Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment

Joanna Perła-Kaján, Olga Włoczkowska, Anetta Zioła-Frankowska, Marcin Frankowski, A. David Smith, Celeste A. De Jager, Helga Refsum, Hieronim Jakubowski

Research output: Contribution to journalArticlepeer-review


Background: Identification of modifiable risk factors that affect cognitive decline is important for the development of preventive and treatment strategies. Status of paraoxonase 1 (PON1), a high-density lipoprotein-associated enzyme, may play a role in the development of neurological diseases, including Alzheimer's disease. Objective: We tested a hypothesis that PON1 status predicts cognition in individuals with mild cognitive impairment (MCI). Methods: Individuals with MCI (n = 196, 76.8-years-old, 60% women) participating in a randomized, double-blind placebo-controlled trial (VITACOG) were assigned to receive a daily dose of folic acid (0.8 mg), vitamin B12 (0.5 mg) and B6 (20 mg) (n = 95) or placebo (n = 101) for 2 years. Cognition was analyzed by neuropsychological tests. Brain atrophy was quantified in a subset of participants (n = 168) by MRI. PON1 status, including PON1 Q192R genotype, was determined by quantifying enzymatic activity of PON1 using paraoxon and phenyl acetate as substrates. Results: In the placebo group, baseline phenylacetate hydrolase (PhAcase) activity of PON1 (but not paraoxonase activity or PON1 Q192R genotype) was significantly associated with global cognition (Mini-Mental State Examination, MMSE; Telephone Inventory for Cognitive Status-modified, TICS-m), verbal episodic memory (Hopkins Verbal Learning Test-revised: Total Recall, HVLT-TR; Delayed Recall, HVLT-DR), and attention/processing speed (Trail Making A and Symbol Digits Modalities Test, SDMT) at the end of study. In addition to PhAcase, baseline iron and triglycerides predicted MMSE, baseline fatty acids predicted SDMT, baseline anti-N-Hcy-protein autoantibodies predicted TICS-m, SDMT, Trail Making A, while BDNF V66M genotype predicted HVLT-TR and HVLT-DR scores at the end of study. B-vitamins abrogated associations of PON1 and other variables with cognition. Conclusion: PON1 is a new factor associated with impaired cognition that can be ameliorated by B-vitamins in individuals with MCI.

Original languageEnglish (US)
Pages (from-to)1211-1229
Number of pages19
JournalJournal of Alzheimer's Disease
Issue number3
StatePublished - 2021

All Science Journal Classification (ASJC) codes

  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Clinical Psychology
  • Neuroscience(all)


  • BDNF V66M genotype
  • PON1 Q192R genotype
  • PON1 activity
  • brain atrophy
  • cognition
  • iron
  • mild cognitive impairment
  • paraoxon
  • phenyl acetate


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