Effects of brain training on brain blood flow (The Cognition and Flow Study-CogFlowS): protocol for a feasibility randomised controlled trial of cognitive training in dementia

Lucy Beishon, Rachel Evley, Ronney B Panerai, Hari Subramaniam, Elizabeta Mukaetova-Ladinska, Thompson Robinson, Victoria Haunton, Lucy Beishon, Rachel Evley, Ronney B Panerai, Hari Subramaniam, Elizabeta Mukaetova-Ladinska, Thompson Robinson, Victoria Haunton

Abstract

Introduction: Cognitive training is an emerging non-pharmacological treatment to improve cognitive and physical function in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). Abnormal brain blood flow is a key process in the development of cognitive decline. However, no studies have explored the effects of cognitive training on brain blood flow in dementia. The primary aim of this study is to assess the feasibility for a large-scale, randomised controlled trial of cognitive training in healthy older adults (HC), MCI and early AD.

Methods and analysis: This study will recruit 60 participants, in three subgroups of 20 (MCI, HC, AD), from primary, secondary and community services. Participants will be randomised to a 12-week computerised cognitive training programme (five × 30 min sessions per week), or waiting-list control. Participants will undergo baseline and follow-up assessments of: mood, cognition, quality of life and activities of daily living. Cerebral blood flow will be measured at rest and during task activation (pretraining and post-training) by bilateral transcranial Doppler ultrasonography, alongside heart rate (3-lead ECG), end-tidal CO2 (capnography) and beat-to-beat blood pressure (Finometer). Participants will be offered to join a focus group or semistructured interview to explore barriers and facilitators to cognitive training in patients with dementia. Qualitative data will be analysed using framework analysis, and data will be integrated using mixed methods matrices.

Ethics and dissemination: Bradford Leeds Research Ethics committee awarded a favourable opinion (18/YH/0396). Results of the study will be published in peer-reviewed journals, and presented at national and international conferences on ageing and dementia.

Trials registration number: NCT03656107; Pre-results.

Keywords: alzheimer’s disease; cerebral haemodynamics; cognitive impairment; mild cognitive impairment; neuroimaging; transcranial doppler ultrasonography.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Flow chart of study recruitment procedures. LPT, Leicestershire Partnership Trust; MoCA, Montreal Cognitive Assessment; UHL, University Hospitals of Leicester.
Figure 2
Figure 2
Flow chart of participant procedures during the study.

