The brain-derived neurotrophic factor val66met polymorphism moderates an effect of physical activity on working memory performance
Open accessAbstract
Physical activity enhances cognitive performance, yet individual variability in its effectiveness limits its widespread therapeutic application. Genetic differences might be one source of this variation. For example, carriers of the methionine-specifying (Met) allele of the brain-derived neurotrophic factor ( BDNF ) Val66Met polymorphism have reduced secretion of BDNF and poorer memory, yet physical activity increases BDNF levels. To determine whether the BDNF polymorphism moderated an association of physical activity with cognitive functioning among 1,032 midlife volunteers (mean age = 44.59 years), we evaluated participants’ performance on a battery of tests assessing memory, learning, and executive processes, and evaluated their physical activity with the Paffenbarger Physical Activity Questionnaire. BDNF genotype interacted robustly with physical activity to affect working memory, but not other areas of cognitive functioning. In particular, greater levels of physical activity offset a deleterious effect of the Met allele on working memory performance. These findings suggest that physical activity can modulate domain-specific genetic ( BDNF ) effects on cognition.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The presence of a val2met substitution hinders working memory and other aspects of cognition, yet high levels of exercise counteracted these cognitive impairments.
“The presence of a val2met substitution has been shown to hinder working memory and other aspects of cognition, yet high levels of exercise counteracted these cognitive impairments, suggesting that exercise may be able to modulate genetic influences (Erickson et al., 2013).”
From Exercise-Mediated Neurogenesis in the Hippocampus via BDNF (2018) · cites this paper as Erickson et al., 2013
The Results (page unavailable) report that Met carriers had poorer working memory at low physical-activity levels and that the genotype difference diminished at higher activity levels. They found no significant interaction for episodic memory, visuospatial memory, or switching, so the claim that exercise counteracted impairments in other aspects of cognition is unsupported. The study measured an association with physical activity, not a causal effect of exercise. (LLM, conf=0.90)
Experimental — accuracy not yet measuredExercise may be able to modulate genetic influences.
“The presence of a val2met substitution has been shown to hinder working memory and other aspects of cognition, yet high levels of exercise counteracted these cognitive impairments, suggesting that exercise may be able to modulate genetic influences (Erickson et al., 2013).”
From Exercise-Mediated Neurogenesis in the Hippocampus via BDNF (2018) · cites this paper as Erickson et al., 2013
The Discussion (page not provided) says greater physical activity mitigated poorer working-memory performance in BDNF Met carriers, supporting the suggestion that activity may moderate a genetic influence. The Results (page not provided) say this interaction was specific to working memory, not the other cognitive domains tested; the citing sentence overextends the counteracting effect to other aspects of cognition. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Be smart, exercise your heart: Exercise effects on brain and cognition
Hillman, C. H., Erickson, K. I., & Kramer, A. F. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2298 · Cited by 3,563 · see citing works
Self-citationSmith, P. J., Blumenthal, J. A., Hoffman, B. M., Cooper, H., Strauman, T. A., Welsh-Bohmer, K., Browndyke, J. N., & Sherwood, A. (2010) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181d14633 · Cited by 1,714 · see citing works
Exercise and brain neurotrophins
Neeper, S. A., Góauctemez-Pinilla, F., Choi, J., & Cotman, C. (1995) · Nature · doi:10.1038/373109a0 · Cited by 1,066 · see citing works
A meta-regression to examine the relationship between aerobic fitness and cognitive performance
Etnier, J. L., Nowell, P. M., Landers, D. M., & Sibley, B. A. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.01.002 · Cited by 749 · see citing works
Exercise and Alzheimer’s disease biomarkers in cognitively normal older adults
Liang, K. Y., Mintun, M. A., Fagan, A. M., Goate, A. M., Bugg, J. M., Holtzman, D. M., Morris, J. C., & Head, D. (2010) · Annals of Neurology · doi:10.1002/ana.22096 · Cited by 340 · see citing works
BDNF genotype moderates the relation between physical activity and depressive symptoms.
