2-fluoro-2-deoxyglucose-6-phosphate and Alzheimer-Disease

PET based tools can improve the early diagnosis of Alzheimer's disease (AD) and differential diagnosis of dementia. The importance of identifying individuals at risk of developing dementia among people with subjective cognitive complaints or mild cognitive impairment has clinical, social, and therapeutic implications. Within the two major classes of AD biomarkers currently identified, that is, markers of pathology and neurodegeneration, amyloid- and FDG-PET imaging represent decisive tools for their measurement. As a consequence, the PET tools have been recognized to be of crucial value in the recent guidelines for the early diagnosis of AD and other dementia conditions. The references based recommendations, however, include large PET imaging literature based on visual methods that greatly reduces sensitivity and specificity and lacks a clear cut-off between normal and pathological findings. PET imaging can be assessed using parametric or voxel-wise analyses by comparing the subject's scan with a normative data set, significantly increasing the diagnostic accuracy. This paper is a survey of the relevant literature on FDG and amyloid-PET imaging aimed at providing the value of quantification for the early and differential diagnosis of AD. This allowed a meta-analysis and GRADE analysis revealing high values for PET imaging that might be useful in considering recommendations.

Topics: Alzheimer Disease; Amyloid; Glucose-6-Phosphate; Humans; Positron-Emission Tomography; Radiography; Radiopharmaceuticals

The objective of this study was to compare glucose metabolism and atrophy, in the precuneus and cingulate cortex, in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), using FreeSurfer.. 47 individuals (17 patients with AD, 17 patients with amnestic MCI, and 13 healthy controls (HC)) were included. MRI and PET images using (18)F-FDG (mean injected dose of 185 MBq) were acquired and analyzed using FreeSurfer to define regions of interest in the hippocampus, amygdala, precuneus, and anterior and posterior cingulate cortex. Regional volumes were generated. PET images were registered to the T1-weighted MRI images and regional uptake normalized by cerebellum uptake (SUVr) was measured.. Mean posterior cingulate volume was reduced in MCI and AD. SUVr were different between the three groups: mean precuneus SUVr was 1.02 for AD, 1.09 for MCI, and 1.26 for controls (p < 0.05); mean posterior cingulate SUVr was 0.96, 1.06, and 1.22 for AD, MCI, and controls, respectively (p < 0.05).. We found graduated hypometabolism in the posterior cingulate cortex and the precuneus in prodromal AD (MCI) and AD, whereas atrophy was not significant. This suggests that the use of (18)F-FDG in these two regions could be a neurodegenerative biomarker.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cerebellar Diseases; Cognitive Dysfunction; Female; Glucose-6-Phosphate; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Parietal Lobe; Positron-Emission Tomography; Radiography

The aim of this study was to investigate the dynamics of four of the most validated biomarkers for Alzheimer's disease (AD), cerebro-spinal fluid (CSF) Abeta 1-42, tau, hippocampal volume, and FDG-PET, in patients at different stage of AD. Two hundred twenty-nine cognitively healthy subjects, 154 mild cognitive impairment (MCI) patients converted to AD, and 193 (95 early and 98 late) AD patients were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. For each biomarker, individual values were Z-transformed and plotted against ADAS-cog scores, and sigmoid and linear fits were compared. For most biomarkers the sigmoid model fitted data significantly better than the linear model. Abeta 1-42 time course followed a steep curve, stabilizing early in the disease course. CSF tau and hippocampal volume changed later showing similar monotonous trends, reflecting disease progression. Hippocampal loss trend was steeper and occurred earlier in time in APOE epsilon4 carriers than in non-carriers. FDG-PET started changing early in time and likely followed a linear decline. In conclusion, this study provides the first evidence in favor of the dynamic biomarker model which has recently been proposed.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Apolipoprotein E4; Biomarkers; Cohort Studies; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Genetic Carrier Screening; Glucose-6-Phosphate; Hippocampus; Humans; Longitudinal Studies; Male; Neurobiology; Organ Size; Peptide Fragments; Positron-Emission Tomography; Prospective Studies; tau Proteins

The purpose of this study was to evaluate and compare the diagnostic ability of 2-[(18)F]-fluoro-2-deoxy-D: -glucose (FDG) positron emission tomography (PET) and N-isopropyl-p-(123)I iodoamphetamine single photon emission computed tomography (IMP-SPECT) using three-dimensional stereotactic surface projections (3D-SSP) in patients with moderate Alzheimer's disease (AD).. FDG-PET and IMP-SPECT were performed within 3 months in 14 patients with probable moderate AD. Z-score maps of FDG-PET and IMP-SPECT images of a patient were obtained by comparison with data obtained from control subjects. Four expert physicians evaluated and graded the glucose hypometabolism and regional cerebral blood flow (rCBF), focusing in particular on the posterior cingulate gyri/precunei and parietotemporal regions, and determined the reliability for AD. Receiver operating characteristic (ROC) curves were applied to the results for clarification. To evaluate the correlation between two modalities, the regions of interest (ROIs) were set in the posterior cingulate gyri/precunei and parietotemporal region on 3D-SSP images, and mean Z-values were calculated.. No significant difference was observed in the area under the ROC curve (AUC) between FDG-PET and IMP-SPECT images (FDG-PET 0.95, IMP-SPECT 0.94). However, a significant difference (P < 0.05) was observed in the AUC for the posterior cingulate gyri/precuneus (FDG-PET 0.94, IMP-SPECT 0.81). The sensitivity and specificity of each modality were 86%, and 97% for FDG-PET and 70% and 100% for IMP-SPECT. We could find no significant difference between FDG-PET and IMP-SPECT in terms of diagnosing moderate AD using 3D-SSP. There was a high correlation between the two modalities in the parietotemporal region (Spearman's r = 0.82, P < 0.001). The correlation in the posterior cingulate gyri/precunei region was lower than that in the parietotemporal region (Spearman's r = 0.63, P < 0.016).

Topics: Alzheimer Disease; Antipyrine; Glucose-6-Phosphate; Humans; Imaging, Three-Dimensional; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon