRgl in the overall cohort and probable AD group. Compared to NC, the probable AD and aMCI groups each had lower CMRgl bilaterally in previously characterized posterior cingulate, precuneus, and parietotemporal regions (P<0.05 corrected for multiple comparisons), and occipital cortex, hippocampus, parahippocampal gyrus and fusiform gyrus (uncorrected P<0.005). Compared to NC, the probable AD group had lower CMRgl in frontal regions (corrected P<0.05). In the overall cohort, lower MMSE scores were correlated with lower CMRgl in the posterior cingulate, precuneus, parietotemporal and frontal regions (P<0.05, corrected for multiple comparisons). In the probable AD group, lower MMSE scores were correlated with lower CMRgl in left frontal and temporal regions (uncorrected P<0.001). Findings from this large multi-center study confirm the previously characterized pattern of regional hypometabolism in AD and aMCI and implicate additional brain regions. Furthermore, they confirm the previously characterized correlation between severity of clinical impairment in a combined group of patients and controls, but suggest strongest correlations between clinical severity of frontal and temporal regions by the time AD patients satisfy criteria for dementia.