Evidence map›Paper›PMID 42201257›Full record

ArticleCNS neuroscience & therapeutics2026

Methionine, Homocysteine, and Methylation Levels Predict Cognitive Decline in Alzheimer's Disease.

Xiaoyu Zhang, Ai Guan, Wanlin Li, Zhenbo Zhao, Liufeng Tang, Xiaoguang Yao, Xiaoyun Liu, Gang Wang, Hualong Wang

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

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No citing paper in PubMed yet.

4 · The record

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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.

Xiaoyu ZhangDepartment of Neurology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Ai GuanDepartment of Neurology, The First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, China.
Wanlin LiDepartment of Neurology, The First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, China.
Zhenbo ZhaoDepartment of Neurology, The First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, China.
Liufeng TangDepartment of Neurology, The First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, China.
Xiaoguang YaoHebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, College of Integrative Medicine, Institute of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China.
Xiaoyun LiuDepartment of Neurology, The First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, China.ORCID 0009-0003-8604-904X
Gang WangDepartment of Neurology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Hualong WangDepartment of Neurology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.ORCID 0000-0002-5741-0313

Funding

Government-funded Outstanding Clinical Medical Talent Training Program ZF2025047National Natural Science Foundation of China 82371416Natural Science Foundation of Hebei Province H2024206494Natural Science Foundation of Hebei Province H2024423038Science and Technology Research Project for Higher Education Institutions in Hebei Province ZD2022146
6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD), the most common cause of dementia, involves metabolic factors such as homocysteine, methionine, and DNA methylation in its pathogenesis. However, the precise interactions among these factors and their impact on cognitive function in AD require further elucidation.

methodsA total of 191 AD patients and 200 cognitively normal (CN) individuals were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Demographic, clinical, and metabolic data, including MMSE scores and white matter hyperintensity (WMH) volumes, were collected. Longitudinal cognitive changes over 1 year were also evaluated in 104 AD patients.

resultsCompared to CN subjects, AD patients exhibited significantly lower MMSE scores, hippocampal volume, total brain volume, methionine levels, and methylation levels, alongside higher homocysteine levels and WMH volumes. Logistic regression and correlation analyses revealed that homocysteine, methionine, and methylation levels were significantly associated with cognitive function in AD patients but not in CN subjects. Elevated homocysteine levels in AD patients correlated with lower MMSE scores, higher WMH volumes, lower vitamin B12 levels, and older age. Similarly, low methionine and methylation levels were associated with more severe cognitive impairment and brain atrophy. Longitudinal analyses showed that AD patients with low methionine, high homocysteine, or low methylation levels experienced significantly greater cognitive decline over 1 year compared to those with more favorable biomarker profiles.

conclusionsOur findings highlight the significant associations between homocysteine, methionine, and methylation levels and cognitive decline in AD patients. These results suggest that metabolic and epigenetic alterations may contribute to AD progression and could serve as potential biomarkers or therapeutic targets in AD.

Indexed as

Alzheimer DiseaseCognitive DysfunctionHomocysteineMethionineAgedAged, 80 and overBiomarkersBrainFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMethylationBiomarkersHomocysteineMethionineAlzheimer's diseasehomocysteinemethioninemethylationwhite matter hyperintensities

Identifiers

PMID42201257
PMCPMC13240123

What Socratic holds

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LicenceCC BY
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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 Socratic graph.