This review examines the prevalence of common geriatric syndromes and their association with patient-centered outcomes. Syndrome definitions varied and overlapped. Prevalence estimates increased with age. Women had higher rates of frailty and all types of disabilities; African Americans had higher prevalence of multiple morbidities, frailty, malnutrition, and disability compared to Caucasians; and evidence on other minority subgroups was sparse.

All syndromes were associated with increased risk of death and institutionalization. Age and sex were strongly associated with mortality, and the additional presence of one or more conditions increased the effect. Using relative risk, several conditions strongly influenced mortality, including poor health, severe BADL disability, low BMI, dementia, and impaired homeostenosis. The syndromes increased the likelihood of death more among the young-old. For those older than age 90 years, factoring in conditions and syndromes in relation to survival added minimal value. Complexity was not associated with better mortality models in older persons.

Our review offers several insights. Previous studies have inconsistently defined the conditions we considered. Two factors influence the structure of the measure: composition (i.e., its combination of elements) and the cut-off score used to determine severity levels. The definition’s nature, or operationalization, affects both the measure’s prevalence and its predictive power—usually in opposite directions. Across all syndromes, we observed a negative association between syndrome prevalence and its effect on mortality, and more severe forms of the same syndrome demonstrated the same negative association. Also across all syndromes, more inclusive definitions led to higher prevalence but lower predictive value. Lower prevalence of severe cognitive impairment and dementia were associated with higher risk of mortality and institutionalization compared to more common mild cognitive impairment. Figure 1 shows how the measure’s composition can affect its prevalence and strength of association with outcomes, while Figure 2 shows how different cut-off scores for the same measure affect its prevalence and strength of association.

Estimates of association varied depending on syndrome definitions, population subgroups, outcome definitions, and adjustment for correlated contributing factors. Some analyses addressed neither the multifactorial nature of geriatric syndromes nor the role of baseline diseases. For example, disability was an outcome of frailty but also part of frailty’s definition. Adjustment for correlated multifactorial syndromes that ignored the definitive primary cause of disability or death may give invalid estimation of the association between syndromes and mortality. Not all studies separately examined age and specific disease contributions.

Geriatric syndromes had overlapping definitions or interacting pathophysiology.¹ For example, multimorbidity increased risk of frailty,^89,117 which in turn was associated with cognitive impairment, comorbidities, and disability. The prevalence of frailty demonstrated a dose response association with a larger number of comorbidities or ADL disabilities.^23,104 Sarcopenia was associated with significantly higher odds of multiple disabilities.^68,123 Elderly adults with impaired homeostasis had significantly greater odds of frailty⁸⁹ and disabilities.⁴⁶

Interaction models are better suited than adjustment models for analyzing the multifactorial interactive nature of syndromes. Linear models that separately examine risk factors for chronic disease and patient outcomes are commonly accepted in disease epidemiology but fail to adequately address the multifactorial nature of geriatric syndromes.¹ The majority of studies, however, provided multivariate adjustment for known confounding factors, causes of death, and the presence of other syndromes. Models that analyzed the association between syndromes and mortality grouped primary causes of death into larger categories of cancer or cardiovascular diseases and adjusted for them. Using multivariate adjustment, the studies demonstrated significant association between each syndrome and outcomes, and concluded that syndromes contributed to the outcome independent of specific diseases included in the models. Concentric models include multiple etiological pathways contributing to the same clinical outcomes. Concentric models evaluate various pathways in developing and treating malignant tumors,¹ but like linear models, concentric models fail to capture the interacting nature of syndromes. Some authors have proposed interactive concentric models that address synergisms in how syndromes develop, and their association with outcomes.¹ However, published studies have provided insufficient evidence for better accuracy of interactive concentric models or of new measurement technologies.

Geriatric wisdom holds that age is a good predictor of average change but not of individual change because health status varies increasingly with age. The question then is whether a more complex approach that assigns varying weights to different syndromes/conditions is more useful than a more general approach that assigns older persons to general risk categories (e.g., high, medium, and low) and applies the 25th, 50th, and 75th percentiles of expected institutionalization or survival accordingly. When adjusted for age, the predictive value of the syndromes diminished by the time of followup to death. Few studies addressed syndrome length or used informative censoring when evaluating survival.³³³ Few studies analyzed the order in which components of the syndromes manifested.

Ideally we would consider outcomes other than mortality, but the measures used present large problems of endogeneity. Measures of frailty and disability, already closely linked, contain elements central to quality of life. They are also the basis for institutionalization. Comparative effectiveness of outpatient management strategies for prevention of disability and institutionalization fell beyond our scope.

Increased knowledge of prevalence, epidemiology, and the relationship between syndromes and health status illuminates the environment in which patients and physicians make decisions about preventive services. At the population level, the relevant measure is population attributable risk, which includes prevalence and risk of death. However, clinicians’ concerns are with individual prognosis. In that light, we based our estimation of life expectancy on the CDC United States Life Tables that incorporate average survival of older adults with different diseases and syndromes. Life expectancy was calculated assuming the same relative risk across the remaining life span. About 26 percent of the risk of death was attributable to the syndromes. Modifiable syndromes, including elevated CRP and allostatic load, were associated with 8.3 percent of all deaths in older persons. The effectiveness of preventive interventions in older persons would depend on their age and the nature of the syndromes. To be effective, preventive interventions targeting multimorbidity and geriatric syndromes in older persons may need to have multiple distinct components and must improve functional status.³³⁴

Our report has limitations. Several factors may affect interpretation of our results, including the metric chosen and population versus individual risks. We could not explain heterogeneity in prevalence estimates using available information about study participants or methodology. We analyzed the differences between self-reported syndromes and objectively assessed syndromes when possible. However, the studies used different methods to measure several syndromes, including disability. We could not address three-way interaction in prevalence estimates by age, sex, and race because the studies inconsistently analyzed these differences. We could not evaluate nonlinearity in the association between age and syndromes because the primary studies did not test the hypothesis of nonlinearity. We were not able to evaluate predictive value for all possible definitions of syndromes because no studies examined risk of death for different definitions of the same syndrome. We found limited evidence with which to examine race and ethnic differences in mortality and institutionalization in older persons with geriatric syndromes.