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Skeletal Muscle Density and Cognitive Function: A Cross-Sectional Study in Men

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Abstract

We aimed to investigate cross-sectional associations between skeletal muscle density, a proxy measure for fatty infiltration into muscle, and cognition. Contributions from body fat mass, systemic inflammation and lifestyle were explored, as these factors have been identified in both muscle and cognitive deterioration. For 281 men (60–95 year) from the Geelong Osteoporosis Study, radial and tibial muscle density were measured using peripheral quantitative computed tomography. Body fat and appendicular lean mass were measured using dual-energy X-ray absorptiometry. Cognitive function was assessed for psychomotor function (DET), visual identification/attention (IDN), visual learning (OCL) and working memory (OBK) (CogState Brief Battery). Composite scores signified overall cognitive function (OCF). Higher scores represent poorer performance except for OCL and OCF. Regression analyses examined associations between muscle density and cognition; potential confounders included age, muscle cross-sectional area (CSA), body composition, lifestyle and serum markers of inflammation. Negative associations with age were evident for muscle density, all cognitive domains and OCF. Muscle density at both sites was positively associated with DET, OCL and OCF. After adjustment for age, the association persisted for DET (radius: B =  − 0.006, p = 0.02; tibia: B =  − 0.003, p = 0.04) and OCL (radius B =  + 0.004, p = 0.02; tibia: B =  + 0.005, p < 0.001). At the radius, further adjustment for serum TNF-α explained the association between muscle density (B =  − 0.002, p = 0.66) and DET. Education and physical activity contributed to the model for radial muscle density and DET. There were no contributions from muscle CSA, appendicular lean mass, body fat mass, other markers of inflammation or other potential confounders. At the tibia, the association between muscle density and DET (B =  − 0.003, p = 0.04) was independent of TNF-α. There was an age-adjusted association between muscle density and OCL at both sites (radius: B =  + 0.004, p = 0.02; tibia: B =  + 0.005, p < 0.001). None of the potential confounders contributed to the models. Muscle density was associated with cognitive function in the DET and OCL domains. However, there was little evidence that this was explained by inflammation or body fat mass. No associations were identified between muscle density and IDN or OBK.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We acknowledge the men who participated in the study, and the staff who contributed to the data collection. The authors thank Professor Graham Giles of the Cancer Epidemiology Centre of The Cancer Council Victoria, for permission to use the Dietary Questionnaire for Epidemiological Studies (Version 2), Melbourne: The Cancer Council Victoria 1996.

Funding

The Geelong Osteoporosis Study was funded by the National Health and Medical Research Council (NHMRC) Australia (projects 251638, 628582). The funding organisations played no role in the design or conduct of the study, in the collection, management, analysis and interpretation of the data, nor in the preparation, review and approval of the manuscript.

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Authors and Affiliations

  1. Deakin University, IMPACT Institute, Geelong, VIC, Australia

    Sophia X. Sui, Lana J. Williams, Kara L. Holloway-Kew, Natalie K. Hyde, Kara B. Anderson, Monica C. Tembo, Alex B. Addinsall & Julie A. Pasco

  2. GMHBA, Geelong, VIC, Australia

    Sarah Leach

  3. Department of Medicine–Western Health, The University of Melbourne, St Albans, VIC, Australia

    Julie A. Pasco

  4. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia

    Julie A. Pasco

  5. University Hospital Geelong, Barwon Health, Geelong, VIC, Australia

    Julie A. Pasco

  6. Epi-Centre for Healthy Ageing, School of Medicine, IMPACT Institute, Deakin University, Barwon Health, PO Box 281, Geelong, VIC, 3220, Australia

    Sophia X. Sui

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Contributions

All authors take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: JAP, LJW, SXS. Drafting of the manuscript: SXS. Acquisition, analysis, or interpretation of data: all authors. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: SXS, JAP. Supervision: JAP, LJW, KLH-K and NKH.

Corresponding author

Correspondence to Sophia X. Sui.

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Conflict of interest

Sophia X. Sui was supported by a Deakin Postgraduate Scholarship in conjunction with the Geelong Medical and Hospital Benefits Association (GMHBA); Lana J. Williams by a NHMRC Career Development Fellowship (1064272) and a NHMRC Investigator grant (1174060); Kara L. Holloway‑Kew by an Alfred Deakin Postdoctoral Research Fellowship; Natalie K. Hyde by a Dean’s Research Postdoctoral Fellowship (Deakin University); Kara B. Anderson by an Australian Government Research Training Program (RTP) Scholarship and MCT by a Deakin Postgraduate Scholarship. Sarah Leach is General Manager Health, People and Community in the Geelong Medical and Hospital Benefits Association (GMHBA) and is an Adjunct Associate Professor in the Office of the Faculty of Health, at Deakin University. JAP has received speaker fees from Amgen, Eli Lilly and Sanofi-Aventis and funding from the National Health and Medical Research Council (NHMRC), Barwon Health, Deakin University, Amgen, the BUPA Foundation, Osteoporosis Australia, Australia and New Zealand Bone and Mineral Society, the Geelong Community Foundation, the Western Alliance, and the Norman Beischer Foundation. Alex B. Addinsall declares that no competing interests exist.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Human Research Ethics Committee at Barwon Health.

Human and Animal Rights and Informed Consent

All participants provided written informed consent to participate in the study. The study was approved by the Human Research Ethics Committee at Barwon Health.

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Appendices

Appendix 1

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Table 3 Pearson correlations (r and p values) between covariates and cognitive function or muscle parameters
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Appendix 2

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Table 4 Intergroup differences in cognitive function and muscle parameters
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Sui, S.X., Williams, L.J., Holloway-Kew, K.L. et al. Skeletal Muscle Density and Cognitive Function: A Cross-Sectional Study in Men. Calcif Tissue Int 108, 165–175 (2021). https://doi.org/10.1007/s00223-020-00759-3

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