Alzheimer's disease (AD) is a neurodegenerative disease. At present, there are currently no drugs that can cure AD.
Objective
A number of empirical studies have shown that transcranial direct current stimulation (tDCS) may be used to treat cognitive abnormalities in patients with AD. We will through meta-analysis reviews tDCS overall research on the effects of cognitive function in patients with AD.
Methods
Systematic searches were performed in the PubMed, Embase, and Cochrane Library databases from their creation until 8 March 2024. Using a fixed effect model and random effect model to evaluate the average difference between the treatment group and control group (MD) and its 95% confidence interval (CI).
Results
The study included 10 randomized controlled trials (Nactive = 165, Nsham = 167). The results of the overall analysis showed that tDCS did not significantly improve the overall cognitive function (SMD = 0.17; 95%CI = −0.05, 0.39; p = 0.14; I² = 51%). Quality of life of AD patients after treatment was also evaluated, but no improvement was seen. Subgroup analysis showed no significant improvement in global cognitive function after tDCS treatment. The sensitivity analysis to confirm the reliability of the data, risk assessment did not find any high-risk projects.
Conclusions
The tDCS treatment did not improve cognitive function in patients with AD. Further empirical research in the future will help to explore new schemes for tDCS to improve cognitive function of patients.
Villarejo-GalendeAGarcía-ArcelayEPiñol-RipollG, et al.Quality of life and the experience of living with early-stage Alzheimer’s disease. J Alzheimers Dis2022; 90: 719–726.
2.
SuelvesNSalekiSIbrahimT, et al.Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology. Acta Neuropathol Commun2023; 11: 82.
3.
LiuR-M. Aging, cellular senescence, and Alzheimer’s disease. Int J Mol Sci2022; 23: 1989.
4.
BokJHaJAhnBJ, et al.Disease-modifying effects of non-invasive electroceuticals on β-amyloid plaques and tau tangles for Alzheimer's disease. Int J Mol Sci2022; 24: 679.
5.
Sudbrack-OliveiraPRazzaLBBrunoniAR. Non-invasive cortical stimulation: transcranial direct current stimulation (tDCS). Int Rev Neurobiol2021; 159: 1–22.
6.
BastinCDelhayeEMoulinC, et al.Novelty processing and memory impairment in Alzheimer's disease: a review. Neurosci Biobehav Rev2019; 100: 237–249.
7.
PitarqueAMeléndezJCSalesA, et al.The effects of healthy aging, amnestic mild cognitive impairment, and Alzheimer's disease on recollection, familiarity and false recognition, estimated by an associative process-dissociation recognition procedure. Neuropsychologia2016; 91: 29–35.
8.
YamamotoSIshiiDIshibashiK, et al.Transcranial direct current stimulation of the dorsolateral prefrontal cortex modulates cognitive function related to motor execution during sequential task: a randomized control study. Front Hum Neurosci2022; 16: 890963.
9.
CammisuliDMCignoniFCeravoloR, et al.Transcranial direct current stimulation (tDCS) as a useful rehabilitation strategy to improve cognition in patients with Alzheimer's disease and Parkinson's disease: an updated systematic review of randomized controlled trials. Front Neurol2021; 12: 798191.
10.
StromAIaccarinoLEdwardsL, et al.Cortical hypometabolism reflects local atrophy and tau pathology in symptomatic Alzheimer’s disease. Brain2022; 145: 713–728.
11.
JinYLiJXiaoB. Efficacy and safety of neuromodulation for apathy in patients with Alzheimer's disease: a systematic review and meta-analysis of randomized controlled trials. J Psychiatr Res2024; 171: 17–24.
12.
TariqRKansalBShaikhR, et al.Outcomes and factors affecting transcranial direct current stimulation in Alzheimer's disease patients: a systematic review. Curr Alzheimer Res2023; 20: 250–266.
13.
MathewJL. Systematic reviews and meta-analysis: a guide for beginners. Indian Pediatr2022; 59: 320–330.
14.
PageMJMcKenzieJEBossuytPM, et al.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ2021; 372: n71.
15.
GangemiAColomboBFabioRA. Effects of short- and long-term neurostimulation (tDCS) on Alzheimer's disease patients: two randomized studies. Aging Clin Exp Res2021; 33: 383–390.
16.
