Abstract and Introduction
Brain metabolism declines with age and do so in an accelerated manner in neurodegenerative disorders. Noninvasive neuroimaging techniques have played an important role to identify the metabolic biomarkers in aging brain. Particularly, PET with fluorine-18 (18F)-labeled 2-fluoro-2-deoxy-D-glucose tracer and proton magnetic resonance spectroscopy (MRS) have been widely used to monitor changes in brain metabolism over time, identify the risk for Alzheimer's disease (AD) and predict the conversion from mild cognitive impairment to AD. Novel techniques, including PET carbon-11 Pittsburgh compound-B, carbon-13 and phosphorus-31 MRS, have also been introduced to determine Aβ plaques deposition, mitochondrial functions and brain bioenergetics in aging brain and neurodegenerative disorders. Here, we introduce the basic principle of the imaging techniques, review the findings from 2-fluoro-2-deoxy-D-glucose-PET, Pittsburgh compound-B PET, proton, carbon-13 and phosphorus-31 MRS on changes in metabolism in normal aging brain, mild cognitive impairment and AD, and discuss the potential of neuroimaging to identify effective interventions and treatment efficacy for neurodegenerative disorders.
The human brain has the highest energy demands of any organ in the body, consuming more than 20% of the body's glucose and oxygen, despite comprising only 2% of total body mass. The majority of this energy is used to support functional processes. Numerous studies have shown that metabolic rates of glucose and oxygen decline with age and do so in an accelerated manner in neurodegenerative disorders, such as Alzheimer's disease (AD).[2–4] The metabolic rate reductions have been considered as major contributors to brain structural alteration (gray matter and white matter atrophy) and cognitive impairment later in life.[2,5–6] Methods that can monitor in vivo brain metabolic changes over time are thus critical for earlier diagnosis and longitudinal investigations of bioenergetic deficit in the aging brain and the risk for neurodegenerative disorders, as well as to assess the value of therapeutic interventions.
Noninvasive neuroimaging techniques have played a major role in identifying the metabolic biomarkers, including PET and magnetic resonance spectroscopy (MRS). Among these, PET with fluorine-18 (18F)-labeled 2-fluoro-2-deoxy-D-glucose (18FDG) tracer and proton (1H) MRS are the well-established methods to quantify cerebral metabolic rate of glucose (CMRglc) and neural metabolites, respectively. Recently, PET-based tracers, such as carbon-11 (11C) Pittsburgh compound-B (PIB), have been introduced to determine Aβ plaque deposition in neurodegenerative disorders. Other novel techniques, including carbon-13 and phosphorus-31 (31P) MRS have also developed to determine brain bioenergetics in aging brain. Here, we review the basic principle of the imaging techniques and their utilization to monitor brain metabolism changes over time, identify the risk for AD and predict the conversion from mild cognitive impairment (MCI) to AD. We will also introduce the potential interplay of neuroimaging methods and interventions that can slow down brain aging and prevent neurodegenerative disorders.
Future Neurology. 2014;9(3):341-354. © 2014 Future Medicine Ltd.