Long-Term Lithium Treatment Reduces Glucose Metabolism in the Cerebellum andHippocampus of Nondemented Older Adults: An 18FFDG-PETStudy

摘要

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 [¹⁸F]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 patientswho had received low-dose lithium carbonate for 4 years were comparedto seven matched controls. Chronic lithium treatment was not associatedwith any significant increase in brain glucose metabolism in the studiedareas. Conversely, we found a significant reduction in glucose uptakein several clusters of the cerebellum and in both hippocampi. Thesefindings were not associated with any clinical evidence of toxicity.The clinical implications of the present findings need to be clarifiedby future controlled studies, particularly in the light of the potentialuse of lithium as a disease-modifying treatment approach for certainneurodegenerative disorders, namely, Alzheimer’s disease andamyotrophic lateral sclerosis.