Skip to main content
Top
Published in: Trials 1/2017

Open Access 01-12-2017 | Study protocol

Transcranial direct current stimulation for depression in Alzheimer’s disease: study protocol for a randomized controlled trial

Authors: Zui Narita, Yuma Yokoi

Published in: Trials | Issue 1/2017

Login to get access

Abstract

Background

Patients with Alzheimer’s disease frequently elicit neuropsychiatric symptoms as well as cognitive deficits. Above all, depression is one of the most common neuropsychiatric symptoms in Alzheimer’s disease but antidepressant drugs have not shown significant beneficial effects on it. Moreover, electroconvulsive therapy has not ensured its safety for potential severe adverse events although it does show beneficial clinical effect. Transcranial direct current stimulation can be the safe alternative of neuromodulation, which applies weak direct electrical current to the brain. Although transcranial direct current stimulation has plausible evidence for its effect on depression in young adult patients, no study has explored it in older subjects with depression in Alzheimer’s disease. Therefore, we present a study protocol designed to evaluate the safety and clinical effect of transcranial direct current stimulation on depression in Alzheimer’s disease in subjects aged over 65 years.

Method

This is a two-arm, parallel-design, randomized controlled trial, in which patients and assessors will be blinded. Subjects will be randomized to either an active or a sham transcranial direct current stimulation group. Participants in both groups will be evaluated at baseline, immediately, and 2 weeks after the intervention.

Discussion

This study investigates the safety and effect of transcranial direct current stimulation that may bring a significant impact on both depression and cognition in patients with Alzheimer’s disease, and may be useful to enhance their quality of life.

