title: Long-term lithium treatment reduces glucose metabolism in the cerebellum and hippocampus of nondemented older adults: an [¹⁸F]FDG-PET study.
abstract: Lithium modulates several intracellular pathways related to neuroplasticity and resilience against neuronal injury. These properties have been consistently reported in experimental models, and involve the up-regulation of neurotrophic response and autophagy, and down-regulation of apoptosis, oxidative stress, and inflammation. Clinical and epidemiological studies in bipolar disorder show that acute treatment with lithium increases plasma concentrations of brain-derived neurotrophic factor, and long-term treatment lowers the risk of dementia. Neuroimaging studies indicate that lithium use is further associated with increased cortical thickness and larger hippocampal volumes. The objective of the present study was to evaluate whether these neurobiological properties of lithium reflect in increased regional brain glucose metabolism, as shown by [(18)F]FDG-PET. Participants (n = 19) were nondemented older adults recruited at the end point of a controlled trial addressing clinical and biological effects of lithium in a sample of patients with amnestic mild cognitive impairment. Twelve patients who had received low-dose lithium carbonate for 4 years were compared to seven matched controls. Chronic lithium treatment was not associated with any significant increase in brain glucose metabolism in the studied areas. Conversely, we found a significant reduction in glucose uptake in several clusters of the cerebellum and in both hippocampi. These findings were not associated with any clinical evidence of toxicity. The clinical implications of the present findings need to be clarified by future controlled studies, particularly in the light of the potential use of lithium as a disease-modifying treatment approach for certain neurodegenerative disorders, namely, Alzheimer's disease and amyotrophic lateral sclerosis.
authors.affiliation: †Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, SP, Brazil.
authors.forename: Orestes V
authors.initials: OV
authors.lastname: Forlenza
authors.affiliation: ‡Laboratory of Clinical Radioisotopy (LIM-43), Nuclear Medicine Center, Department and Institute of Radiology, Faculty of Medicine, University of São Paulo, SP, Brazil.
authors.forename: Artur Martins Novaes
authors.initials: AM
authors.lastname: Coutinho
authors.affiliation: †Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, SP, Brazil.
authors.forename: Ivan
authors.initials: I
authors.lastname: Aprahamian
authors.affiliation: ‡Laboratory of Clinical Radioisotopy (LIM-43), Nuclear Medicine Center, Department and Institute of Radiology, Faculty of Medicine, University of São Paulo, SP, Brazil.
authors.forename: Silvana
authors.initials: S
authors.lastname: Prando
authors.affiliation: ‡Laboratory of Clinical Radioisotopy (LIM-43), Nuclear Medicine Center, Department and Institute of Radiology, Faculty of Medicine, University of São Paulo, SP, Brazil.
authors.forename: Luciana Lucas
authors.initials: LL
authors.lastname: Mendes
authors.affiliation: §Department of Mental Health and National Institute of Science and Technology, Molecular Medicine, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Breno S
authors.initials: BS
authors.lastname: Diniz
authors.affiliation: †Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, SP, Brazil.
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.affiliation: ‡Laboratory of Clinical Radioisotopy (LIM-43), Nuclear Medicine Center, Department and Institute of Radiology, Faculty of Medicine, University of São Paulo, SP, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Buchpiguel
mesh_terms: D000368:Aged; D001931:Brain Mapping; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D049268:Positron-Emission Tomography; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D019275:Radiopharmaceuticals
chemical_list: D011619:Psychotropic Drugs; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D016651:Lithium Carbonate; D005947:Glucose
keywords: Lithium; [18F]FDG-PET; brain metabolism; mild cognitive impairment
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