SmirniDOliveriMMisuracaE, et al.Verbal fluency in mild Alzheimer's disease: transcranial direct current stimulation over the dorsolateral prefrontal cortex. J Alzheimers Dis2021; 81: 1273–1283.
17.
KhedrEMGamalNFEl-FetohNA, et al.A double-blind randomized clinical trial on the efficacy of cortical direct current stimulation for the treatment of Alzheimer's disease. Front Aging Neurosci2014; 6: 275.
18.
KhedrEMSalamaRHAbdel HameedM, et al.Therapeutic role of transcranial direct current stimulation in Alzheimer disease patients: double-blind, placebo-controlled clinical trial. Neurorehabil Neural Repair2019; 33: 384–394.
19.
ImJJJeongHBiksonM, et al.Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer's disease. Brain Stimul2019; 12: 1222–1228.
20.
MeléndezJCSatorresEPitarqueA, et al.Transcranial direct current stimulation intervention in Alzheimer's disease and its follow-up. J Alzheimers Dis2023; 96: 1685–1693.
21.
CotelliMManentiRBrambillaM, et al.Anodal tDCS during face-name associations memory training in Alzheimer's patients. Front Aging Neurosci2014; 6: 38.
22.
BoggioPSFerrucciRMameliF, et al.Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease. Brain Stimul2012; 5: 223–230.
23.
AndradeSMMachadoDGDSSilva-SauercLD, et al.Effects of multisite anodal transcranial direct current stimulation combined with cognitive stimulation in patients with Alzheimer's disease and its neurophysiological correlates: a double-blind randomized clinical trial. Neurophysiol Clin2022; 52: 117–127.
24.
HuYJiaYSunY, et al.Efficacy and safety of simultaneous rTMS-tDCS over bilateral angular gyrus on neuropsychiatric symptoms in patients with moderate Alzheimer's disease: a prospective, randomized, sham-controlled pilot study. Brain Stimul2022; 15: 1530–1537.
25.
MostafaeiHGhojazadehMHajebrahimiS. Fixed-effect versus random-effects models for meta-analyses: fixed-effect models. Eur Urol Focus2023; 9: 691–692.
26.
KantersS. Fixed- and random-effects models. Methods Mol Biol2022; 2345: 41–65.
27.
GueorguievaIChuaLWillisBA, et al.Disease progression model using the integrated Alzheimer's disease rating scale. Alzheimers Dement2022; 19: 2253–2264.
28.
HemrungrojnSAmrapalaAMaesM. Construction of a short version of the Montreal Cognitive Assessment (MoCA) rating scale for the Thai population using partial least squares analysis. Int J Neurosci2022; 134: 16–27.
29.
SchuchJBBeckerNRabelo-da-PonteFD, et al.Assessment of cognitive functioning using the mini mental state examination in men with alcohol and crack cocaine use disorder. Trends Psychiatry Psychother2023; 45: e20220567.
30.
KatsanosAHLeeSFCukierman-YaffeT, et al.World-wide variations in tests of cognition and activities of daily living in participants of six international randomized controlled trials. Cereb Circ Cogn Behav2023; 5: 100176.
31.
BukhbinderASHinojosaMHarrisK, et al.Population-based mini-mental state examination norms in adults of Mexican heritage in the Cameron County Hispanic cohort. J Alzheimers Dis2023; 92: 1323–1339.
32.
LinC-PFrigerioIBolJGJM, et al.Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer’s disease and Parkinson’s disease. Transl Neurodegener2024; 13: 9.
33.
AbdelnourCAgostaFBozzaliM, et al.Perspectives and challenges in patient stratification in Alzheimer’s disease. Alzheimers Res Ther2022; 14: 112.
34.
HigginsJPTAltmanDGGotzschePC, et al.The Cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ2011; 343: d5928–d5928.
35.
SterneJACSavovićJPageMJ, et al.Rob 2: a revised tool for assessing risk of bias in randomised trials. BMJ2019; 366: l4898.
36.
AfonsoJRamirez-CampilloRClementeFM, et al.The perils of misinterpreting and misusing “publication bias” in meta-analyses: an education review on funnel plot-based. Sports Med2023; 54: 257–269.
37.
JeongS-KChoK-HKimJ-M. The usefulness of the Korean version of modified mini-mental state examination (K-mMMSE) for dementia screening in community dwelling elderly people. BMC Public Health2004; 4: 31.
38.
