The Efficacy of Cognitive Intervention in Mild Cognitive Impairment (MCI): a Meta-Analysis of Outcomes on Neuropsychological Measures

Dale S Sherman, Justin Mauser, Miriam Nuno, Dean Sherzai, Dale S Sherman, Justin Mauser, Miriam Nuno, Dean Sherzai

Abstract

Cognitive training in MCI may stimulate pre-existing neural reserves or recruit neural circuitry as "compensatory scaffolding" prompting neuroplastic reorganization to meet task demands (Reuter-Lorenz & Park, 2014). However, existing systematic reviews and meta-analytic studies exploring the benefits of cognitive interventions in MCI have been mixed. An updated examination regarding the efficacy of cognitive intervention in MCI is needed given improvements in adherence to MCI diagnostic criteria in subject selection, better defined interventions and strategies applied, increased use of neuropsychological measures pre- and post-intervention, as well as identification of moderator variables which may influence treatment. As such, this meta-analytic review was conducted to examine the efficacy of cognitive intervention in individuals diagnosed with mild cognitive impairment (MCI) versus MCI controls based on performance of neuropsychological outcome measures in randomized controlled trials (RCT). RCT studies published from January 1995 to June 2017 were obtained through source databases of MEDLINE-R, PubMed, Healthstar, Global Health, PSYCH-INFO, and Health and Psychological Instruments using search parameters for MCI diagnostic category (mild cognitive impairment, MCI, pre-Alzheimer's disease, early cognitive decline, early onset Alzheimer's disease, and preclinical Alzheimer's disease) and the intervention or training conducted (intervention, training, stimulation, rehabilitation, or treatment). Other inclusion and exclusion criteria included subject selection based on established MCI criteria, RCT design in an outpatient setting, MCI controls (active or passive), and outcomes based on objective neuropsychological measures. From the 1199 abstracts identified, 26 articles met inclusion criteria for the meta-analyses completed across eleven (11) countries; 92.31% of which have been published within the past 7 years. A series of meta-analyses were performed to examine the effects of cognitive intervention by cognitive domain, type of training, and intervention content (cognitive domain targeted). We found significant, moderate effects for multicomponent training (Hedges' g observed = 0.398; CI [0.164, 0.631]; Z = 3.337; p = 0.001; Q = 55.511; df = 15; p = 0.000; I 2 = 72.978%; τ 2 = 0.146) as well as multidomain-focused strategies (Hedges' g = 0.230; 95% CI [0.108, 0.352]; Z = 3.692; p < 0.001; Q = 12.713; df = 12; p = 0.390; I 2 = 5.612; τ 2 = 0.003). The effects for other interventions explored by cognitive domain, training type, or intervention content were indeterminate due to concerns for heterogeneity, bias, and small cell sizes. In addition, subgroup and meta-regression analyses were conducted with the moderators of MCI category, mode of intervention, training type, intervention content, program duration (total hours), type of control group (active or passive), post-intervention follow-up assessment period, and control for repeat administration. We found significant overall effects for intervention content with memory focused interventions appearing to be more effective than multidomain approaches. There was no evidence of an influence on outcomes for the other covariates examined. Overall, these findings suggest individuals with MCI who received multicomponent training or interventions targeting multiple domains (including lifestyle changes) were apt to display an improvement on outcome measures of cognition post-intervention. As such, multicomponent and multidomain forms of intervention may prompt recruitment of alternate neural processes as well as support primary networks to meet task demands simultaneously. In addition, interventions with memory and multidomain forms of content appear to be particularly helpful, with memory-based approaches possibly being more effective than multidomain methods. Other factors, such as program duration, appear to have less of an influence on intervention outcomes. Given this, although the creation of new primary network paths appears strained in MCI, interventions with memory-based or multidomain forms of content may facilitate partial activation of compensatory scaffolding and neuroplastic reorganization. The positive benefit of memory-based strategies may also reflect transfer effects indicative of compensatory network activation and the multiple-pathways involved in memory processes. Limitations of this review are similar to other meta-analysis in MCI, including a modest number studies, small sample sizes, multiple forms of interventions and types of training applied (some overlapping), and, while greatly improved in our view, a large diversity of instruments used to measure outcome. This is apt to have contributed to the presence of heterogeneity and publication bias precluding a more definitive determination of the outcomes observed.

Keywords: Cognitive rehabilitation; Cognitive strategies; Cognitive training; Meta-analysis; Mild cognitive impairment (MCI): Cognitive interventions; Neuropsychological outcomes; Treatment efficacy.