Trial registration

ClinicalTrials.gov, NCT02351388. Registered on 27 January 2015. Last updated on 30 May 2016.
Appendix
Available only for authorised users
Literature
1.
go back to reference American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Association; 2013.CrossRef American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Association; 2013.CrossRef
2.
go back to reference Alzheimer’s Disease International. World Alzheimer Report 2015 The global impact of dementia. An analysis of prevalence, incidence, cost and trends. 2015 Alzheimer’s Disease International. World Alzheimer Report 2015 The global impact of dementia. An analysis of prevalence, incidence, cost and trends. 2015
3.
go back to reference Rocca WA, Petersen RC, Knopman DS, Hebert LE, Evans DA, Hall KS, et al. Trends in the incidence and prevalence of Alzheimer’s disease, dementia, and cognitive impairment in the United States. Alzheimers Dement J Alzheimers Assoc. 2011;7(1):80–93.CrossRef Rocca WA, Petersen RC, Knopman DS, Hebert LE, Evans DA, Hall KS, et al. Trends in the incidence and prevalence of Alzheimer’s disease, dementia, and cognitive impairment in the United States. Alzheimers Dement J Alzheimers Assoc. 2011;7(1):80–93.CrossRef
4.
go back to reference Ganguli M, Hendrie HC. Screening for cognitive impairment and depression in ethnically diverse older populations. Alzheimer Dis Assoc Disord. 2005;19(4):275–8.CrossRefPubMed Ganguli M, Hendrie HC. Screening for cognitive impairment and depression in ethnically diverse older populations. Alzheimer Dis Assoc Disord. 2005;19(4):275–8.CrossRefPubMed
5.
go back to reference Llibre Rodriguez JJ, Ferri CP, Acosta D, Guerra M, Huang Y, Jacob KS, et al. Prevalence of dementia in Latin America, India, and China: a population-based cross-sectional survey. Lancet Lond Engl. 2008;372(9637):464–74.CrossRef Llibre Rodriguez JJ, Ferri CP, Acosta D, Guerra M, Huang Y, Jacob KS, et al. Prevalence of dementia in Latin America, India, and China: a population-based cross-sectional survey. Lancet Lond Engl. 2008;372(9637):464–74.CrossRef
6.
go back to reference Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement J Alzheimers Assoc. 2013;9(1):63–75.e2.CrossRef Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement J Alzheimers Assoc. 2013;9(1):63–75.e2.CrossRef
7.
go back to reference Sosa-Ortiz AL, Acosta-Castillo I, Prince MJ. Epidemiology of dementias and Alzheimer’s disease. Arch Med Res. 2012;43(8):600–8.CrossRefPubMed Sosa-Ortiz AL, Acosta-Castillo I, Prince MJ. Epidemiology of dementias and Alzheimer’s disease. Arch Med Res. 2012;43(8):600–8.CrossRefPubMed
8.
go back to reference Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology. 2013;80(19):1778–83.CrossRefPubMedPubMedCentral Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology. 2013;80(19):1778–83.CrossRefPubMedPubMedCentral
9.
go back to reference León-Salas B, Olazarán J, Muñiz R, González-Salvador MT, Martínez-Martín P. Caregivers’ estimation of patients’ quality of life (QoL) in Alzheimer’s disease (AD): an approach using the ADRQL. Arch Gerontol Geriatr. 2011;53(1):13–8.CrossRefPubMed León-Salas B, Olazarán J, Muñiz R, González-Salvador MT, Martínez-Martín P. Caregivers’ estimation of patients’ quality of life (QoL) in Alzheimer’s disease (AD): an approach using the ADRQL. Arch Gerontol Geriatr. 2011;53(1):13–8.CrossRefPubMed
10.
go back to reference León-Salas B, Olazarán J, Cruz-Orduña I, Agüera-Ortiz L, Dobato JL, Valentí-Soler M, et al. Quality of life (QoL) in community-dwelling and institutionalized Alzheimer’s disease (AD) patients. Arch Gerontol Geriatr. 2013;57(3):257–62.CrossRefPubMed León-Salas B, Olazarán J, Cruz-Orduña I, Agüera-Ortiz L, Dobato JL, Valentí-Soler M, et al. Quality of life (QoL) in community-dwelling and institutionalized Alzheimer’s disease (AD) patients. Arch Gerontol Geriatr. 2013;57(3):257–62.CrossRefPubMed
11.
go back to reference Acosta-Castillo GI, Luisa Sosa A, Orozco R, Borges G. Neuropsychiatric symptoms in older adults with dementia and their relationship to disease severity. Rev Investig Clin Organo Hosp Enfermedades Nutr. 2012;64(4):354–63. Acosta-Castillo GI, Luisa Sosa A, Orozco R, Borges G. Neuropsychiatric symptoms in older adults with dementia and their relationship to disease severity. Rev Investig Clin Organo Hosp Enfermedades Nutr. 2012;64(4):354–63.
12.
go back to reference Aalten P, Verhey FRJ, Boziki M, Bullock R, Byrne EJ, Camus V, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I. Dement Geriatr Cogn Disord. 2007;24(6):457–63.CrossRefPubMed Aalten P, Verhey FRJ, Boziki M, Bullock R, Byrne EJ, Camus V, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I. Dement Geriatr Cogn Disord. 2007;24(6):457–63.CrossRefPubMed
13.
go back to reference Nelson JC, Devanand DP. A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia. J Am Geriatr Soc. 2011;59(4):577–85.CrossRefPubMed Nelson JC, Devanand DP. A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia. J Am Geriatr Soc. 2011;59(4):577–85.CrossRefPubMed
14.
