FDG- and amyloid-PET in Alzheimer's disease: is the whole greater than the sum of the parts?

Abstract

The development of prevention therapies for Alzheimer's disease (AD) would greatly benefit from biomarkers that are sensitive to subtle brain changes occurring prior to the onset of clinical symptoms, when the potential for preservation of function is at the greatest. In vivo brain imaging is a promising tool for the early detection of AD through visualization of abnormalities in brain structure, function and histopathology. Currently, positron emission tomography (PET) imaging with amyloid-beta (Aβ) tracers and 2-[(18)F]fluoro-2-Deoxy-D-glucose (FDG) is largely utilized in the diagnosis of AD. This paper reviews brain Aβ- and FDG-PET studies in AD patients as well as in non-demented individuals at risk for AD. We then discuss the potential of combining symptoms-sensitive FDG-PET measures with pathology-specific Aβ-PET to improve the early detection of AD.

Figures

Figure 1

FDG-PET scans in 6 representative individuals with negative (FH−) or positive (FH+) first degree family history of late-onset AD, including two cognitively normal (NL) individuals, two patients with MCI, and two patients with AD. A reduction in brain metabolism is evidence for each FH+ individual with respect to their FH− counterpart. Standardized uptake value ratios (SUVR) to cerebellum are displayed for each image using a color coded scale.

Figure 2

Statistical parametric maps (SPMs) showing higher PiB retention in asymptomatic individuals with a first degree family history of late-onset AD compared to controls with negative family history of any dementia. Areas of increased PiB retention are represented on a red-to-yellow color-coded scale, reflecting P values between 0.01–0.001, as indicated on the right side of figure. SPMs are displayed onto the axial and sagittal views of a standard, spatially normalized MRI. Data is from Mosconi et al.

Figure 3

“Food for thought”:coregistered PIB- and FDG-PET scans in 4 representative clinically and cognitively normal individuals: A) Negative PIB and normal FDG uptake. This individual is at conceivably low risk for AD; B) positive PIB and abnormal FDG uptake; this individual is at conceivably high risk for AD; C) negative PIB and abnormal FDG uptake. Based on absence of significant PiB uptake, this individual would be at low risk for AD. However, the FDG scan shows abnormalities, which may therefore reflect presence of a disease other than AD, or suggest that, at least in some cases, metabolic reductions may precede amyloid deposition. In this case, follow up in 1–2 years is recommended. D) Positive PIB and normal FDG uptake. Based on presence of significant PiB uptake, this individual may be at increased risk for AD. However, the FDG scan does not show signs of neurodegeneration. Increased amyloidosis may therefore reflect normal brain aging. Alternatively, the subject may be showing a compensatory reaction against AD pathology due to “cognitive reserve” (20 years of education). In this case, follow-up in 1–2 years is recommended. Standardized uptake value ratios (SUVR) to cerebellum are displayed for each modality using a color coded scale.