%0 Journal Article %J J Alzheimers Dis %D 2021 %T B Vitamins Prevent Iron-Associated Brain Atrophy and Domain-Specific Effects of Iron, Copper, Aluminum, and Silicon on Cognition in Mild Cognitive Impairment. %A Jakubowski, Hieronim %A Zioła-Frankowska, Anetta %A Frankowski, Marcin %A Perła-Kaján, Joanna %A Refsum, Helga %A de Jager, Celeste A %A Smith, A David %B J Alzheimers Dis %V 84 %P 1039-1055 %8 2021 Nov 23 %G eng %N 3 %R 10.3233/JAD-215085 %0 Journal Article %J J Alzheimers Dis %D 2021 %T Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment. %A Perła-Kaján, Joanna %A Włoczkowska, Olga %A Zioła-Frankowska, Anetta %A Frankowski, Marcin %A David Smith, A %A de Jager, Celeste A %A Refsum, Helga %A Jakubowski, Hieronim %X

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.

%B J Alzheimers Dis %V 81 %P 1211-1229 %8 2021 Jun 01 %G eng %N 3 %R 10.3233/JAD-210137