Categorical and correlational analyses of baseline fluorodeoxyglucose positron emission tomography images from the Alzheimer's Disease Neuroimaging Initiative (ADNI)

Abstract

In mostly small single-center studies, Alzheimer's disease (AD) is associated with characteristic and progressive reductions in fluorodeoxyglucose positron emission tomography (PET) measurements of the regional cerebral metabolic rate for glucose (CMRgl). The AD Neuroimaging Initiative (ADNI) is acquiring FDG PET, volumetric magnetic resonance imaging, and other biomarker measurements in a large longitudinal multi-center study of initially mildly affected probable AD (pAD) patients, amnestic mild cognitive impairment (aMCI) patients, who are at increased AD risk, and cognitively normal controls (NC), and we are responsible for analyzing the PET images using statistical parametric mapping (SPM). Here we compare baseline CMRgl measurements from 74 pAD patients and 142 aMCI patients to those from 82 NC, we correlate CMRgl with categorical and continuous measures of clinical disease severity, and we compare apolipoprotein E (APOE) varepsilon4 carriers to non-carriers in each of these subject groups. In comparison with NC, the pAD and aMCI groups each had significantly lower CMRgl bilaterally in posterior cingulate, precuneus, parietotemporal and frontal cortex. Similar reductions were observed when categories of disease severity or lower Mini-Mental State Exam (MMSE) scores were correlated with lower CMRgl. However, when analyses were restricted to the pAD patients, lower MMSE scores were significantly correlated with lower left frontal and temporal CMRgl. These findings from a large, multi-site study support previous single-site findings, supports the characteristic pattern of baseline CMRgl reductions in AD and aMCI patients, as well as preferential anterior CMRgl reductions after the onset of AD dementia.

Figure 1

Regions with significantly lower CMRgl in pAD and aMCI patients. (A) Lower CMRgl in pAD patients than in elderly NC. (B) Lower CMRgl in aMCI patients than in elderly NC (p < 0.005, uncorrected for multiple comparisons). Significance levels in these brain maps are uncorrected for multiple comparisons. Findings are projected on to the lateral and medial surfaces of the left and right cerebral hemispheres and are also shown on horizontal sections in relationship to a horizontal section between the anterior and posterior commissures.

Figure 2

Significant correlations between clinical disease severity and lower CMRgl. (A) Correlations between higher CDR score (a categorical measure of clinical disease severity) and lower CMRgl using data from the three subject groups. (B) Correlations between lower MMSE score (a continuous measure of clinical disease severity) and lower CMRgl using data from the three subject groups. (C). Correlations between lower MMSE score and lower CMRgl when the analysis is restricted to the pAD group. Significance levels in these brain maps are uncorrected for multiple comparisons. Findings are projected on to the lateral and medial surfaces of the left and right cerebral hemispheres and are also shown on horizontal sections in relationship to a horizontal section between the anterior and posterior commissures.

Figure 3

Mean regional-to-whole brain CMRgl in ten different brain regions between Normal, aMCI, and pAD groups. Error bars represent the standard error of the mean. For each region displayed in Table 4, data from the local maxima was extracted and used to compare the mean regional-to-whole brain CMRgl between patient groups