The Effect of Transcranial Alternating Current Stimulation With Cognitive Training on Executive Brain Function in Individuals With Dementia: Protocol for a Crossover Randomized Controlled Trial

Natasha Jacobson, Brian Lithgow, Mohammad Jafari Jozani, Zahra Moussavi, Natasha Jacobson, Brian Lithgow, Mohammad Jafari Jozani, Zahra Moussavi

Abstract

Background: Although memory and cognitive declines are associated with normal brain aging, they may also be precursors to dementia.

Objective: We aim to offer a novel approach to prevent or slow the progress of neurodegenerative dementia, or plausibly, improve the cognitive functions of individuals with dementia.

Methods: We will recruit and enroll 75 participants (older than 50 years old with either mild cognitive impairment or probable early or moderate dementia) for this double-blind randomized controlled study to estimate the efficacy of active transcranial alternating current stimulation with cognitive treatment (in comparison with sham transcranial alternating current stimulation). This will be a crossover study; a cycle consists of sham or active treatment for a period of 4 weeks (5 days per week, in two 30-minute sessions with a half-hour break in between), and participants are randomized into 2 groups, with stratification by age, sex, and cognitive level (measured with the Montreal Cognitive Assessment). Outcomes will be assessed before and after each treatment cycle. The primary outcomes are changes in Wechsler Memory Scale Older Adult Battery and Alzheimer Disease Assessment Scale scores. Secondary outcomes are changes in performance on tests of frontal lobe functioning (verbal fluency), neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire), mood changes (Montgomery-Åsberg Depression Rating Scale), and short-term recall (visual 1-back task). Exploratory outcome measures will also be assessed: static and dynamic vestibular response using electrovestibulography, neuronal changes using functional near-infrared spectroscopy, and change in spatial orientation using virtual reality navigation.

Results: As of February 10, 2022, the study is ongoing: 7 patients have been screened, and all were deemed eligible for and enrolled in the study; 4 participants have completed baseline assessments.

Conclusions: We anticipate that transcranial alternating current stimulation will be a well-tolerated treatment, with no serious side effects and with considerable short- and long-term cognitive improvements.

Trial registration: Clinicaltrials.gov NCT05203523; https://ichgcp.net/clinical-trials-registry/NCT05203523.

International registered report identifier (irrid): DERR1-10.2196/37282.

Keywords: Alzheimer disease; cognitive; cognitive impairment; crossover; dementia; double blind; placebo-controlled; randomized; transcranial alternating current stimulation; treatment.

Conflict of interest statement

Conflicts of Interest: ZM holds the copyright of the MindTriggers app, which is one of the tools used in this study; however, none of the participants are required to purchase the app because practice is conducted onsite where the app is provided for them.

©Natasha Jacobson, Brian Lithgow, Mohammad Jafari Jozani, Zahra Moussavi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 27.04.2022.

Figures

Figure 1
Figure 1
Study flowchart for groups 1 to 3.

