Abstract
Imaging brain glucose metabolism with fluorine-labelled fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET) has long been utilized to aid the diagnosis of memory disorders, in particular in differentiating Alzheimer’s disease (AD) from other neurological conditions causing cognitive decline. The interest for studying brain glucose metabolism in the context of metabolic disorders has arisen more recently. Obesity and type 2 diabetes—two diseases characterized by systemic insulin resistance—are associated with an increased risk for AD. Along with the well-defined patterns of fasting [18F]-FDG-PET changes that occur in AD, recent evidence has shown alterations in fasting and insulin-stimulated brain glucose metabolism also in obesity and systemic insulin resistance. Thus, it is important to clarify whether changes in brain glucose metabolism are just an epiphenomenon of the pathophysiology of the metabolic and neurologic disorders, or a crucial determinant of their pathophysiologic cascade. In this review, we discuss the current knowledge regarding alterations in brain glucose metabolism, studied with [18F]-FDG-PET from metabolic disorders to AD, with a special focus on how manipulation of insulin levels affects brain glucose metabolism in health and in systemic insulin resistance. A better understanding of alterations in brain glucose metabolism in health, obesity, and neurodegeneration, and the relationships between insulin resistance and central nervous system glucose metabolism may be an important step for the battle against metabolic and cognitive disorders.
Highlights
The incidence and prevalence of obesity and type 2 diabetes (T2D) have reached epidemic dimensions [1,2]
Inflammatory cells in the brain utilize glucose, and neuroinflammation has been demonstrated both in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) subjects when compared to controls with positron emission tomography (PET) imaging by utilizing the radiotracers [11C]-(R)PK11195 [86] and [11C]-PBR28 [87,88] that bind to 18 kDa translocator protein (TSPO), a molecule that is overexpressed by activated microglial cells in the brain [86,87,88]
As the disease progresses, neuroinflammation might accelerate the neuropathological changes and neurodegeneration typical for AD [88]. These studies on neuroinflammation in MCI and AD, and a recent study that suggested that part of the brain [18F]-FDG signal could be attributed to astrocytes [75], indicate that neuroinflammation in response to accumulating beta-amyloid in the cerebral cortex could be the driver of increased brain glucose metabolism in MCI subjects at risk for developing AD dementia
Summary
The incidence and prevalence of obesity and type 2 diabetes (T2D) have reached epidemic dimensions [1,2] Both obesity and T2D have been linked to an increased risk of several neurodegenerative disorders, including the most prevalent form of dementia, Alzheimer’s disease (AD) [3,4], but the exact pathophysiological mechanisms that link obesity and T2D to AD are not yet clear. We aim to combine results from both lines of research in an attempt to clarify the latest results evaluating the association between peripheral IR and brain glucose uptake, with a special emphasis on the interpretation of the differences in findings from [18F]-FDGPET scans performed in the fasting state and during an insulin-stimulated state, i.e., the hyperinsulinemic euglycemic clamp. We have chosen to use the term BGU for consistency with our previously reported [18F]-FDG PET findings [13,14,21,22]
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