Conflict of interest statement

None

Figures

Fig. 1
Fig. 1
Literature review flow diagram
Fig. 2
Fig. 2
Effects of cognitive interventions on all outcome measures. Test for heterogeneity Q = 205.409, df = 25; p = 0.000; I2 = 87.829; τ2 = 0.484
Fig. 3
Fig. 3
a Meta-analysis of interventions on mental status and general cognition. HKSJ point estimate adjustment SMD = 0.218; t = 3.146; p = 0.007. Test for heterogeneity Q = 19.462; df = 15; p = 0.194; I2 = 22.928; τ2 = 0.017. b Meta-analysis of interventions on working memory/attention. HKSJ point estimate adjustment SMD = 0.627; t = 3.062; p = 0.011. Test for heterogeneity Q = 43.068; df = 11; p <  0.001; I2 = 74.459; τ2 = 0.227. c Meta-analysis of interventions on speed of information processing. HKSJ point estimate adjustment SMD = −0.441; t = −1.759; p = 0.139. Test for heterogeneity Q = 58.656; df = 5; p = 0.000; I2 = 91.476; τ2 = 0.701. d Meta-analysis of interventions on language. HKSJ point estimate adjustment SMD = 0.519; t = 3.730; p = 0.010. Test for heterogeneity Q = 13.457; df = 6; p <  0.001; I2 = 55.141; τ2 = 0.072. e Meta-analysis of interventions on memory: verbal + non-verbal combined. HKSJ point estimate adjustment SMD = 0.675; t = 3.823; p = 0.001. Test for heterogeneity Q = 90.898; df = 19; p <  0.001; I2 = 79.098; τ2 = 0.277. f Meta-analysis of interventions on memory: verbal. HKSJ point estimate adjustment SMD = 0.775; t = 2.833; p = 0.013. Test for heterogeneity Q = 95.811; df = 14; p <  0.001; I2 = 85.388; τ2 = 0.421. g Meta-analysis of interventions on memory: non-verbal. HKSJ point estimate adjustment SMD = 0.593; t = 2.705; p = 0.054. Test for heterogeneity Q = 5.082; df = 4; p = 0.279; I2 = 21.292; τ2 = 0.047. h Meta-analysis of interventions on executive functions. HKSJ point estimate adjustment SMD = 0.585; t = 1.505; p = 0.158. Test for heterogeneity Q = 126.404; df = 12; p < 0.001; I2 = 90.507; τ2 = 0.669
Fig. 3
Fig. 3
a Meta-analysis of interventions on mental status and general cognition. HKSJ point estimate adjustment SMD = 0.218; t = 3.146; p = 0.007. Test for heterogeneity Q = 19.462; df = 15; p = 0.194; I2 = 22.928; τ2 = 0.017. b Meta-analysis of interventions on working memory/attention. HKSJ point estimate adjustment SMD = 0.627; t = 3.062; p = 0.011. Test for heterogeneity Q = 43.068; df = 11; p <  0.001; I2 = 74.459; τ2 = 0.227. c Meta-analysis of interventions on speed of information processing. HKSJ point estimate adjustment SMD = −0.441; t = −1.759; p = 0.139. Test for heterogeneity Q = 58.656; df = 5; p = 0.000; I2 = 91.476; τ2 = 0.701. d Meta-analysis of interventions on language. HKSJ point estimate adjustment SMD = 0.519; t = 3.730; p = 0.010. Test for heterogeneity Q = 13.457; df = 6; p <  0.001; I2 = 55.141; τ2 = 0.072. e Meta-analysis of interventions on memory: verbal + non-verbal combined. HKSJ point estimate adjustment SMD = 0.675; t = 3.823; p = 0.001. Test for heterogeneity Q = 90.898; df = 19; p <  0.001; I2 = 79.098; τ2 = 0.277. f Meta-analysis of interventions on memory: verbal. HKSJ point estimate adjustment SMD = 0.775; t = 2.833; p = 0.013. Test for heterogeneity Q = 95.811; df = 14; p <  0.001; I2 = 85.388; τ2 = 0.421. g Meta-analysis of interventions on memory: non-verbal. HKSJ point estimate adjustment SMD = 0.593; t = 2.705; p = 0.054. Test for heterogeneity Q = 5.082; df = 4; p = 0.279; I2 = 21.292; τ2 = 0.047. h Meta-analysis of interventions on executive functions. HKSJ point estimate adjustment SMD = 0.585; t = 1.505; p = 0.158. Test for heterogeneity Q = 126.404; df = 12; p < 0.001; I2 = 90.507; τ2 = 0.669
Fig. 3
Fig. 3
a Meta-analysis of interventions on mental status and general cognition. HKSJ point estimate adjustment SMD = 0.218; t = 3.146; p = 0.007. Test for heterogeneity Q = 19.462; df = 15; p = 0.194; I2 = 22.928; τ2 = 0.017. b Meta-analysis of interventions on working memory/attention. HKSJ point estimate adjustment SMD = 0.627; t = 3.062; p = 0.011. Test for heterogeneity Q = 43.068; df = 11; p <  0.001; I2 = 74.459; τ2 = 0.227. c Meta-analysis of interventions on speed of information processing. HKSJ point estimate adjustment SMD = −0.441; t = −1.759; p = 0.139. Test for heterogeneity Q = 58.656; df = 5; p = 0.000; I2 = 91.476; τ2 = 0.701. d Meta-analysis of interventions on language. HKSJ point estimate adjustment SMD = 0.519; t = 3.730; p = 0.010. Test for heterogeneity Q = 13.457; df = 6; p <  0.001; I2 = 55.141; τ2 = 0.072. e Meta-analysis of interventions on memory: verbal + non-verbal combined. HKSJ point estimate adjustment SMD = 0.675; t = 3.823; p = 0.001. Test for heterogeneity Q = 90.898; df = 19; p <  0.001; I2 = 79.098; τ2 = 0.277. f Meta-analysis of interventions on memory: verbal. HKSJ point estimate adjustment SMD = 0.775; t = 2.833; p = 0.013. Test for heterogeneity Q = 95.811; df = 14; p <  0.001; I2 = 85.388; τ2 = 0.421. g Meta-analysis of interventions on memory: non-verbal. HKSJ point estimate adjustment SMD = 0.593; t = 2.705; p = 0.054. Test for heterogeneity Q = 5.082; df = 4; p = 0.279; I2 = 21.292; τ2 = 0.047. h Meta-analysis of interventions on executive functions. HKSJ point estimate adjustment SMD = 0.585; t = 1.505; p = 0.158. Test for heterogeneity Q = 126.404; df = 12; p < 0.001; I2 = 90.507; τ2 = 0.669
Fig. 3
Fig. 3