Mata, J., Thompson, R. J., & Gotlib, I. H. (2010) · Health Psychology · doi:10.1037/a0017261 · Cited by 119 · see citing works
Vigorous physical activity, mediating biomarkers, and risk of myocardial infarction
CHOMISTEK, A. K., CHIUVE, S. E., JENSEN, M. K., COOK, N. R., & RIMM, E. B. (2011) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31821b4d0a · Cited by 99 · see citing works
Choo, J., Elci, O. U., Yang, K., Turk, M. W., Styn, M. A., Sereika, S. M., Music, E., & Burke, L. E. (2010) · European Journal of Applied Physiology · doi:10.1007/s00421-009-1203-6 · Cited by 17 · see citing works
Flagged first, then by citations
Research works printed but not linked: 30
- Ainsworth BE Leon AS Richardson MT Jacobs DR Paffenbarger RS Jr 1993 Accuracy of the College Alumnus Physical Activity Questionnaire Journal of Clinical Epidemiology 46 1403 1411 8263567
- Bleil ME Gianaros PJ Jennings JR Flory JD Manuck SB 2008 Trait negative affect: Toward an integrated model of understanding psychological risk for impairment in cardiac autonomic function Psychosomatic Medicine 70 328 337 18378862
- Chen X Levine L Kwok PY 1999 Fluorescence polarization in homogeneous nucleic acid analysis Genome Research 9 492 498 10330129 PMC310763
- Chen ZY Bath K McEwen B Hempstead B Lee F 2008 Impact of genetic variant BDNF (Val66Met) on brain structure and function Chadwick DJ Goode J Novartis Foundation Symposium 289: Growth factors and psychiatric disorders 180 192 Chichester, England Wiley PMC2735856 18497103
- Cheng CY Hong CF Yu YW Chen TJ Wu HC Tsai SD 2005 Brain-derived neurotrophic factor (Val66Met) genetic polymorphism is associated with substance abuse in males Brain Research Molecular Brain Research 140 86 90 16109452
- Colcombe S Kramer AF 2003 Fitness effects on the cognitive function of older adults: A meta-analytic study Psychological Science 14 125 130 12661673
- Egan MF Kojima M Callicott JH Goldberg TE Kolachana BS Bertolino A Weinberger DR 2003 The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function Cell 112 257 269 12553913
- Erickson KI Kramer AF 2009 Aerobic exercise effects on cognitive and neural plasticity in older adults British Journal of Sports Medicine 43 22 24 18927158 PMC2853472
- Erickson KI Miller DL Roecklein KA 2012 The aging hippocampus: Interactions between exercise, depression, and BDNF Neuroscientist 18 82 97 21531985 PMC3575139
- Erickson KI Voss MW Prakash RS Basak C Szabo A Chaddock L Kramer AF 2011 Exercise training increases size of hippocampus and improves memory Proceedings of the National Academy of Sciences, USA 108 3017 3022 PMC3041121 21282661
- Falush D Stephens M Pritchard JK 2003 Inference of population structure using multilocus genotype data: Linked loci and correlated allele frequencies Genetics 164 1567 1587 12930761 PMC1462648
- Gapin JI Labban JD Etnier JL 2011 The effects of physical activity on attention deficit hyperactivity disorder symptoms: The evidence Preventive Medicine 52 Suppl 1 S70 S74 21281664
- Harris SE Fox H Wright AF Hayward C Starr JM Whalley LJ Deary IJ 2006 The brain-derived neurotrophic factor Val66Met polymorphism is associated with age-related change in reasoning skills Molecular Psychiatry 11 505 513 16446742
- Head D Bugg JM Goate AM Fagan AM Mintun MA Benzinger T Morris JC 2012 Exercise engagement as a moderator of the effects of APOE genotype on amyloid deposition Archives of Neurology 69 636 643 22232206 PMC3583203
- Knaepen K Goekint M Heyman EM Meeusen R 2010 Neuroplasticity-exercise-induced response of peripheral brain-derived neurotrophic factor: A systematic review of experimental studies in human subjects Sports Medicine 40 765 801 20726622
