Functional Magnetic Resonance Spectroscopy of Lactate in Alzheimer Disease: A Comprehensive Review of Alzheimer Disease Pathology and the Role of Lactate

Functional 1H magnetic resonance spectroscopy (fMRS) is a derivative of dynamic MRS imaging. This modality links physiologic metabolic responses with available activity and measures absolute or relative concentrations of various metabolites. According to clinical evidence, the mitochondrial glycolysis pathway is disrupted in many nervous system disorders, especially Alzheimer disease, resulting in the activation of anaerobic glycolysis and an increased rate of lactate production. Our study evaluates fMRS with J-editing as a cutting-edge technique to detect lactate in Alzheimer disease. In this modality, functional activation is highlighted by signal subtractions of lipids and macromolecules, which yields a much higher signal-to-noise ratio and enables better detection of trace levels of lactate compared with other modalities. However, until now, clinical evidence is not conclusive regarding the widespread use of this diagnostic method. The complex machinery of cellular and noncellular modulators in lactate metabolism has obscured the potential roles fMRS imaging can have in dementia diagnosis. Recent developments in MRI imaging such as the advent of 7 Tesla machines and new image reconstruction methods, coupled with a renewed interest in the molecular and cellular basis of Alzheimer disease, have reinvigorated the drive to establish new clinical options for the early detection of Alzheimer disease. Based on the latter, lactate has the potential to be investigated as a novel diagnostic and prognostic marker for Alzheimer disease.