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 |
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| Institution: | 1. Neuropsychopharmacology Research Group, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada;2. Hurvitz Brain Sciences Program, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada;3. Department of Pharmacology & Toxicology, University of Toronto, 1 King''s College Circle, Toronto, ON, M5S 1A8, Canada;4. Department of Psychiatry, Faculty of Medicine, University of Toronto, 250 College Street, 8th floor, Toronto, ON, M5T 1R8, Canada;5. KITE Toronto Rehabilitation Institute, University Health Network, 347 Rumsey Rd, East York, ON, M4G 2V6, Canada;6. Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada;1. Department of Neurology, University of California, San Francisco, San Francisco, CA, USA;2. Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institue of Cognitive Neuroscience, School of Psychology and Cognitive Science, East China Normal University, Shanghai, China;3. Department of Physiology and Psychiatry, University of California, San Francisco, San Francisco, CA, USA;1. Unité de Stimulation Magnétique, Clinique Bretéché, Groupe Elsan, Nantes, France;2. Service de Neurologie, Hôpital Laennec, Centre Hospitalier Universitaire de Nantes, Nantes, France;3. Service de Gériatrie, Hôpital Bellier, Centre Hospitalier Universitaire de Nantes, Nantes, France;4. Centre Fédératif Douleur, Soins Palliatifs et de Support, Ethique Clinique et Thérapies Complémentaires, Hôpital Laennec, Centre Hospitalier Universitaire de Nantes, Nantes, France;5. EA 4391, équipe ENT (Nerve Excitability and Therapeutics), Université Paris-Est Créteil, Créteil, France;6. Inserm U955, équipe CEpiA (Clinical Epidemiology and Ageing), Institut Mondor de Recherche Biomédicale (IMRB), Université Paris Est Créteil (UPEC), Créteil, France;7. Service de Santé Publique, Hôpital Universitaire Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France;8. Unité de Neurophysiologie Clinique, Hôpital Universitaire Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France;1. Discipline of Geriatrics, Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil;2. Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil;3. Department of Pathology, LIM/22, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil;4. Department of Neurology, University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil;5. Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA;1. Department of Radiology, Incheon St. Mary''s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea;2. Department of Biomedical Engineering, The City College of New York, New York, NY, USA;3. Center for Cognitive Aging and Memory, McKnight Brain Institute, Department of Clinical and Health Psychology, University of Florida, FL, USA;4. Department of Neurology, Incheon St. Mary''s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea;5. MJHS Institute for Innovation in Palliative Care, New York, NY, USA;6. Department of Family and Social Medicine, Albert Einstein College of Medicine, The Bronx, NY, USA |
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| Abstract: | BackgroundNon-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.MethodMulti-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.ResultThe 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.ConclusionrTMS 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. |
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| Keywords: | Cognitive impairment Non-invasive brain stimulation Repetitive transcranial magnetic stimulation Transcranial direct current stimulation Neuropsychiatric symptoms Alzheimer’s disease |
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