Evidence map›Paper›PMID 37658433›Full record

ArticleJournal of neuroinflammation2023

Atorvastatin rescues hyperhomocysteinemia-induced cognitive deficits and neuroinflammatory gene changes.

Erica M Weekman, Sherika N Johnson, Colin B Rogers, Tiffany L Sudduth, Kevin Xie, Qi Qiao, David W Fardo, Teodoro Bottiglieri, Donna M Wilcock

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Current perspectives on the pathogenesis of cerebral atherosclerosis.Journal of inflammation (London, England) · 2025
    Review
  6. Review
  7. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Erica M WeekmanSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA. eweekman@iu.edu.
Sherika N JohnsonSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
Colin B RogersSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
Tiffany L SudduthSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
Kevin XieSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
Qi QiaoSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
David W FardoSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
Teodoro BottiglieriCenter of Metabolomics, Institute of Metabolic Disease, Baylor Scott and White Research Institute, Dallas, TX, 75204, USA.
Donna M WilcockSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA.
University of Kentucky · USBaylor Medical Center at Garland · USIndiana University – Purdue University Indianapolis · USIndiana University School of Medicine

Funding

University of Kentucky Alzheimer's Disease Research CenterP30AG072946 · NIA · UNIVERSITY OF KENTUCKY · PI LINDA J VAN ELDIK · 2021 to 2026
$23.5M
Neurovascular astrocyte dysfunction in VCIDR01NS097722 · NINDS · UNIVERSITY OF KENTUCKY · PI WILCOCK, DONNA M · 2017 to 2021
$2.1M
NIA NIH HHS P30 AG072946NINDS NIH HHS 1RO1NS097722NINDS NIH HHS R01 NS097722
6 · The paper itself

Abstract

backgroundEpidemiological data suggests statins could reduce the risk of dementia, and more specifically, Alzheimer's disease (AD). Pre-clinical data suggests statins reduce the risk of dementia through their pleiotropic effects rather than their cholesterol lowering effects. While AD is a leading cause of dementia, it is frequently found co-morbidly with cerebral small vessel disease and other vascular contributions to cognitive impairment and dementia (VCID), which are another leading cause of dementia. In this study, we determined if atorvastatin ameliorated hyperhomocysteinemia (HHcy)-induced VCID.

methodsWild-type (C57Bl6/J) mice were placed on a diet to induce HHcy or a control diet each with or without atorvastatin for 14 weeks. Mice underwent novel object recognition testing before tissue collection. Plasma total cholesterol and total homocysteine as well as related metabolites were measured. Using qPCR and NanoString technology, we profiled glial cell-associated gene expression changes. Finally, microglial morphology, astrocyte end feet, and microhemorrhages were analyzed using histological methods.

resultsAtorvastatin treatment of HHcy in mice led to no changes in total cholesterol but decreases in total homocysteine in plasma. While HHcy decreased expression of many glial genes, atorvastatin rescued these gene changes, which mostly occurred in oligodendrocytes and microglia. Microglia in HHcy mice with atorvastatin were trending towards fewer processes compared to control with atorvastatin, but there were no atorvastatin effects on astrocyte end feet. While atorvastatin treatment was trending towards increasing the area of microhemorrhages in HHcy mice in the frontal cortex, it only slightly (non-significantly) reduced the number of microhemorrhages. Finally, atorvastatin treatment in HHcy mice led to improved cognition on the novel object recognition task.

conclusionsThese data suggest that atorvastatin rescued cognitive changes induced by HHcy most likely through lowering plasma total homocysteine and rescuing gene expression changes rather than impacts on vascular integrity or microglial changes.

Indexed as

Alzheimer DiseaseCognitive DysfunctionDementia, VascularHydroxymethylglutaryl-CoA Reductase InhibitorsHyperhomocysteinemiaAnimalsAtorvastatinCognitionHomocysteineMiceAtorvastatinHomocysteineHydroxymethylglutaryl-CoA Reductase InhibitorsAstrocyte end-feetAtorvastatinCholesterolHyperhomocysteinemiaMicrogliaMicrohemorrhagesNeuroinflammationVascular contributions to cognitive impairment and dementia

Identifiers

PMID37658433
PMCPMC10474691
OpenAlexW4386385448

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.