Long-Term Lithium Treatment Reduces Glucose Metabolism in the Cerebellum and Hippocampus of Nondemented Older Adults: An [F-18]FDG-PET Study

Autor(es)

Forlenza, Orestes V. ^[1] ; Novaes Coutinho, Artur Martins ^[2] ; Aprahamian, Ivan ^[1] ; Prando, Silvana ^[2] ; Mendes, Luciana Lucas ^[2] ; Diniz, Breno S. ^{[3, 4]} ; Gattaz, Wagner F. ^[1] ; Buchpiguel, Carlos A. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, Lab Neurosci LIM 27, BR-05403010 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Dept & Inst Radiol, Lab Clin Radioisotopy LIM 43, Nucl Med Ctr, BR-05403010 Sao Paulo - Brazil

^[3] Univ Fed Minas Gerais, Fac Med, Dept Mental Hlth, Belo Horizonte, MG - Brazil

^[4] Univ Fed Minas Gerais, Fac Med, Natl Inst Sci & Technol, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ACS Chemical Neuroscience; v. 5, n. 6, p. 484-489, JUN 2014.
• Citações Web of Science: 10

Resumo

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 {[}F-18]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. (AU)

• Processo FAPESP: 09/52825-8 - Neurobiologia da doença de Alzheimer: marcadores de risco, prognóstico e resposta terapêutica
• Beneficiário: Wagner Farid Gattaz
• Modalidade de apoio: Auxílio à Pesquisa - Temático