a Meta-analysis of interventions on mental status and general cognition. HKSJ point estimate adjustment SMD = 0.218; t = 3.146; p = 0.007. Test for heterogeneity Q = 19.462; df = 15; p = 0.194; I2 = 22.928; τ2 = 0.017. b Meta-analysis of interventions on working memory/attention. HKSJ point estimate adjustment SMD = 0.627; t = 3.062; p = 0.011. Test for heterogeneity Q = 43.068; df = 11; p <  0.001; I2 = 74.459; τ2 = 0.227. c Meta-analysis of interventions on speed of information processing. HKSJ point estimate adjustment SMD = −0.441; t = −1.759; p = 0.139. Test for heterogeneity Q = 58.656; df = 5; p = 0.000; I2 = 91.476; τ2 = 0.701. d Meta-analysis of interventions on language. HKSJ point estimate adjustment SMD = 0.519; t = 3.730; p = 0.010. Test for heterogeneity Q = 13.457; df = 6; p <  0.001; I2 = 55.141; τ2 = 0.072. e Meta-analysis of interventions on memory: verbal + non-verbal combined. HKSJ point estimate adjustment SMD = 0.675; t = 3.823; p = 0.001. Test for heterogeneity Q = 90.898; df = 19; p <  0.001; I2 = 79.098; τ2 = 0.277. f Meta-analysis of interventions on memory: verbal. HKSJ point estimate adjustment SMD = 0.775; t = 2.833; p = 0.013. Test for heterogeneity Q = 95.811; df = 14; p <  0.001; I2 = 85.388; τ2 = 0.421. g Meta-analysis of interventions on memory: non-verbal. HKSJ point estimate adjustment SMD = 0.593; t = 2.705; p = 0.054. Test for heterogeneity Q = 5.082; df = 4; p = 0.279; I2 = 21.292; τ2 = 0.047. h Meta-analysis of interventions on executive functions. HKSJ point estimate adjustment SMD = 0.585; t = 1.505; p = 0.158. Test for heterogeneity Q = 126.404; df = 12; p < 0.001; I2 = 90.507; τ2 = 0.669
Fig. 4
Fig. 4
a Meta-analysis of restorative training on cognition (all outcomes). HKSJ point estimate adjustment SMD = 0.568; t = 1.196; p = 0.271. Test for heterogeneity Q = 111.092; df = 7; p <  0.001; I2 = 93.699; τ2 = 1.886. b Meta-analysis of multicomponent training on cognition (all outcomes). HKSJ point estimate adjustment SMD = 0.404; t = 2.810; p = 0.013. Test for heterogeneity Q = 55.511; df = 15; p < 0.001; I2 = 72.978; τ2 = 0.146
Fig. 5
Fig. 5
a Meta-analysis of interventions by targeted domain: memory (verbal + non-verbal combined). HKSJ point estimate adjustment SMD = 1.099; t = 2.465; p = 0.049. Test for heterogeneity Q = 51.777; df = 6; p = 0.000; I2 = 88.412; τ2 = 1.219. b Meta-analysis of interventions by targeted domain: multidomain. HKSJ point estimate adjustment SMD = 0.232; t = 3.667; p = 0.003. Test for heterogeneity Q = 12.713; df = 12; p = 0.390; I2 = 5.612; τ2 = 0.003
Fig. 6
Fig. 6
Scatterplot of regression of Hedges’ g on training duration

References

    1. Albert MS, Dekosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, 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 of Alzheimer’s disease. Alzheimers & Dementia. 2011;7(3):270–279. doi: 10.1016/j.jalz.2011.03.008.
    1. Bahar-Fuchs, A, Clare, L., & Woods, B. (2013). Cognitive training and cognitive rehabilitation for mild to moderate Alzheimer’s disease and vascular dementia. Cochrane Database of Systematic Reviews, Issue 6. Art. No.: CD003260. 10.1002/14651858.CD003260.pub2
    1. Balietti M, Giuli C, Fattoretti P, Fabbietti P, Postacchini D, Conti F. Cognitive stimulation modulated platelet total phospholipases A2 activity in subjects with mild cognitive impairment. Journal of Alzheimer’s Disease. 2016;50(4):957–962. doi: 10.3233/JAD-150714.
    1. Ballesteros S, Kraft E, Santana S, Tziraki C. Maintaining older brain functionality: A targeted review. Neuroscience and Behavioral Reviews. 2015;55:452–477. doi: 10.1016/j.neubiorev.2015.06.008.
    1. Bamidis PD, Vivas AB, Styiadid C, Frantzidis C, Klados M, Schlee W, et al. A review of physical and cognitive interventions in aging. Neuroscience and Biobehavioral Reviews. 2014;44:206–220. doi: 10.1016/j.neubiorev.2014.03.019.
    1. Barban R, Annicchiarico R, Pantelopoulos S, Federici A, Perri R, Fadda L, et al. Protecting cognition from aging and Alzheimer’s disease: A computerized cognitive training combined with reminiscence therapy. International Journal of Geriatric Psychiatry. 2016;31(4):340–348. doi: 10.1002/gps.4328.
    1. Barban F, Mancini M, Cercignani M, Adriano F, Perri R, Annicchiarico R, et al. A pilot study on brain plasticity of functional connectivity modulated by cognitive training in mild Alzheimer’s disease and mild cognitive impairment. Brain Sciences. 2017;7(5):50. doi: 10.3390/brainsci7050050.
    1. Barnes DE, Yaffe K, Belfor N, Jagust WJ, DeCarli C, Reed BR, et al. Computer-based cognitive training for mild cognitive impairment: Results form a pilot randomized, controlled trial. Alzheimer’s Disease & Associated Disorders. 2009;23(3):205–210. doi: 10.1097/WAD.0b013e31819c6137.
    1. Belleville S. Cognitive training for persons with mild cognitive impairment. International Psychogeriatrics. 2008;20(1):57–66. doi: 10.1017/S104161020700631X.
    1. Belleville S, Clement F, Mellah S, Gilbert B, Fontaine F, Gauthier S. Training-related brain plasticity in subjects at risk of developing Alzhiemer’s disease. Brain. 2011;134(6):1623–1634. doi: 10.1093/brain/awr037.
    1. Borenstein M, Higgins JP. Meta-analysis and subgroups. Prevention Science. 2013;14(2):134–143. doi: 10.1007/s11121-013-0377-7.
    1. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to meta-analysis. West Sussex: John Wiley & Sons; 2009.
    1. Borenstein M, Higgins JPT, Hedges LV, Rothstein HR. Basics of meta-analysis: I2 is not an absolute measure of heterogeneity. Research Synthesis Methods. 2016;8(1):5–18. doi: 10.1002/jrsm.1230.
    1. Buschert VC, Friese E, Teipel SJ, Schneider P, Merensky W, Rujescu D, et al. Effects of a newly developed cognitive intervention in amnestic mild cognitive impairment and mild Alzheimer’s disease: A pilot study. Journal of Alzheimer’s Disease. 2011;25(4):679–694.
    1. Cabeza, R. (2002). Hemispheric asymmetry reduction in older adults: The HAROLD model. Psychology and Aging, 17(1), 85–100
    1. Cabeza, R., Nyberg, L., & Park, D.C. (Eds.). (2017). Cognitive neuroscience of aging: Linking cognitive and cerebral aging, Second Edition. New York: Oxford University Press.
