ReviewBiochimica et biophysica acta2016
Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID).
Review in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- Homocysteine and cognitive function in depression: a systematic review and meta-analysis.Frontiers in psychiatry · 2026Pooled it
- Homocysteine and Folic Acid: Risk Factors for Alzheimer's Disease-An Updated Meta-Analysis.Frontiers in aging neuroscience · 2021Pooled it
- Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.JAMA neurology · 2022Trial
- Diet-Induced Hyperhomocysteinemia in C57BL/6 Mice: Simultaneous Evaluation of Plasma Homocysteine, Methionine, and Cysteine by LC-MS/MS and Assessment of Associated Oxidative Stress in Brain Homogenates.Antioxidants (Basel, Switzerland) · 2026Article
- Betaine Attenuates Hyperhomocysteinemia-Induced Cognitive Impairment by Suppressing Oxidative Stress and Activating the PI3K/AKT/GSK-3β Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- Cystathionine β-synthase is inhibited by epinephrine and norepinephrine over-secretion via NF-κB activation in stress-induced hyperhomocysteinemia.Scientific reports · 2026Article
- Development of a clinical nomogram to assess the risk of cognitive impairment in community-dwelling middle-aged and older adults.BMC neurology · 2026Article
- Recurrent venous thrombosis in an adolescent male with CBS mutation and persistent antiphospholipid antibody positivity: a case report.Thrombosis journal · 2026Article
- Homocysteine levels do not impact cognitive profile in frontotemporal dementia.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Muscle Ultrasound Parameters and Cognitive Function in H‑type Hypertension: A Cross-Sectional Study.Clinical interventions in aging · 2026Article
- Uncovering Hyperhomocysteinemia: Global Risk Patterns and Molecular Disruption in Brain and Vascular Health.Journal of neurochemistry · 2025Review
- Burning mouth syndrome: updates on pathogenesis and diagnostic algorithms.Journal of oral & facial pain and headache · 2025Review
- Metabolic toxicity and neurological dysfunction in methylmalonic acidemia: from mechanisms to therapeutics.Molecular medicine (Cambridge, Mass.) · 2025Review
- Vascular dementia increases levels of methylenetetrahydrofolate reductase and cystathionine β-synthase in female patients and changes gene expression of acetylcholine and glutamate clathrin-sculpted transport vesicles.bioRxiv : the preprint server for biology · 2025Article
- Hyperhomocysteinemia-Driven Ischemic Stroke: Unraveling Molecular Mechanisms and Therapeutic Horizons.Food science & nutrition · 2025Review
- Unraveling Homocysteine's Role in Dementia: No Specific Association with Alzheimer's Disease, but a Connection to White Matter Hyperintensities.Aging and disease · 2025Observational
- Role ofFrontiers in pharmacology · 2025Review
- Study on the relationship between homocysteine and general metabolic indexes in healthy population in Hebei Province, China.Frontiers in endocrinology · 2025Article
- Joint effects of elevated homocysteine levels and low eGFR on post-stroke cognitive impairment.Frontiers in neurology · 2025Article
- Chronic cerebral hypoperfusion: a critical feature in unravelling the etiology of vascular cognitive impairment.Acta neuropathologica communications · 2023Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3-10μM). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100-200μM), mild-moderate hyperhomocysteinemia ([HCy]: 10-100μM) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID). Here we review the biochemical and cellular actions of HCy related to VCID. Neuronal actions of HCy were at concentrations above the clinically-relevant range. Effects of HCy <100μM were primarily vascular, including myocyte proliferation, vessel wall fibrosis, impaired nitric oxide signalling, superoxide generation and pro-coagulant actions. HCy-lowering clinical trials relevant to VCID are discussed. Extensive clinical and preclinical data support HCy as a mediator for VCID. In our view further trials of combined B-vitamin supplementation are called for, incorporating lessons from previous trials and from recent experimental work. To maximise likelihood of treatment effect, a future trial should: supply a high-dose, combination supplement (B6, B12 and folate); target the at-risk age range; and target cohorts with low baseline B-vitamin status. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.