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Is Non-invasive brain stimulation an effective tool for cognitive enhancement in Alzheimer’s disease and mild cognitive impairment? Results from the meta-analysis

      Abstract
      Introduction: Alzheimer's disease (AD) and its preclinical stage, mild cognitive impairment (MCI), are critical issues confronting the aging society. Non-invasive brain stimulation (NIBS) techniques have the potential for improving cognitive functioning. The main objective of our meta-analysis was to update the status of the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS) when applied in AD and MCI with a focus on the methodological quality of the studies and potential cognitive enhancement by a concomitant cognitive training (CT).
      Methods: We conducted a systematic search on PubMed / Web of Science for blinded randomized control studies or studies with a crossover design involving human subjects using rTMS, tDCS as a tool for cognitive enhancement in AD and MCI. Risk of Bias (RoB) assessment was used to only include works with high methodological quality. Hedge’s g was used to determine effect sizes. We focused on the immediate and long-term effects (∼1-month follow-up).
      Results and Conclusion: Based on the PRISMA-statement and RoB analysis we included 16 rTMS and 16 tDCS studies into the meta-analysis. Both rTMS and tDCS revealed significant immediate cognition-enhancing effect in AD and MCI with rTMS having a moderate effect (g=0.57; 95% CI=0.4, 0.73) and tDCS a small effect (g=42; 95% CI=0.13, 0.70). The rTMS effects were moderate after at least 1 month of follow-up (g=0.82; 95%CI=0.2, 1.45; p<0.01). For tDCS, the long-term effects were statistically heterogeneous. We found no evidence for an add-on effect of concomitant CT in AD or MCI. However, one of the most effective rTMS protocol in AD, the NEURO-ADTM system included CT. Other probably effective protocols included high-frequency rTMS and anodal tDCS over the left DLPFC in AD. Regarding NIBS in MCI, further research and replication of existing studies are required to identify optimal protocol(s).
      Keywords: mild cognitive impairment, Non-invasive brain stimulation, Meta-analysis, Alzheimer's disease