    1. Cai Y, Abrahamson K. How exercise influences cognitive performance when mild cognitive impairment exists – A literature review. Journal of Psychosocial Medicine. 2016;54(1):25–35.
    1. Carretti B, Borella E, Fostinelli S, Zavagnin M. Benefits of training working memory in amnestic mild cognitive impairment: Specific and transfer effects. International Psychogeriatrics. 2013;25(4):617–626. doi: 10.1017/S1041610212002177.
    1. Ciarmiello A, Gaeta MC, Benso F, Del Sette M. FDG-PET in the evaluation of brain metabolic changes induced by cognitive stimulation in aMCI subjects. Current Radiopharmaceuticals. 2015;8(1):69–75. doi: 10.2174/1874471008666150428122924.
    1. Cohen, J. (1988). Statistical power analysis for the behavioral sciences, Second Edition. New York: Lawrence Earlbaum.
    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. American Journal of Geriatric Psychiatry. 2015;23(4):335–359. doi: 10.1016/j.jagp.2014.04.009.
    1. Craik FIM, Winocur G, Palmer H, Binns MA, Edwards M, Bridges K, et al. Cognitive rehabilitation in the elderly: Effects on memory. Journal of the International Neuropsychological Society. 2007;13(1):132–142. doi: 10.1017/S1355617707070166.
    1. Curlik DM, Shors TJ. Training your brain: Do mental and physical (MAP) training enhance cognition through the process of neurogenesis in the hippocampus? Neuropharmacology. 2013;64:506–514. doi: 10.1016/j.neuropharm.2012.07.027.
    1. Davey J, Turner RM, Clarke MJ, Higgins JPT. Characteristics of meta-analyses and their component studies in the Cochrane database of systematic reviews: A cross-sectional, descriptive analysis. BMC Medical Research Methodology. 2011;11(160):1–11.
    1. Davis SW, Dennis NA, Daselaar SM, Fleck MS, Cabeza R. Que PASA? The posterior-anterior shift in aging. Cerebral Cortex. 2008;18(5):1201–1209. doi: 10.1093/cercor/bhm155.
    1. De Marco M, Meneghello F, Duzzi D, Rigon J, Pilosio C, Venneri A. Cognitive stimulation of the default-mode network modulates functional connectivity in healthy aging. Brain Research Bulletin. 2016;121:26–41. doi: 10.1016/j.brainresbull.2015.12.001.
    1. Demakis GJ. Meta-analysis in neuropsychology: Basic approaches, findings and applications. The Clinical Neuropsychologist. 2006;20(1):10–26. doi: 10.1080/13854040500203282.
    1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clinical Trials. 1986;7(3):177–188. doi: 10.1016/0197-2456(86)90046-2.
    1. Durlack JA. How to select, calculate, and interpret effect sizes. Journal of Pediatric Psychology. 2009;34(9):917–928. doi: 10.1093/jpepsy/jsp004.
    1. Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56(2):455–463. doi: 10.1111/j.0006-341X.2000.00455.x.
    1. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. British Medical Journal. 1997;315(7109):629–634. doi: 10.1136/bmj.315.7109.629.
    1. Ellis KA, Bush AI, Darby D, DeFazio D, Foster J, Hudson P, et al. The Australian imaging, biomarkers and lifestyle (AIBL) study of aging: Methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer’s disease. International Psychogeriatrics. 2009;21(4):672–687. doi: 10.1017/S1041610209009405.
    1. Ellis KA, Rowe CC, Villemagne VL, Martins RN, Masters CL, Salvado O, Ames D. Addressing population aging and Alzheimer’s disease through the Australian imaging biomarkers and lifestyle study: Collaboration with the Alzheimer’s Disease Neuroimaging Initiative. Alzheimer’s & Dementia. 2010;6(3):291–296. doi: 10.1016/j.jalz.2010.03.009.
    1. Faucounau V, Wu Y-H, Boulay M, DeRotrou J, Rigaud AS. Cognitive intervention programs on patients affected by mild cognitive impairment: Promising intervention tool for MCI? The Journal of Nutrition, Health & Aging. 2010;14(1):31–35. doi: 10.1007/s12603-010-0006-0.
    1. Fiatarone Singh MA, Gates N, Saigal N, Wilson GC, Meiklejohn J, Brodaty H, et al. The study of mental and resistance training (SMART) study – Resistance training and/ or cognitive training in mild cognitive impairment: A randomized, double-blind, double-sham controlled trial. Journal of the American Medical Directors (JAMDA) 2014;15(12):873–880. doi: 10.1016/j.jamda.2014.09.010.
    1. Fillenbaum GG, van Belle G, Morris JC, Mohs RC, Mirra SS, Davis PD, et al. CERAD (consortium to establish a registry for Alzheimer’s disease): The first 20 years. Alzheimer’s & Dementia. 2008;4(2):96–109. doi: 10.1016/j.jalz.2007.08.005.
    1. Finn M, McDonald S. Computerised cognitive training for older persons with mild cognitive impairment: A pilot study using a randomized controlled trial design. Brain Impairment. 2011;12(3):187–199. doi: 10.1375/brim.12.3.187.
    1. Finn M, McDonald S. Repetition-lag training to improve recollection memory in older people with amnestic mild cognitive impairment. A randomized controlled trial. Aging, Neuropsychology, and Cognition. 2015;22(2):244–258. doi: 10.1080/13825585.2014.915918.
    1. Forster S, Buschert VC, Teipel SJ, Friese U, Bucholz HG. Effects of a 6-month cognitive intervention on brain metabolism in patients with amnestic MCI and mild Alzheimer’s disease. Journal of Alzheimer’s Disease. 2011;26:337–348.
    1. Fu, R., Gartlehner, G., Grant, M., Shamliyan, T., Sedrakyan, A., Wilt, TJ., ... Trikalinos, T.A. (2010). Conducting quantitative synthesis when comparing medical interventions: AHRQ and the effective health care program. Agency for Healthcare Research and Quality. Methods Guide for Comparative Effectiveness Reviews [posted October 2010]. Rockville, MD. Available at: .
