Plasma homocysteine and cognitive decline in older hypertensive subjects

Narayan, Shyam; Saxby, Brian K.; Firbank, Michael; O’Brien, John T.; Harrington, Frances; McKeith, Ian G.; Hansrani, Monica; Stansby, Gerard; Ford, Gary A.

doi:10.1017/s1041610211000779

Cited by 22 publications

(21 citation statements)

References 37 publications

(37 reference statements)

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“…Previous reports revealed that elevated Hcy levels may be an independent risk factor for cognitive impairment. Higher Hcy levels have been found to be associated with more serious degrees of cognitive impairment [27,28]. A novel treatment targeting Hcy via a high dose of supplementary B vitamins might decrease the accelerated rate of brain atrophy in MCI [29].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Values of Serum Levels of Homocysteine and Uric Acid for Predicting Vascular Mild Cognitive Impairment in Patients with Cerebral Small Vessel Disease

et al. 2017

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BackgroundThis study aimed to investigate the diagnostic values of serum levels of Hcy and UA for predicting vascular mild cognitive impairment (VMCI) in patients with cerebral small vessel disease (SVD).Material/MethodWe selected 172 cerebral SVD patients and divided them into a VMCI group and a non-VMCI group. Eighty-six healthy individuals without nervous system diseases were selected as the control group. Enzymatic cycling method was performed to detect serum Hcy and UA levels. Serum levels of folic acid (FOA) and vitamin B12 (VitB12) were detected by chemiluminescence immunoassay. Montreal cognitive assessment (MoCA) was applied to evaluate the cognitive function. The ROC curve was used to evaluate the diagnostic values of serum Hcy and UA levels for predicting VMCI. Logistic regression analysis was used to determine the possible risk factors.ResultsCompared with the non-VMCI and control groups, serum FOA and VitB12 levels were lower and serum Hcy and UA levels were higher in the VMCI group. AUC values of serum Hcy and UA levels were 0.703 and 0.829, respectively. Serum Hcy and UA levels were negatively correlated with serum FOA and VitB12 levels, total MoCA score, and subscores on visuospatial ability and executive function, on language ability and on delayed recall, and they were positively correlated with serum cholesterol (CH) level. Serum Hcy and UA levels were indicated as risk factors for VMCI in cerebral SVD patients.ConclusionsThese results suggest that serum Hcy and UA levels may serve as predictive factors for VMCI in cerebral SVD patients.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Values of Serum Levels of Homocysteine and Uric Acid for Predicting Vascular Mild Cognitive Impairment in Patients with Cerebral Small Vessel Disease

et al. 2017

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“…There is accumulating evidence indicating that hHcys contributes to the development of a number of degenerative or sclerotic diseases including coronary artery disease, multiple sclerosis, Parkinson’s disease and many complications associated with aging in general, like osteoporosis and cognitive decline [4, 39–43]. Elevated levels of this methionine amino acid intermediate have also been considered to be an independent risk factor for chronic renal disease, promoting glomerular dysfunction and end-stage renal disease.…”

Section: Discussionmentioning

confidence: 99%

Contribution of endogenously produced reactive oxygen species to the activation of podocyte NLRP3 inflammasomes in hyperhomocysteinemia

Abais

Xia

et al. 2014

Free Radical Biology and Medicine

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Hyperhomocysteinemia (hHcys) is an important pathogenic factor contributing to the progression of end-stage renal disease. Recent studies have demonstrated the implication of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated NLRP3 inflammasome activation in the development of podocyte injury and glomerular sclerosis during hHcys. However, it remains unknown which reactive oxygen species (ROS) are responsible for this activation of NLRP3 inflammasomes and how such action of ROS is controlled. The present study tested the contribution of common endogenous ROS including superoxide (O2•−), hydrogen peroxide (H2O2), and hydroxyl radical (•OH) to the activation of NLRP3 inflammasomes in mouse podocytes and glomeruli. In vitro, confocal microscopy and size exclusion chromatography demonstrated that dismutation of O2•− by 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and decomposition of H2O2 by catalase prevented Hcys-induced aggregation of NLRP3 inflammasome proteins and inhibited Hcys-induced caspase-1 activation and IL-1β production in mouse podocytes. However, •OH scavenger tetramethylthiourea (TMTU) had no significant effect on either Hcys-induced NLRP3 inflammasome formation or activation. In vivo, scavenging of O2•− by TEMPOL and removal of H2O2 by catalase substantially inhibited NLRP3 inflammasome formation and activation in glomeruli of hHcys mice as shown by reduced colocalization of NLRP3 with ASC or caspase-1 and inhibition of caspase-1 activation and IL-1β production. Furthermore, TEMPOL and catalase significantly attenuated hHcys-induced glomerular injury. In conclusion, endogenously produced O2•− and H2O2 primarily contribute to NLRP3 inflammasome formation and activation in mouse glomeruli resulting in glomerular injury or consequent sclerosis during hHcys.