go back to reference Banerjee S, Hellier J, Dewey M, Romeo R, Ballard C, Baldwin R, et al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. Lancet Lond Engl. 2011;378(9789):403–11.CrossRef Banerjee S, Hellier J, Dewey M, Romeo R, Ballard C, Baldwin R, et al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. Lancet Lond Engl. 2011;378(9789):403–11.CrossRef
15.
go back to reference Gábor G, László T. The efficacy of ECT treatment in depression: a meta-analysis. Psychiatr Hung Magy Pszichiatriai Tarsasag Tudomanyos Folyoirata. 2005;20(3):195–200. Gábor G, László T. The efficacy of ECT treatment in depression: a meta-analysis. Psychiatr Hung Magy Pszichiatriai Tarsasag Tudomanyos Folyoirata. 2005;20(3):195–200.
16.
go back to reference Pagnin D, de Queiroz V, Pini S, Cassano GB. Efficacy of ECT in depression: a meta-analytic review. J ECT. 2004;20(1):13–20.CrossRefPubMed Pagnin D, de Queiroz V, Pini S, Cassano GB. Efficacy of ECT in depression: a meta-analytic review. J ECT. 2004;20(1):13–20.CrossRefPubMed
17.
go back to reference Oudman E. Is electroconvulsive therapy (ECT) effective and safe for treatment of depression in dementia? A short review. J ECT. 2012;28(1):34–8.CrossRefPubMed Oudman E. Is electroconvulsive therapy (ECT) effective and safe for treatment of depression in dementia? A short review. J ECT. 2012;28(1):34–8.CrossRefPubMed
18.
go back to reference Hausner L, Damian M, Sartorius A, Frölich L. Efficacy and cognitive side effects of electroconvulsive therapy (ECT) in depressed elderly inpatients with coexisting mild cognitive impairment or dementia. J Clin Psychiatry. 2011;72(1):91–7.CrossRefPubMed Hausner L, Damian M, Sartorius A, Frölich L. Efficacy and cognitive side effects of electroconvulsive therapy (ECT) in depressed elderly inpatients with coexisting mild cognitive impairment or dementia. J Clin Psychiatry. 2011;72(1):91–7.CrossRefPubMed
19.
go back to reference Rao V, Lyketsos CG. The benefits and risks of ECT for patients with primary dementia who also suffer from depression. Int J Geriatr Psychiatry. 2000;15(8):729–35.CrossRefPubMed Rao V, Lyketsos CG. The benefits and risks of ECT for patients with primary dementia who also suffer from depression. Int J Geriatr Psychiatry. 2000;15(8):729–35.CrossRefPubMed
20.
go back to reference Fong TG, Jones RN, Shi P, Marcantonio ER, Yap L, Rudolph JL, et al. Delirium accelerates cognitive decline in Alzheimer disease. Neurology. 2009;72(18):1570–5.CrossRefPubMedPubMedCentral Fong TG, Jones RN, Shi P, Marcantonio ER, Yap L, Rudolph JL, et al. Delirium accelerates cognitive decline in Alzheimer disease. Neurology. 2009;72(18):1570–5.CrossRefPubMedPubMedCentral
21.
go back to reference Brunoni AR, Nitsche MA, Bolognini N, Bikson M, Wagner T, Merabet L, et al. Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimulat. 2012;5(3):175–95.CrossRef Brunoni AR, Nitsche MA, Bolognini N, Bikson M, Wagner T, Merabet L, et al. Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimulat. 2012;5(3):175–95.CrossRef
22.
go back to reference Loo CK, Alonzo A, Martin D, Mitchell PB, Galvez V, Sachdev P. Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. Br J Psychiatry J Ment Sci. 2012;200(1):52–9.CrossRef Loo CK, Alonzo A, Martin D, Mitchell PB, Galvez V, Sachdev P. Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. Br J Psychiatry J Ment Sci. 2012;200(1):52–9.CrossRef
23.
go back to reference Brunoni AR, Valiengo L, Baccaro A, Zanão TA, de Oliveira JF, Goulart A, et al. The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. JAMA Psychiat. 2013;70(4):383–91.CrossRef Brunoni AR, Valiengo L, Baccaro A, Zanão TA, de Oliveira JF, Goulart A, et al. The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. JAMA Psychiat. 2013;70(4):383–91.CrossRef
24.
go back to reference Brunoni AR, Moffa AH, Fregni F, Palm U, Padberg F, Blumberger DM, et al. Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data. Br J Psychiatry J Ment Sci. 2016;208(6):522–31.CrossRef Brunoni AR, Moffa AH, Fregni F, Palm U, Padberg F, Blumberger DM, et al. Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data. Br J Psychiatry J Ment Sci. 2016;208(6):522–31.CrossRef
25.
go back to reference Brunoni AR, Teng CT, Correa C, Imamura M, Brasil-Neto JP, Boechat R, et al. Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting. Arq Neuropsiquiatr. 2010;68(3):433–51.CrossRefPubMed Brunoni AR, Teng CT, Correa C, Imamura M, Brasil-Neto JP, Boechat R, et al. Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting. Arq Neuropsiquiatr. 2010;68(3):433–51.CrossRefPubMed
26.
go back to reference Alonzo A, Brassil J, Taylor JL, Martin D, Loo CK. Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation. Brain Stimulat. 2012;5(3):208–13.CrossRef Alonzo A, Brassil J, Taylor JL, Martin D, Loo CK. Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation. Brain Stimulat. 2012;5(3):208–13.CrossRef
27.
go back to reference Suemoto CK, Apolinario D, Nakamura-Palacios EM, Lopes L, Leite REP, Sales MC, et al. Effects of a non-focal plasticity protocol on apathy in moderate Alzheimer’s disease: a randomized, double-blind, sham-controlled trial. Brain Stimulat. 2014;7(2):308–13.CrossRef Suemoto CK, Apolinario D, Nakamura-Palacios EM, Lopes L, Leite REP, Sales MC, et al. Effects of a non-focal plasticity protocol on apathy in moderate Alzheimer’s disease: a randomized, double-blind, sham-controlled trial. Brain Stimulat. 2014;7(2):308–13.CrossRef
