title: Noninvasive brain stimulation in Alzheimer's disease: systematic review and perspectives for the future.
abstract: BACKGROUND
  A number of studies have applied transcranial magnetic stimulation (TMS) to physiologically characterize Alzheimer's disease (AD) and to monitor effects of pharmacological agents, while others have begun to therapeutically use TMS and transcranial direct current stimulation (tDCS) to improve cognitive function in AD. These applications are still very early in development, but offer the opportunity of learning from them for future development.
  
  
  METHODS
  We performed a systematic search of all studies using noninvasive stimulation in AD and reviewed all 29 identified articles. Twenty-four focused on measures of motor cortical reactivity and (local) plasticity and functional connectivity, with eight of these studies assessing also effects of pharmacological agents. Five studies focused on the enhancement of cognitive function in AD.
  
  
  RESULTS
  Short-latency afferent inhibition (SAI) and resting motor threshold are significantly reduced in AD patients as compared to healthy elders. Results on other measures of cortical reactivity, e.g. intracortical inhibition (ICI), are more divergent. Acetylcholine-esterase inhibitors and dopaminergic drugs may increase SAI and ICI in AD. Motor cortical plasticity and connectivity are impaired in AD. TMS/tDCS can induce acute and short-duration beneficial effects on cognitive function, but the therapeutic clinical significance in AD is unclear. Safety of TMS/tDCS is supported by studies to date.
  
  
  CONCLUSIONS
  TMS/tDCS appears safe in AD, but longer-term risks have been insufficiently considered. TMS holds promise as a physiologic biomarker in AD to identify therapeutic targets and monitor pharmacologic effects. In addition, TMS/tDCS may have therapeutic utility in AD, though the evidence is still very preliminary and cautious interpretation is warranted.
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Catarina
authors.initials: C
authors.lastname: Freitas
authors.forename: Helena
authors.initials: H
authors.lastname: Mondragón-Llorca
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology* / Q000628:therapy; D002540:Cerebral Cortex / Q000503:physiopathology*; D003071:Cognition; D005260:Female; D005544:Forecasting; D006801:Humans; D008297:Male; D009473:Neuronal Plasticity; D050781:Transcranial Magnetic Stimulation / Q000379:methods*