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“…Elevated plasma concentrations of homocysteine have been shown to be associated with poor cognitive function, cognitive decline and dementia [3,4]. High plasma homocysteine concentration has been associated with silent brain infarcts and atherosclerosis causing cognitive impairment [5,6], and activation of Nmethyl-D-aspartate receptors resulting in neuronal cell damage and hippocampal atrophy [6].…”

Section: Introductionmentioning

confidence: 99%

A randomized placebo-controlled trial of using B vitamins to prevent cognitive decline in older mild cognitive impairment patients

Kwok

Lee

et al. 2020

Clinical Nutrition

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Background & aims: Mild cognitive impairment (MCI) patients are at risk of cognitive decline, while elevated serum homocysteine is also associated with cognitive impairment. Thus, older people with MCI and hyperhomocysteinemia may be under greater risk of cognitive decline. We therefore performed a randomized trial of homocysteine-lowering by B vitamins supplementation to prevent cognitive decline in older MCI patients with elevated serum homocysteine. Methods: 279 MCI outpatients aged !65 years with serum homocysteine !10.0 mmol/L were randomly assigned to take either methylcobalamin 500 mg and folic acid 400 mg once daily, or two placebo tablets for 24 months. All subjects were followed up at 12 monthly intervals. The primary outcome was cognitive decline as defined by an increase in clinical dementia rating scale (CDR) sum of boxes (CDR_SOB). The secondary outcomes were global CDR, memory Z score, executive function Z score and Hamilton depression rating scale (HDRS) score. Results: The clinical characteristics between two groups were well matched, except that the supplement group had better executive function. The supplement effectively lowered serum homocysteine (mean 13.9 ± sd 3.5 mmol at baseline to 9.3 ± 2.4 mmol/L at month 24). At month 24, there was no significant group difference in CDR_SOB or any secondary outcomes (mean changes in CDR_SOB 0.36 versus 0.22 in supplement and placebo groups respectively). At month 12, the supplement group significantly improved in executive function and had lower HDRS score (P ¼ 0.004 and 0.012 respectively). Group difference was significant for HDRS, but borderline significant for executive function. (P ¼ 0.01; 0.06 respectively) These effects were not significant at month 24. Subgroup analysis showed that aspirin use had significant interaction with B supplements in CDR_SOB at month 24 (Beta 0.189, P ¼ 0.005). Conclusions: Vitamin B 12 and folic acid supplementation did not reduce cognitive decline in older people with MCI and elevated serum homocysteine, though the cognitive decline over two years in placebo group was small. The supplement led to a significant reduction in depressive symptoms at month 12, though this effect was not sustained. Aspirin use had a negative interaction effect on cognitive functioning with B supplements. Clinical trial registration: Centre for Clinical Research and Biostatistics (CCRB) Clinical Trials Registry: CUHK_CCT00373.

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Plasma homocysteine and cognitive decline in older hypertensive subjects

Abstract: In a population of older hypertensive patients, higher plasma homocysteine was associated with cognitive decline.

Cited by 22 publications

References 37 publications

Diagnostic Values of Serum Levels of Homocysteine and Uric Acid for Predicting Vascular Mild Cognitive Impairment in Patients with Cerebral Small Vessel Disease

Diagnostic Values of Serum Levels of Homocysteine and Uric Acid for Predicting Vascular Mild Cognitive Impairment in Patients with Cerebral Small Vessel Disease

Contribution of endogenously produced reactive oxygen species to the activation of podocyte NLRP3 inflammasomes in hyperhomocysteinemia

A randomized placebo-controlled trial of using B vitamins to prevent cognitive decline in older mild cognitive impairment patients

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