Evidence map›Paper›PMID 41943508›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Accelerated epigenetic aging as a modifier of homocysteine-associated cognitive decline: Findings from NHANES.

Haoxuan Li, Yuhan Chen, Zhe Wang, Yankun Wang, Ran Bi, Jiayu Hou, Huan Chen, Zixuan Zhang, Zhenhao Guo, Zhuo Chen and 2 more

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Haoxuan LiGrade 2023, Clinical Medicine, Hebei Medical University, Shijiazhuang, China.
Yuhan ChenDepartment of Human Anatomy, Neuroscience Research Center, Hebei Medical University, Shijiazhuang, China.
Zhe WangGrade 2024, Clinical Medicine, Hebei Medical University, Shijiazhuang, China.
Yankun WangGrade 2024, Clinical Medicine, Hebei Medical University, Shijiazhuang, China.
Ran BiGrade 2024, Integrated Traditional Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, China.
Jiayu HouGrade 2023, Clinical Medicine, Hebei Medical University, Shijiazhuang, China.
Huan ChenDepartment of Human Anatomy, Neuroscience Research Center, Hebei Medical University, Shijiazhuang, China.
Zixuan ZhangDepartment of Human Anatomy, Neuroscience Research Center, Hebei Medical University, Shijiazhuang, China.
Zhenhao GuoGrade 2022, Basic Medicine, Hebei Medical University, Shijiazhuang, China.
Zhuo ChenGrade 2023, Clinical Medicine, Hebei Medical University, Shijiazhuang, China.
Huixian CuiDepartment of Human Anatomy, Neuroscience Research Center, Hebei Medical University, Shijiazhuang, China.
Sha LiDepartment of Human Anatomy, Neuroscience Research Center, Hebei Medical University, Shijiazhuang, China.

Funding

National Natural Science Foundation of China 82171582
6 · The paper itself

Abstract

introductionHyperhomocysteinemia represents a modifiable risk factor for cognitive decline and dementia, yet the role of epigenetic aging mechanisms in mediating this association remain poorly characterized, limiting development of targeted interventions.

methodsWe analyzed 1343 National Health and Nutrition Examination Survey participants aged ≥ 60 years using weighted regression, cubic splines, and mediation analyses. An independent cohort of 2073 participants validated findings.

resultsElevated homocysteine concentrations were significantly associated with reduced cognitive processing speed. GrimAge2 epigenetic age acceleration significantly mediated this association, accounting for 33.3% of the total effect. β2-microglobulin emerged as the strongest mediating component, explaining 38.8% of the homocysteine-cognition relationship. Folate demonstrated cognitive protection through homocysteine reduction (18.7% of total effect) without modulating downstream pathological cascades.

conclusionEpigenetic aging-associated neuroinflammation serves as a key mechanistic link between hyperhomocysteinemia and cognitive decline. The neuroprotective effects of folate are mediated specifically through homocysteine reduction, providing novel mechanistic insights for precision prevention strategies in cognitive aging.

Indexed as

AgingCognitive DysfunctionEpigenesis, GeneticHomocysteineHyperhomocysteinemiaAgedAged, 80 and overbeta 2-MicroglobulinFemaleFolic AcidHumansMaleMediation AnalysisMiddle AgedNutrition SurveysProcessing Speedbeta 2-MicroglobulinFolic AcidHomocysteinecognitive declineepigenetic agingfolatehomocysteineneuroinflammationβ2‐microglobulin

Identifiers

PMID41943508
PMCPMC13053932

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.