title: Effects of a non-focal plasticity protocol on apathy in moderate Alzheimer's disease: a randomized, double-blind, sham-controlled trial.
abstract: BACKGROUND
  Apathy is the most common neuropsychiatric symptom in Alzheimer's disease (AD) and it is associated with changes in prefrontal neural circuits involved with generation of voluntary actions. To date no effective treatment for apathy has been demonstrated.
  
  
  OBJECTIVE
  We aimed to investigate the effects and safety of repetitive transcranial direct current stimulation (tDCS) on apathy in moderate AD patients.
  
  
  METHODS
  Forty patients were randomized to receive either active or sham-tDCS over the left dorsolateral prefrontal cortex (DLPFC). Patients received six sessions of intervention during 2 weeks and were evaluated at baseline, at week 1 and 2, and after 1 week without intervention. Clinical raters, patients, and caregivers were blinded. The primary outcome was apathy. Global cognition and neuropsychiatric symptoms were examined as secondary outcomes.
  
  
  RESULTS
  The mean MMSE score at baseline was 15.2 ± 2.9 and the mean Apathy Scale score was 27.7 ± 6.7. Changes on apathy scores over time were not different between active and sham tDCS (P = 0.552 for repeated measures). Further analyses confirm that changes from baseline did not differ between groups after the sixth session (active tDCS -1.95 (95%CI -3.49, -0.41); sham-tDCS -2.05 (95%CI -3.68, -0.42); P = 0.989]. Similarly, tDCS had no effect on secondary outcomes (P > 0.40). tDCS was well tolerated and not associated with significant adverse effects.
  
  
  CONCLUSIONS
  In this adequately powered study for minimal clinically significant difference, our findings show that using the parameters we chose for this study, repeated anodal tDCS over the left DLPFC had no effect on apathy in elderly patients with moderate AD.
authors.affiliation: Discipline of Geriatrics, Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil. Electronic address: cksuemoto@usp.br.
authors.forename: Claudia Kimie
authors.initials: CK
authors.lastname: Suemoto
authors.affiliation: Discipline of Geriatrics, Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Apolinario
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil.
authors.forename: Ester Miyuki
authors.initials: EM
authors.lastname: Nakamura-Palacios
authors.affiliation: Discipline of Geriatrics, Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lopes
authors.affiliation: Department of Pathology, LIM/22, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Renata Elaine Paraizo
authors.initials: RE
authors.lastname: Leite
authors.affiliation: Discipline of Geriatrics, Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Manuela Castro
authors.initials: MC
authors.lastname: Sales
authors.affiliation: Department of Neurology, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Nitrini
authors.affiliation: Department of Neurology, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Sonia Maria
authors.initials: SM
authors.lastname: Brucki
authors.affiliation: Discipline of Geriatrics, Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Lilian Shafirovitz
authors.initials: LS
authors.lastname: Morillo
authors.affiliation: Discipline of Geriatrics, Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Regina Miksian
authors.initials: RM
authors.lastname: Magaldi
authors.affiliation: Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology / Q000523:psychology* / Q000628:therapy; D057565:Apathy / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D017397:Prefrontal Cortex / Q000503:physiopathology*; D065908:Transcranial Direct Current Stimulation / Q000379:methods*; D016896:Treatment Outcome
keywords: Alzheimer's disease; Apathy; Cognition; Dementia; Depression; Transcranial direct current stimulation