Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment.
J Alzheimers Dis
; 81(3): 1211-1229, 2021.
Article
em En
| MEDLINE
| ID: mdl-33935094
ABSTRACT
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 (nâ=â196, 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 (0.8âmg), vitamin B12 (0.5âmg) and B6 (20 mg) (nâ=â95) or placebo (nâ=â101) for 2 years. Cognition was analyzed by neuropsychological tests. Brain atrophy was quantified in a subset of participants (nâ=â168) 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complexo Vitamínico B
/
Cognição
/
Arildialquilfosfatase
/
Disfunção Cognitiva
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article