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

Abstract

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.

Distribution of Monocarboxylate Transporters in Brain and Choroid Plexus Epithelium

“…Recent developments in brain imaging have increased the capacity to diagnose brain diseases. Functional 1 H magnetic resonance spectroscopy (fMRS) is becoming a powerful diagnostic tool for brain diseases [ 81 ]. It was reported that lactate evaluated with fMRS has the potential to be a new diagnostic and prognostic marker for AD [ 81 ].…”

“…Functional 1 H magnetic resonance spectroscopy (fMRS) is becoming a powerful diagnostic tool for brain diseases [ 81 ]. It was reported that lactate evaluated with fMRS has the potential to be a new diagnostic and prognostic marker for AD [ 81 ]. As the mitochondrial glycolysis pathway is considered to be disrupted in many brain disorders, the activation of anaerobic glycolysis with increased lactate production must occur in the presence of various brain disorders.…”

Lactate: A Theranostic Biomarker for Metabolic Psychiatry?

“…The MRS techniques enable spatiotemporal resolution of metabolites relevant to bioenergetics, and the characterisation of brain lactate dynamic responses through functional MRS (fMRS) is a promising tool to enable the direct assessment of mitochondrial homeostatic responses to neurometabolic stress [ 48 ]. Although measurement of lactate with MRS is challenging due to a low signal-to-noise ratio (SNR) in vivo, we opine that lactate has a key role that enables an integrated and precise approach for appreciating and understanding energy allocation and mitochondrial efficiency within the CNS that goes beyond oxygen and blood flow measurement [ 49 ]. Indeed, changes in brain lactate metabolism measured with MRS have already been used to characterise and monitor the response to pharmacological therapy in psychiatric conditions (see Section 4 ).…”