BDNF mediates improvement in cognitive performance after computerized cognitive training in healthy older adults

Casey M Nicastri, Brittany M McFeeley, Sharon S Simon, Aurélie Ledreux, Krister Håkansson, Ann-Charlotte Granholm, Abdul H Mohammed, Kirk R Daffner, Casey M Nicastri, Brittany M McFeeley, Sharon S Simon, Aurélie Ledreux, Krister Håkansson, Ann-Charlotte Granholm, Abdul H Mohammed, Kirk R Daffner

Abstract

Introduction: The often-cited mechanism linking brain-derived neurotrophic factor (BDNF) to cognitive health has received limited experimental study. There is evidence that cognitive training, physical exercise, and mindfulness meditation may improve cognition. Here, we investigated whether improvements in cognition after these three types of structured interventions are facilitated by increases in BDNF.

Methods: A total of 144 heathy older adults completed a 5-week intervention involving working memory/cognitive training, physical exercise, mindfulness meditation, or an active control condition. Serum BDNF levels and Digit Symbol Test (DST) performance were measured pre- and post-intervention.

Results: Linear mixed models suggested that only the cognitive training group demonstrated augmentation of BDNF and DST performance relative to the control condition. Path analysis revealed that changes in BDNF mediate intervention-related improvement in task performance. Regression analyses showed that, across all intervention conditions, increased BDNF levels were associated with increased DST scores.

Discussion: This study appears to be the first to suggest that BDNF helps mediate improvements in cognition after working memory training in healthy older adults.

Highlights: Older adults were randomized to physical activity, mindfulness, cognitive training (computerized cognitive training (CCT), or control.CCT, but no other condition, led to increased serum brain-derived neurotrophic factor (BDNF) levels.CCT led to improvement on the untrained Digit Symbol Test (DST) of speed/working memory.Path analysis: increases in BDNF mediate intervention-related improvement on DST.Increases in BDNF associated with improved DST across all experimental groups.

Keywords: Brain‐derived neurotrophic factor (BDNF); cognition; cognitive training; cognitively stimulating activities; mindfulness meditation; older adults; physical exercise; processing speed; working memory.

Conflict of interest statement

The authors of this manuscript have no activities or interests to disclose related to the content of this submission. Author disclosures are available in the supporting information.

© 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Figures

FIGURE 1
FIGURE 1
Consolidated Standards of Reporting Trials (CONSORT) flow chart
FIGURE 2
FIGURE 2
(A) Mean brain‐derived neurotrophic factor (BDNF) measurements at baseline and post‐intervention. (B) Mean Digit Symbol Test scores at baseline and post‐intervention. Error bars represent standard errors.
FIGURE 3
FIGURE 3
Path analysis examining the relationship between intervention group, changes in BDNF levels, and changes in Digit Symbol Test scores. Path coefficients are bolded, and zero‐order correlations are presented in parentheses. BDNF, serum brain derived neurotrophic factor; Digit Symbol Test, raw score performance on Digit Symbol Test; change, post‐ minus pre‐ intervention values.
FIGURE 4
FIGURE 4
Scatterplots depicting change in Digit Symbol Test scores versus change in brain‐derived neurotrophic factor (BDNF) levels for each group (Adaptive computerized cognitive training [CCT], Mindfulness, Physical Exercise, Active Control). The first scatterplot collapses across all groups. Each line is representative of results of linear regression.