- Kramer AF Erickson KI 2007 Capitalizing on cortical plasticity: Influence of physical activity on cognition and brain function Trends in Cognitive Sciences 11 342 348 17629545
- Krueger F Pardini M Huey ED Raymont V Solomon J Lipsky RH Grafman J 2011 The role of the Met66 brain-derived neurotrophic factor allele in the recovery of executive functioning after combat-related traumatic brain injury Journal of Neuroscience 31 598 606 21228168 PMC3195417
- Li Y Luikart BW Birnbaum S Chen J Kwon CH Kernie SG Parada LF 2008 TrkB regulates hip-pocampal neurogenesis and governs sensitivity to antide-pressive treatment Neuron 59 399 412 18701066 PMC2655199
- Mandelman SD Grigorenko EL 2012 BDNF Val66Met and cognition: All, none, or some? A meta-analysis of the genetic association Genes, Brain and Behavior 11 127 136 PMC3268899 21980924
- Manuck SB Phillips JE Gianaros PJ Flory JD Muldoon MF 2010 Subjective socioeconomic status and presence of the metabolic syndrome in midlife community volunteers Psychosomatic Medicine 72 35 45 19933505 PMC2807361
- McFarlin BK Flynn MG Campbell WW Craig BA Robinson JP Stewart LK Coen PM 2006 Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4 Journals of Gerontology Series A: Biological Sciences and Medical Sciences 61 388 393 16611706
- Nowak Z Plewa M Skowron M Markiewicz A Kucio C Osiadlo G 2010 Paffenbarger Physical Activity Questionnaire as an additional tool in clinical assessment of patients with coronary artery disease treated with angioplasty Kardiologia Polska 68 32 39 20131186
- Paffenbarger RS Jr Wing AL Hyde RT 1978 Physical activity as an index of heart attack risk in college alumni American Journal of Epidemiology 108 161 175 707484
- Pajonk FG Wobrock T Gruber O Scherk H Berner D Kaizl I Falkai P 2010 Hippocampal plasticity in response to exercise in schizophrenia Archives of General Psychiatry 67 133 143 20124113
- Rockwood K Middleton L 2007 Physical activity and the maintenance of cognitive function Alzheimer’s & Dementia 3 Suppl 2 S38 S44 19595973
- Schuit AJ Feskens EJ Launer LJ Kromhout D 2001 Physical activity and cognitive decline, the role of the apoli-poprotein e4 allele Medicine & Science in Sports & Exercise 33 772 777 11323547
- Shedd KM Hanson KB Alekel DL Schiferl DJ Hanson LN Van Loan MD 2007 Quantifying leisure physical activity and its relation to bone density and strength Medicine & Science in Sports & Exercise 39 2189 2198 18046190 PMC2829844
- Smith JC Nielson KA Woodard JL Seidenberg M Durgerian S Antuono P Rao SM 2011 Interactive effects of physical activity and APOE-epsilon4 on BOLD semantic memory activation in healthy elders NeuroImage 54 635 644 20691792 PMC2962671
- Vaynman S Ying Z Gomez-Pinilla F 2004 Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition European Journal of Neuroscience 20 2580 2590 15548201
- Wechsler D 1997 Wechsler Memory Scale—Third edition San Antonio, TX The Psychological Corp
Cited by
Sorted by citations
Physical activity, fitness, and gray matter volume
Erickson, K. I., Leckie, R. L., & Weinstein, A. M. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.03.034 · Cited by 630 · see citing works
Self-citationExercise-Mediated Neurogenesis in the Hippocampus via BDNF
Liu, P. Z., & Nusslock, R. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00052 · Cited by 533 · see citing works
Firth, J., Stubbs, B., Rosenbaum, S., Vancampfort, D., Malchow, B., Schuch, F., Elliott, R., Nuechterlein, K. H., & Yung, A. R. (2016) · Schizophrenia Bulletin · doi:10.1093/schbul/sbw115 · Cited by 488 · see citing works
Physical activity, brain, and cognition
