Modeling Frailty Risk Based on Biochemical and Hematological Parameters Using Multiple and Logistic Regression: Cross-Sectional Analysis of the Toledo Study for Healthy Aging

Frailty is a complex syndrome characterized by diminished physiological reserves, resulting in increased vulnerability among older adults. Scalable tools that leverage routinely collected laboratory data could enable earlier risk stratification in aging populations.

The aim of the study is to model frailty risk using Frailty Trait Scale (FTS)-12 scores and biochemical or hematological parameters, and to examine sex-specific patterns in predictors and performance.

This study analyzed data from a population-based cohort of 1485 individuals aged 65 years or older, drawn from the Toledo Study for Healthy Aging (TSHA). Multiple and logistic regression analyses were used to investigate the relationships between biochemical and hematological parameters, and the FTS-12 score. Predictive models were developed separately for female and male participants, incorporating both single and composite risk factors. Model performance was evaluated using correlation coefficients, coefficients of determination, Akaike information criterion, log-likelihood values, and receiver operating characteristic curves, which summarize how well the models distinguish between higher and lower frailty risk.

The regression models accounted for approximately 40% of the variability in FTS-12 scores, revealing distinct risk factors for each sex. Gamma-glutamyl transferase, albumin, and age were kept as key predictors in the selected models. Several composite risk factor functions were also significantly associated with the FTS-12 score. Correlations between observed and predicted FTS-12 scores were moderately strong, with values of 0.621 (P<.001) for female participants and 0.615 (P<.001) for male participants. Logistic regression models showed moderate-to-good discriminative performance for high frailty probability, achieving receiver operating characteristic area under the curve values of 0.799 for female participants and 0.824 for male participants.

This analysis is an exploratory proof-of-concept study, and the developed models do not constitute validated clinical prediction tools. Routine laboratory profiles demonstrate moderate, sex-specific predictive performance for FTS-12-defined frailty and may, in principle, complement comprehensive geriatric assessment by facilitating the early identification of patients who could benefit from further evaluation and closer clinical follow-up. External validation in independent cohorts is required before any clinical use, alongside longitudinal designs with repeated biomarker measures and integration of additional biological layers, to enhance generalizability and confirm clinical utility. Within these limits, the analysis highlights the potential of routine laboratory data to support digitally enabled frailty screening and workflow-integrated risk stratification in primary care and remote geriatric care settings.