Pre-clinical detection of Alzheimer's disease using FDG-PET, with or without amyloid imaging

Abstract

The development of prevention therapies for Alzheimer's disease (AD) would greatly benefit from biomarkers that are sensitive to subtle brain changes occurring in the preclinical stage of the disease. Early diagnostics is necessary to identify and treat at risk individuals before irreversible neuronal loss occurs. In vivo imaging has long been used to evaluate brain structural and functional abnormalities as predictors of future AD in non-demented persons. Prior to development of amyloid-beta (Abeta) tracers for positron emission tomography (PET), the most widely utilized PET tracer in AD was 2-[18F]fluoro-2-Deoxy-D-glucose (FDG) PET. For over 20 years, FDG-PET has been used to measure cerebral metabolic rates of glucose (CMRglc), a proxy for neuronal activity, in AD. Many studies have shown that CMRglc reductions occur early in AD, correlate with disease progression, and predict histopathological diagnosis. This paper reviews reports of clinical and preclinical CMRglc reductions observed in association with genetic and non-genetic risk factors for AD. We then briefly review brain Abeta PET imaging studies in AD and discuss the potential of combining symptoms-sensitive FDG-PET measures with pathology-specific Abeta-PET to improve the early detection of AD.

Figure 1

Brain regions showing reduced CMRglc on FDG-PET in cognitively normal individuals with a maternal family history of AD (FHm) as compared to demographically matched subjects with a paternal family history (FHp) and with a negative family history of AD (FH-) [57]. Statistical parametric maps showing regions of hypometabolism in NL FHm are displayed on a purple-to-yellow color coded scale at P<0.001. Figure shows the left lateral and superior views of a 3D volume-rendered MRI.

Figure 2

Coregistered PIB and FDG-PET scans in 2 representative cognitively normal individuals at conceivably low risk for AD (top row: negative PIB and normal FDG uptake), and at high risk for AD (bottom row: positive PIB and reduced FDG uptake) based on PET imaging findings. Cerebral-to-cerebellar PIB StandardizedUptake Value ratios (SUVR) are displayed for each modality using a color coded scale.