Erickson, K. I., Hillman, C. H., & Kramer, A. F. (2015) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2015.01.005 · Cited by 406 · see citing works
Self-citationPhysical Activity and Cognitive Vitality
Prakash, R. S., Voss, M. W., Erickson, K. I., & Kramer, A. F. (2015) · Annual Review of Psychology · doi:10.1146/annurev-psych-010814-015249 · Cited by 376 · see citing works
Self-citationJoggin’ the Noggin: Towards a Physiological Understanding of Exercise-Induced Cognitive Benefits
Stimpson, N. J., Davison, G., & Javadi, A.-H. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.03.018 · Cited by 134 · see citing works
Erickson, M. L., Allen, J. M., Beavers, D. P., Collins, L. M., Davidson, K. W., Erickson, K. I., Esser, K. A., Hesselink, M. K. C., Moreau, K. L., Laber, E. B., et al. (2023) · GeroScience · doi:10.1007/s11357-022-00668-3 · Cited by 47 · see citing works
Self-citationGenetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging
Papenberg, G., Salami, A., Persson, J., Lindenberger, U., & Bäckman, L. (2015) · Neuropsychology Review · doi:10.1007/s11065-015-9279-8 · Cited by 39 · see citing works
Mikoteit, T., Hemmeter, U., Eckert, A., Brand, S., Bischof, R., Delini-Stula, A., Holsboer-Trachsler, E., & Beck, J. (2015) · Neuropsychobiology · doi:10.1159/000437439 · Cited by 25 · see citing works
Brown, B. M., Castalanelli, N., Rainey-Smith, S. R., Doecke, J., Weinborn, M., Sohrabi, H. R., Laws, S. M., Martins, R. N., & Peiffer, J. J. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.01.013 · Cited by 16 · see citing works
Decoupling personality and acute psychiatric symptoms in a depressed sample and a community sample.
Fournier, J. C., Wright, A. G. C., Tackett, J. L., Uliaszek, A. A., Pilkonis, P. A., Manuck, S. B., & Bagby, R. M. (2019) · Clinical Psychological Science · doi:10.1177/2167702618813989 · Cited by 10 · see citing works
Self-citation
- Authors
- Erickson, K. I., Banducci, S. E., Weinstein, A. M., MacDonald, A. W., Ferrell, R. E., Halder, I., Flory, J. D., & Manuck, S. B.
- Affiliations
- University of Pittsburgh (US)
- University of Illinois Urbana-Champaign (US)
- University of Minnesota (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Erickson, Kirk I.
- Venue
- Psychological Science
- Publisher
- SAGE Publications
- Published
- 2013-08-01
- Volume
- 24
- Issue
- 9
- Pages
- 1770-1779
- ISSN
- 0956-7976 (ISSN-L)
- 1467-9280
- PMC
- PMC3947596
- OpenAlex
- W2108933668
- Cited by
- 134
- References
- 8
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 12 · 2023: 12 · 2022: 12 · 2021: 4 · 2020: 11 · 2019: 13 · 2018: 12 · 2017: 11 · 2016: 10 · 2015: 16 · 2014: 14 · 2013: 1
- FWCI
- 9.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychological Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000005)
- National Institute on Aging (P50AG005133, P30AG024827)
- National Heart, Lung, and Blood Institute (R01HL065137, P01HL040962)
- National Institute of Mental Health (P30MH090333)
- National Institute of General Medical Sciences (T32GM081760)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK095172)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- brain-derived neurotrophic factor, BDNF Val66Met polymorphism, physical activity, working memory, gene-environment interaction, cognitive performance, middle-aged adults, executive function, learning
- MeSH terms
- Adult, Female, Humans, Male, Memory, Short-Term, Methionine, Motor Activity, Neuropsychological Tests, Polymorphism, Genetic, Surveys and Questionnaires, Valine, Brain-Derived Neurotrophic Factor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
