Evidence map›Paper›PMID 40339909›Full record

ArticleThe Journal of nutrition2025

Warfarin Treatment is Associated With Lower Postmortem Brain Vitamin K Concentrations in Older Adults.

M Kyla Shea, Erica A Israel, Xueyan Fu, Bryan D James, Puja Agarwal, Julie A Schneider, Sarah L Booth

Abstract read
In one paragraph

Article in The Journal of nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

7 authors.

M Kyla SheaUSDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States. Electronic address: kyla.shea@tufts.edu.
Erica A IsraelUSDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States.
Xueyan FuUSDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States.
Bryan D JamesDepartment of Internal Medicine, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States.
Puja AgarwalDepartment of Internal Medicine, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States.
Julie A SchneiderDepartment of Neurological Sciences, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States.
Sarah L BoothUSDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States.

Funding

EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Vitamins D and K and Neuropathologically-Defined Alzheimer and Other Dementias in Older PersonsRF1AG051641 · NIA · TUFTS UNIVERSITY BOSTON · PI BOOTH, SARAH LOUISE · 2016 to 2016
$3.7M
Predictors and consequences of the timing and accuracy of clinical dementia diagnosisR01AG072559 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Bryan David James · 2022 to 2026
$2.9M
Vitamin K and D and Cognitive Impairment in Older AdultsR01AG051641 · NIA · TUFTS UNIVERSITY BOSTON · PI BOOTH, SARAH LOUISE · 2022 to 2025
$2.7M
Dietary factors, neuroinflammation, plasma neurodegenerative biomarkers and Alzheimer’s disease in diverse cohortsR01AG085483 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Puja Agarwal · 2024 to 2026
$2.3M
NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG051641NIA NIH HHS R01 AG072559NIA NIH HHS R01 AG085483NIA NIH HHS RF1 AG051641
6 · The paper itself

Abstract

backgroundMenaquinone 4 (MK-4) is the primary form of vitamin K found in the brain. In rodent studies, treatment with the vitamin K-antagonist warfarin lowered brain MK-4 concentrations.

objectivesIt is not known whether brain MK-4 levels are influenced by warfarin treatment in humans. To address this, we compared postmortem brain MK-4 concentrations in older adults treated with warfarin prior to death to older adults not treated with warfarin. We also determined the likelihood of having mild cognitive impairment (MCI) or dementia in warfarin users, compared to nonusers.

methodsWe used data from 381 autopsied participants, 76% female, mean (SD) age at death 92(6) y, in the Rush Memory and Aging Project (MAP) in whom MK-4 was measured in 4 brain regions: the mid-frontal and temporal cortices, anterior watershed (AWS), and cerebellum. Brain MK-4 concentrations were compared between those treated with warfarin and those not treated, using linear regression adjusted for age, sex, and cognitive diagnosis at death. The association of warfarin use prior to death with cognitive diagnosis at death was evaluated using logistic regression, adjusted for age, sex, education, and apolipoprotein E4 status.

resultsWarfarin users [n = 73, median (IQR) duration of warfarin use = 585 (479-656) d] had 68%-79% lower brain MK-4 concentrations in all measured regions, and the mean across all regions, compared with nonwarfarin users (unstandardized β -1.538 to -1.140; all P < 0.001, fully adjusted). The likelihood of having MCI or dementia, compared with no cognitive impairment, at death did not significantly differ between those treated with warfarin prior to death and those not [OR (95% confidence interval) for MCI: 0.82 (0.41, 1.62), dementia: 1.04 (0.57, 1.93), fully adjusted].

conclusionsThese findings suggest that warfarin treatment influences MK-4 concentrations in the human brain. Future studies are needed to elucidate the mechanisms underlying this effect and its clinical implications.

Indexed as

AnticoagulantsBrainVitamin KVitamin K 2WarfarinAgedAged, 80 and overAutopsyCognitive DysfunctionDementiaFemaleHumansMaleAnticoagulantsmenatetrenoneVitamin KVitamin K 2Warfarinagingbraincognitive impairmentmenaquinone-4vitamin Kvitamin K antagonist

Identifiers

PMID40339909
PMCPMC12405923

What OpenQuestion holds

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Registered trials

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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.