28.
go back to reference Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346, e7586.CrossRefPubMedPubMedCentral Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346, e7586.CrossRefPubMedPubMedCentral
29.
go back to reference McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939–44.CrossRefPubMed McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939–44.CrossRefPubMed
30.
go back to reference Teng E, Ringman JM, Ross LK, Mulnard RA, Dick MB, Bartzokis G, et al. Diagnosing depression in Alzheimer disease with the national institute of mental health provisional criteria. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2008;16(6):469–77.CrossRef Teng E, Ringman JM, Ross LK, Mulnard RA, Dick MB, Bartzokis G, et al. Diagnosing depression in Alzheimer disease with the national institute of mental health provisional criteria. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2008;16(6):469–77.CrossRef
31.
go back to reference Tombaugh TN, McIntyre NJ. The Mini-Mental State Examination: a comprehensive review. J Am Geriatr Soc. 1992;40(9):922–35.CrossRefPubMed Tombaugh TN, McIntyre NJ. The Mini-Mental State Examination: a comprehensive review. J Am Geriatr Soc. 1992;40(9):922–35.CrossRefPubMed
32.
go back to reference Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43(11):2412–4.CrossRefPubMed Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43(11):2412–4.CrossRefPubMed
33.
go back to reference Kørner A, Lauritzen L, Abelskov K, Gulmann N, Marie Brodersen A, Wedervang-Jensen T, et al. The Geriatric Depression Scale and the Cornell Scale for Depression in Dementia. A validity study. Nord J Psychiatry. 2006;60(5):360–4.CrossRefPubMed Kørner A, Lauritzen L, Abelskov K, Gulmann N, Marie Brodersen A, Wedervang-Jensen T, et al. The Geriatric Depression Scale and the Cornell Scale for Depression in Dementia. A validity study. Nord J Psychiatry. 2006;60(5):360–4.CrossRefPubMed
34.
go back to reference Brunoni AR, Schestatsky P, Lotufo PA, Benseñor IM, Fregni F. Comparison of blinding effectiveness between sham tDCS and placebo sertraline in a 6-week major depression randomized clinical trial. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 2014;125(2):298–305.CrossRef Brunoni AR, Schestatsky P, Lotufo PA, Benseñor IM, Fregni F. Comparison of blinding effectiveness between sham tDCS and placebo sertraline in a 6-week major depression randomized clinical trial. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 2014;125(2):298–305.CrossRef
35.
go back to reference Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48(5 Suppl 6):S10–16.CrossRefPubMed Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48(5 Suppl 6):S10–16.CrossRefPubMed
36.
go back to reference Pedersen KF, Alves G, Larsen JP, Tysnes O-B, Møller SG, Brønnick K. Psychometric properties of the Starkstein Apathy Scale in patients with early untreated Parkinson disease. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2012;20(2):142–8.CrossRef Pedersen KF, Alves G, Larsen JP, Tysnes O-B, Møller SG, Brønnick K. Psychometric properties of the Starkstein Apathy Scale in patients with early untreated Parkinson disease. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2012;20(2):142–8.CrossRef
37.
go back to reference Wolak-Thierry A, Novella J-L, Barbe C, Morrone I, Mahmoudi R, Jolly D. Comparison of QoL-AD and DQoL in elderly with Alzheimer’s disease. Aging Ment Health. 2015;19(3):274–8.CrossRefPubMed Wolak-Thierry A, Novella J-L, Barbe C, Morrone I, Mahmoudi R, Jolly D. Comparison of QoL-AD and DQoL in elderly with Alzheimer’s disease. Aging Ment Health. 2015;19(3):274–8.CrossRefPubMed
38.
go back to reference Bédard M, Molloy DW, Squire L, Dubois S, Lever JA, O’Donnell M. The Zarit Burden Interview: a new short version and screening version. Gerontologist. 2001;41(5):652–7.CrossRefPubMed Bédard M, Molloy DW, Squire L, Dubois S, Lever JA, O’Donnell M. The Zarit Burden Interview: a new short version and screening version. Gerontologist. 2001;41(5):652–7.CrossRefPubMed
39.
go back to reference Niina R, Honma A, Sugai Y. Reliability, validity, and utility of Japanese version of the SIB and the modified ADCS-ADL. Rounen Seishin Igaku. 2005-6;16(6);683-91. Japanese. Niina R, Honma A, Sugai Y. Reliability, validity, and utility of Japanese version of the SIB and the modified ADCS-ADL. Rounen Seishin Igaku. 2005-6;16(6);683-91. Japanese.
41.
go back to reference Brunoni AR, Amadera J, Berbel B, Volz MS, Rizzerio BG, Fregni F. A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int J Neuropsychopharmacol. 2011;14(8):1133–45.CrossRefPubMed Brunoni AR, Amadera J, Berbel B, Volz MS, Rizzerio BG, Fregni F. A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int J Neuropsychopharmacol. 2011;14(8):1133–45.CrossRefPubMed
Metadata
Title
Transcranial direct current stimulation for depression in Alzheimer’s disease: study protocol for a randomized controlled trial
Authors
Zui Narita
Yuma Yokoi
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Trials / Issue 1/2017
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-017-2019-z

Other articles of this Issue 1/2017

Trials 1/2017 Go to the issue