References

    1. Miranda M, Morici JF, Zanoni MB, Bekinschtein P. Brain‐Derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain. Front Cell Neurosci. 2019;13:363.
    1. Scott‐Solomon E, Kuruvilla R. Mechanisms of neurotrophin trafficking via Trk receptors. Mol Cell Neurosci. 2018;91:25‐33.
    1. Mohammed AH, Zhu SW, Darmopil S, et al. Environmental enrichment and the brain. Prog Brain Res. 2002;138(February):109‐133.
    1. Reichardt LF. Neurotrophin‐regulated signalling pathways. Philos Trans R Soc B Biol Sci. 1473;361:1545‐1564.
    1. Yoshii A, Constantine‐Paton M. Postsynaptic BDNF‐TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol. 2010;70(5):304‐322.
    1. Bramham CR, Messaoudi E. BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog Neurobiol. 2005;76(2):99‐125.
    1. Rossi C, Angelucci A, Costantin L, et al. Brain‐derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neurosci. 2006;24(7):1850‐1856.
    1. Smith PA. BDNF: no gain without pain? Neuroscience. 2014;283:107‐123.
    1. Lu B, Nagappan G, Guan X, Nathan PJ, Wren P. BDNF‐based synaptic repair as a disease‐modifying strategy for neurodegenerative diseases. Nat Rev Neurosci. 2013;14(6):401‐416.
    1. Weinstein G, Beiser AS, Choi SH, et al. Serum brain‐derived neurotrophic factor and the risk for dementia: the Framingham Heart Study. JAMA Neurol. 2014;71(1):55‐61.
    1. Pham TM, Winblad B, Granholm A‐C, Mohammed AH. Environmental influences on brain neurotrophins in rats. Pharmacol Biochem Behav. 2002;73(1):167‐175.
    1. Ickes BR, Pham TM, Sanders LA, Albeck DS, Mohammed AH, Granholm AC. Long‐term environmental enrichment leads to regional increases in neurotrophin levels in rat brain. Exp Neurol. 2000;164(1):45‐52.
    1. Kazlauckas V, Pagnussat N, Mioranzza S, et al. Enriched environment effects on behavior, memory and BDNF in low and high exploratory mice. Physiol Behav. 2011;102(5):475‐480.
    1. Radecki DT, Brown LM, Martinez J, Teyler TJ. BDNF protects against stress‐induced impairments in spatial learning and memory and LTP. Hippocampus. 2005;15(2):246‐253.
    1. Mu JS, Li WP, Yao ZB, Zhou XF. Deprivation of endogenous brain‐derived neurotrophic factor results in impairment of spatial learning and memory in adult rats. Brain Res. 1999;835(2):259‐265.
    1. Vaynman S, Ying Z, Gomez‐Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci. 2004;20(10):2580‐2590.
    1. Hakansson K, Ledreux A, Daffner K, et al. BDNF responses in healthy older persons to 35 minutes of physical exercise, cognitive training, and mindfulness: associations with working memory function. J Alzheimers Dis. 2017;55(2):645‐657.
    1. Erickson KI, Prakash RS, Voss MW, et al. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus. 2009;19(10):1030‐1039.
    1. Erickson KI, Kramer AF. Aerobic exercise effects on cognitive and neural plasticity in older adults. Br J Sports Med. 2009;43(1):22‐24.
    1. Lauenroth A, Ioannidis AE, Teichmann B. Influence of combined physical and cognitive training on cognition: a systematic review. BMC Geriatr. 2016;16(1):21‐23.
    1. Najar J, Östling S, Gudmundsson P, et al. Cognitive and physical activity and dementia: a 44‐year longitudinal population study of women. Neurology. 2019;92(12):E1322‐E1330.
    1. Dinoff A, Herrmann N, Swardfager W, et al. The effect of exercise training on resting concentrations of peripheral brain‐derived neurotrophic factor (BDNF): a meta‐analysis. PLoS One. 2016;11(9):1‐21.
    1. Szuhany KL, Bugatti M, Otto MW. A meta‐analytic review of the effects of exercise on brain‐derived neurotrophic factor. J Psychiatr Res. 2015;60:56‐64.
    1. Zoladz JA, Pilc A. The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies. J Physio and Pharma. 2010;61(5):533‐541.
    1. Chiesa A, Calati R, Serretti A. Does mindfulness training improve cognitive abilities? A systematic review of neuropsychological findings. Clin Psychol Rev. 2011;31(3):449‐464.
    1. Bamidis PD, Vivas AB, Styliadis C, et al. A review of physical and cognitive interventions in aging. Neurosci Biobehav Rev. 2014;44:206‐220.
    1. Vinogradov S, Fisher M, Holland C, Shelly W, Wolkowitz O, Mellon SH. Is serum brain‐derived neurotrophic factor a biomarker for cognitive enhancement in schizophrenia? Biol Psychiatry. 2009;66(6):549‐553.
