Identifying factors influencing cognitive outcomes after anodal transcranial direct current stimulation in older adults with and without cognitive impairment: A systematic review.

Anodal transcranial direct current stimulation (tDCS) can improve cognition in healthy older adults, those with Alzheimer's disease (AD) and mild cognitive impairment (MCI), albeit with considerable variability in response. This systematic review identifies interindividual factors that may influence tDCS outcomes in older individuals with or without cognitive impairment. Peer-reviewed articles were included if they assessed whether cognitive outcomes (memory or global cognition) after tDCS were associated with pre-intervention factors in healthy older adults or individuals with AD/MCI. We identified eight factors that may affect cognitive outcomes after tDCS. Improved tDCS outcomes were predicted by lower baseline cognitive function when tDCS was combined with a co-intervention (but not when used alone). Preserved brain structure and better baseline functional connectivity, genetic polymorphisms, and the use of concomitant medications may predict better tDCS outcomes, but further research is warranted. tDCS outcomes were not consistently associated with age, cognitive reserve, sex, and AD risk factors. Accounting for individual differences in baseline cognition, particularly for combined interventions, may thus maximize the therapeutic potential of tDCS.

Efficacy of non-invasive brain stimulation on global cognition and neuropsychiatric symptoms in Alzheimer's disease and mild cognitive impairment: A meta-analysis and systematic review.

BACKGROUND: Non-invasive brain stimulation (NIBS) techniques have shown some promise in improving cognitive and neuropsychiatric symptoms (NPS) in people with Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). However, data from clinical trials involving NIBS have shown inconsistent results. This meta-analysis investigated the efficacy of NIBS, specifically repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) compared to sham stimulation on global cognition and NPS in people with AD and MCI. METHOD: Multi-session randomized sham-controlled clinical trials were identified through MEDLINE, PsycINFO, and Embase until June 2021. Standardized mean difference (SMD) and 95% confidence interval (CI) between the active and sham treatments were calculated using random-effects meta-analyses. Included studies reported outcome measures for global cognition and/or NPS. Heterogeneity, from different NIBS techniques, disease populations, or tests used to assess global cognition or NPS, was measured using chi-square and I2, and investigated using subgroup analyses. Possible effects of covariates were also investigated using meta-regressions. RESULT: The pooled meta-analyses included 19 studies measuring global cognition (Nactive=288, Nsham=264), and 9 studies investigating NPS (Nactive=165, Nsham=140). NIBS significantly improved global cognition (SMD=1.14; 95% CI=0.49,1.78; p = 0.001; I2 = 90.2%) and NPS (SMD=0.82; 95% CI=0.13, 1.50; p = 0.019; I2 = 86.1%) relative to sham stimulation in patients with AD and MCI. Subgroup analyses found these effects were restricted to rTMS but not tDCS, and to patients with AD but not MCI. Meta-regression showed that age was significantly associated with global cognition response (Nstudies=16, p = 0.020, I2 = 89.51%, R2 = 28.96%), with larger effects sizes in younger populations. All significant meta-analyses had large effect sizes (SMD ≥0.8), suggesting clinical utility of NIBS in the short term. There remained substantial heterogeneity across all subgroup analyses and meta-regressions (all I2 > 50%). Egger's tests showed no evidence of publication biases. CONCLUSION: rTMS improved global cognition and NPS in those with AD. Further studies in MCI and using tDCS will help to fully evaluate the specific NIBS techniques and populations most likely to benefit on global cognition and NPS measures. Additional research should investigate the long term clinical utility of NIBS in these populations.