Current Journal of Neurology

The effects of dual-site transcranial direct current stimulation and computerized cognitive rehabilitation on mild-to-moderate post-stroke cognitive impairment in middle-aged patients: A randomized controlled trial

Articles in Press

Document Type : Original Article

Authors

Marjan Erfani 1
Hanieh Salehi-Pourmehr 2
Elyar Sadeghi-Hokmabadi 1
Leila Mehdizadeh Fanid 3
Mehdi Farhoudi 1
Saeed Sadigh-Eteghad 1

1 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Research Center for Evidence-Based Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Cognitive Neuroscience, Faculty of Educational Science and Psychology, University of Tabriz, Tabriz Iran

Abstract
Background: Post-stroke cognitive impairment (PSCI) is common after ischemic stroke and may impede recovery. We evaluated the short-term cognitive effects of dual-site transcranial direct current stimulation (tDCS), computerized cognitive rehabilitation (RehaCom), and their combined application in patients with subacute PSCI.
Methods: In this single-center, four-arm randomized controlled trial (RCT), 60 adults aged 40–65 years with first-ever unilateral middle cerebral artery (MCA) ischemic stroke, mild PSCI, and National Institutes of Health Stroke Scale (NIHSS) scores of 1–15 were randomized equally to control, real tDCS alone, sham tDCS + RehaCom, or real tDCS + RehaCom. Interventions were administered three times weekly for eight weeks. The primary outcome was post-intervention Montreal Cognitive Assessment (MoCA) score. Secondary outcomes included Paired Associates Learning (PAL), Reaction Time (RTI), and Spatial Working Memory (SWM) measures from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Post-intervention outcomes were analyzed using analysis of covariance (ANCOVA) adjusted for corresponding baseline scores. Multiplicity was addressed using Holm-adjusted omnibus tests and false discovery rate (FDR)-adjusted pairwise contrasts.
Results: All randomized participants completed follow-up. Adjusted post-intervention MoCA scores differed across groups [F(3, 55) = 24.68, P < 0.001, partial η² = 0.574]. At the mean baseline MoCA score, the adjusted mean was 26.90 in the real tDCS + RehaCom group and 23.85 in the control group; the adjusted mean difference was 3.05 points [95% confidence interval (CI): 2.32–3.78, P < 0.001]. The combined-treatment group also showed favorable adjusted performance on several PAL, RTI, and SWM outcomes, with the most consistent advantages observed for SWM measures.
Conclusion: In selected adults with subacute MCA ischemic stroke and PSCI, combined real dual-site tDCS and RehaCom training was associated with greater short-term improvement in several cognitive outcomes compared to comparator groups. Larger multicenter trials incorporating functional outcomes and long-term follow-up are required.

