Evidence map›Paper›PMID 41579261›Full record

ArticleGeroScience2026

Metabolic signatures, vitamin D, and red cell distribution width in dementia risk: UK Biobank insights.

May A Beydoun, Tianyi Huang, Nicole Noren Hooten, Hind A Beydoun, Mustapha Bouhrara, Jordan Weiss, Michele K Evans, Alan B Zonderman

Abstract read
PubMed Publisher
In one paragraph

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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

May A BeydounLaboratory of Epidemiology and Population Sciences, National Institute On Aging, NIA/NIH/IRP, 251 Bayview Blvd, Suite 100, Baltimore, MD, 21224, USA. baydounm@mail.nih.gov.ORCID http://orcid.org/0000-0002-1050-4523
Tianyi HuangLaboratory of Epidemiology and Population Sciences, National Institute On Aging, NIA/NIH/IRP, 251 Bayview Blvd, Suite 100, Baltimore, MD, 21224, USA.
Nicole Noren HootenLaboratory of Epidemiology and Population Sciences, National Institute On Aging, NIA/NIH/IRP, 251 Bayview Blvd, Suite 100, Baltimore, MD, 21224, USA.ORCID http://orcid.org/0000-0002-1683-3838
Hind A BeydounVA National Center On Homelessness Among Veterans, U.S. Department of Veterans Affairs, Washington, DC, 20420, USA.
Mustapha BouhraraLaboratory of Clinical Investigation, National Institute On Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA.
Jordan WeissOptimal Aging Institute, New York University Grossman School of Medicine, New York, NY, 10012, USA.
Michele K EvansLaboratory of Epidemiology and Population Sciences, National Institute On Aging, NIA/NIH/IRP, 251 Bayview Blvd, Suite 100, Baltimore, MD, 21224, USA.
Alan B ZondermanLaboratory of Epidemiology and Population Sciences, National Institute On Aging, NIA/NIH/IRP, 251 Bayview Blvd, Suite 100, Baltimore, MD, 21224, USA.

Funding

NIA NIH HHS AG000513
6 · The paper itself

Abstract

Red cell distribution width (RDW), reflecting erythrocyte size variability, and serum vitamin D are emerging biomarkers for dementia. We examined the independent and joint associations of RDW and 25-hydroxyvitamin D [25(OH)D] with incident dementia and the potential mediating role of plasma metabolomic profiles in a large prospective cohort study. We analyzed data from 162,606 UK Biobank participants aged ≥ 50 years and dementia-free with RDW and 25(OH)D measurements at baseline. Incident dementia was identified via electronic health records for ≤ 15 years. Cox proportional hazards models adjusted for sociodemographic, cardiovascular, and genetic factors. Mediation was assessed using generalized structural equation models based on 15 metabolomic principal components (zMETAB1-zMETAB15) derived from 249 NMR-based plasma metabolites. Higher RDW was associated with increased dementia risk (HR = 1.05; 95% CI: 1.02-1.08) and a atherogenic lipid signature (zMETAB1: Cholesteryl Esters in VLDL), while higher 25(OH)D was associated with lower risk (HR = 0.89; 95% CI: 0.86-0.92) and more favorable metabolomic profiles (zMETAB7: higher Omega-3 Fatty Acids; zMETAB12: lower Saturated Fatty Acids). zMETAB1, zMETAB2 (Free Cholesterol in Small HDL), and zMETAB4 (Phospholipids in Small HDL) significantly mediated RDW's effect on dementia (up to 8.8%), whereas ~ 10.8% of the association with vitamin D was mediated by zMETAB1, with additional contributions from zMETAB7 and zMETAB12. Omega-3 fatty acids partially mediated both associations, while RDW and 25(OH)D did not interact significantly in relation to dementia risk. RDW and vitamin D exert opposing, non-interactive influences on dementia risk. Lipid metabolism, particularly omega-3 fatty acids, partially mediates both associations, highlighting a common metabolic pathway that could be targeted for prevention. These findings suggest that interventions aimed at increasing omega-3 intake may simultaneously modulate the effects of both RDW and vitamin D on dementia risk, offering a promising translational strategy for early risk reduction.

Indexed as

DementiaMetabolomicsRed cell distribution widthUK BiobankVitamin D

Identifiers

What OpenQuestion holds

Textmetadata
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.