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The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease

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Abstract

Parkinson’s disease (PD) patients show a range of cognitive deficits,which may relate to abnormalities in dopaminergic transmission in fronto–striatal circuitry. In this study, we have investigated the impact of brainderived neurotrophic factor (BDNF) val66met polymorphisms on performance of the Tower of London (TOL) test of planning by PD patients. This polymorphism significantly influences BDNF secretion in the CNS, and BDNF is known to influence dopaminergic neurons and cognitive processes. Patients with PD totalling 291 who had undergone detailed motor and cognitive assessments as part of a population–based study of PD were genotyped for the BDNF val66met polymorphism. The impact of this polymorphism on cognitive ability was determined using multivariate analysis to adjust for possible confounding variables. Patients with low rates of BDNF secretion (met alleles) performed significantly better at the TOL task than those with high rates of secretion (val alleles). Furthermore, subgroup analyses revealed that the effect is most apparent in women and among patients with prior dopaminergic exposure. We speculate that BDNF may interact with dopaminergic transmission and dopamine receptor stimulation in the frontostriatal circuitry, with subsequent consequences on cognition in Parkinson’s disease.

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Authors and Affiliations

  1. Cambridge Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 2PY, UK

    Th. Foltynie PhD, S. G. J. Lewis MRCP & R. A. Barker PhD

  2. National Institute of Mental Health, Clinical Brain Disorders Branch, Bethesda (MD), USA

    T. E. Goldberg PhD,  B. S. Kolachana PhD & D. R. Weinberger MD

  3. Dept. of Psychiatry, Addenbrooke’s hospital, Cambridge, UK

    A. D. Blackwell PhD

  4. Dept. of Experimental Psychology, University of Cambridge, Cambridge, UK

    T. W. Robbins PhD

Authors
  1. Th. Foltynie PhD
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  2. S. G. J. Lewis MRCP
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  3. T. E. Goldberg PhD
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  4. A. D. Blackwell PhD
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  5. B. S. Kolachana PhD
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  6. D. R. Weinberger MD
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  7. T. W. Robbins PhD
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  8. R. A. Barker PhD
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Correspondence to Th. Foltynie PhD.

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Foltynie, T., Lewis, S.G.J., Goldberg, .E. et al. The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson’s disease. J Neurol 252, 833–838 (2005). https://doi.org/10.1007/s00415-005-0756-5

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  • DOI: https://doi.org/10.1007/s00415-005-0756-5

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