Neuroenergetic alterations in neurodegenerative diseases: A systematic review and meta-analysis of in vivo 31P-MRS studies

Phosphorus magnetic resonance spectroscopy ( 31 P-MRS) is applied for non-invasive studies of neuroenergetic metabolism in neurodegenerative diseases. However, the findings are inconsistent and have not yet been tested in meta-analyses. To address this gap, we performed a systematic review of 29 studies and conducted meta-analyses for 9 studies on Alzheimer’s disease (AD, n = 140 patients), 9 studies on Parkinson’s disease (PD, n = 183 patients), 3 studies on Progressive Supranuclear Palsy (PSP, n = 42 patients), and 2 studies on Multiple System Atrophy (MSA, n = 24 patients). Compared to controls, AD patients had a higher ratio of phosphomonoesters/phosphodiesters (PME/PDE) in the frontal lobe (MD = 0.049, p = 0.0003); PD patients showed decreases in PME/PDE in the putamen (MD = -0.050, p = 0.023) and adenosine triphosphate/inorganic phosphate (ATP/Pi) in the midbrain (MD = -0.274, p = 0.002); PSP patients presented increased phosphocreatine (PCr)/Pi in the basal ganglia (MD = 0.556, p = 0.030) and adenosine diphosphate (ADP)/Pi in the occipital lobe (MD = 0.005, p = 0.009); no significant effects were observed in MSA. Here, our review underlines the importance of 31 P-MRS in the characterization of distinct neuroenergetic changes and its potential to improve the diagnosis and follow-up of neurodegenerative diseases. • 31 P-MRS is a promising method to separate neurodegenerative diseases by identifying changes in neuroenergetic metabolisms. • Frontal PME/PDE for AD, as well as putamen PME/PDE and midbrain ATP/Pi for PD are potentially sensitive and stable markers. • PCr/Pi is a vulnerable indicator depending on the MRS methodology.