    1. Gagnon JG, Belleville S. Training of attentional control in mild cognitive impairment with executive deficits: Results from a double-blind randomized controlled study. Neuropsychological Rehabilitation. 2012;22(6):809–835. doi: 10.1080/09602011.2012.691044.
    1. Gates N, March EG. A neuropsychologist’s guide to undertaking a systematic review for publication: Making the most of the PRISMA guidelines. Neuropsychology Review. 2016;26(2):109–120. doi: 10.1007/s11065-016-9318-0.
    1. Gates N, Valenzuela M. Cognitive exercise and its role in cognitive function in older adults. Current Psychiatry Reports. 2010;12(1):20–27. doi: 10.1007/s11920-009-0085-y.
    1. Gates NJ, Sachdev PS, Singh MAF, Valenzuela M. Cognitive and memory training in adults at risk of dementia: A systematic review. Biomedcentral Geriatrics. 2011;11(1):55. doi: 10.1186/1471-2318-11-55.
    1. Giuli C, Papa R, Lattanzio F, Postacchini D. The effects of cognitive training for elderly: Results from My Mind Project. Rejuvenation Research. 2016;19(6):485–494. doi: 10.1089/rej.2015.1791.
    1. Greenaway MC, Duncan NL, Smith GE. The memory support system for mild cognitive impairment: Randomized trial of a cognitive rehabilitation intervention. Geriatric Psychiatry. 2012;28(4):402–409. doi: 10.1002/gps.3838.
    1. Hall CB, Lipton RB, Silwinski M, Katz MJ, Derby CA, Verghese J. Cognitive activities delay onset of memory decline in persons who develop dementia. Neurology. 2009;73(5):356–361. doi: 10.1212/WNL.0b013e3181b04ae3.
    1. Hampstead BM, Stringer AY, Stilla RF, Deshpande G, Hu X, Moore AB, Sathian K. Activation of effective connectivity changes following explicit-memory training for face-name pairs in patients with mild cognitive impairment: A pilot study. Neurorehabilitation and Neural Repair. 2011;25(3):210–222. doi: 10.1177/1545968310382424.
    1. Hampstead BM, Sathian K, Phillips PA, Ameraneni A, Delaune WR, Stringer AY. Mnemonic strategy training improves memory for object location associations in both healthy elderly and patients with amnestic mild cognitive impairment – A randomized, single blinded study. Neuropsychology. 2012;26(3):385–399. doi: 10.1037/a0027545.
    1. Hampstead BM, Stringer AY, Stilla RF, Giddens M, Sathian K. Mnemonic strategy training partially restores hippocampal activity in patients with mild cognitive impairment. Hippocampus. 2012;22(8):1652–1658. doi: 10.1002/hipo.22006.
    1. Hampstead BM, Gillis MM, Stringer AY. Cognitive rehabilitation of memory of mild cognitive impairment: A methodological review and model for future research. Journal of the International Neuropsychological Society. 2014;20(02):135–151. doi: 10.1017/S1355617713001306.
    1. Han, S. D., Nguyen, C. P., Stricker, N. H., & Nation, D. A. (2017). Detectable neuropsychological differences in early preclinical Alzheimer’s disease – A meta-analysis. Neuropsychology Review. 10.1007/s11065-017-9345-5.
    1. Herholz SC, Herholz RS, Herholz K. Non-pharmacological interventions and neuroplasticity in early stage Alzheimer’s disease. Expert Reviews Neurotherapeutics. 2013;13(11):1235–1245. doi: 10.1586/14737175.2013.845086.
    1. Herrera C, Chambon C, Michel BF, Paban V, Alescio-Lautier B. Positive effects of computer-based cognitive training in adults with mild cognitive impairment. Neuropsychologia. 2012;50(8):1871–1881. doi: 10.1016/j.neuropsychologia.2012.04.012.
    1. Higgins JPT. Commentary: Heterogeneity in meta-analysis should be expected and appropriately quantified. International Journal of Epidemiology. 2008;37(5):1158–1160. doi: 10.1093/ije/dyn204.
    1. Higgins JPT, Thomson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. British Medical Journal. 2003;327(7414):557–560. doi: 10.1136/bmj.327.7414.557.
    1. Hill MTM, Mowszowski L, Naismith SL, Chadwick VL, Valenzuela M, Lampit A. Computerized cognitive training in older adults with mild cognitive impairment or dementia: A systematic review and meta-analysis. American Journal of Psychiatry. 2017;174(4):329–340. doi: 10.1176/appi.ajp.2016.16030360.
    1. Hong YJ, Jang EH, Hwang J, Roh JH, Lee JH. The efficacy of cognitive intervention programs for mild cognitive impairment. Current Alzheimer Research. 2015;12(6):527–542. doi: 10.2174/1567205012666150530201636.
    1. Hosseini, S. M. H., Kramer, J. H., & Kesler, S. R. (2014). Neural correlates of cognitive intervention in persons at risk of developing Alzheimer’s disease. Frontiers in Aging Neuroscience, 6. 10.3389/fnagi.2014.00231.
    1. Huckans M, Hutson L, Twamley E, Jak A, Kaye J, Storzbach D. Efficacy of cognitive rehabilitation therapies for mild cognitive impairment (MCI) in older adults: Working toward a theoretical model and evidence-based interventions. Neuropsychology Review. 2013;23(1):63–80. doi: 10.1007/s11065-013-9230-9.
    1. Ibanez A, Richly P, Roca M, Manes F. Methodological considerations regarding cognitive interventions in dementia. Frontiers in Aging Neuroscience. 2014;6:212. doi: 10.3389/fnagi.2014.00212.
    1. IntHout J, Ioannidis JPA, Born GF. The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method. BMC Medical Research Methodology. 2014;14(1):25. doi: 10.1186/1471-2288-14-25.
    1. Jacquemont T, Fallani FDV, Bertrand A, Epelbaum S, Routier A, Dubois B, et al. Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment. Neurobiology of Aging. 2017;55:177–189. doi: 10.1016/j.neurobiolaging.2017.03.023.
