BDNF Val66Met polymorphism and cognitive impairment in Parkinson’s disease—a meta-analysis

  • Yanying Yin
  • Xuening Su
  • Lishou Pan
  • Chen LiEmail author
Original Article



Conflicting results identifying the association between Brain-derived neurotrophic factor (BDNF) polymorphism, Val66Met, and cognitive impairment in Parkinson’s disease (PD) have been reported.

Methods and results

To clarify whether Val66Met is related to cognitive impairment in PD, we carried out this meta-analysis by searching literature from PubMed, Web of Science, and Embase databases regarding this polymorphism. Six eligible studies involving 1467 PD patients were included in this meta-analysis. Our results showed statistically significant association between Val66Met and risk of cognitive impairment in PD patients in additive model (Met/Met vs. Val/Val: OR 3.82, 95%CI 1.32 to 11.08, p = 0.01) and recessive model (Met/Met vs. Val-carrier: OR 3.81, 95%CI 1.38 to 10.53, p = 0.01) except for dominant model.


Our meta-analysis implicates Val66Met BDNF polymorphism may be associated with Parkinson’s disease cognitive impairment, further well-designed studies with larger populations are required to validate these results owing to the limited research.


BDNF Polymorphism PD-related cognitive impairment  Meta-analysis 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Kalia LV, Lang AE (2015) Parkinson's disease. Lancet 386:896–912CrossRefGoogle Scholar
  2. 2.
    Williams-Gray CH, Foltynie T, Brayne CE, Robbins TW, Barker RA (2007) Evolution of cognitive dysfunction in an incident Parkinson's disease cohort. Brain 130:1787–1798CrossRefGoogle Scholar
  3. 3.
    Papagno C, Trojano L (2018) Cognitive and behavioral disorders in Parkinson's disease: an update. I: cognitive impairments. Neurol Sci 39:215–223CrossRefGoogle Scholar
  4. 4.
    Jokinen P, Brück A, Aalto S, Forsback S, Parkkola R, Rinne JO (2009) Impaired cognitive performance in Parkinson’s disease is related to caudate dopaminergic hypofunction and hippocampal atrophy. Parkinsonism Relat Disord 15:88–93CrossRefGoogle Scholar
  5. 5.
    Aleksovski D, Miljkovic D, Bravi D, Antonini A (2018) Disease progression in Parkinson subtypes: the PPMI dataset. Neurol Sci 39:1971–1976CrossRefGoogle Scholar
  6. 6.
    Kempster PA, O'Sullivan SS, Holton JL, Revesz T, Lees AJ (2010) Relationships between age and late progression of Parkinson’s disease: a clinico-pathological study. Brain 133:1755–1762CrossRefGoogle Scholar
  7. 7.
    Dujardin K, Leentjens AF, Langlois C, Moonen AJ, Duits AA, Carette AS, Duhamel A (2013) The spectrum of cognitive disorders in Parkinson’s disease: a data-driven approach. Mov Disord 28:183–189CrossRefGoogle Scholar
  8. 8.
    Kehagia AA, Barker RA, Robbins TW (2010) Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson’s disease. Lancet Neurol 9:1200–1213CrossRefGoogle Scholar
  9. 9.
    Teixeira AL, Barbosa IG, Diniz BS, Kummer A (2010) Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function. Biomark Med 4:871–887CrossRefGoogle Scholar
  10. 10.
    Guerini FR, Beghi E, Riboldazzi G, Zangaglia R, Pianezzola C, Bono G, Casali C, Di Lorenzo C, Agliardi C, Nappi G, Clerici M, Martignoni E (2009) BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson's disease. Eur J Neurol 16(11):1240–1245CrossRefGoogle Scholar
  11. 11.
    Gao L, Díaz-Corrales FJ, Carrillo F, Díaz-Martín J, Caceres-Redondo MT, Carballo M, Palomino A, López-Barneo J, Mir P (2010) Brain-derived neurotrophic factor G196A polymorphism and clinical features in Parkinson's disease. Acta Neurol Scand 122(1):41–45CrossRefGoogle Scholar
  12. 12.
    Svetel M, Pekmezovic T, Markovic V, Novaković I, Dobričić V, Djuric G, Stefanova E, Kostić V (2013) No association between brain-derived neurotrophic factor G196A polymorphism and clinical features of Parkinson's disease. Eur Neurol 70:257–262CrossRefGoogle Scholar
  13. 13.
    van der Kolk NM, Speelman AD, van Nimwegen M, Kessels RP, IntHout J, Hakobjan M, Munneke M, Bloem BR, van de Warrenburg BP (2015) BDNF polymorphism associates with decline in set shifting in Parkinson's disease. Neurobiol Aging 36:1605.e1–1605.e6CrossRefGoogle Scholar
  14. 14.
    Białecka M, Kurzawski M, Roszmann A, Robowski P, Sitek EJ, Honczarenko K, Mak M, Deptuła-Jarosz M, Gołąb-Janowska M, Droździk M, Sławek J (2014) BDNF G196A (Val66Met) polymorphism associated with cognitive impairment in Parkinson's disease. Neurosci Lett 561:86–90CrossRefGoogle Scholar
  15. 15.
    Altmann V, Schumacher-Schuh AF, Rieck M, Callegari-Jacques SM, Rieder CR, Hutz MH (2016) Val66Met BDNF polymorphism is associated with Parkinson's disease cognitive impairment. Neurosci Lett 615:88–91CrossRefGoogle Scholar
  16. 16.
    Foltynie T, Lewis SG, Goldberg TE, Blackwell AD, Kolachana BS, Weinberger DR, Robbins TW, Barker RA (2005) The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease. J Neurol 252(7):833–838CrossRefGoogle Scholar
  17. 17.
    Baydyuk M, Russell T, Liao GY, Zang K, An JJ, Reichardt LF, Xu B (2011) TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons. Proc Natl Acad Sci U S A 108(4):1669–1674CrossRefGoogle Scholar
  18. 18.
    Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350:230–232CrossRefGoogle Scholar
  19. 19.
    McAllister AK, Katz LC, Lo DC (1999) Neurotrophins and synaptic plasticity. Annu Rev Neurosci 22:295–318CrossRefGoogle Scholar
  20. 20.
    Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112(2):257–269CrossRefGoogle Scholar
  21. 21.
    Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, Lee FS (2004) Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 24(18):4401–4411CrossRefGoogle Scholar
  22. 22.
    Bueller JA, Aftab M, Sen S, Gomez-Hassan D, Burmeister M, Zubieta JK (2006) BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects. Biol Psychiatry 59:812–815CrossRefGoogle Scholar
  23. 23.
    Pezawas L, Verchinski BA, Mattay VS, Callicott JH, Kolachana BS, Straub RE, Egan MF, Meyer-Lindenberg A, Weinberger DR (2004) The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J Neurosci 24:10099–10102CrossRefGoogle Scholar

Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  1. 1.Department of NeurologyThe Fifth Central Hospital of TianjinTianjinPeople’s Republic of China
  2. 2.Department of Neurology, The People’s Hospital of Yichun CityYichun UniversityYichunPeople’s Republic of China

Personalised recommendations