ArticleCell death & disease2019
High cholesterol triggers white matter alterations and cognitive deficits in a mouse model of cerebrovascular disease: benefits of simvastatin.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pooled it
- Sex- and age-dependent mitochondrial dysfunction and cognitive impairment in a mouse model of familial hypercholesterolemia.Biology of sex differences · 2026Article
- Modulation of gut-heart axis by synbiotic (Lactiplantibacillus plantarum M10 and Isomaltose) in high cholesterol diet induced atherosclerotic murine model.BMC microbiology · 2026Article
- From Cerebrovascular Injury to Vascular Cognitive Impairment and Dementia: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles.Biomedicines · 2026Review
- Exopolysaccharides from lactic acid bacteria: functional ingredients with biotechnological potential - a critical review.International microbiology : the official journal of the Spanish Society for Microbiology · 2026Review
- Dietary cholesterol impairs cognition via gut microbiota-derived deoxycholic acid in obese mice.Gut microbes · 2025Article
- Neuropsychiatric Abnormalities in Metabolic Disturbances: Interplay of Adipokines and Neurotransmission.Molecular neurobiology · 2025Review
- Interplay Between Vascular Dysfunction and Neurodegenerative Pathology: New Insights into Molecular Mechanisms and Management.Biomolecules · 2025Review
- The Role of Oxidative Stress and Inflammation in the Pathogenesis and Treatment of Vascular Dementia.Cells · 2025Review
- Review
- Neuroimaging correlates of Alzheimer's disease biomarker concentrations in a racially diverse high-risk cohort of middle-aged adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study.Cardiovascular diabetology · 2024Article
- Article
- Impaired Cholesterol Metabolism, Neurons, and Neuropsychiatric Disorders.Experimental neurobiology · 2023Review
- Fornix degeneration in risk factors of Alzheimer's disease, possible trigger of cognitive decline.Cerebral circulation - cognition and behavior · 2023Review
- Characterization of a mutantFrontiers in immunology · 2023Article
- Simvastatin-Loaded Lipid Emulsion Nanoparticles: Characterizations and Applications.ACS omega · 2022Article
- A functional cerebral endothelium is necessary to protect against cognitive decline.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Repurposing beta-3 adrenergic receptor agonists for Alzheimer's disease: beneficial effects in a mouse model.Alzheimer's research & therapy · 2021Article
- Understanding the Connection Between Common Stroke Comorbidities, Their Associated Inflammation, and the Course of the Cerebral Ischemia/Reperfusion Cascade.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Transgenic mice overexpressing transforming growth factor-β1 (TGF mice) display impaired cerebrovascular reactivity, cerebral hypoperfusion and neurovascular uncoupling, but no overt cognitive deficits until old age. Cardiovascular diseases are a major risk factor for vascular cognitive impairment and dementia (VCID). We investigated the impact of a high cholesterol diet (HCD) on cerebrovascular and cognitive function in adult (6 months) and aged (12 months) TGF mice, together with the potential benefit of simvastatin (SV), an anti-cholesterol drug with pleiotropic effects, in adult mice. HCD increased blood, but not brain, cholesterol levels in treated mice, which SV did not reduce. In WT mice, HCD induced small, albeit significant, impairment in endothelium-dependent dilatory function. In TGF mice, HCD worsened the established brain vessel dilatory dysfunction in an age-dependent manner and increased the number of string vessels in the white matter (WM), alterations respectively normalized and significantly countered by SV. HCD triggered cognitive decline only in TGF mice at both ages, a deficit prevented by SV. Concurrently, HCD upregulated galectin-3 immunoreactivity in WM microglial cells, a response significantly reduced in SV-treated TGF mice. Grey matter astrogliosis and microgliosis were not affected by HCD or SV. In the subventricular zone of adult HCD-treated TGF mice, SV promoted oligogenesis and migration of oligodendrocyte progenitor cells. The results demonstrate that an underlying cerebrovascular pathology increases vulnerability to cognitive failure when combined to another risk factor for dementia, and that WM alterations are associated with this loss of function. The results further indicate that myelin repair mechanisms, as triggered by SV, may bear promise in preventing or delaying cognitive decline related to VCID.
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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 OpenQuestion graph.