References

    1. Alzheimer’s-society. Demography: Alzheimer’s Society. 2016. (updated 28 Nov 2018).
    1. Alzheimer’s Association. 2014 Alzheimer’s disease facts and figures. Alzheimers Dement 2014;10:e47–e92. 10.1016/j.jalz.2014.02.001
    1. Robinson L, Tang E, Taylor JP. Dementia: timely diagnosis and early intervention. BMJ 2015;350:h3029 10.1136/bmj.h3029
    1. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004;256:183–94. 10.1111/j.1365-2796.2004.01388.x
    1. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 2011;12:723–38. 10.1038/nrn3114
    1. Beishon L, Haunton VJ, Panerai RB, et al. . Cerebral Hemodynamics in Mild Cognitive Impairment: A Systematic Review. J Alzheimers Dis 2017;59:369–85. 10.3233/JAD-170181
    1. Belleville S. Cognitive training for persons with mild cognitive impairment. Int Psychogeriatr 2008;20:57–66. 10.1017/S104161020700631X
    1. Martin M, Clare L, Altgassen AM, et al. . Cognition-based interventions for healthy older people and people with mild cognitive impairment. Cochrane Database Syst Rev 2011;1:Cd006220 10.1002/14651858.CD006220.pub2
    1. Bahar-Fuchs A, Clare L, Woods B. Cognitive training and cognitive rehabilitation for persons with mild to moderate dementia of the Alzheimer’s or vascular type: a review. Alzheimers Res Ther 2013;5:35 10.1186/alzrt189
    1. Woods B, Aguirre E, Spector AE, et al. . Cognitive stimulation to improve cognitive functioning in people with dementia. Cochrane Database Syst Rev 2012;2:Cd005562 10.1002/14651858.CD005562.pub2
    1. Gates NJ, Sachdev P. Is cognitive training an effective treatment for preclinical and early Alzheimer’s disease? J Alzheimers Dis 2014;42(Suppl 4):S551–9. 10.3233/JAD-141302
    1. Hill NT, Mowszowski L, Naismith SL, et al. . Computerized Cognitive Training in Older Adults With Mild Cognitive Impairment or Dementia: A Systematic Review and Meta-Analysis. Am J Psychiatry 2017;174:329–40. 10.1176/appi.ajp.2016.16030360
    1. Gates NJ, Sachdev PS, Fiatarone Singh MA, et al. . Cognitive and memory training in adults at risk of dementia: a systematic review. BMC Geriatr 2011;11:55 10.1186/1471-2318-11-55
    1. Li H, Li J, Li N, et al. . Cognitive intervention for persons with mild cognitive impairment: A meta-analysis. Ageing Res Rev 2011;10:285–96. 10.1016/j.arr.2010.11.003
    1. Huntley JD, Gould RL, Liu K, et al. . Do cognitive interventions improve general cognition in dementia? A meta-analysis and meta-regression. BMJ Open 2015;5:e005247 10.1136/bmjopen-2014-005247
    1. Reijnders J, van Heugten C, van Boxtel M. Cognitive interventions in healthy older adults and people with mild cognitive impairment: a systematic review. Ageing Res Rev 2013;12:263–75. 10.1016/j.arr.2012.07.003
    1. Coyle H, Traynor V, Solowij N. Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: systematic review of the literature. Am J Geriatr Psychiatry 2015;23:335–59. 10.1016/j.jagp.2014.04.009
    1. Panerai RB. Transcranial Doppler for evaluation of cerebral autoregulation. Clin Auton Res 2009;19:197–211. 10.1007/s10286-009-0011-8
    1. Stroobant N, Vingerhoets G. Transcranial Doppler ultrasonography monitoring of cerebral hemodynamics during performance of cognitive tasks: a review. Neuropsychol Rev 2000;10:213–31. 10.1023/A:1026412811036
    1. van Beek AH, Claassen JA, Rikkert MG, et al. . Cerebral autoregulation: an overview of current concepts and methodology with special focus on the elderly. J Cereb Blood Flow Metab 2008;28:1071–85. 10.1038/jcbfm.2008.13
    1. Tomek A, Urbanová B, Hort J. Utility of transcranial ultrasound in predicting Alzheimer’s disease risk. J Alzheimers Dis 2014;42:S365–74. 10.3233/JAD-141803
    1. Vemuri P, Fields J, Peter J, et al. . Cognitive interventions in Alzheimer’s and Parkinson’s diseases: emerging mechanisms and role of imaging. Curr Opin Neurol 2016;29:405–11. 10.1097/WCO.0000000000000346
    1. Belleville S, Clément F, Mellah S, et al. . Training-related brain plasticity in subjects at risk of developing Alzheimer’s disease. Brain 2011;134(Pt 6):1623–34. 10.1093/brain/awr037
    1. Vermeij A, Claassen JA, Dautzenberg PL, et al. . Transfer and maintenance effects of online working-memory training in normal ageing and mild cognitive impairment. Neuropsychol Rehabil 2016;26(5-6):783–809. 10.1080/09602011.2015.1048694
    1. Belleville S, Bherer L. Biomarkers of Cognitive Training Effects in Aging. Curr Transl Geriatr Exp Gerontol Rep 2012;1:104–10. 10.1007/s13670-012-0014-5
