Objective: Skeletal muscle fat infiltration (myosteatosis) increases with age and is an emerging risk factor for dementia. We aimed to determine the association between myosteatosis and cognitive decline among middle-aged White and Black Americans. Methods: Data were on men (n=1,080; 41.9% Black) and women (n=1,432; 49.0% Black) from the CARDIA study. CT-measured abdominal intermuscular fat (IMAT) volume was assessed at baseline. Cognition was assessed by Digit Symbol Substitution (DSST), Rey Auditory Verbal Learning (RAVLT), and Stroop Test at baseline and 5-year follow-up. Multivariable linear regression was used to assess associations of IMAT with cognitive change. Results: Participants were aged 50.2 (3.6) years and had IMAT of 2.3 (1.6) cm3, 5-year change in DSST of -2.8% (21.8), RAVLT 2.8% (17.5) and Stroop 6.5% (49.5). Greater IMAT was associated with steeper DSST decline (β =-0.52 points per SD, p-value=0.035), but not with Stroop or RAVLT. Stratified by race, greater IMAT predicted DSST decline among White (β =-0.73, p =0.044), but not Black (β =-0.44, p =0.195), participants. Conclusions: Abdominal myosteatosis may be a novel risk factor for decline in psychomotor speed, especially in middle-aged Whites. Further research on mechanisms, including metabolic mediators, is warranted to understand myosteatosis's role in mid-life cognitive decline.

The authors have declared no competing interest.

Adrianna I. Acevedo-Fontanez was supported by the Cardiovascular Epidemiology Training Grant at the University of Pittsburgh (National Heart, Lung, and Blood Institute T32-HL-083825). The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (75N92023D00002 & 75N92023D00005), Northwestern University (75N92023D00004), University of Minnesota (75N92023D00006), and Kaiser Foundation Research Institute (75N92023D00003) and NHLBI grant R01‐HL098445 to Vanderbilt University and Wake Forest University.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Ethics committee/IRB of each field center and the coordinating center for the Coronary Artery Risk Development in Young Adults Study (CARDIA) gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data from CARDIA are available to investigators.