SaxenaVPalA. Role of transcranial direct current stimulation in the management of Alzheimer’s disease: a meta-analysis of effects, adherence and adverse effects. Clin Psychopharmacol Neurosci2021; 19: 589–599.
39.
PhilippenSHanertASchönfeldR, et al.Transcranial direct current stimulation of the right temporoparietal junction facilitates hippocampal spatial learning in Alzheimer's disease and mild cognitive impairment. Clin Neurophysiol2024; 157: 48–60.
40.
Valera-BermejoJMDe MarcoMVenneriA. Altered interplay among large-scale brain functional networks modulates multi-domain anosognosia in early Alzheimer’s disease. Front Aging Neurosci2022; 13: 781465.
41.
BautistaJGarcía-CabezasMÁMedallaM, et al.Pattern of ventral temporal lobe interconnections in rhesus macaques. J Comp Neurol2023; 531: 1963–1986.
42.
KaiserMSoleimaniGKuplikiR, et al.Dose-response in modulating brain function with transcranial direct current stimulation: from local to network levels. PLoS Comput Biol2023; 19: e1011572.
43.
MajdiAvan BoekholdtLSadigh-EteghadS, et al.A systematic review and meta-analysis of transcranial direct-current stimulation effects on cognitive function in patients with Alzheimer’s disease. Mol Psychiatry2022; 27: 2000–2009.
44.
RezaMSJinLJeongYJ, et al.Electrospun rubber nanofiber web-based dry electrodes for biopotential monitoring. Sensors (Basel)2023; 23: 7377.
45.
IshikuroKHattoriNOtomuneH, et al.Neural mechanisms of neuro-rehabilitation using transcranial direct current stimulation (tDCS) over the front-polar area. Brain Sci2023; 13: 1604.
46.
YanYTianMWangT, et al.Transcranial magnetic stimulation effects on cognitive enhancement in mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis. Front Neurol2023; 14: 1209205.
47.
TeselinkJBawaKKKooGK, et al.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. Ageing Res Rev2021; 72: 101499.
48.
AberraASWangRGrillWM, et al.Multi-scale model of axonal and dendritic polarization by transcranial direct current stimulation in realistic head geometry. Brain Stimul2023; 16: 1776–1791.
49.
BlinkouskayaYCaçoiloAGollamudiT, et al.Brain aging mechanisms with mechanical manifestations. Mech Ageing Dev2021; 200: 111575.
50.
SakugawaRLOrssattoLBRSampaioLT, et al.Pressure on the electrode to reduce discomfort during neuromuscular electrical stimulation in individuals with different subcutaneous-fat thickness: is the procedure effective and reliable?IEEE Trans Neural Syst Rehabil Eng2022; 30: 1–7.
51.
LiuXHuYHaoY, et al.Individual differences in the neural architecture in semantic processing. Sci Rep2024; 14: 170.
52.
KotikalapudiRKincsesBZunhammerM, et al.Brain morphology predicts individual sensitivity to pain: a multicenter machine learning approach. Pain2023; 164: 2516–2527.
53.
ThakurSDhapolaRSarmaP, et al.Neuroinflammation in Alzheimer’s disease: current progress in molecular signaling and therapeutics. Inflammation2022; 46: 1–17.
54.
CaoSFisherDWRodriguezG, et al.Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice. J Neuroinflammation2021; 18: 10.
55.
GalganiAGiorgiFS. Exploring the role of locus coeruleus in Alzheimer’s disease: a comprehensive update on MRI studies and implications. Curr Neurol Neurosci Rep2023; 23: 925–936.
56.
McKinneyAHuMHoskinsA, et al.Cellular composition and circuit organization of the locus coeruleus of adult mice. Elife2023; 12: e80100.
57.
PiniLPizziniFBBoscolo-GalazzoI, et al.Brain network modulation in Alzheimer's and frontotemporal dementia with transcranial electrical stimulation. Neurobiol Aging2022; 111: 24–34.
58.
BarbatiSAPoddaMVGrassiC. Tuning brain networks: the emerging role of transcranial direct current stimulation on structural plasticity. Front Cell Neurosci2022; 16: 945777.
59.
Mohamed NourAEAJiaoYTengG-J. Neuroanatomical associations of depression, anxiety and apathy neuropsychiatric symptoms in patients with Alzheimer’s disease. Acta Neurol Belg2020; 121: 1469–1480.