    1. Vermeij A, Kessels RPC, Heskamp L, et al. . Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment. Brain Imaging Behav 2017;11:1–14. 10.1007/s11682-016-9508-7
    1. Engvig A, Fjell AM, Westlye LT, et al. . Effects of memory training on cortical thickness in the elderly. Neuroimage 2010;52:1667–76. 10.1016/j.neuroimage.2010.05.041
    1. Yang H, Leaver AM, Siddarth P, et al. . Neurochemical and Neuroanatomical Plasticity Following Memory Training and Yoga Interventions in Older Adults with Mild Cognitive Impairment. Front Aging Neurosci 2016:8.
    1. Ciarmiello A, Gaeta MC, Benso F, et al. . FDG-PET in the Evaluation of Brain Metabolic Changes Induced by Cognitive Stimulation in aMCI Subjects. Curr Radiopharm 2015;8:69–75. 10.2174/1874471008666150428122924
    1. Förster S, Buschert VC, Teipel SJ, et al. . Effects of a 6-month cognitive intervention on brain metabolism in patients with amnestic MCI and mild Alzheimer’s disease. J Alzheimers Dis 2011;26(Suppl 3):337–48. 10.3233/JAD-2011-0025
    1. Chan AW, 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. Sim J, Lewis M. The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency. J Clin Epidemiol 2012;65:301–8. 10.1016/j.jclinepi.2011.07.011
    1. Julious SA. Sample sizes for clinical trials with normal data. Stat Med 2004;23:1921–86. 10.1002/sim.1783
    1. Albert MS, DeKosky ST, Dickson D, et al. . 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. Alzheimers Dement 2011;7:270–9. 10.1016/j.jalz.2011.03.008
    1. Saczynski JS, Inouye SK, Guess J, et al. . The Montreal Cognitive Assessment: Creating a Crosswalk with the Mini-Mental State Examination. J Am Geriatr Soc 2015;63:2370–4. 10.1111/jgs.13710
    1. Borland E, Nägga K, Nilsson PM, et al. . The Montreal Cognitive Assessment: Normative Data from a Large Swedish Population-Based Cohort. J Alzheimers Dis 2017;59:893–901. 10.3233/JAD-170203
    1. Tan JP, Li N, Gao J, et al. . Optimal cutoff scores for dementia and mild cognitive impairment of the Montreal Cognitive Assessment among elderly and oldest-old Chinese population. J Alzheimers Dis 2015;43:1403–12. 10.3233/JAD-141278
    1. Kesler S, Hadi Hosseini SM, Heckler C, et al. . Cognitive training for improving executive function in chemotherapy-treated breast cancer survivors. Clin Breast Cancer 2013;13:299–306. 10.1016/j.clbc.2013.02.004
    1. Finn M, McDonald S. A single case study of computerised cognitive training for older persons with mild cognitive impairment. NeuroRehabilitation 2014;35:261–70. 10.3233/NRE-141121
    1. 6 Ballesteros S, Prieto A, Mayas J, et al. . Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial. Front Aging Neurosci 2014;6 10.3389/fnagi.2014.00277
    1. Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Med 2014;11:e1001756 10.1371/journal.pmed.1001756
    1. Beishon L, Williams CAL, Panerai RB, et al. . Reproducibility of task activation using the Addenbrooke’s cognitive examination in healthy controls: A functional Transcranial Doppler ultrasonography study. J Neurosci Methods 2017;291:131–40. 10.1016/j.jneumeth.2017.08.019
    1. Beishon LC, Williams CAL, Panerai RB, et al. . The assessment of neurovascular coupling with the Addenbrooke’s Cognitive Examination: a functional transcranial Doppler ultrasonographic study. J Neurophysiol 2018;119:1084–94. 10.1152/jn.00698.2017
    1. Beishon LC, Panerai RB, Robinson TG, et al. . The assessment of cerebrovascular response to a language task from the addenbrooke’s cognitive examination in cognitive impairment: a feasibility functional transcranial doppler ultrasonography study. J Alzheimers Dis Rep 2018;2:153–64. 10.3233/ADR-180068
    1. Jones CL, Jensen JD, Scherr CL, et al. . The Health Belief Model as an explanatory framework in communication research: exploring parallel, serial, and moderated mediation. Health Commun 2015;30:566–76. 10.1080/10410236.2013.873363
    1. Hansen EC. Successful qualitative health research: a practical introduction. Maidenhead: Open University Press, 2006.
    1. O’Cathain A, Murphy E, Nicholl J. Three techniques for integrating data in mixed methods studies. BMJ 2010;341:c4587 10.1136/bmj.c4587
    1. Vijayananthan A, Nawawi O. The importance of good clinical practice guidelines and its role in clinical trials. Biomed Imaging Interv J 2008;4 10.2349/biij.4.1.e5

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