Symptoms provide predictive information on daily functioning beyond signs and diseases in middle-aged and older adults, particularly those with multimorbidity.

Symptoms, signs, and diseases together explained 13.3% of variability in functional limitations in the total sample.

• Sample consisted of 4025 participants in the Longitudinal Aging Study Amsterdam (1995-2022).
• Six symptoms, five signs, and eight diseases were used as exposures; a sum score of six functional limitations was the outcome.
• Partial Information Decomposition was used to partition total variability into unique, redundant, and synergistic components.
• None of the three domains (symptoms, signs, diseases) contributed unique information in the total sample.
• Synergy accounted for most of the explained variability: signs = 9.2%, symptoms = 34.3%, diseases = 34.3%.

In the multimorbidity subgroup, symptoms uniquely contributed 35.5% of their information to functional limitations, while signs and diseases were redundant.

• 59% of the total sample had multimorbidity.
• Symptoms, signs, and diseases together explained 8.7% of variability in functional limitations in the multimorbidity subgroup.
• Symptoms provided unique information in the multimorbidity subgroup, whereas signs and diseases were found to be redundant.
• This contrasts with the total sample, where none of the three domains contributed unique information.

Adding symptoms to diseases in prediction models resulted in a 110% increase in predictive agreement in the multimorbidity subgroup, compared to a 58% increase in the total sample.

• Random forest prediction models were used to examine the added predictive value of symptoms, signs, and diseases.
• The increase in predictive agreement when adding symptoms to diseases was 110% in the multimorbidity subgroup.
• The corresponding increase in the total sample was 58%.
• These results indicate that symptoms provided substantial predictive value beyond diseases alone, particularly for people with multimorbidity.

Traditional, disease-oriented approaches may overlook the impact of symptoms on daily functioning in people with multimorbidity.

• The study was motivated by the assumption that symptoms and signs provide information on functional limitations beyond that of diseases in older adults.
• The authors specifically focused on whether this was more pronounced in people with multimorbidity.
• The Longitudinal Aging Study Amsterdam data spanned 1995-2022.
• The study used Partial Information Decomposition to explore unique, redundant, and synergistic information across domains.

The findings support the need for a symptom-oriented approach in clinical care and research for people with multimorbidity.

• In the multimorbidity subgroup, symptoms and signs explained more variability in functional limitations than diseases alone.
• Symptoms uniquely contributed information not captured by signs or diseases in the multimorbidity subgroup.
• The 110% increase in predictive agreement from adding symptoms to diseases in the multimorbidity subgroup supports the clinical relevance of symptom assessment.
• The authors conclude that a symptom-oriented approach is warranted in both clinical care and research contexts.