Keywords

Ischemic Stroke
Cognitive Dysfunction
Cognitive Rehabilitation
Transcranial Direct Current Stimulation
Neurorehabilitation
Subjects
1.     Pu L, Wang L, Zhang R, Zhao T, Jiang Y, Han L. Projected Global Trends in Ischemic Stroke Incidence, Deaths and Disability-Adjusted Life Years From 2020 to 2030. Stroke 2023; 54(5): 1330-9.
2.     Mehdizadehfar E, Sadeghi Hokmabadi E, Taheraghdam A, Sadeghpour Y, Khabbaz A, Hosseinzadeh N, et al. Optimizing Acute Ischemic Stroke Care: Evaluating Emergency Stroke Code Activation and Thrombolytic Therapy in East Azerbaijan Province. Arch Neurosci 2024; 11(4): e147803.
3.     Huang YY, Chen SD, Leng XY, Kuo K, Wang ZT, Cui M, et al. Post-Stroke Cognitive Impairment: Epidemiology, Risk Factors, and Management. J Alzheimers Dis 2022; 86(3): 983-99.
4.     Rahnemayan S, Vakilipour P, Ala A, Mehdizadehfar E, Gharabaghi MA, Roumiani PH, et al. A four-year assessment of demographic information, clinical presentations, risk factors and outcomes in lacunar stroke patients. BMC Neurol 2025; 25(1): 248.
5.     Rost NS, Brodtmann A, Pase MP, van Veluw SJ, Biffi A, Duering M, et al. Post-Stroke Cognitive Impairment and Dementia. Circ Res 2022; 130(8): 1252-71.
6.     Parikh S, Parekh S, Vaghela N. Impact of stroke on quality of life and functional independence. Natl J Physiol Pharm Pharmacol 2018; 8(12): 1595-8.
7.     Merriman NA, Sexton E, McCabe G, Walsh ME, Rohde D, Gorman A, et al. Addressing cognitive impairment following stroke: systematic review and meta-analysis of non-randomised controlled studies of psychological interventions. BMJ Open 2019; 9(2): e024429.
8.     Jeffares I, Merriman NA, Doyle F, Horgan F, Hickey A. Designing stroke services for the delivery of cognitive rehabilitation: A qualitative study with stroke rehabilitation professionals. Neuropsychol Rehabil 2023; 33(1): 24-47.
9.     Winstein CJ, Stein J, Arena R, Bates B, Cherney LR, Cramer SC, et al. Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2016; 47(6): e98-e169.
10.  Beristain X, Golombievski E. Pharmacotherapy to Enhance Cognitive and Motor Recovery Following Stroke. Drugs Aging 2015; 32(10): 765-72.
11.  Li W, Liu X, Gao C, Li W, Liao X. Network meta-analysis of the efficacy of pharmacological treatments for post-stroke cognitive impairment and vascular cognitive impairment. Front Neurol 2025; 16: 1683496.
12.  Rahnemayan S, Mehdizadehfar E, Fathalizadeh A. Modulating Cognitive Function with Antihypertensive Medications: a Comprehensive Systematic Review on FMRI Studies. Clin Neuroradiol 2025; 35(2): 231-7.
13.  Ge S, Zhu Z, Wu B, McConnell ES. Technology-based cognitive training and rehabilitation Interventions for individuals with mild cognitive impairment: A systematic review. BMC Geriatr 2018; 18(1): 213.
14.  Soni AK, Kumar M, Kothari S. Efficacy of home based computerized adaptive cognitive training in patients with post stroke cognitive impairment: A randomized controlled trial. Sci Rep 2025; 15(1): 1072.
15.  Amiri S, Hassani-Abharian P, Vaseghi S, Kazemi R, Nasehi M. Effect of RehaCom cognitive rehabilitation software on working memory and processing speed in chronic ischemic stroke patients. Assist Technol 2023; 35(1): 41-7.
16.  Sarpourian F, Bahaadinbeigy K, Fatemi Aghda SA, Fatehi F, Ebrahimi S, Fallahnezhad M. Effectiveness of computer-based telerehabilitation software (RehaCom) compared to other treatments for patients with cognitive impairments: A systematic review. Digit Health 2024; 10: 20552076241290957.
17.  Veisi-Pirkoohi S, Hassani-Abharian P, Kazemi R, Vaseghi S, Zarrindast MR, Nasehi M. Efficacy of RehaCom cognitive rehabilitation software in activities of daily living, attention and response control in chronic stroke patients. J Clin Neurosci 2020; 71: 101-7.
18.  Giordano J, Bikson M, Kappenman ES, Clark VP, Coslett HB, Hamblin MR, et al. Mechanisms and Effects of Transcranial Direct Current Stimulation. Dose Response 2017; 15(1): 1559325816685467.
19.  Najibi AM, Rahnemayan S, Poursoleimani A, Heshmati R, Nazari MA, Shali EG, et al. Transcranial Direct Current Stimulation and Mindfulness for Cognitive and Mood Recovery in Stroke Survivors: A Pilot Randomized Controlled Study. Stroke Res Treat 2025; 2025: 3893469.
20.  Malerba P, Straudi S, Fregni F, Bazhenov M, Basaglia N. Using Biophysical Models to Understand the Effect of tDCS on Neurorehabilitation: Searching for Optimal Covariates to Enhance Poststroke Recovery. Front Neurol 2017; 8: 58.
21.  Qi F, Zhang N, Nitsche MA, Yi L, Zhang Y, Yue T. Effects of Dual-Site Anodal Transcranial Direct Current Stimulation on Attention, Decision-Making, and Working Memory during Sports Fatigue in Elite Soccer Athletes. J Integr Neurosci 2025; 24(1): 26401.
22.  Yue T, Liu L, Nitsche MA, Kong Z, Zhang M, Qi F. Effects of high-intensity interval training combined with dual-site transcranial direct current stimulation on inhibitory control and working memory in healthy adults. Hum Mov Sci 2024; 96: 103240.
23.  Lees R, Selvarajah J, Fenton C, Pendlebury ST, Langhorne P, Stott DJ, et al. Test accuracy of cognitive screening tests for diagnosis of dementia and multidomain cognitive impairment in stroke. Stroke 2014; 45(10): 3008-18.
24.  Roebuck-Spencer TM, Glen T, Puente AE, Denney RL, Ruff RM, Hostetter G, et al. Cognitive Screening Tests Versus Comprehensive Neuropsychological Test Batteries: A National Academy of Neuropsychology Education Paper†. Arch Clin Neuropsychol 2017; 32(4): 491-8.
25.  Langley C, Sahakian B, Robbins T. Cambridge Neuropsychological Test Automated Battery (CANTAB). In: Boyle GJ, Stern Y, Stein D, Sahakian B, Golden C, Lee T, et al., editors. The SAGE Handbook of Clinical Neuropsychology: Clinical Neuropsychological Assessment and Diagnosis California, CA: SAGE Publications Ltd; 2023. p. 435-68.
26.  Hobson J. The Montreal Cognitive Assessment (MoCA). Occup Med (Lond) 2015; 65(9): 764-5.
27.  Mahoney FI, Barthel DW. Functional Evaluation: The Barthel Index. Md State Med J 1965; 14: 61-5.
28.  Williams N. PHQ-9. Occup Med (Lond) 2014; 64(2): 139-40.
29.  Saber H, Saver JL. Distributional Validity and Prognostic Power of the National Institutes of Health Stroke Scale in US Administrative Claims Data. JAMA Neurol 2020; 77(5): 606-12.
30.  Roberts PS, Krishnan S, Burns SP, Ouellette D, Pappadis MR. Inconsistent Classification of Mild Stroke and Implications on Health Services Delivery. Arch Phys Med Rehabil 2020; 101(7): 1243-59.
31.  Shi D, Chen X, Li Z. Diagnostic test accuracy of the Montreal Cognitive Assessment in the detection of post-stroke cognitive impairment under different stages and cutoffs: a systematic review and meta-analysis. Neurol Sci 2018; 39(4): 705-16.
32.  Wei X, Liu Y, Li J, Zhu Y, Li W, Zhu Y, et al. MoCA and MMSE for the detection of post-stroke cognitive impairment: a comparative diagnostic test accuracy systematic review and meta‑analysis. J Neurol 2025; 272(6): 407.
33.  Shaker HA, Sawan SAE, Fahmy EM, Ismail RS, Elrahman S. Effect of transcranial direct current stimulation on cognitive function in stroke patients. Egypt J Neurol Psychiatr Neurosurg 2018; 54(1): 32.
34.  Lee SY, Cheon HJ, Yoon KJ, Chang WH, Kim YH. Effects of dual transcranial direct current stimulation for aphasia in chronic stroke patients. Ann Rehabil Med 2013; 37(5): 603-10.
35.  Pisano F, Caltagirone C, Incoccia C, Marangolo P. DUAL-tDCS Treatment over the Temporo-Parietal Cortex Enhances Writing Skills: First Evidence from Chronic Post-Stroke Aphasia. Life (Basel) 2021; 11(4): 343.
36.  Sunwoo H, Kim YH, Chang WH, Noh S, Kim EJ, Ko MH. Effects of dual transcranial direct current stimulation on post-stroke unilateral visuospatial neglect. Neurosci Lett 2013; 554: 94-8.
37.  Park HK, Song MK, Kim JH, Han JY. A randomized controlled trial to evaluate the effectiveness and safety of electro acupuncture and transcranial direct current stimulation with computerized cognitive rehabilitation in patients with vascular cognitive impairment. Medicine (Baltimore) 2020; 99(29): e21263.
38.  Park SH, Koh EJ, Choi HY, Ko MH. A double-blind, sham-controlled, pilot study to assess the effects of the concomitant use of transcranial direct current stimulation with the computer assisted cognitive rehabilitation to the prefrontal cortex on cognitive functions in patients with stroke. J Korean Neurosurg Soc 2013; 54(6): 484-8.
39.  Kazuta T, Takeda K, Osu R, Tanaka S, Oishi A, Kondo K, et al. Transcranial Direct Current Stimulation Improves Audioverbal Memory in Stroke Patients. Am J Phys Med Rehabil 2017; 96(8): 565-71.
40.  Manenti R, Petesi M, Brambilla M, Rosini S, Miozzo A, Padovani A, et al. Efficacy of semantic-phonological treatment combined with tDCS for verb retrieval in a patient with aphasia. Neurocase 2015; 21(1): 109-19.
41. Marangolo P, Fiori V, Gelfo F, Shofany J, Razzano C, Caltagirone C, et al. Bihemispheric tDCS enhances language recovery but does not alter BDNF levels in chronic aphasic patients. Restor Neurol Neurosci 2014; 32(2): 367-79.
Current Journal of Neurology

Articles in Press, Accepted Manuscript
Available Online from 10 November 2026

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