Evidence map›Paper›PMID 39976843›Full record

ArticleGeroScience2025

Metabolomic insight into the link of intermuscular fat with cognitive performance: the Health ABC Study.

Richard Xu, Qu Tian, Megan M Marron, Luigi Ferrucci, Shanshan Yao, Seyoung Kim, Ravi V Shah, Venkatesh L Murthy, Anne B Newman, Iva Miljkovic and 1 more

Abstract read
In one paragraph

Article in GeroScience, 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. Review
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.

Richard XuDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA. rbx1@pitt.edu.ORCID 0000-0003-4722-7790
Qu TianLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Megan M MarronDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
Luigi FerrucciLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Shanshan YaoDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
Seyoung KimDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
Ravi V ShahCardiology Division, Vanderbilt Translational and Clinical Research Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Venkatesh L MurthyDivision of Cardiovascular Medicine, Department of Medicine, and Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA.
Anne B NewmanDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
Iva MiljkovicDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
Caterina RosanoDepartment of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.

Funding

VARIABILITY, STABILITY & SMOOTHNESS OF WALKINGP30AG024827 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JENNIFER S BRACH · 2004 to 2026
$28.6M
Peripheral Nerve Function Decline in an Aged CohortR01AG028050 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STROTMEYER, ELSA S. · 2007 to 2015
$3.5M
Implications of metabolism on healthy aging in African and Caucasian Americans: the Health ABC studyR01AG059729 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MURTHY, VENKATESH LOCHARLA, NEWMAN, ANNE B. · 2018 to 2022
$3.1M
End of Life in the Very OldR01NR012459 · NINR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ALBERT, STEVEN M, LUNNEY, JUNE R · 2011 to 2015
$2.7M
Population Neuroscience of Aging and Alzheimer's Disease (PNA)T32AG055381 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Caterina Rosano, Andrea L Rosso · 2018 to 2026
$2.7M
Metabolic architecture of insulin action in Southwest American IndiansU01DK123013 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MURTHY, VENKATESH LOCHARLA, SHAH, RAVI · 2020 to 2025
$2.4M
NIA NIH HHS 5T32AG055381-07NIA NIH HHS K01-AG-075143NIA NIH HHS N01-AG-6-2101NIA NIH HHS N01-AG-6-2103NIA NIH HHS N01-AG-6-2106NIA NIH HHS P30 AG024827NIA NIH HHS R01 AG028050NIA NIH HHS R01-AG-028050NIA NIH HHS R01 AG059729NIA NIH HHS R01-AG059729NIA NIH HHS T32 AG055381NIDDK NIH HHS U01 DK123013NINR NIH HHS R01 NR012459NINR NIH HHS R01-NR-012459
6 · The paper itself

Abstract

There is growing evidence that higher intermuscular fat (IMF) is associated with worse processing speed, measured by the digit symbol substitution test (DSST) in older adults. However, the underlying biological mechanisms are not well understood. Considering that both muscle and the brain are metabolically active organs, we sought to identify metabolites that may explain the IMF-DSST association. We assessed 613 plasma metabolites in 2388 participants from the Health, Aging, and Body Composition Study (mean age ± SD 74.7 ± 2.9 years, 50% men, 63% white), using liquid chromatography-mass spectrometry. We confirmed that higher IMF was associated with worse DSST scores (standardized beta (95% CI) - 0.08 (- 0.12, - 0.03), p < 0.001). Sixty-six metabolites were significantly associated with both IMF and DSST. Four of the 66 metabolites attenuated the association by ≥ 10%: higher levels of adrenic acid (polyunsaturated fatty acid), and lower levels of C20:5 lysophosphatidylcholine (lysophospholipid), 1-methylnicotinamide (vitamin B3-related myokine), and maslinic acid (triterpene) were associated with higher IMF and worse DSST. Together, they explained 41% of the IMF-DSST association. Pathway enrichment analyses identified two significant shared pathways: unsaturated fatty acid metabolism and the citrate (TCA) cycle. This study provides hypothesis-generating evidence that a set of circulating metabolites related to unsaturated fatty acids, energy metabolism, and myokines may partially explain the inverse association of IMF with processing speed. The findings, if further confirmed by independent studies, advance our understanding of molecular pathways underlying muscle-brain crosstalk. Whether the identified metabolites are early predictors of future decline in processing speed should be further investigated.

Indexed as

Adipose TissueAgingCognitionMuscle, SkeletalAgedBody CompositionChromatography, LiquidFemaleHumansMaleMetabolomicsCognitionHealth ABC StudyIntermuscular fatMetabolome

Identifiers

PMID39976843
PMCPMC12181493

What Socratic 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 Socratic graph.