    1. Angelucci F, Peppe A, Carlesimo GA, et al. A pilot study on the effect of cognitive training on BDNF serum levels in individuals with Parkinson's disease. Front Hum Neurosci. 2015;9(MAR):1‐11.
    1. Pressler SJ, Titler M, Koelling TM, et al. Nurse‐enhanced computerized cognitive training increases serum brain‐derived neurotropic factor levels and improves working memory in heart failure. J Card Fail. 2015;21(8):630‐641.
    1. Berk L, van Boxtel M, van Os J. Can mindfulness‐based interventions influence cognitive functioning in older adults? A review and considerations for future research. Aging Ment Health. 2017;21(11):1113‐1120.
    1. Rahe J, Becker J, Fink GR, et al. Cognitive training with and without additional physical activity in healthy older adults: cognitive effects, neurobiological mechanisms, and prediction of training success. Front Aging Neurosci. 2015;7(Oct):1‐15.
    1. Leckie RL, Oberlin LE, Voss MW, et al. BDNF mediates improvements in executive function following a 1‐year exercise intervention. Front Hum Neurosci. 2014;8(Dec):1‐12.
    1. Erickson KI, Voss MW, Prakash RS, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011;108(7):3017‐3022.
    1. Damirchi A, Hosseini F, Babaei P. Mental training enhances cognitive function and BDNF more than either physical or combined training in elderly women with MCI: a small‐scale study. Am J Alzheimers Dis Other Demen. 2018;33(1):20‐29.
    1. Ledreux A, Håkansson K, Carlsson R, et al. Differential effects of physical exercise, cognitive training, and mindfulness practice on serum BDNF levels in healthy older adults: a randomized controlled intervention study. J Alzheimer's Dis. 2019;71(4):1245‐1261.
    1. Simon SS, Tusch ES, Feng NC, Håkansson K, Mohammed AH, Daffner KR. Is computerized working memory training effective in healthy older adults? Evidence from a multi‐site, randomized controlled trial. J Alzheimer's Dis. 2018;65(3):931‐949.
    1. Feng NC, Ryan E, Kidane M, et al. Feasibility of an at‐home, web‐based, interactive exercise program for older adults. Alheimers Dement. 2019;5:825‐833.
    1. Wechsler D. Wechsler adult intelligence scale‐fourth edition (WAIS‐IV). Pearson; 2008.
    1. Rolstad S, Nordlund A, Gustavsson MH, et al. The Swedish National Adult Reading Test (NART‐SWE): a test of pre‐morbid IQ. Scand J Psychol. 2008;49:577‐582.
    1. Wechsler D. Wechsler memory scale‐third edition (WMS‐III). The Psychological Corporation; 1997.
    1. Giese M, Beck J, Brand S, et al. Fast BDNF serum level increase and diurnal BDNF oscillations are associated with therapeutic response after partial sleep deprivation. J Psychiatr Res. 2014;59:1‐7.
    1. Salthouse TA. The processing‐speed theory of adult age differences in cognition. Psychol Rev. 1996;103(3):403‐428.
    1. McCoy CE. Understanding the intention‐to‐treat principle in randomized controlled trials. West J Emerg Med. 2017;18(6):1075‐1078.
    1. Streiner DL. Finding our way: an introduction to path analysis. Can J Psychiatry. 2005;50(2):115‐122.
    1. Traut HJ, Guild RM, Munakata Y. Why does cognitive training yield inconsistent benefits? A meta‐analysis of individual differences in baseline cognitive abilities and training outcomes. Front Psychol. 2021;12(May):1‐20.
    1. Dinoff A, Herrmann N, Swardfager W, Lanctôt KL. The effect of acute exercise on blood concentrations of brain‐derived neurotrophic factor in healthy adults: a meta‐analysis. Eur J Neurosci. 2017;46(1):1635‐1646.
    1. Knaepen K, Goekint M, Heyman EM, Meeusen R. Neuroplasticity‐exercise‐induced response of peripheral brain‐derived neurotrophic factor a systematic review of experimental studies in human subjects. Sports Med. 2010;40(9):765‐801.
    1. Hillman CH, Erickson KI, Kramer AF. Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci. 2008;9:58‐65.
    1. Nilsson J, Ekblom Ö, Ekblom M, et al. Acute increases in brain‐derived neurotrophic factor in plasma following physical exercise relates to subsequent learning in older adults. Sci Rep. 2020;10(1):1‐15.
    1. Gomes‐Osman J, Cabral DF, Morris TP, et al. Exercise for cognitive brain health in aging: a system‐atic review for an evaluation of dose. Neurol Clin Pract. 2018;8:257‐265.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera