As depressive symptom is considered a prodrome, a risk factor for progression from mild cognitive impairment (MCI) to dementia, improving depressive symptoms should be considered a clinical priority in patients with MCI undergoing transcranial direct current stimulation (tDCS) intervention. We aimed to comprehensively evaluate the efficacy of the home-based and remotely monitored tDCS in patients with both MCI and depression, by integrating cognitive, psychological, and electrophysiological indicators. In a 6-week, randomized, double blind, and sham-controlled study, 37 community-dwelling patients were randomly assigned to either an active or a sham stimulation group, and received 30 home-based sessions of 2 mA tDCS for 30 min with the anode located over the left and cathode over the right dorsolateral prefrontal cortex. We measured depressive symptoms, neurocognitive function, and resting-state electroencephalography. In terms of effects of both depressive symptoms and cognitive functions, active tDCS was not significantly different from sham tDCS. However, compared to sham stimulation, active tDCS decreased and increased the activation of delta and beta frequencies, respectively. Moreover, the increase in beta activity was correlated with the cognitive enhancement only in the active group. It was not possible to reach a definitive conclusion regarding the efficacy of tDCS on depression and cognition in patients with both MCI and depression. Nevertheless, the relationship between the changes of electrophysiology and cognitive performance suggests potential neuroplasticity enhancement implicated in cognitive processes by tDCS.
WinbladBPalmerKKivipeltoM, et al.Mild cognitive impairment–beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment. J Int Med. 2004;256(3):240-246.
3.
PanzaFFrisardiVCapursoC, et al.Late-life depression, mild cognitive impairment, and dementia: Possible continuum?Am J Geriatr Psychiatr. 2010;18(2):98-116.
4.
MouraoRJMansurGMalloy-DinizLFCastro CostaEDinizBS. Depressive symptoms increase the risk of progression to dementia in subjects with mild cognitive impairment: Systematic review and meta-analysis. Int J Geriatri Psychiatr. 2016;31(8):905-911.
5.
LyketsosCGSteeleCBakerL, et al.Major and minor depression in Alzheimer's disease: Prevalence and impact. J Neuropsychiatr Clin Neurosci. 1997;9(4):556-561.
6.
CooperCLiRLyketsosCLivingstonG. A systematic review of treatments for mild cognitive impairment. Br J Psychiatr. 2013;203(3):255-264.
7.
ChanJYYiuKKKwokTCWongSYTsoiKK. Depression and antidepressants as potential risk factors in dementia: A systematic review and meta-analysis of 18 longitudinal studies. J Am Med Direct Assoc. 2019;20(3):279-286.
8.
CassanoTCalcagniniSCarboneA, et al.Pharmacological treatment of depression in Alzheimer’s disease: A challenging task. Front Pharmacol. 2019;10:1067.
9.
BirbaAIbáñezASedeñoLFerrariJGarcíaAMZimermanM. Non-invasive brain stimulation: A new strategy in mild cognitive impairment?Front Aging Neurosci. 2017;9:16.
10.
BrunoniARMoffaAHSampaio-JuniorB, et al.Trial of electrical direct-current therapy versus escitalopram for depression. New Eng J Med. 2017;376(26):2523-2533.
11.
RazzaLBPalumboPMoffaAH, et al.A systematic review and meta-analysis on the effects of transcranial direct current stimulation in depressive episodes. Dep Anx. 2020;37(7):594-608.
12.
DedonckerJBrunoniARBaekenCVanderhasseltM-A. A systematic review and meta-analysis of the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex in healthy and neuropsychiatric samples: Influence of stimulation parameters. Brain Stimul. 2016;9(4):501-517.
13.
InagawaTNaritaZSugawaraN, et al.A meta-analysis of the effect of multisession transcranial direct current stimulation on cognition in dementia and mild cognitive impairment. Clini EEG Neurosci. 2019;50(4):273-282.
14.
FrithCDolanR. The role of the prefrontal cortex in higher cognitive functions. Cog Brain Res. 1996;5(1-2):175-181.
15.
BrosnanMBWiegandI. The dorsolateral prefrontal cortex, a dynamic cortical area to enhance top-down attentional control. J Neurosci. 2017;37(13):3445-3446.
16.
GbadeyanOMcMahonKSteinhauserMMeinzerM. Stimulation of dorsolateral prefrontal cortex enhances adaptive cognitive control: A high-definition transcranial direct current stimulation study. J Neurosci. 2016;36(50):12530-12536.
17.
LiangPWangZYangYJiaXLiK. Functional disconnection and compensation in mild cognitive impairment: Evidence from DLPFC connectivity using resting-state fMRI. PloS One. 2011;6(7):e22153.
18.
SalehinejadMAGhanavaiERostamiRNejatiV. Cognitive control dysfunction in emotion dysregulation and psychopathology of major depression (MD): Evidence from transcranial brain stimulation of the dorsolateral prefrontal cortex (DLPFC). J Affect Dis. 2017;210:241-248.
19.
KrishnanKRRTaylorWDMcQuoidDR, et al.Clinical characteristics of magnetic resonance imaging-defined subcortical ischemic depression. Biol Psychiatr. 2004;55(4):390-397.
20.
JeonSYHanSJ. Improvement of the working memory and naming by transcranial direct current stimulation. Ann Rehab Med. 2012;36(5):585.
21.
JavadiAHChengP. Transcranial direct current stimulation (tDCS) enhances reconsolidation of long-term memory. Brain Stimul. 2013;6(4):668-674.
22.
PripflJNeumannRKöhlerULammC. Effects of transcranial direct current stimulation on risky decision making are mediated by ‘hot’and ‘cold’ decisions, personality, and hemisphere. Euro J Neurosci. 2013;38(12):3778-3785.
23.
Dubreuil-VallLChauPRuffiniGWidgeASCamprodonJA. tDCS to the left DLPFC modulates cognitive and physiological correlates of executive function in a state-dependent manner. Brain Stimul. 2019;12(6):1456-1463.
24.
TremblaySLepageJ-FLatulipe-LoiselleAFregniFPascual-LeoneAThéoretH. The uncertain outcome of prefrontal tDCS. Brain Stimul. 2014;7(6):773-783.
25.
MancusoLEIlievaIPHamiltonRHFarahMJ. Does transcranial direct current stimulation improve healthy working memory?: A meta-analytic review. J Cog Neurosci. 2016;28(8):1063-1089.
26.
DedonckerJBrunoniARBaekenCVanderhasseltM-A. The effect of the interval-between-sessions on prefrontal transcranial direct current stimulation (tDCS) on cognitive outcomes: A systematic review and meta-analysis. J Neur Transm. 2016;123(10):1159-1172.
27.
MedinaJCasonS. No evidential value in samples of transcranial direct current stimulation (tDCS) studies of cognition and working memory in healthy populations. Cortex. 2017;94:131-141.
28.
HorvathJCForteJDCarterO. Quantitative review finds no evidence of cognitive effects in healthy populations from single-session transcranial direct current stimulation (tDCS). Brain Stimul. 2015;8(3):535-550.
29.
FeeserMPrehnKKazzerPMungeeABajboujM. Transcranial direct current stimulation enhances cognitive control during emotion regulation. Brain Stimul. 2014;7(1):105-112.
30.
VanderhasseltM-ARaedtDBrunoniR, et al.tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli. PloS One. 2013;8(5):e62219.
31.
VanderhasseltM-ASanchezAJosephyHBaekenCBrunoniARDe RaedtR. Anodal tDCS over the right dorsolateral prefrontal cortex modulates cognitive processing of emotional information as a function of trait rumination in healthy volunteers. Biol Psychol. 2017;123:111-118.
32.
MoffaAHMartinDAlonzoA, et al.Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: An individual patient data meta-analysis. Prog Neuro-Psychopharmacol Biol Psychiatr. 2020;99:109836.
33.
RazzaLBDe SmetSMoffaASudbrack-OliveiraPVanderhasseltM-ABrunoniAR. Follow-up effects of transcranial direct current stimulation (tDCS) for the major depressive episode: A systematic review and meta-analysis. Psychiatr Res. 2021;302:114024.
34.
ZhangRLamCLPengX, et al.Efficacy and acceptability of transcranial direct current stimulation for treating depression: A meta-analysis of randomized controlled trials. Neurosci Biobehav Rev. 2021;126:481-490.
35.
ParkJOhYChungKKimKJKimCOParkJY. Effect of home-based transcranial direct current stimulation (tDCS) on cognitive function in patients with mild cognitive impairment: A study protocol for a randomized, double-blind, cross-over study. Trials. 2019;20(1):1-9.
36.
Cruz GonzalezPFongKNBrownT. The effects of transcranial direct current stimulation on the cognitive functions in older adults with mild cognitive impairment: A pilot study. Behav Neurol. 2018;2018:1-14.
37.
MurugarajaVShivakumarVSivakumarPTSinhaPVenkatasubramanianG. Clinical utility and tolerability of transcranial direct current stimulation in mild cognitive impairment. As J Psychiatr. 2017;30:135-140.
38.
StonsaovapakCHemrungrojSTerachindaPPiravejK. Effect of anodal transcranial direct current stimulation at the right dorsolateral prefrontal cortex on the cognitive function in patients with mild cognitive impairment: A randomized double-blind controlled trial. Arch Phys Med Rehab. 2020;101(8):1279-1287.
39.
ImJJJeongHBiksonM, et al.Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer's disease. Brain Stimul. 2019;12(5):1222-1228.
40.
YunKSongI-UChungY-A. Changes in cerebral glucose metabolism after 3 weeks of noninvasive electrical stimulation of mild cognitive impairment patients. Alzh Res Ther. 2016;8(1):1-9.
41.
OwenAMMcMillanKMLairdARBullmoreE. N-back working memory paradigm: A meta-analysis of normative functional neuroimaging studies. Hum Brain Map. 2005;25(1):46-59.
42.
KwonYHJangSH. Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation: A functional MRI study. Neur Regen Res. 2012;7(24):1889.
43.
LindenbergRNachtigallLMeinzerMSiegMMFlöelA. Differential effects of dual and unihemispheric motor cortex stimulation in older adults. J Neurosci. 2013;33(21):9176-9183.
44.
RajjiTKBowieCRHerrmannN, et al.Design and rationale of the PACt-MD randomized clinical trial: Prevention of Alzheimer’s dementia with cognitive remediation plus transcranial direct current stimulation in mild cognitive impairment and depression. J Alzh Dis. 2020;76(2):733-751.
45.
RichardEReitzCHonigLH, et al.Late-life depression, mild cognitive impairment, and dementia. JAMA Neurol. 2013;70(3):383-389.
46.
AzarpaikanATaherii TorbatiHSohrabiMBoostaniRGhoshuniM. Power spectral parameter variations after transcranial direct current stimulation in a bimanual coordination task. Adapt Behav. 2021;29(1):25-38.
47.
MarcegliaSMrakic-SpostaSRosaM, et al.Transcranial direct current stimulation modulates cortical neuronal activity in Alzheimer's disease. Front Neurosci. 2016;10:134.
48.
FerrucciRMrakic-SpostaSGardiniS, et al.Behavioral and neurophysiological effects of transcranial direct current stimulation (tDCS) in fronto-temporal dementia. Front Behav Neurosci. 2018;12:235.
49.
KoberdaJLMosesAKoberdaPKoberdaL. Clinical advantages of quantitative electroencephalogram (QEEG)–electrical neuroimaging application in general neurology practice. Clin EEG Neurosci. 2013;44(4):273-285.
50.
ChiaramontiRMuscasGPaganiniM, et al.Correlations of topographical EEG features with clinical severity in mild and moderate dementia of Alzheimer type. Neuropsychobiol. 1997;36(3):153-158.
51.
IhlRDierksTMartinE-MFrölichLMaurerK. Topography of the maximum of the amplitude of EEG frequency bands in dementia of the Alzheimer type. Biol Psychiatr. 1996;39(5):319-325.
52.
AdlerGBramesfeldAJajcevicA. Mild cognitive impairment in old-age depression is associated with increased EEG slow-wave power. Neuropsychobiol. 1999;40(4):218-222.
53.
DierksTFrölichLIhlRMaurerK. Correlation between cognitive brain function and electrical brain activity in dementia of Alzheimer type. J Neur Transm/Gen Sect. 1995;99(1):55-62.
54.
BrassenSBrausDFWeber-FahrWTostHMoritzSAdlerG. Late-onset depression with mild cognitive deficits: Electrophysiological evidences for a preclinical dementia syndrome. Dement Geriatr Cog Dis. 2004;18(3-4):271-277.
55.
MartensGLejeuneN'BrienO, et al.Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state. Brain Stimul. 2018;11(5):982-990.
56.
AhnHSorkporSMiaoH, et al.Home-based self-administered transcranial direct current stimulation in older adults with knee osteoarthritis pain: An open-label study. J Clin Neurosci. 2019;66:61-65.
57.
RiggsAPatelVPaneriBPortenoyRKBiksonMKnotkovaH. At-home transcranial direct current stimulation (tDCS) with telehealth support for symptom control in chronically-ill patients with multiple symptoms. Front Behav Neurosci. 2018;12:93.
ReisbergBFerrisSHDe LeonMCrookT. Global deterioration scale (GDS). Psychopharmacol Bull. 1988;24(4):661-663.
60.
MontgomerySAÅsbergM. A new depression scale designed to be sensitive to change. Br J Psychiatr. 1979;134(4):382-389.
61.
Müller-ThomsenTArltSMannUMaßRGanzerS. Detecting depression in Alzheimer’s disease: Evaluation of four different scales. Arch Clin Neuropsychol. 2005;20(2):271-276.
62.
FolsteinMFolsteinSMcHughP. Mini-mental state (mmse) journal of psychiatric research, 12. J Psychiatr Res. 1975;12(3):189-198.
63.
BlessedGTomlinsonBERothM. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatr. 1968;114(512):797-811.
64.
KatzmanRBrownTFuldPPeckASchechterRSchimmelH. Validation of a short orientation-memory-concentration test of cognitive impairment. Am J Psychiatr. 1983;140(6):734-739.
65.
KatzS. Assessing self-maintenance: Activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc. 1983;31:721-727.
66.
EatonWWSmithCYbarraMMuntanerCTienA. Center for Epidemiologic Studies Depression Scale: review and revision (CESD and CESD-R). The Use of Psychological Testing for Treatment Planning and Outcomes Assessment; 2004.
67.
HamiltonM. The Hamilton rating scale for depression. Assessment of Depression. 1986:143-152.
68.
HamiltonM. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32:50-55.
69.
KaplanEGoodglassHWeintraubS. Boston naming test. University of Pittsburgh; 2001.
70.
KangYNaD. Seoul verbal learning test (SVLT). Human Brain Research & Consulting Co; 2003.
StroopJR. Studies of interference in serial verbal reactions. J Exper Psychol. 1935;18(6):643-662.
73.
ReitanRM. Validity of the trail making test as an indicator of organic brain damage. Percept Motor Skills. 1958;8(3):271-276.
74.
LeeJHLeeKULeeDY, et al.Development of the Korean version of the consortium to establish a registry for Alzheimer's disease assessment packet (CERAD-K) clinical and neuropsychological assessment batteries. J Gerontol. 2002;57(1):P47-P53.
75.
AhnH-JChinJParkA, et al.Seoul neuropsychological screening battery-dementia version (SNSB-D): A useful tool for assessing and monitoring cognitive impairments in dementia patients. J Kor Med Sci. 2010;25(7):1071-1076.
76.
FerreeTCLuuPRussellGSTuckerDM. Scalp electrode impedance, infection risk, and EEG data quality. Clin Neurophysiol. 2001;112(3):536-544.
77.
GonzalezPCFongKNBrownT. Transcranial direct current stimulation as an adjunct to cognitive training for older adults with mild cognitive impairment: A randomized controlled trial. Ann Phys Rehab Med. 2021;64(5):101536.
78.
MeronDHedgerNGarnerMBaldwinDS. Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability. Neurosci Biobehav Rev. 2015;57:46-62.
79.
PalmUHasanAStrubeWPadbergF. tDCS for the treatment of depression: A comprehensive review. Euro Arch Psychiatr Clin Neurosci. 2016;266(8):681-694.
GálvezVHoK-AAlonzoAMartinDGeorgeDLooCK. Neuromodulation therapies for geriatric depression. Curr Psychiatr Rep. 2015;17(7):1-15.
82.
LooCKHusainMMMcDonaldWM, et al.International randomized-controlled trial of transcranial direct current stimulation in depression. Brain Stimul. 2018;11(1):125-133.
83.
LiuCSRauAGallagherDRajjiTKLanctôtKLHerrmannN. Using transcranial direct current stimulation to treat symptoms in mild cognitive impairment and Alzheimer's disease. Neurodegen Dis Manage. 2017;7(5):317-329.
84.
BystadMGrønliORasmussenID, et al.Transcranial direct current stimulation as a memory enhancer in patients with Alzheimer’s disease: A randomized, placebo-controlled trial. Alzh Res Ther. 2016;8(1):1-7.
85.
JonesKTGözenmanFBerryhillME. The strategy and motivational influences on the beneficial effect of neurostimulation: A tDCS and fNIRS study. Neuroimage. 2015;105:238-247.
86.
BerryhillMEJonesKT. tDCS selectively improves working memory in older adults with more education. Neurosci Lett. 2012;521(2):148-151.
87.
StollFMWilsonCRFarautMCVezoliJKnoblauchKProcykE. The effects of cognitive control and time on frontal beta oscillations. Cereb Cort. 2016;26(4):1715-1732.
88.
GolaMMagnuskiMSzumskaIWróbelA. EEG beta band activity is related to attention and attentional deficits in the visual performance of elderly subjects. Int J Psychophysiol. 2013;89(3):334-341.
89.
Cardenas-RojasACastelo-BrancoLPacheco-BarriosK, et al.Recruitment characteristics and non-adherence associated factors of fibromyalgia patients in a randomized clinical trial: A retrospective survival analysis. Contemp Clin Trial Commun. 2021;24:100860.
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