    1. Jean L, Simard M, Wiederkehr S, Bergeron ME, Turgeon Y, Hudon C, et al. Efficacy of a cognitive training program for mild cognitive impairment: Results of a randomized controlled study. Neuropsychological Rehabilitation: An International Journal. 2010;20(3):377–405. doi: 10.1080/09602010903343012.
    1. Jean L, Bergeron ME, Thivierge S, Simard M. Cognitive intervention programs for individuals with mild cognitive impairment: Systematic review of the literature. American Journal of Geriatric Psychiatry. 2010;18(4):281–296. doi: 10.1097/JGP.0b013e3181c37ce9.
    1. Jeong JH, Na HR, Choi SH, Kim J, Na DK, Seo SW, et al. Group- and home-based cognitive intervention for patients with mild cognitive impairment: A randomized controlled trial. Psychotherapy and Psychosomatics. 2016;85(4):198–207. doi: 10.1159/000442261.
    1. Kim, E.Y. & Kim, K.W. (2014). A theoretical framework for cognitive and non-cognitive interventions for older adults: Stimulation versus compensation. Aging & Mental Health, 18(3), 304–315.
    1. Kinsella GJ, Mullaly E, Rand E, Ong B, Burton C, Price S, et al. Early intervention for mild cognitive impairment: A randomized controlled trial. Journal of Neurology, Neurosurgery, and Psychiatry. 2009;80(7):730–736. doi: 10.1136/jnnp.2008.148346.
    1. Kivipelto M, Solomon A, Ahtiluoto S, Ngandu T, Lehtisalo J, Antikainen, et al. The finnish geriatric intervention study to prevent cognitive impairment and disability (FINGER): Study design and progress. Alzheimer’s & Dementia. 2013;9(6):657–665. doi: 10.1016/j.jalz.2012.09.012.
    1. Kontopantelis E, Reeves D. Meta Easy: A meta-analysis add-in for Microsoft excel. Journal of Statistical Software. 2009;30(7):1–25. doi: 10.18637/jss.v030.i07.
    1. Kontopantelis E, Reeves D. Performance of statistical methods for meta-analysis when true study effects are non-normally distributed: A simulation study. Statistical Methods in Medical Research. 2010;21(4):409–426. doi: 10.1177/0962280210392008.
    1. Kurz AF, Leucht S, Lautenschlager NT. The clinical significance of cognition-focused interventions for cognitively impaired older adults: A systematic review of controlled clinical trials. International Psychogeriatrics. 2011;23(9):1364–1375. doi: 10.1017/S1041610211001001.
    1. Lam LC, Chan WC, Leung T, Fung A, Leung EM. Would older adults with mild cognitive impairment adhere to an benefit from a structured lifestyle activity intervention to enhance cognition?: A cluster randomized controlled trial. PLoS One. 2015;10(3):e0118173. doi: 10.1371/journal.pone.0118173.
    1. Lehert P, Villaseca P, Hogervorst E, Maki PM, Henderson VW. Individually modifiable risk factors to ameliorate cognitive aging: A systematic review and meta-analysis. International Menopausal Society: Climacteric. 2015;18(5):678–689.
    1. Li H, Li J, Li N, Li B, Wang P, Zhou T. Cognitive intervention for persons with mild cognitive impairment: A meta-analysis. Ageing Research Reviews. 2011;10(2):285–296. doi: 10.1016/j.arr.2010.11.003.
    1. Li, R., Zhu, Z., Yin, S., Niu, Y., Zheung, Z., Huang, X., et al. (2014). Multimodal intervention in older adults improves resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe. Frontiers in Aging Neuroscience, 6. 10.3389/fnagi.2014.00039.
    1. Li BY, Wang Y, Tang HD, Chen SD. The role of cognitive activity in cognition protection: From bedside to bench. Translational Neurodegeneration. 2017;6(1):7. doi: 10.1186/s40035-017-0078-4.
    1. Maffei L, Picano E, Andreassi MG, Angelucci A, Baldacci F, Baroncelli L, et al. Randomized trial of the effects of a combined physical/cognitive training in aged MCI subjects: The train the brain study. Scientific Reports. 2017;7:39471. doi: 10.1038/srep39471.
    1. Mahncke HW, Connor BB, Appelman J, Ahsanuddin ON, Hardy JL, Wood RA, et al. Memory enhancement in healthy older adults using a brain plasticity-based training program: A randomized, controlled study. Proceedings of the National Academy of Sciences. 2006;103(33):12523–12528. doi: 10.1073/pnas.0605194103.
    1. Martin, M., Clare, L. Altgassen, A.M., Cameron, M.H., & Zehnder, F. (2011). Cognition-based interventions for healthy people and people with mild cognitive impairment. Intervention Review. Cochrane Database of Systematic Reviews, Issue 1, Art. No. CD006220. 10.1002.14651858.CD006220.pub2.
    1. Matias-Guiu JA, Cabrera-Martin MN, Valles-Salgado M, Perez-Perez A, Rognoni T, Moreno-Ramos R, et al. Neural basis of cognitive assessment in Alzheimer disease, amnestic mild cognitive impairment, and subjective memory complaints. American Journal of Geriatric Psychiatry. 2017;25(7):730–740. doi: 10.1016/j.jagp.2017.02.002.
    1. Mitchell AJ. A meta-analysis of the accuracy of the mini-mental status examination in the detection of dementia and mild cognitive impairment. Journal of Psychiatric Research. 2009;43(4):411–431. doi: 10.1016/j.jpsychires.2008.04.014.
    1. Mitrushina M, Satz P. Effect of repeated administration of a neuropsychological battery in the elderly. Journal of Clinical Psychology. 1991;47(6):790–801. doi: 10.1002/1097-4679(199111)47:6<790::AID-JCLP2270470610>;2-C.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analysis: The PRISMA statement, the PRISMA GROUP. PLoS Medicine. 2009;6(6):e1000097. doi: 10.1371/journal.pmed.1000097.
    1. Mowszowski L, Hermens DF, Diamond K, Norrie L, Cockayne N, et al. Cognitive training enhances pre-attentive neurophysiological responses in older adults ‘at risk’ of dementia. Journal of Alzheimer’s Disease. 2014;41(4):1095–1108.
