Commentary: Transcranial direct current stimulation for depression in Alzheimer's disease: study protocol for a randomized controlled trial

Abstract

Dementia is a progressive neurodegenerative disorder that is characterized by a decline in cognition in one or more cognitive domains such as learning and memory, language, executive function, complex attention, perceptual-motor, social cognition . The cholinergic drugs, introduced first in 1997, have been approved worldwide and considered to be the first line pharmacotherapy for mild to severe AD. The mechanism of these drugs is to inhibit the breakdown of acetylcholine, a neurotransmitter associated with memory or cognitive activity, by blocking the enzyme acetylcholinesterase 10 . Although these drugs can slow the progression of AD, a review study revealed the limited efficacy of these compounds 10 . Future disease-modifying treatments and therapeutic interventions augmenting current pharmacologic treatments are awaited.Neuropsychiatric symptoms in patients with AD also compromise their QOL 11. Depressive mood is one of the most frequent neuropsychiatric symptoms in AD as well as agitation and apathy 12. The prevalence rate of depression in AD is estimated as from 36.7 % 13 to 47.8 % 12. On the other hand, antidepressant drugs and electroconvulsive therapy (ECT) have not shown significant effect on depression in AD. A meta-analysis revealed that selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors did not show significant effect on depression in AD 14. A randomized controlled trial (RCT) with a large sample, also revealed that neither selective serotonin reuptake inhibitors nor noradrenergic and specific serotonergic antidepressants showed superiority to placebo, and concluded that antidepressants should not be used first for depression in AD considering adverse events induced by antidepressants 15 . Moreover, a recent thorough review, in neither older patients over 65 years nor patients with dementia, verified the effect of ECT 16 .Our recent study entitled "Transcranial direct current stimulation for depression in Alzheimer's disease: study protocol for a randomized controlled trial" was designed to evaluate the safety and effect of transcranial direct current stimulation (tDCS) on depression in patients with AD over 65 years 17 . tDCS is a simple, cheap, and safe technique of neuromodulation, based on the application of weak, direct electrical current to the brain through relatively large electrodes. Two