Evidence map›Paper›PMID 38769578›Full record

ArticleAlzheimer's research & therapy2024

Plasma trimethylamine N-oxide (TMAO): associations with cognition, neuroimaging, and dementia.

Amber Yaqub, Dina Vojinovic, Meike W Vernooij, P Eline Slagboom, Mohsen Ghanbari, Marian Beekman, Jeroen van der Grond, Thomas Hankemeier, Cornelia M van Duijn, M Arfan Ikram and 1 more

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In one paragraph

Article in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 3 pooled it
–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

22 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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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

11 authors.

Amber YaqubDepartment of Epidemiology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam, CA, 3000, the Netherlands.
Dina VojinovicDepartment of Epidemiology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam, CA, 3000, the Netherlands.
Meike W VernooijDepartment of Epidemiology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam, CA, 3000, the Netherlands.
P Eline SlagboomSection of Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
Mohsen GhanbariDepartment of Epidemiology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam, CA, 3000, the Netherlands.
Marian BeekmanSection of Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
Jeroen van der GrondDepartment of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Thomas HankemeierDivision of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands.
Cornelia M van DuijnNuffield Department of Population Health, University of Oxford, Oxford, UK.
M Arfan IkramDepartment of Epidemiology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam, CA, 3000, the Netherlands. m.a.ikram@erasmusmc.nl.
Shahzad AhmadDepartment of Epidemiology, Erasmus MC, University Medical Center, PO Box 2040, Rotterdam, CA, 3000, the Netherlands.

Funding

Deltaplan Dementie from ZonMW Memorabel 73305095005
6 · The paper itself

Abstract

backgroundThe gut-derived metabolite Trimethylamine N-oxide (TMAO) and its precursors - betaine, carnitine, choline, and deoxycarnitine - have been associated with an increased risk of cardiovascular disease, but their relation to cognition, neuroimaging markers, and dementia remains uncertain.

methodsIn the population-based Rotterdam Study, we used multivariable regression models to study the associations between plasma TMAO, its precursors, and cognition in 3,143 participants. Subsequently, we examined their link to structural brain MRI markers in 2,047 participants, with a partial validation in the Leiden Longevity Study (n = 318). Among 2,517 participants, we assessed the risk of incident dementia using multivariable Cox proportional hazard models. Following this, we stratified the longitudinal associations by medication use and sex, after which we conducted a sensitivity analysis for individuals with impaired renal function.

resultsOverall, plasma TMAO was not associated with cognition, neuroimaging markers or incident dementia. Instead, higher plasma choline was significantly associated with poor cognition (adjusted mean difference: -0.170 [95% confidence interval (CI) -0.297;-0.043]), brain atrophy and more markers of cerebral small vessel disease, such as white matter hyperintensity volume (0.237 [95% CI: 0.076;0.397]). By contrast, higher carnitine concurred with lower white matter hyperintensity volume (-0.177 [95% CI: -0.343;-0.010]). Only among individuals with impaired renal function, TMAO appeared to increase risk of dementia (hazard ratio (HR): 1.73 [95% CI: 1.16;2.60]). No notable differences were observed in stratified analyses.

conclusionsPlasma choline, as opposed to TMAO, was found to be associated with cognitive decline, brain atrophy, and markers of cerebral small vessel disease. These findings illustrate the complexity of relationships between TMAO and its precursors, and emphasize the need for concurrent study to elucidate gut-brain mechanisms.

Indexed as

CognitionDementiaMagnetic Resonance ImagingMethylaminesNeuroimagingAgedBiomarkersBrainCholineFemaleHumansMaleMiddle AgedProspective StudiesBiomarkersCholineMethylaminestrimethyloxamineCognitionDementiaGut-microbiomeMetabolitesNeuroimagingPopulation-based

Identifiers

PMID38769578
PMCPMC11103865

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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.