    1. NIH Quality of Assessment of Controlled Intervention Studies Scale (2017). Retreived from .
    1. Olchik MR, Farina J, Steibel N, Teixeira AR, Yassuda MS. Memory training (MT) in mild cognitive impairment (MCI) generates change in cognitive performance. Archives of Geriatrics. 2013;56:442–447. doi: 10.1016/j.archger.2012.11.007.
    1. Onur, O.A., Kukolja, J., Nolfo, N., Schlegel, M., Kaesberg, S., Kessler, J., ... Kalbe, E., (2016). Cognitive training fosters compensatory mechanisms in MCI. Alzheimer’s & Dementia, 12(7), Supplement, P420.
    1. Park, D.C. & Festini, S.B. (2017). Theories of memory and aging: A look at the past and a glimpse of the future. Journals of Gerontology: Psychological Sciences, 72(1), 82–90.
    1. Petersen RC. Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine. 2004;256(3):183–194. doi: 10.1111/j.1365-2796.2004.01388.x.
    1. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: Early detection of dementia: Mild cognitive impairment (an evidence-based review) Neurology. 2001;56(9):1133–1142. doi: 10.1212/WNL.56.9.1133.
    1. Petersen RC, Roberts RO, Knopman DS, Boeve BF, Geda YE, Ivnivk RJ, et al. Mild cognitive impairment ten years later. Neurological Review. 2009;66(12):1447–1455.
    1. Polito L, Abbondanza S, Vaccaro R, Valle E, Davin A, Degrate A, et al. Cognitive stimulation in cognitively impaired individuals and cognitively healthy individuals with a family history of dementia: Short-term results from the “Allena-Mente” randomized controlled trial. International Journal of Geriatric Psychiatry. 2015;30(6):631–638. doi: 10.1002/gps.4194.
    1. Purath J, Keck A, Fitzgerald CE. Motivational interviewing for older adults in primary care: A systematic review. Geriatric Nursing. 2014;35(3):219–224. doi: 10.1016/j.gerinurse.2014.02.002.
    1. Rapp S, Brenes G, March AP. Memory enhancement training for older adults with mild cognitive impairment: A preliminary study. Aging & Mental Health. 2002;6(1):5–11. doi: 10.1080/13607860120101077.
    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 Research Reviews. 2013;12(1):263–275. doi: 10.1016/j.arr.2012.07.003.
    1. Reuter-Lorenz, P.A. & Cappell, K.A. (2008). Neurocognitive aging and the compensation hypothesis. Current Directions in Psychological Science, 17(3), 177–182.
    1. Reuter-Lorenz, P.A. & Park, D.C. (2014). How does it STAC up? Revisiting the scaffolding theory of aging and cognition. Neuropsychology Review, 24, 355–370.
    1. Reuter-Lorenz, P.A. & Lustig, C. (2017). Working memory and executive functions in the aging brain. In R. Cabeza, L. Nyberg, D.C. Park (Eds.), Cognitive Neuroscience of Aging: Linking Cognitive and Cerebral Aging Second Edition (pp 235–258). New York: Oxford University Press.
    1. Rog LA, Fink JW. Handbook on the neuropsychology of aging and dementia. New York: Springer; 2013. Mild cognitive impairment and normal aging; pp. 239–256.
    1. Rojas GJ, Villar V, Iturry M, Harris P, Serrano CM, Herrera JA, et al. Efficacy of a cognitive intervention program in patients with mild cognitive impairment. International Psychogeriatrics. 2013;25(5):825–831. doi: 10.1017/S1041610213000045.
    1. Rosen AC, Suigiura L, Kramer JH, Whitfield-Cabrieli S, Gabrieli JD. Cognitive training changes hippocampal function in mild cognitive impairment: A pilot study. Journal of Alzheimer’s Disease. 2011;26:349–357.
    1. Rosenthal R. The ‘file drawer problem’ and tolerance for null results. Psychological Bulletin. 1979;86(3):638–641. doi: 10.1037/0033-2909.86.3.638.
    1. Rutter CM, Gatsonis CA. A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Statistics in Medicine. 2001;20(19):2865–2884. doi: 10.1002/sim.942.
    1. Salthouse TA. The processing-speed theory of adult age differences in cognition. Psychological Review. 1996;103(3):403–428. doi: 10.1037/0033-295X.103.3.403.
    1. Salthouse TA. Neuroanatomical substrates of age-related cognitive decline. Psychological Bulletin. 2011;137(5):753–784. doi: 10.1037/a0023262.
    1. Saunders NLJ, Summers MJ. Longitudinal deficits to attention, executive, and working memory in subtypes of mild cognitive impairment. Neuropsychology. 2011;25(3):237–248. doi: 10.1037/a0021134.
    1. Schaie, K.W., & Willis, S. (2010).The Seattle Longitudinal Study of adult cognitive development. ISSBD Bulletin, 57(1), 24–29.
    1. Schmiter-Edgecombe M, Dyck DG. Cognitive rehabilitation multi-family group intervention for individuals with mild cognitive impairment and their care-partners. Journal of the International Neuropsychological Society. 2014;20(09):897–908. doi: 10.1017/S1355617714000782.
    1. Sedgewick, P. (2013). Meta-analysis: Heterogeneity and subgroup analysis. British Medical Journal. 10.1136/bmj.f4040.
    1. Shatenstein B, Bargerger-Gateau P. Prevention of age-related cognitive decline: Which strategies, when, and for whom? Journal of Alzheimer’s disease. 2015;48(1):35–53. doi: 10.3233/JAD-150256.
    1. Simon SS, Yokomizo JE, Bottino CMC. Cognitive intervention in amnestic mild cognitive impairment: A systematic review. Neuroscience and Biobehavioral Reviews. 2012;36(4):1163–1178. doi: 10.1016/j.neubiorev.2012.01.007.
    1. Simons DJ, Boot WR, Charness N, Gathercole SE, Chabris CF, Hambrick DZ, Stine-Morrow EAL. Do “brain-training” programs work? Psychological Science in the Public Interest. 2016;17(3):103–186. doi: 10.1177/1529100616661983.
    1. Sitzer DI, Twamley EW, Jeste DV. Cognitive training in Alzheimer’s disease: A meta-analysis of the literature. Acta Psychiatrica Scandinavica. 2006;114(2):75–90. doi: 10.1111/j.1600-0447.2006.00789.x.
