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Reference centiles for intrinsic capacity throughout adulthood and their association with clinical outcomes: a cross-sectional analysis from the INSPIRE-T cohort

Nature Aging volume 3, pages 1521–1528 (2023)Cite this article

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Abstract

Intrinsic capacity (IC), a function-centered construct, is defined as the composite of all physical and mental capacities of an individual. IC and surrounding environmental factors determine an individual’s functional ability to do what they want or feel valued. Current literature lacks evidence on how IC varies throughout adulthood. In this study, we demonstrated a method to establish age-specific and sex-specific reference centiles for IC using the Human Translational Research Cohort of the INSPIRE Platform (975 adults, aged 20–102 years, living in the southwest France, Toulouse area). IC was operationalized as the mean score of the five key domains (cognition, locomotion, psychology, sensory and vitality) and the factor score from a bifactor model, respectively. Both IC operationalizations showed higher IC levels in young and middle age and markedly lower levels after age 65 years, with greater inter-individual variation in old age than in youth. Individuals with IC ≤10th percentile tended to have high comorbidity, prefrailty/frailty, difficulties in basic and instrumental activities of daily living and falls than individuals with IC >90th percentile. These findings suggest that IC reference centiles can help monitor the functional capacity of individuals during aging, similar to tracking children’s development with growth charts.

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Fig. 1: Distribution of IC score in adults aged 20–102 years.

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Data availability

The data underlying the results reported in this manuscript (that is, text, tables, figures and the supplementary information) will be shared in de-identified form owing to privacy protections. Request for de-identified data and a data dictionary will be evaluated by the INSPIRE data access committee, which can be contacted at the following addresses: guyonnet.s@chu-toulouse.fr and nicola.coley@inserm.fr. Data will be made available for other researchers upon reasonable request for a specified scientific purpose outlined in a methodologically sound research proposal, subject to the approval of the appropriate INSPIRE committee and after signing a data use agreement.

Given the ongoing nature of the INSPIRE-T study, the authors are unable to make the dataset publicly accessible at this time. In addition, according to the INSPIRE policy, all analyses using INSPIRE-T data (including the present study) should be first evaluated and approved by the committee after submission of a comprehensive analysis proposal. Therefore, for researchers interested in accessing the data used for the current study, the same evaluation procedure should be followed.

Code availability

The code that supports the results of the present study is available from the corresponding authors upon reasonable request. All models were built using publicly available packages and functions in the R and SAS programming languages.

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Acknowledgements

The INSPIRE platform was supported by grants from the Region Occitanie/Pyrénées-Méditerranée (reference no.: 1901175) and the European Regional Development Fund (ERDF) (project no.: MP0022856) and the Inspire Chairs of Excellence funded by: Alzheimer Prevention in Occitania and Catalonia (APOC), EDENIS, KORIAN, Pfizer and Pierre-Fabre.

W.-H.L. has been partially supported through the grant EUR CARe N°ANR-18-EURE-0003 in the framework of the Programme des Investissements d’Avenir.

The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Members of the INSPIRE platform group:

INSPIRE-T human cohort group: coordinators: S. Guyonnet and B. Vellas; project managers: L. Brigitte and A. Milhet; clinical research assistants: E. Paez, E. Muller and S. Le Floch; investigators: C. Takeda, C. Faisant, F. Lala, G. Abellan Van Kan, Z. Steinmeyer, A. Piau, T. Macaron, D. Angioni and P.-J. Ousset; nurses: M. Comté, N. Daniaud and F. Boissou-Parachaud; methodology, statistical analysis and data management subgroup: S. Andrieu and C. Cantet; body composition, VO2 max and isocinetism subgroup: Y. Rolland, P. de Souto Barreto and F. Pillard; technician DXA: B. Teysseyre; MRI subgroup: M. Faruch and P. Payoux; ICOPE subgroup: C. Takeda and N. Tavassoli; and biological sample collection subgroup: M. Dorard, B. Razat, C. Champigny and S. Guyonnet.

INSPIRE animal cohort groups: C. Dray and J.-P. Pradère (fish colony) and A. Parini and Y. Santin (murine cohort).

Associated research teams: D. Langin, P. Gourdy, L. Martinez, A. Bouloumié and A. Parini (I2MC lab); N. Fazilleau, R. Liblau, J.-C. Guéry, M. Simon, N. Gaudenzio, L. Bostan, H. El Costa and N. J. Ferrat (Infinity lab); P. Valet, C. Dray, I. Ader and V. Planat (Restore); P. Payoux and P. Peran (Tonic lab); C. Delpierre and S. Andrieu (CERPOP lab); C. Rampon, N. Davezac and B. Guiard (CRCA/CBI lab); N. Vergnolles, J.-P. Motta, S. Djelabi and P. Floch (IRSD lab); and J.-E. Sarry (CRCT lab).

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Authors and Affiliations

  1. IHU HealthAge, Toulouse, France

    Wan-Hsuan Lu, Yves Rolland, Sophie Guyonnet, Philipe de Souto Barreto & Bruno Vellas

  2. CERPOP UMR 1295, Inserm, Université Paul Sabatier, Toulouse, France

    Wan-Hsuan Lu, Yves Rolland, Sophie Guyonnet, Philipe de Souto Barreto & Bruno Vellas

  3. Institute of Aging, Toulouse University Hospital (CHU Toulouse), Toulouse, France

    Wan-Hsuan Lu, Yves Rolland, Sophie Guyonnet, Philipe de Souto Barreto & Bruno Vellas

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  1. Wan-Hsuan Lu
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Contributions

W.-H.L. designed and conceptualized the research, performed the analyses, interpreted the data and drafted the manuscript. Y.R. and S.G. revised the draft critically for important intellectual content. P.S.d.B. designed and conceptualized the research, interpreted the data and revised the draft critically for important intellectual content. B.V. conceived the INSPIRE platform, interpreted the data and revised the draft critically for important intellectual content. All authors have read and agreed with the final version to be submitted.

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Correspondence to Wan-Hsuan Lu.

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Competing interests

B.V. is the founder president of IHU HealthAge at Toulouse University Hospital and is an investigator in clinical trials sponsored by several industry partners (IHU and the INSPIRE geroscience platform). Other authors report no competing interests.

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Nature Aging thanks Jean Woo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Sensitivity analysis on the IC factor score extracted from the CFA bifactor model showed a similar distribution across age as the IC mean score.

a. Scatterplot of the IC factor score among the 948 INSPIRE-T participants aged 20 to 102 (588 women and 360 men). Red represents women, and blue represents men. Like the distribution of the IC mean score, the IC factor score showed a negative, non-linear association with age. b,c. Smoothed reference centile curves for the IC factor score based on the INSPIRE-T cohort, derived using the LMS method (b for female and c for male). Seven percentile curves are shown: 3rd, 10th, 25th, 50th, 75th, 90th, and 97th. Numerical results of IC reference values for each percentile curve are provided in Supplementary Table 1.

Extended Data Fig. 2 Sensitivity analysis on the subgroup younger than 70 using four cognitive tests to assess the cognitive domain.

A composite measure of four cognitive tests – the Free and Cued Selective Reminding Test (FCSRT), the Digit Symbol Substitution Test (DSST), the Category Naming Test (CNT), and ten MMSE orientation items – was used to assess the cognitive domain of IC. a. Scatterplot of IC across age among 575 participants younger than 70, stratified by sex (379 women and 196 men). b,c. Smoothed reference centile curves for IC based on the INSPIRE-T cohort, derived using the LMS method (b for female and c for male). Seven percentile curves are shown: 3rd, 10th, 25th, 50th, 75th, 90th, and 97th. Numerical results of IC reference values for each percentile curve are provided in Supplementary Table 2.

Extended Data Fig. 3 All participants with IC ≤ P10 had at least one abnormal IC domain identified by the ICOPE Step 1 tools.

We examined the number of IC domains with potential abnormality according to the WHO ICOPE Step 1 screening tools among subjects with available data (n = 960). The details of the ICOPE Step 1 screening tools are summarized in Extended Data Table 3. This figure illustrates how individuals are distributed within each IC centile category based on the number of abnormal IC domains ranging from 0 to 6. Values in the bars indicate the participant numbers and percentages. All participants with IC ≤ P10 had at least one abnormal IC domain identified by the ICOPE Step 1 tools. Participants with IC > P90 tended to have fewer abnormal domains.

Extended Data Table 1 Age-specific and sex-specific reference values of IC for the INSPIRE-T cohort
Full size table
Extended Data Table 2 Association between IC centile groups and frailty outcome after excluding handgrip strength
Full size table
Extended Data Table 3 Assessments for ICOPE Step 1 screening
Full size table

Supplementary information

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Lu, WH., Rolland, Y., Guyonnet, S. et al. Reference centiles for intrinsic capacity throughout adulthood and their association with clinical outcomes: a cross-sectional analysis from the INSPIRE-T cohort. Nat Aging 3, 1521–1528 (2023). https://doi.org/10.1038/s43587-023-00522-x

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