A Double-Blind Randomized Clinical Trial on the Efficacy of Cortical Direct Current Stimulation for the Treatment of Alzheimer’s Disease

Abstract

Background: The purpose of this study was to investigate the long-term efficacy of transcranial direct current stimulation (tDCS) in the neurorehabilitation of Alzheimer’s disease (AD).Methods: Thirty-four AD patients were randomly assigned to three groups: anodal, cathodal, and sham tDCS. Stimulation was applied over the left dorsolateral prefrontal cortex for 25 min at 2 mA, daily for 10 days. Each patient was submitted to the following psychometric assessments: mini-mental state examination (MMSE) and Wechsler adult intelligence scale-third edition at base line, at the end of the 10th sessions and then at 1 and 2 months after the end of the sessions. Motor cortical excitability and the P300 event-related potential were assessed at baseline and after the last tDCS session.Results: Significant treatment group × time interactions were observed for the MMSE and performance IQ of the WAIS. Post hoc comparisons showed that both anodal and cathodal tDCS (ctDCS) improved MMSE in contrast to sham tDCS. Whereas, this was only true for ctDCS in the performance IQ. Remarkably, tDCS also reduced the P300 latency, but had no effect on motor cortex excitability.Conclusion: Our findings reveal that repeated sessions of tDCS could not only improve cognitive function but also reduce the P300 latency, which is known to be pathologically increased in AD.

Transcranial direct current stimulation in patients with Alzheimer’s disease: Challenges and responses

“…The other study found no significant differences in apathy after 1 and 2 weeks compared with baseline [23]. The last study found that tDCS improved cognitive function via both anodal and cathodal interventions [24]. We believe that the differences in individual responses are an important source of variation.…”

“…Furthermore, these types of individual differences may be more obvious in older adults because individual differences in life experience and cognitive abilities increase with age [25]. These differences may be enhanced when parallel-sham controlled study designs are used [5,23,24], as presented in Table 1. MRI studies of the human brain have demonstrated inter-individual variability in a wide range of basic and higher cognitive functions, including perception, motor control, memory, aspects of consciousness and introspection. This variability may be predicted based on the local structure of grey and white matter, as assessed by either voxel-based morphometry or diffusion tensor imaging [19].…”

“…The Mini-Mental Status Examination (MMSE), which is used in the majority of studies, is a commonly administered measure of global cognitive functioning that is thought to be sensitive to dementia [5,[20][21][22][23][24]28]. Compared with the traditional cut-off score of 24 for highly educated individuals, a cut-off score of 27 or more generates better estimates among individuals of different ethnicities [29], as less educated and older individuals tend to receive lower scores [30,31], and among illiterate patients, as both atDCS and ctDCS facilitate improvements in MMSE scores compared with sham tDCS [24]. Therefore, educational level also modulates participant recruitment and outcome measures.…”

Application of transcranial direct current stimulation to psychiatric disorders: trends and perspectives

“…However, we excluded two of them (Boggio et al 2009;Ferrucci et al 2008), which investigated single-session effects. On the other hand, we noticed two other RCTs; one (Khedr et al 2014) reports a significant improvement in the Mini-Mental Scale Examination score after 10 sessions of anodal or cathodal stimulations over left DLPFC in 34 AD patients . The other (Suemoto et al 2014), employing 40 apathetic AD patients, investigated the effect of six sessions of tDCS over 2 weeks on apathy, and found the lack of a significant benefit on apathy and cognitive outcomes.…”

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

“…Seven double-blind RCTs have been so far conducted for AD [20][21][22][23][24][25][26] . Here we review five of them that evaluated multiple-session effects 20,22,23,25,26 since a meta-analysis suggests that a larger number of sessions may be more effective 27 .…”