The implication of BDNF Val66Met polymorphism in progression from subjective cognitive decline to mild cognitive impairment and Alzheimer's disease: a 9-year follow-up study

Eur Arch Psychiatry Clin Neurosci. 2020 Jun;270(4):471-482. doi: 10.1007/s00406-019-01069-y. Epub 2019 Sep 27.


Brain-derived natriuretic factor (BDNF) Val66Met polymorphism has been frequently reported to be associated with Alzheimer's disease (AD) with contrasting results. Numerous studies showed that Met allele increased the risk of AD only in women, while other studies have found worse cognitive performance in Val/Val carriers. We aimed to inquire the effects of Val66Met polymorphism on the progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and from MCI to AD and to ascertain if this effect is modulated by demographic and cognitive variables. For this purpose, we followed up 74 subjects (48 SCD, 26 MCI) for a mean time of 9 years. All participants underwent extensive neuropsychological assessment, cognitive reserve estimation, BDNF and apolipoprotein E (ApoE) genotype analysis at baseline. Personality traits and leisure activities were assessed in a subgroup. Each patient underwent clinical-neuropsychological follow-up, during which 18 out of 48 SCD subjects progressed to MCI and 14 out of 26 MCI subjects progressed to AD. We found that Val66Met increased the risk of progression from SCD to MCI and from MCI to AD only in women. Nevertheless, Val/Val carriers who progressed from SCD to MCI had a shorter conversion time compared to Met carriers. We concluded that Val66Met polymorphism might play different roles depending on sex and stage of the disease.

Keywords: Alzheimer’s disease; ApoE; BDNF; Cognitive reserve; Mild cognitive impairment; Subjective cognitive decline.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / physiopathology*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cognitive Dysfunction / genetics*
  • Cognitive Dysfunction / physiopathology*
  • Diagnostic Self Evaluation
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human