title: Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial.
abstract: BACKGROUND
  Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment.
  
  
  OBJECTIVE
  To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI).
  
  
  METHODS
  Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ(42)), total tau (T-tau), phosphorylated-tau) (P-tau).
  
  
  BACKGROUND
  NCT01055392.
  
  
  RESULTS
  Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%.
  
  
  CONCLUSIONS
  The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.
authors.affiliation: Laboratory of Neuroscience (LIM 27) Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010 - São Paulo, SP, Brazil. forlenza@usp.br.
authors.forename: Orestes V
authors.initials: OV
authors.lastname: Forlenza
authors.forename: Breno S
authors.initials: BS
authors.lastname: Diniz
authors.forename: Márcia
authors.initials: M
authors.lastname: Radanovic
authors.forename: Franklin S
authors.initials: FS
authors.lastname: Santos
authors.forename: Leda L
authors.initials: LL
authors.lastname: Talib
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000503:physiopathology / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D004311:Double-Blind Method; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects* / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018020:Lithium Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009483:Neuropsychological Tests; D013129:Spinal Puncture; D016896:Treatment Outcome; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D018020:Lithium Compounds; D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3