References

    1. Smith G, Housen P, Yaffe K, Ruff R, Kennison R, Mahncke H, Zelinski E. A cognitive training program based on principles of brain plasticity: results from the Improvement in Memory with Plasticity-based Adaptive Cognitive Training (IMPACT) study. J Am Geriatr Soc. 2009 Sep;57(4):594–603. doi: 10.1111/j.1532-5415.2008.02167.x. JGS2167
    1. Boudreaux E. Individual differences and memory aging concerns of older adults. Louisiana State University Digital Commons. 2010. [2022-04-19].
    1. Didic M, Barbeau EJ, Felician O, Tramoni E, Guedj E, Poncet M, Ceccaldi M. Which memory system is impaired first in Alzheimer's disease? J Alzheimers Dis. 2011;27(1):11–22. doi: 10.3233/JAD-2011-110557.L54524M45221N4V5
    1. Stern Y. Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurol. 2012 Nov;11(11):1006–12. doi: 10.1016/S1474-4422(12)70191-6. S1474-4422(12)70191-6
    1. Baltes P, Baltes M. Psychological perspectives on successful aging: the model of selective optimization with compensation. In: Baltes P, Baltes M, editors. Successful Aging: Perspectives From the Behavioral Sciences. Cambridge: Cambridge University Press; 1990. pp. 1–34.
    1. Reuter-Lorenz P, Jonides J, Smith E, Hartley A, Miller A, Marshuetz C, Koeppe R. Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET. J Cogn Neurosci. 2000 Jan;12(1):174–87. doi: 10.1162/089892900561814.
    1. Cabeza R, Anderson ND, Locantore JK, McIntosh AR. Aging gracefully: compensatory brain activity in high-performing older adults. Neuroimage. 2002 Nov;17(3):1394–402. doi: 10.1006/nimg.2002.1280.S1053811902912802
    1. Willis SL, Tennstedt SL, Marsiske M, Ball K, Elias J, Koepke KM, Morris JN, Rebok GW, Unverzagt FW, Stoddard AM, Wright E, ACTIVE Study Group FT. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA. 2006 Dec 20;296(23):2805–14. doi: 10.1001/jama.296.23.2805. 296/23/2805
    1. Garcia-Campuzano Mari Tere, Virues-Ortega Javier, Smith S, Moussavi Z. Effect of cognitive training targeting associative memory in the elderly: a small randomized trial and a longitudinal evaluation. J Am Geriatr Soc. 2013 Dec 12;61(12):2252–2254. doi: 10.1111/jgs.12574.
    1. Park D, Bischof G. The aging mind: neuroplasticity in response to cognitive training. Dialogues Clin Neurosci. 2013 Mar;15(1):109–19.
    1. Stojanoski B, Lyons KM, Pearce AA, Owen AM. Targeted training: converging evidence against the transferable benefits of online brain training on cognitive function. Neuropsychologia. 2018 Aug;117:541–550. doi: 10.1016/j.neuropsychologia.2018.07.013.S0028-3932(18)30321-X
    1. Garcia-Campuzano M. Investigating the effect of associative memory exercises in aging populations. University of Manitoba Librairies. 2013. [2022-04-19]. .
    1. Kehler L, Francisco C, Uehara M, Moussavi Z. The effect of transcranial alternating current stimulation (tACS) on cognitive function in older adults with dementia. Annual International Conference IEEE Engineering Medical Biology Society; July 20-24, 2020; Virtual. 2020. Jul, pp. 3649–3653.
    1. Moussavi Z, Kimura K, Kehler L, de Oliveira Francisco C, Lithgow B. A novel program to improve cognitive function in individuals with dementia using transcranial alternating current stimulation (tACS) and tutored cognitive exercises. Front Aging. 2021 Mar 12;2:1–11. doi: 10.3389/fragi.2021.632545.
    1. Antal A, Paulus W. Transcranial alternating current stimulation (tACS) Front Hum Neurosci. 2013;7:317–4. doi: 10.3389/fnhum.2013.00317. doi: 10.3389/fnhum.2013.00317.
    1. Thut G, Bergmann T, Fröhlich F, Soekadar S, Brittain J, Valero-Cabré A, Sack A, Miniussi C, Antal A, Siebner H, Ziemann U, Herrmann C. Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper. Clin Neurophysiol. 2017 May;128(5):843–857. doi: 10.1016/j.clinph.2017.01.003. S1388-2457(17)30025-1
    1. Neuling T, Rach S, Herrmann CS. Orchestrating neuronal networks: sustained after-effects of transcranial alternating current stimulation depend upon brain states. Front Hum Neurosci. 2013;7:161–12. doi: 10.3389/fnhum.2013.00161. doi: 10.3389/fnhum.2013.00161.
    1. Bland NS, Sale MV. Current challenges: the ups and downs of tACS. Exp Brain Res. 2019 Dec 16;237(12):3071–3088. doi: 10.1007/s00221-019-05666-0.10.1007/s00221-019-05666-0
    1. Kensinger EA, Shearer DK, Locascio JJ, Growdon JH, Corkin S. Working memory in mild Alzheimer's disease and early Parkinson's disease. Neuropsychology. 2003 Apr;17(2):230–9. doi: 10.1037/0894-4105.17.2.230.
