Comparative Study

. 2021 Feb;92(2):195-203.

doi: 10.1136/jnnp-2020-323870. Epub 2020 Oct 28.

Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis

Che-Sheng Chu^#^{1

2

3}, Cheng-Ta Li^#^{4

5

6

7}, Andre R Brunoni⁸, Fu-Chi Yang⁹, Ping-Tao Tseng¹⁰, Yu-Kang Tu¹¹, Brendon Stubbs^{12

13

14}, André F Carvalho^{15

16}, Trevor Thompson¹⁷, Tarek K Rajji^{15

18}, Ta-Chuan Yeh¹⁹, Chia-Kuang Tsai⁹, Tien-Yu Chen^{9

20}, Dian-Jeng Li^{2

21}, Chih-Wei Hsu²², Yi-Cheng Wu²³, Chia-Ling Yu²⁴, Chih-Sung Liang^{25

26}

Affiliations

¹ Department of Psychiatry and Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
² Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Non-invasive Neuromodulation Consortium for Mental Disorders, Society of Psychophysiology, Taipei, Taiwan.
⁴ Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵ Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
⁶ Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁷ nstitute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan.
⁸ Service of Interdisciplinary Neuromodulation (SIN), Laboratory of Neurosciences (LIM-27), and National Institute of Biomarkers in Neuropsychiatry (INBioN), Department of Internal Medicine and Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil.
⁹ Department of Neurology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan.
¹⁰ WinShine Clinics in Specialty of Psychiatry, Kaohsiung, Taiwan.
¹¹ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
¹² Department of Physiotherapy, South London and Maudsley NHS Foundation Trust, London, UK.
¹³ Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, De Crespigny Park, London, UK.
¹⁴ Positive Ageing Research Institute (PARI), Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK.
¹⁵ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Centre for Addiction & Mental Health (CAMH), Toronto, Ontario, Canda.
¹⁷ School of Human Sciences, University of Greenwich, London, UK.
¹⁸ Adult Neurodevelopment and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
¹⁹ Department of Psychiatry, Tri-Service General Hospital, Schoool of Medicine, National Defense Medical Center, Taipei, Taiwan.
²⁰ Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
²¹ Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.
²² Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
²³ Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan.
²⁴ Department of Pharmacy, Chang Gung Memorial Hospital, Linkou, Taiwan.
²⁵ Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan lcsyfw@gmail.com.
²⁶ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.

^# Contributed equally.

PMID: 33115936
PMCID: PMC7841477
DOI: 10.1136/jnnp-2020-323870

Comparative Study

Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis

Che-Sheng Chu et al. J Neurol Neurosurg Psychiatry. 2021 Feb.

. 2021 Feb;92(2):195-203.

doi: 10.1136/jnnp-2020-323870. Epub 2020 Oct 28.

Authors

Affiliations

¹ Department of Psychiatry and Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
² Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Non-invasive Neuromodulation Consortium for Mental Disorders, Society of Psychophysiology, Taipei, Taiwan.
⁴ Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵ Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
⁶ Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁷ nstitute of Cognitive Neuroscience, National Central University, Jhongli, Taiwan.
⁸ Service of Interdisciplinary Neuromodulation (SIN), Laboratory of Neurosciences (LIM-27), and National Institute of Biomarkers in Neuropsychiatry (INBioN), Department of Internal Medicine and Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil.
⁹ Department of Neurology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan.
¹⁰ WinShine Clinics in Specialty of Psychiatry, Kaohsiung, Taiwan.
¹¹ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
¹² Department of Physiotherapy, South London and Maudsley NHS Foundation Trust, London, UK.
¹³ Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, De Crespigny Park, London, UK.
¹⁴ Positive Ageing Research Institute (PARI), Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK.
¹⁵ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Centre for Addiction & Mental Health (CAMH), Toronto, Ontario, Canda.
¹⁷ School of Human Sciences, University of Greenwich, London, UK.
¹⁸ Adult Neurodevelopment and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
¹⁹ Department of Psychiatry, Tri-Service General Hospital, Schoool of Medicine, National Defense Medical Center, Taipei, Taiwan.
²⁰ Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
²¹ Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.
²² Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
²³ Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan.
²⁴ Department of Pharmacy, Chang Gung Memorial Hospital, Linkou, Taiwan.
²⁵ Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan lcsyfw@gmail.com.
²⁶ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.

^# Contributed equally.

PMID: 33115936
PMCID: PMC7841477
DOI: 10.1136/jnnp-2020-323870

Abstract

Objectives: To compare cognitive effects and acceptability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), and to determine whether cognitive training (CT) during rTMS or tDCS provides additional benefits.

Methods: Electronic search of PubMed, Medline, Embase, the Cochrane Library and PsycINFO up to 5 March 2020. We enrolled double-blind, randomised controlled trials (RCTs). The primary outcomes were acceptability and pre-post treatment changes in general cognition measured by Mini-Mental State Examination, and the secondary outcomes were memory function, verbal fluency, working memory and executive function. Durability of cognitive benefits (1, 2 and ≥3 months) after brain stimulation was examined.

Results: We included 27 RCTs (n=1070), and the treatment components included high-frequency rTMS (HFrTMS) and low-frequency rTMS, anodal tDCS (atDCS) and cathodal tDCS (ctDCS), CT, sham CT and sham brain stimulation. Risk of bias of evidence in each domain was low (range: 0%-11.1%). HFrTMS (1.08, 9, 0.35-1.80) and atDCS (0.56, 0.03-1.09) had short-term positive effects on general cognition. CT might be associated with negative effects on general cognition (-0.79, -2.06 to 0.48) during rTMS or tDCS. At 1-month follow-up, HFrTMS (1.65, 0.77-2.54) and ctDCS (2.57, 0.20-4.95) exhibited larger therapeutic responses. Separate analysis of populations with pure AD and MCI revealed positive effects only in individuals with AD. rTMS and tDCS were well tolerated.

Conclusions: HFrTMS is more effective than atDCS for improving global cognition, and patients with AD may have better responses to rTMS and tDCS than MCI.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1**
(A) Network of eligible comparisons for general cognition: short-term effects. (B) Network of eligible comparisons for general cognition: long-lasting effects after 1 month. atDCS, anodal transcranial direct current stimulation; ctDCS, cathodal transcranial direct current stimulation; HFrTMS, high-frequency repetitive transcranial magnetic stimulation; LFrTMS, low-frequency repetitive transcranial magnetic stimulation; sham_BS, sham brain stimulation; sham_CT, sham cognitive training.

**Figure 2**
(A) Forest plot of NMA of changes of general cognition: short-term effects. (B) Forest plot of NMA of changes of general cognition: long-lasting effects after 1 month. atDCS, anodal transcranial direct current stimulation; BS, brain stimulation; CT, cognitive training; ctDCS, cathodal transcranial direct current stimulation; HFrTMS, high-frequency repetitive transcranial magnetic stimulation; LFrTMS, low-frequency repetitive transcranial magnetic stimulation; LL, lower limit; MD, mean difference; MMSE, Mini-Mental State Examination; NMA, network meta-analysis; UL, upper limit.

**Figure 3**
(A) Forest plot of NMA of changes of memory function: short-term effects. (B) Forest plot of NMA of changes of memory function: long-lasting effects after 1 month. atDCS, anodal transcranial direct current stimulation; BS, brain stimulation; CT, cognitive training; ctDCS, cathodal transcranial direct current stimulation; HFrTMS, high-frequency repetitive transcranial magnetic stimulation; NMA, network meta-analysis; SMD, standardised mean difference.

**Figure 4**
(A) Forest plot of NMA of changes of verbal fluency: short-term effects. (B) Forest plot of NMA of changes of verbal fluency: long-lasting effects after 1 month. atDCS, anodal transcranial direct current stimulation; BS, brain stimulation; CT, cognitive training; ctDCS, cathodal transcranial direct current stimulation; HFrTMS, high-frequency repetitive transcranial magnetic stimulation; LL, lower limit; NMA, network meta-analysis; SMD, standardised mean difference; UL, upper limit.

**Figure 5**
(A) Forest plot of NMA of changes of working memory: short-term effects. (B) Forest plot of NMA of changes of working memory: long-lasting effects after 1 month. atDCS, anodal transcranial direct current stimulation; BS, brain stimulation; CT, cognitive training; ctDCS, cathodal transcranial direct current stimulation; HFrTMS, high-frequency repetitive transcranial magnetic stimulation; LL, lower limit; NMA, network meta-analysis; SMD, standardised mean difference; UL, upper limit.

**Figure 6**
NMA estimates and SUCRA values. BS, brain stimulation; CT, cognitive training; HFrTMS, high-frequency repetitive transcranial magnetic stimulation; LFrTMS, low-frequency repetitive transcranial magnetic stimulation; NMA, network meta-analysis; SUCRA, surface under the cumulative ranking curve; tDCS, transcranial direct current stimulation.

See this image and copyright information in PMC

References

1. Livingston G, Sommerlad A, Orgeta V, et al. . Dementia prevention, intervention, and care. Lancet 2017;390:2673–734. 10.1016/S0140-6736(17)31363-6 - DOI - PubMed
1. Polanía R, Nitsche MA, Ruff CC. Studying and modifying brain function with non-invasive brain stimulation. Nat Neurosci 2018;21:174–87. 10.1038/s41593-017-0054-4 - DOI - PubMed
1. Rajji TK. Transcranial magnetic and electrical stimulation in Alzheimer's disease and mild cognitive impairment: a review of randomized controlled trials. Clin Pharmacol Ther 2019;106:776–80. 10.1002/cpt.1574 - DOI - PubMed
1. George MS, Aston-Jones G. Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Neuropsychopharmacology 2010;35:301–16. 10.1038/npp.2009.87 - DOI - PMC - PubMed
1. Brunoni AR, Nitsche MA, Bolognini N, et al. . Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimul 2012;5:175–95. 10.1016/j.brs.2011.03.002 - DOI - PMC - PubMed

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Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis

Affiliations

Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical