Teselink Johannes, Bawa Kritleen K, Koo Grace Ky, Sankhe Krushnaa, Liu Celina S, Rapoport Mark, Oh Paul, Marzolini Susan, Gallagher Damien, Swardfager Walter, Herrmann Nathan, Lanctôt Krista L
Neuropsychopharmacology Research Group, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada; Hurvitz Brain Sciences Program, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
Neuropsychopharmacology Research Group, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada; Hurvitz Brain Sciences Program, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada; Department of Pharmacology & Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
Ageing Res Rev. 2021 Dec;72:101499. doi: 10.1016/j.arr.2021.101499. Epub 2021 Oct 23.
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.
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 I, and investigated using subgroup analyses. Possible effects of covariates were also investigated using meta-regressions.
The pooled meta-analyses included 19 studies measuring global cognition (N=288, N=264), and 9 studies investigating NPS (N=165, N=140). NIBS significantly improved global cognition (SMD=1.14; 95% CI=0.49,1.78; p = 0.001; I = 90.2%) and NPS (SMD=0.82; 95% CI=0.13, 1.50; p = 0.019; I = 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 (N=16, p = 0.020, I = 89.51%, R = 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 I > 50%). Egger's tests showed no evidence of publication biases.
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.
非侵入性脑刺激（NIBS）技术在改善阿尔茨海默病（AD）及其前驱阶段轻度认知障碍（MCI）患者的认知和神经精神症状（NPS）方面已显示出一定前景。然而，涉及NIBS的临床试验数据结果并不一致。本荟萃分析调查了NIBS，特别是重复经颅磁刺激（rTMS）和经颅直流电刺激（tDCS）与假刺激相比，对AD和MCI患者整体认知和NPS的疗效。
通过MEDLINE、PsycINFO和Embase检索截至2021年6月的多阶段随机假对照临床试验。使用随机效应荟萃分析计算活性治疗与假治疗之间的标准化平均差（SMD）和95%置信区间（CI）。纳入的研究报告了整体认知和/或NPS的结局指标。使用卡方和I统计量测量来自不同NIBS技术、疾病人群或用于评估整体认知或NPS的测试的异质性，并通过亚组分析进行研究。还使用荟萃回归研究协变量的可能影响。
汇总的荟萃分析包括19项测量整体认知的研究（N = 288，N = 264）和9项调查NPS的研究（N = 165，N = 140）。与假刺激相比，NIBS在AD和MCI患者中显著改善了整体认知（SMD = 1.14；95% CI = 0.49，1.78；p = 0.001；I = 90.2%）和NPS（SMD = 0.82；95% CI = 0.13，1.50；p = 0.019；I = 86.1%）。亚组分析发现这些效应仅限于rTMS而非tDCS，且仅限于AD患者而非MCI患者。荟萃回归显示年龄与整体认知反应显著相关（N = 16，p = 0.020，I = 89.51%，R = 28.96%），在年轻人群中效应量更大。所有显著的荟萃分析效应量都很大（SMD≥0.8），表明NIBS在短期内具有临床实用性。所有亚组分析和荟萃回归中仍存在大量异质性（所有I>50%）。Egger检验未显示发表偏倚的证据。
rTMS改善了AD患者的整体认知和NPS。对MCI和使用tDCS的进一步研究将有助于全面评估最有可能从整体认知和NPS测量中受益的特定NIBS技术和人群。更多研究应调查NIBS在这些人群中的长期临床实用性。
