Feasibility of Cognitive Training in Combination With Transcranial Direct Current Stimulation in a Home-Based Context (TrainStim-Home): study protocol for a randomised controlled trial

Friederike Thams, Merle Rocke, Robert Malinowski, Rafal Nowak, Ulrike Grittner, Daria Antonenko, Agnes Flöel, Friederike Thams, Merle Rocke, Robert Malinowski, Rafal Nowak, Ulrike Grittner, Daria Antonenko, Agnes Flöel

Abstract

Introduction: With the worldwide increase of life expectancy leading to a higher proportion of older adults experiencing age-associated deterioration of cognitive abilities, the development of effective and widely accessible prevention and therapeutic measures has become a priority and challenge for modern medicine. Combined interventions of cognitive training and transcranial direct current stimulation (tDCS) have shown promising results for counteracting age-associated cognitive decline. However, access to clinical centres for repeated sessions is challenging, particularly in rural areas and for older adults with reduced mobility, and lack of clinical personnel and hospital space prevents extended interventions in larger cohorts. A home-based and remotely supervised application of tDCS would make the treatment more accessible for participants and relieve clinical resources. So far, studies assessing feasibility of combined interventions with a focus on cognition in a home-based setting are rare. With this study, we aim to provide evidence for the feasibility and the effects of a multisession home-based cognitive training in combination with tDCS on cognitive functions of healthy older adults.

Methods and analysis: The TrainStim-Home trial is a monocentric, randomised, double-blind, placebo-controlled study. Thirty healthy participants, aged 60-80 years, will receive 2 weeks of combined cognitive training and anodal tDCS over left dorsolateral prefrontal cortex (target intervention), compared with cognitive training plus sham stimulation. The cognitive training will comprise a letter updating task, and the participants will be stimulated for 20 min with 1.5 mA. The intervention sessions will take place at the participants' home, and primary outcome will be the feasibility, operationalised by two-thirds successfully completed sessions per participant. Additionally, performance in the training task and an untrained task will be analysed.

Ethics and dissemination: Ethical approval was granted by the ethics committee of the University Medicine Greifswald. Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.

Trial registration number: NCT04817124.

Keywords: clinical trials; neurology; preventive medicine.

Conflict of interest statement

Competing interests: RN is a part-time employee with NE. The other authors declare no actual or potential conflicts of interest.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
TrainStim-Home study flowchart. tDCS, transcranial direct current stimulation.

References

    1. United Nations . World population ageing. New York: Department of Economic and Social Affairs, Population Division, 2015.
    1. Woods AJ, Cohen RA, Pahor M. Cognitive frailty: frontiers and challenges. J Nutr Health Aging 2013;17:741–3. 10.1007/s12603-013-0398-8
    1. Yam A, Marsiske M. Cognitive longitudinal predictors of older adults' self-reported IADL function. J Aging Health 2013;25:163S–85. 10.1177/0898264313495560
    1. Mameli F, Fumagalli M, Ferrucci R. Transcranial direct current stimulation and cognition in the elderly A2 - kadosh, roi cohen the stimulated brain. san diego. Academic Press 2014;Chapter 13:371–95. 10.1136/jnnp-2012-302825
    1. Passow S, Thurm F, Li S-C. Activating developmental reserve capacity via cognitive training or non-invasive brain stimulation: potentials for promoting fronto-parietal and Hippocampal-Striatal network functions in old age. Front Aging Neurosci 2017;9:33. 10.3389/fnagi.2017.00033
    1. Flöel A. tDCS-enhanced motor and cognitive function in neurological diseases. Neuroimage 2014;85 Pt 3:934–47. 10.1016/j.neuroimage.2013.05.098
    1. Perceval G, Flöel A, Meinzer M. Can transcranial direct current stimulation counteract age-associated functional impairment? Neurosci Biobehav Rev 2016;65:157–72. 10.1016/j.neubiorev.2016.03.028
    1. Ruf SP, Fallgatter AJ, Plewnia C. Augmentation of working memory training by transcranial direct current stimulation (tDCS). Sci Rep 2017;7:876 p. 10.1038/s41598-017-01055-1
    1. Au J, Katz B, Buschkuehl M, et al. . Enhancing working memory training with transcranial direct current stimulation. J Cogn Neurosci 2016;28:1419–32. 10.1162/jocn_a_00979
    1. Nissim NR, O'Shea A, Indahlastari A, et al. . Effects of transcranial direct current stimulation paired with cognitive training on functional connectivity of the working memory network in older adults. Front Aging Neurosci 2019;11:340. 10.3389/fnagi.2019.00340
    1. Park S-H, Seo J-H, Kim Y-H, et al. . Long-term effects of transcranial direct current stimulation combined with computer-assisted cognitive training in healthy older adults. Neuroreport 2014;25:122–6. 10.1097/WNR.0000000000000080
    1. Jones KT, Stephens JA, Alam M, et al. . Longitudinal neurostimulation in older adults improves working memory. PLoS One 2015;10:e0121904. 10.1371/journal.pone.0121904
    1. Reuter-Lorenz PA, Festini SB, Jantz TK. Executive functions and neurocognitive aging. Handbook of the psychology of aging. Elsevier 2016.:p 245–62.
    1. Andrews-Hanna JR, Snyder AZ, Vincent JL, et al. . Disruption of large-scale brain systems in advanced aging. Neuron 2007;56:924–35. 10.1016/j.neuron.2007.10.038
    1. Geerligs L, Renken RJ, Saliasi E, et al. . A brain-wide study of age-related changes in functional connectivity. Cereb Cortex 2015;25:1987–99. 10.1093/cercor/bhu012
    1. Grady C, Sarraf S, Saverino C, et al. . Age differences in the functional interactions among the default, frontoparietal control, and dorsal attention networks. Neurobiol Aging 2016;41:159–72. 10.1016/j.neurobiolaging.2016.02.020
    1. Martin DM, Liu R, Alonzo A, et al. . Can transcranial direct current stimulation enhance outcomes from cognitive training? A randomized controlled trial in healthy participants. Int J Neuropsychopharmacol 2013;16:1927–36. 10.1017/S1461145713000539
    1. Monte-Silva K, Kuo M-F, Hessenthaler S, et al. . Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation. Brain Stimul 2013;6:424–32. 10.1016/j.brs.2012.04.011
    1. Fritsch B, Reis J, Martinowich K, et al. . Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron 2010;66:198–204. 10.1016/j.neuron.2010.03.035
    1. Liebetanz D, Nitsche MA, Tergau F, et al. . Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. Brain 2002;125:2238–47. 10.1093/brain/awf238
    1. Nitsche MA, Fricke K, Henschke U, et al. . Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J Physiol 2003;553:293–301. 10.1113/jphysiol.2003.049916
    1. Palm U, Kumpf U, Behler N, et al. . Home use, remotely supervised, and remotely controlled transcranial direct current stimulation: a systematic review of the available evidence. Neuromodulation 2018;21:323–33. 10.1111/ner.12686
    1. André S, Heinrich S, Kayser F, et al. . At-home tDCS of the left dorsolateral prefrontal cortex improves visual short-term memory in mild vascular dementia. J Neurol Sci 2016;369:185–90. 10.1016/j.jns.2016.07.065
    1. Charvet L, Shaw M, Dobbs B, et al. . Remotely supervised transcranial direct current stimulation increases the benefit of at-home cognitive training in multiple sclerosis. Neuromodulation 2018;21:383–9. 10.1111/ner.12583
    1. Hagenacker T, Bude V, Naegel S, et al. . Patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviates pain in trigeminal neuralgia. J Headache Pain 2014;15:78. 10.1186/1129-2377-15-78
    1. Cha Y-H, Urbano D, Pariseau N. Randomized single blind sham controlled trial of adjunctive home-based tDCS after rTMS for mal de debarquement syndrome: safety, efficacy, and participant satisfaction assessment. Brain Stimul 2016;9:537–44. 10.1016/j.brs.2016.03.016
    1. Carvalho F, Brietzke AP, Gasparin A, et al. . Home-Based transcranial direct current stimulation device development: an updated protocol used at home in healthy subjects and fibromyalgia patients. J Vis Exp 2018;137. 10.3791/57614. [Epub ahead of print: 14 07 2018].
    1. Maceira-Elvira P, Popa T, Schmid A-C, et al. . Feasibility of home-based, self-applied transcranial direct current stimulation to enhance motor learning in middle-aged and older adults. Brain Stimul 2020;13:247–9. 10.1016/j.brs.2019.08.014
    1. Eldridge SM, Chan CL, Campbell MJ. Consort 2010 statement: extension to randomised pilot and feasibility trials. BMJ 2016;i:5239. 10.1136/bmj.i5239
    1. Bréchet L, Yu W, Biagi MC, et al. . Patient-Tailored, home-based non-invasive brain stimulation for memory deficits in dementia due to Alzheimer's disease. Front Neurol 2021;12:598135. 10.3389/fneur.2021.598135
    1. Chan A-W, Tetzlaff JM, Altman DG, et al. . Spirit 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 2013;158:200–7. 10.7326/0003-4819-158-3-201302050-00583
    1. Chan A-W, Tetzlaff JM, Gøtzsche PC, et al. . Spirit 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:e7586. 10.1136/bmj.e7586
    1. Jessen F, Amariglio RE, van Boxtel M, et al. . A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease. Alzheimers Dement 2014;10:844–52. 10.1016/j.jalz.2014.01.001
    1. Albert MS, DeKosky ST, Dickson D. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging‐Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer's & Dementia 2011;7:270–9. 10.1016/j.jalz.2011.03.008
    1. Antal A, Alekseichuk I, Bikson M, et al. . Low intensity transcranial electric stimulation: safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol 2017;128:1774–809. 10.1016/j.clinph.2017.06.001
    1. Dahlin E, Neely AS, Larsson A, et al. . Transfer of learning after updating training mediated by the striatum. Science 2008;320:1510–2. 10.1126/science.1155466
    1. Cheng Y, Wu W, Feng W, et al. . The effects of multi-domain versus single-domain cognitive training in non-demented older people: a randomized controlled trial. BMC Med 2012;10:1–13. 10.1186/1741-7015-10-30
    1. Ten Brinke LF, Davis JC, Barha CK, et al. . Effects of computerized cognitive training on neuroimaging outcomes in older adults: a systematic review. BMC Geriatr 2017;17:139. 10.1186/s12877-017-0529-x
    1. Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 1988;54:1063–70. 10.1037/0022-3514.54.6.1063
    1. Hyvärinen P, Mäkitie A, Aarnisalo AA. Self-administered domiciliary tDCS treatment for tinnitus: a double-blind sham-controlled study. PLoS One 2016;11:[e0154286 p.]. 10.1371/journal.pone.0154286
    1. Dahlin E, Nyberg L, Bäckman L, et al. . Plasticity of executive functioning in young and older adults: immediate training gains, transfer, and long-term maintenance. Psychol Aging 2008;23:720–30. 10.1037/a0014296
    1. Lezak MD, Howieson DB, et al. . Neuropsychological assessment. 5th edition ed. Oxford1161 p. New York: Oxford University Press, 2012.
    1. Morris JC, Heyman A, Mohs RC, et al. . The Consortium to establish a Registry for Alzheimer's disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 1989;39:1159–65. 10.1212/wnl.39.9.1159
    1. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 1971;9:97–113. 10.1016/0028-3932(71)90067-4
    1. Brink TL, Yesavage J, Lum O. Evidence-based diagnosis: a Handbook of clinical prediction rules. 297, 2013.
    1. Hagen NA, Biondo PD, Brasher PMA, et al. . Formal feasibility studies in palliative care: why they are important and how to conduct them. J Pain Symptom Manage 2011;42:278–89. 10.1016/j.jpainsymman.2010.11.015
    1. Rahbek MA, Mikkelsen EE, Overgaard K, et al. . Exercise in myasthenia gravis: a feasibility study of aerobic and resistance training. Muscle Nerve 2017;56:700–9. 10.1002/mus.25552
    1. Antonenko D, Külzow N, Sousa A, et al. . Neuronal and behavioral effects of multi-day brain stimulation and memory training. Neurobiol Aging 2018;61:245–54. 10.1016/j.neurobiolaging.2017.09.017
    1. Elmasry J, Loo C, Martin D. A systematic review of transcranial electrical stimulation combined with cognitive training. Restor Neurol Neurosci 2015;33:263–78. 10.3233/RNN-140473
    1. Floel A, Cohen LG. Recovery of function in humans: cortical stimulation and pharmacological treatments after stroke. Neurobiol Dis 2010;37:243–51. 10.1016/j.nbd.2009.05.027
    1. Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol 2006;117:845–50. 10.1016/j.clinph.2005.12.003
    1. Kuo H-I, Bikson M, Datta A, et al. . Comparing cortical plasticity induced by conventional and high-definition 4 × 1 ring tDCS: a neurophysiological study. Brain Stimul 2013;6:644–8. 10.1016/j.brs.2012.09.010
    1. Schlaug G, Renga V. Transcranial direct current stimulation: a noninvasive tool to facilitate stroke recovery. Expert Rev Med Devices 2008;5:759–68. 10.1586/17434440.5.6.759
    1. Lezak MD, Howieson DB, Loring DW. Neuropsychological assessment. USA: Oxford University Press, 2004.
    1. Antonenko D, Thams F, Uhrich J, et al. . Effects of a multi-session cognitive training combined with brain stimulation (TrainStim-Cog) on Age-Associated Cognitive Decline - Study Protocol for a Randomized Controlled Phase IIb (Monocenter) Trial. Front Aging Neurosci 2019;11:200. 10.3389/fnagi.2019.00200
    1. Bock BC, Thind H, Fava JL, et al. . Feasibility of yoga as a complementary therapy for patients with type 2 diabetes: the healthy active and in control (HA1C) study. Complement Ther Med 2019;42:125–31. 10.1016/j.ctim.2018.09.019

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren