Impact of Physical and Cognitive Frailty on Long-Term Mortality in Older Patients undergoing Elective Non-cardiac Surgery

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Ann Geriatr Med Res. 2025;29(1):111-118

Publication date (electronic) : 2025 January 17

doi : https://doi.org/10.4235/agmr.24.0163

Min-Jie Low¹, Zhen Yi Liau¹, Jun Leong Cheong², Pui San Loh², Ina Ismiarti Shariffuddin², Hui Min Khor^,1

¹Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

²Department of Anaesthesiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

Corresponding Author: Hui Min Khor, MBBS Department of Medicine, Faculty of Medicine, Universiti Malaya, 59100 Kuala Lumpur, Malaysia E-mail: hmkhor@ummc.edu.my

Received 2024 October 5; Revised 2024 December 31; Accepted 2025 January 11.

Abstract

INTRODUCTION

With the population ageing and the growing expectations towards healthcare and quality of life in later years, the demand for surgical procedures amongst the older population is increasing. In England, one in five individuals aged 75 years and above underwent surgery in 2015, compared to one in 10 people aged 15–59 years.1) Surgery is often necessary for older patients and has been well proven to be beneficial in several aspects including improved life expectancy and symptom relief.2) However, many of these patients are burdened with multiple comorbidities, geriatric syndromes and poorer physical and cognitive reserves. Consequently, older patients suffer from increased surgical risks, perioperative complications as well as poorer operative outcomes compared to younger patients.2,3) Multiple studies have identified specific predictors of adverse surgical outcomes in older patients, including physical frailty, cognitive ability, and preoperative functional and nutrition status.4,5)

Conventionally, physical frailty and cognitive impairment have been studied independently, and both have proven to be significant predictors of adverse health and surgical outcomes.6,7) Fried et al.8) developed and operationalised the frailty phenotype and defined frailty as a syndrome characterised by three or more of the following five criteria: unintentional weight loss, self-reported exhaustion, weakness, slowness, and low physical activity. A systematic review and meta-analysis by Panayi et al.7) concluded that frailty is a strong predictor of post-surgical morbidity and mortality, with frail patients having approximately twice the risk of major complications and four times risk of mortality. On the other hand, older patients with cognitive impairment have an increased predisposition to developing adverse outcomes including postoperative delirium, which leads to 7-fold higher 5-year mortality risk.9) In recent years, the understanding of frailty has expanded beyond its predominantly physical construct, leading to the advent of the concept and operational definition of cognitive frailty, which is the presence of physical frailty and mild cognitive impairment without concurrent dementia.10)

An increasing number of studies have demonstrated a positive association between the presence of both physical frailty and cognitive impairment with adverse health outcomes in the older population. The French Three-City Study and the Singapore Longitudinal Ageing Studies concluded that the presence of cognitive impairment and frailty in community-dwelling older adults without dementia leads to increased mortality and a higher risk of functional disability.11,12) In one systematic review and meta-analysis, cognitive frailty was found to be a significant predictor of all-cause mortality in community-dwelling older adults and to be better than frailty alone.13) Recognising cognitive frailty as a heterogeneous and potentially reversible clinical syndrome is thought to improve the identification and subsequent early intervention of older patients who are at a higher risk of adverse surgical outcomes. While studies on cognitive frailty are predominantly conducted in the community, there are limited studies on older people undergoing surgery. Hence, this study aims to determine the association between physical and cognitive frailty with long-term mortality among older surgical patients undergoing elective non-cardiac surgery in a tertiary center.

MATERIALS AND METHODS

RESULTS

A total of 514 patients were admitted for elective surgery during the study period. Of those, 109 did not meet the inclusion criteria (Fig. 1). As a result, 406 patients were included in the analysis. Demographic and clinical characteristics of the patients are shown in Table 1. The mean age of the patients was 75.1±5.8 years, and 219 (53.9%) were women. The majority of patients were from the general orthopaedic ward (25.6%), followed by general surgery (23.4%) and ophthalmology (20.2%). More than half of the patients underwent general anaesthesia (n=218; 53.7%) during surgery. The mean MoCA score was 20.4±5.8 among all the patients. Using the FFI, 56 (13.8%) patients were found to be frail, 185 (45.6%) pre-frail, and 165 (40.6%) non-frail.

Fig. 1.

Flow diagram of patient selection.

Table 1.

Demographic and clinical characteristics of participants

The median follow-up of patients who were living was 806 days (interquartile range [IQR], 763–835), and of deceased patients was 344 days (IQR, 108–509). The 1-year mortality rate was 8.6% (n=35) with a total of 63 deaths at the end of the study period. Table 2 highlights the significant predictors of long-term mortality following elective surgery. From the adjusted Cox proportional hazard analysis, men (hazard ratio [HR]=1.96; 95% confidence interval [CI], 1.14–3.37; p=0.015), the presence of malignancy (HR=3.86; 95% CI, 2.14–6.95; p<0.001) and physical frailty (HR=1.38; 95% CI, 1.07–1.77; p=0.013) were independent predictors of long-term mortality.

Table 2.

Predictors of mortality in older patients who underwent elective surgery

Patients were categorized into six groups with different combinations of physical and cognitive status as shown in Table 3. The largest patient group comprised individuals with MCI and frailty, accounting for 24.9%, whilst the smallest group included patients with dementia but no frailty, representing 4.18%. Patients with MCI and frailty had a high risk of mortality (HR=3.17; 95% CI, 1.36–7.38; p<0.01), as were patients with dementia and frailty (HR=3.91; 95% CI, 1.62–9.43; p<0.01). After adjusting for the type of surgery these two groups remained predictive of mortality, despite an attenuation in risk as shown in Table 3. On the other hand, following the inclusion of other confounders of mortality, specifically sex and the presence of malignancy, Group 4 (MCI and frail), Group 5 (dementia and non-frail), and Group 6 (dementia and frail) demonstrated a stepwise increase in risk. Notably, none of the Group 5 patients underwent major surgery. The differences in survival between groups with different combinations of cognitive and frailty status are illustrated in Fig. 2.

Table 3.

Hazard ratio of cognitive function and frailty status of different patient groups

Fig. 2.

Survival curves for 6 different patient groups of combined cognitive and physical status. The number of patients at risk for each category is indicated at the bottom. MCI, mild cognitive impairment.

DISCUSSION

More than half of the patients in this study were either pre-frail or frail. This study demonstrated that the effect of physical frailty was more pronounced when it coexisted with cognitive impairment, resulting in higher mortality risk in patients with mild cognitive impairment and dementia but not in those with normal cognition. Patients with cognitive frailty represented the largest category in the study with increased long-term mortality, followed by the cohort with dementia and frailty, which was considered the most vulnerable group of patients in this study.

Cognitive impairment is known to contribute to poor surgical outcomes, including mortality, though most study factors were determined as moderate to severe cognitive impairment.20,21) Recent studies have shown an inter-relationship between frailty and cognitive decline. Buchman et al. found that common neuropathologies (e.g., Alzheimer disease pathology, macroinfarcts, and nigral neuronal loss) contribute to progressive physical frailty in old age, even in individuals who were not clinically diagnosed with dementia, Parkinson disease, or stroke.22) The effects of physical frailty on cognitive function were also demonstrated in several studies.23-25) Our findings corroborate with results from longitudinal studies conducted across three continents: France, Singapore, and Peru, which showed that the presence of both cognitive impairment and cognitive frailty was a stronger predictor of mortality than either condition alone.11,12,26)

Similar observations were reported in a prospective study by Makhani et al.27) on 330 surgical patients undergoing major surgery, which demonstrated a four times higher risk of death and poorer survival in patients with both physical frailty and cognitive impairment compared to robust patients. Additionally, a recent study on a Chinese population undergoing elective orthopaedic or abdominal surgery under general anaesthesia showed that patients with cognitive frailty had the highest risk of postoperative complications, mobility disability, and prolonged hospitalisation, regardless of the type of surgery.28) In comparison, our study, which included a larger population of cognitive frailty patients across various surgical specialties, identified cognitive frailty as a significant predictor of mortality, even after adjusting for type of surgery, sex, and the presence of malignancy. Similarly, a study by Itagaki et al.29) investigating other adverse outcomes, such as postoperative delirium, found that the risk was higher in patients with cognitive frailty, whereas patients with mild cognitive impairment but without physical functional decline did not develop postoperative delirium. As manifestations of mild cognitive impairment are oftentimes subtle and prone to be underdiagnosed by attending doctors, this stresses the importance of comprehensive preoperative cognitive and frailty assessments to identify this vulnerable group of older patients so that interventions can be done to minimise adverse surgical outcomes. Preoperative assessments during outpatient clinic reviews provide an opportunity to identify individuals at risk and implement appropriate interventions

Our analysis found that the male sex and presence of active malignancy were significant predictors of mortality. The sex discrepancy in mortality that has been observed in the past century is multifactorial in nature—greater predisposition to cardiovascular diseases and preponderance of male smokers, comparatively passive health-seeking behavior such as indifference towards health problems, delay in seeking treatment, and poorer compliance to treatment, on top of other biopsychosocial differences.30,31) This reflects the need for a more global approach in public health policies to address such differences. Active malignancy and malignancy-related complications necessitate surgery in over one-fifth of our patients. Its impact on perioperative mortality differs with specific patient and disease factors, though advanced disease and low to lower-middle income status generally contribute to poorer outcomes.32)

The implication of this study lies in identifying high-risk groups among older surgical patients through physical and cognitive functional assessments that are feasible to carry out in day-to-day ward practice. This lays the foundation for patient-centred perioperative care, whilst advocating objective and systematic decision-making in the context of healthcare resource allocation, especially in a developing country such as Malaysia, where manpower and funding are limited. Management to optimise cognitive and physical reserve of older surgical patients involves a multidisciplinary team consisting of the primary attending doctor, geriatricians, physiotherapists and dietitians, as well as multimodal intervention which includes multicomponent exercise programmes, cognitive training and nutritional supplementation.33-36) Published and ongoing studies evaluate the benefits and effectiveness of these interventions to reduce cognitive frailty among community-dwelling seniors, though future studies should seek to better apply these interventions in the geriatric preoperative setting such that patients can be better prepared for surgery. Furthermore, research is also yet to establish better strategies to assess and identify cognitive frailty, as well as the reversibility of cognitive frailty, an increasingly important clinical question with the emergence of more evidenced-based intervention models.

This study has several strengths and limitations. Firstly, one of the strengths is having a considerably large cohort of patients, which reduces margins of error and enhances reliability of the findings. Secondly, despite being a single-centre study, the study population reflects a unique group of older surgical patients due to their multiracial and multilingual backgrounds, as well as the diversity of elective surgeries included. That said, being conducted in a tertiary center, this study may be less generalizable to local, more resource-limited institutions. Patients who were unable to ambulate were included in the study by identifying them as positive for slowness in the FFI. While immobility is a strong indicator of an older patient’s physical frailty status, this subjects the study to some degree of selection bias. Lastly, the study population was limited to elective surgeries with a significant proportion of patients undergoing ophthalmology procedures, which are less invasive compared to other surgical procedures. This may have introduced selection bias in the patient population, although efforts were made to analyse the data by adjusting for the type of surgery performed.

In conclusion, the combination of physical and cognitive frailty was strongly associated with long-term mortality among older patients who underwent surgery, with greater predictive value compared to cognitive or physical status alone. This study emphasizes the importance of comprehensive geriatric assessment of physical frailty and cognitive function for all older patients undergoing surgery to guide the prehabilitation efforts and improve surgical outcomes. Identifying these potentially reversible factors early can help optimize preoperative care, reduce risk of postoperative complications and long-term adverse outcomes.

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