    1. Smith PJ, Blumenthal JA, Hoffman BM, Cooper H, Strauman TA, Welsh-Bohmer K, et al. Aerobic exercise and neurocognitive performance: A meta-analytic review of randomized controlled trials. Psychosomatic Medicine. 2010;72(3):239–252. doi: 10.1097/PSY.0b013e3181d14633.
    1. Stern, Y. (2012). Cognitive reserve in ageing and Alzheimer’s disease. The Lancet Neurology, 11(11), 1006–1012.
    1. Sterne JAC, Gavaghan D, Egger M. Publication and related bias in meta-analysis: Power of statistical tests and prevalence in the literature. Journal of Clinical Epidemiology. 2000;53(11):1119–1129. doi: 10.1016/S0895-4356(00)00242-0.
    1. Sterne JAC, Sutton AJ, Ioannidis JPA, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. British Medical Journal. 2011;342:d4002. doi: 10.1136/bmj.d4002.
    1. Stott J, Spector A. A review of the effectiveness of memory interventions in mild cognitive impairment (MCI) International Psychogeriatrics. 2011;23(4):526–538. doi: 10.1017/S1041610210001973.
    1. Stuss DT, Robertson IH, Craik FIM, Levine B, Alexander MP, Black S, et al. Cognitive rehabilitation in the elderly: A randomized trial to evaluate a new protocol. Journal of International Neuropsychological Society. 2007;13:120–131. doi: 10.1017/S1355617707070154.
    1. Suo C, Singh MF, Gates N, Wen W, Sachdev P, Brodaty H, et al. Therapeutically relevant structural and functional mechanisms triggered by physical exercise and cognitive exercise. Molecular Psychiatry. 2016;21(11):1633–1642. doi: 10.1038/mp.2016.19.
    1. Tardif, S. & Simard, M. (2011). Cognitive stimulation programs in healthy elderly: A review. International Journal of Alzheimer’s Disease, Article ID 378934. 10.4061/2011/378934.
    1. Thompson SG, Higgins JPT. How should meta-regression analyses be undertaken and interpreted? Statistics in Medicine. 2002;21(11):1559–1573. doi: 10.1002/sim.1187.
    1. Toepper M. Dissociating normal aging from Alzheimer’s disease: A view from cognitive neuroscience. Journal of Alzhiemer’s Disease. 2017;57(2):331–352. doi: 10.3233/JAD-161099.
    1. Tsolaki M, Kounti F, Agogiatou C, Poptsi E, Bakoglidou E, Zafeiropoulou M, et al. Effectiveness of nonpharmacological approaches in patients with mild cognitive impairment. Neurodegenerative Diseases. 2011;8(3):138–145. doi: 10.1159/000320575.
    1. Uchida S, Kawashima R. Reading and solving arithmetic problems improves cognitive functions in normal aged people: A randomized controlled study. Age. 2008;30(1):21–29. doi: 10.1007/s11357-007-9044-x.
    1. Valdes EG, O’Connor ML, Edwards JD. The effects of cognitive speed of processing training among older adults with psychometrically-defined mild cognitive impairment. Current Alzheimer’s Research. 2012;9(9):999–1009. doi: 10.2174/156720512803568984.
    1. Valentine JC, Pigott TD, Rothstein HR. How many studies do you need?: A primer on statistical power for meta-analysis. Journal of Educational and Behavioral Statistics. 2010;35(2):215–247. doi: 10.3102/1076998609346961.
    1. van Paasschen J, Clare L, Woods RT, Linden DEJ. Can we change brain functioning with cognition-focused interventions in Alzheimer’s disease? The role of functional neuroimaging. Restorative Neurology and Neuroscience. 2009;27:473–491.
    1. Verhaeghen P, Marcoen A, Goossens J. Improving memory performance in the aged through mnemonic training: A meta-analytic study. Psychology and Aging. 1992;7(2):242–251. doi: 10.1037/0882-7974.7.2.242.
    1. Vermeij A, Kessels RPC, Heskamp L, Simons EMF, Dautzenberg PLJ, Claassen JAHR. Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment. Brain Imaging and Behavior. 2017;11(1):141–154. doi: 10.1007/s11682-016-9508-7.
    1. Vidovich M, Almeida OP. Cognition-focused interventions for older adults: The state of play. Australasian Psychiatry. 2011;19(4):313–316. doi: 10.3109/10398562.2011.579973.
    1. Vidovich M, Lautenschlager NT, Flicker L, Clare L, McCaul K, Almeida OP. The PACE study: A randomized clinical trial of cognitive activity strategy training for older people with mild cognitive impairment. American Journal Geriatric Psychiatry. 2015;23(4):360–372. doi: 10.1016/j.jagp.2014.04.002.
    1. Willis SJ, Caskie GIL. Reasoning training in the ACTIVE study: How much is needed and who benefits? Journal of Aging and Health. 2013;25(8S):43S–64S. doi: 10.1177/0898264313503987.
    1. Winbald B, Palmer K, Kivipelto M, Jelic V, Fratiglino L, Wahlund LO, et al. Mild cognitive impairment – Beyond controversies, towards a consensus: Report of the international working group on mild cognitive impairment. Journal of Internal Medicine. 2004;256(3):240–246. doi: 10.1111/j.1365-2796.2004.01380.x.
    1. Wirth M, Haase CM, Villeneuve S, Vogel J, Jagust WJ. Neuroprotective pathways: Lifestyle activity, brain pathology, and cognition in cognitively normal older adults. Neurobiology of Aging. 2014;35(8):1873–1882. doi: 10.1016/j.neurobiolaging.2014.02.015.
    1. Yin S, Zhu X, Li R, Niu Y, Wang B, Huang X, et al. Intervention-induced enhancement in intrinsic brain activity in healthy older adults. Scientific Reports. 2014;4(1):7309. doi: 10.1038/srep07309.
    1. Zehnder F, Martin M, Altgassen M, Clare L. Memory training effects in old age as markers of plasticity: A meta-analysis. Restorative Neurology and Neuroscience. 2009;27(5):507–520.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다