    1. Nasreddine Ziad S, Phillips Natalie A, Bédirian Valérie, Charbonneau Simon, Whitehead Victor, Collin Isabelle, Cummings Jeffrey L, Chertkow Howard. The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695–9. doi: 10.1111/j.1532-5415.2005.53221.x.JGS53221
    1. Suresh K. An overview of randomization techniques: an unbiased assessment of outcome in clinical research. J Hum Reprod Sci. 2011 Jan;4(1):8–11. doi: 10.4103/0974-1208.82352. JHRS-4-8
    1. Vidal Juan R, Chaumon Maximilien, O'Regan J Kevin, Tallon-Baudry Catherine. Visual grouping and the focusing of attention induce gamma-band oscillations at different frequencies in human magnetoencephalogram signals. J Cogn Neurosci. 2006 Nov;18(11):1850–62. doi: 10.1162/jocn.2006.18.11.1850.
    1. da Silva V, Ribeiro A, Dos Santos V, Nardi A, King A, Calomeni M. Stimulation by light and sound: therapeutics effects in humans. systematic review. Clin Pract Epidemiol Ment Health. 2015 Jun;11:150–4. doi: 10.2174/1745017901511010150. CPEMH-11-150
    1. Hoy KE, Bailey N, Arnold S, Windsor K, John J, Daskalakis ZJ, Fitzgerald PB. The effect of γ-tACS on working memory performance in healthy controls. Brain Cogn. 2015 Dec;101:51–6. doi: 10.1016/j.bandc.2015.11.002.S0278-2626(15)30034-8
    1. Hopfinger J, Parsons J, Fröhlich Flavio. Differential effects of 10-Hz and 40-Hz transcranial alternating current stimulation (tACS) on endogenous versus exogenous attention. Cogn Neurosci. 2017 Apr;8(2):102–111. doi: 10.1080/17588928.2016.1194261.
    1. Dhaynaut M, Cappon Davide, Paciorek Rachel, Macone J, Connor Ann, Guehl N, Pascual-Leone Alvaro, El Fakhri Georges, Santarnecchi Emiliano. Effect of modulating gamma oscillations using tACS. Clinial Trials. [2022-04-19]. .
    1. Cullum C, Larrabee G. WAIS-IV use in neuropsychological assessment. In: Weiss L, Saklofske D, Coalson D, Raiford S, editors. WAIS-IV Clinical Use and Interpretation. London: Elsevier; 2010. pp. 167–187.
    1. Owen AM, McMillan KM, Laird AR, Bullmore E. N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum Brain Mapp. 2005 May;25(1):46–59. doi: 10.1002/hbm.20131.
    1. Byagowi A, Mohaddes D, Moussavi Z. Design and application of a novel virtual reality navigational technology (VRNChair) J Exp Neurosci. 2014;8:7–14. doi: 10.4137/JEN.S13448. jen-8-2014-007
    1. Lithgow B. A methodology for detecting field potentials from the external ear canal: NEER and EVestG. Ann Biomed Eng. 2012 Aug;40(8):1835–50. doi: 10.1007/s10439-012-0526-3.
    1. Lithgow BJ, Garrett AL, Moussavi ZM, Gurvich C, Kulkarni J, Maller JJ, Fitzgerald PB. Major depression and electrovestibulography. World J Biol Psychiatry. 2015 Mar 27;16(5):334–50. doi: 10.3109/15622975.2015.1014410.
    1. Lithgow BJ, Moussavi Z, Gurvich C, Kulkarni J, Maller JJ, Fitzgerald PB. Bipolar disorder in the balance. Eur Arch Psychiatry Clin Neurosci. 2019 Oct;269(7):761–775. doi: 10.1007/s00406-018-0935-x.10.1007/s00406-018-0935-x
    1. Chen W, Wagner J, Heugel N, Sugar J, Lee Y, Conant L, Malloy M, Heffernan J, Quirk B, Zinos A, Beardsley S, Prost R, Whelan H. Functional near-infrared spectroscopy and its clinical application in the field of neuroscience: advances and future directions. Front Neurosci. 2020;14:724. doi: 10.3389/fnins.2020.00724. doi: 10.3389/fnins.2020.00724.
    1. Benussi Alberto, Cantoni Valentina, Cotelli Maria Sofia, Cotelli Maria, Brattini Chiara, Datta Abhishek, Thomas Chris, Santarnecchi Emiliano, Pascual-Leone Alvaro, Borroni Barbara. Exposure to gamma tACS in Alzheimer's disease: a randomized, double-blind, sham-controlled, crossover, pilot study. Brain Stimul. 2021;14(3):531–540. doi: 10.1016/j.brs.2021.03.007. S1935-861X(21)00058-9
    1. Guo Y, Logan H, Glueck D, Muller K. Selecting a sample size for studies with repeated measures. BMC Med Res Methodol. 2013 Jul 31;13:100. doi: 10.1186/1471-2288-13-100. 1471-2288-13-100
    1. Senn S. Cross-over Trials in Clinical Research. 2nd edition. West Sussex: John Wiley and Sons Ltd; 2002.
    1. Wallenstein S, Fisher AC. The analysis of the two-period repeated measurements crossover design with application to clinical trials. Biometrics. 1977 Mar;33(1):261–9. doi: 10.2307/2529321.
    1. Freeman PR. The performance of the two-stage analysis of two-treatment, two-period crossover trials. Stat Med. 1989 Dec;8(12):1421–32. doi: 10.1002/sim.4780081202.
    1. Johnson WD, Grender JM. Multivariate nonparametric analysis for the two-period crossover design with application in clinical trials. J Biopharm Stat. 1993 Mar;3(1):1–12. doi: 10.1080/10543409308835045.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel