Introduction

Approximately 15% of the global population is estimated to have some form of disability due to the rapid rise in the global aging population and a parallel increase in the prevalence of chronic health conditions [1]. With the progressive surge in longevity and lifespan, disability is steadily becoming an integral factor of disease burden worldwide. Several chronic diseases, including ischemic heart disease, stroke, diabetes, and dementia in mid-life or late life, have been identified as causes of disability-adjusted life years (DALYs), which is the sum of years lost due to premature mortality [2]. Functional disability in late life appears to be linked with gradual age-related deterioration and the coexistence of multiple diseases [3, 4]. Consequently, this strongly predicts future needs for assisted living and long-term nursing care, which heavily burden the healthcare system in addition to economic and personal burdens [2]. Disability risk factors include gender, age, socioeconomic status, lifestyle, and chronic diseases [5, 6]. This phenomenon is also a known adverse outcome of both frailty and cognitive impairment in older adults [7, 8].

Notably, frailty and cognitive impairment were often viewed as two independent concepts in previous studies until cognitive frailty (CF) was introduced by the consensus group of the International Academy on Nutrition and Aging (IANA) and the International Association of Gerontology and Geriatrics (IAGG) [9]. The simultaneous coexistence of physical frailty and cognitive impairment, or CF, seems to entail a greater risk of all-cause mortality and adverse health outcomes than their respective effects alone, as reported in both community-based and population-based studies [10,11,12]. The higher prevalence and incidence of CF, specifically among community-dwelling Malaysian older adults (39.6%; 7.1 per 100 person-years), has become a worrisome issue as those with CF are predicted to develop disability incidence by fivefold as compared to frailty and mild cognitive impairment on its own, based on five years cohort study [13,14,15].

Both physical frailty and cognitive impairment have been identified as risk factors for physical disability [8, 15], where these may act independently or, more often, in synergistic combinations. Individuals with CF are more likely to experience difficulties in performing activities of daily living (ADLs) and instrumental activities of daily living (IADLs) by two- to fivefold, leading to functional impairment and dependence on others for care [16]. Chronic low-grade inflammation, often observed in individuals with CF, can impair the regeneration of muscle tissue following injury and exacerbate muscle mass loss and functional decline, limiting an individual’s ability to perform activities of daily living and subsequent disability incidence [15, 17].

Furthermore, the presence of chronic diseases in older adults with CF further exacerbates the decline of physiological reserve function in multiple systems, thereby increasing the risk of adverse health outcomes [47]. Therefore, integrating exercises with cognitive stimulation, nutritional support, and psychosocial interventions holds promise in reducing disability risk associated with comorbidities while enhancing cognitive function and emotional well-being.

This study also demonstrated the synergistic effect of older adults with CF and heart diseases on the incidence of disability by more than three-fold, as compared to those without both conditions. Heart diseases have been identified as the most common self-reported cause of the overall decline in functional status [48], which in turn progresses to disability in later life. Besides, research has demonstrated that reduced cerebral blood flow resulting from decreased cardiac output in individuals with heart failure can potentially lead to both sarcopenia and cognitive impairment [49, 50]. Furthermore, modifiable risk factors such as educational level, exercise capacity, sleep disturbance, and depressive symptoms are associated with an elevated likelihood of cognitive decline among individuals with heart failure, which can be addressed through non-pharmacological interventions [51, 52]. It has also been demonstrated that a combined program of aerobic exercise and cognitive training significantly improved verbal memory, self-care management, quality of life, and functional capacity in persons with heart failure [51, 53]. Thus, these findings highlights the potential effectiveness of multifaceted non-pharmacological interventions improving various aspects of well-being, with the potential to act as preventive measures against disability in later life.

Next, this study also reported that CF and depression had synergistic effects on disability incidence by three-fold greater than those who did not report either condition. A recent systematic review and meta-analysis indicated that the prevalence of CF with depression in older adults is high wherein both are mutually affected and share common physiologic processes (e.g. inflammation) and risk factors (e.g. physical inactivity) [54, 55]. Therefore, a possible pathological mechanism underlying these associations could be due to high inflammation levels, such as elevated interleukin-6 (IL-6), which impacts future adverse health problems, including the incidence of disability among older adults [56, 57]. Depressive symptoms have been identified as a significant predictor of CF incidence in previous research [13, 14], highlighting the importance of addressing depression in older individuals. Implementing interventions targeting depressive symptoms is crucial not only for mental health but also as a preventive measure against disability. Non-pharmacological interventions like psychotherapy, cognitive-behavioral therapy, and psychosocial support programs can be instrumental in treating depression among older adults [58], aiming to alleviate symptoms and enhance overall well-being, potentially reducing the risk of cognitive frailty and associated disabilities.

Among the older adults reported to have CF, diabetes mellitus demonstrated synergistic relationships with the incidence of disability. The combined effect of these two conditions is three-fold higher than these risk factors on its own, highlighting the importance of addressing the medical comorbidities in CF interventions. This is consistent with a published report that cognitive impairment and physical frailty are powerful prognostic factors in predicting disability and mortality among older adults with diabetes mellitus [59]. Metabolic and vascular dysregulation, characterized by hyperglycemia, dyslipidemia, and chronic inflammation, have been identified as the primary biological mechanisms underlying the observed synergistic relationship between diabetes and CF [60, 61]. Additionally, hypoglycemia in individuals with diabetes is linked to CF, depressive symptoms, low psychological well-being, and reduced quality of life. These factors can impede the performance of daily activities and increase the risk of disability [19]. Hence, prioritizing mental well-being through personalized care plans that include counseling, support groups, and fostering community connections is essential for improving overall resilience and quality of life among older adults confronting both cognitive frailty and diabetes mellitus.

To the best of our knowledge, this study is the first of its kind which specifically looks into the synergistic effects of individual comorbidities that co-occur with CF in Malaysian older adults on disability indices. After accounting for a broad range of confounding factors, the results of this longitudinal study shed light on the intricate and dynamic cause-and-effect relationship between the synergistic effects of CF and comorbidities on disability incidence among older adults in Malaysia. While the independent effects of CF and chronic diseases are expected, our findings are important as they highlight the multiplicative effects of co-existing CF and medical comorbidities on disability incidence. This study is not without its limitations. Firstly, data regarding the presence of comorbidities were self-reported which may be influenced by misunderstanding or inaccurate responses from the participants. However, it should be noted that self-reported disease diagnoses have been used widely and reported to be valid [29]. Secondly, it is important to note that we did not consider the interval between the initial diagnosis of comorbidities and the index date, as older adults with CF may not accurately provide this information. However, this data could have been obtained from the medical records of older adults, with prior instructions for them to bring along their medical follow-up records if available. Thirdly, the generalizability of the current findings to the general population may not be possible owing to the smaller sample size included in this analysis. Nonetheless, this study provides novel findings and can be a step** stone for more in-depth, explorative future research undertakings. Hence, there is a need for future large-scale longitudinal studies with extended follow-up periods among older adults to validate our current findings. In future studies with a larger sample size, CF could be defined into several subtypes, and data could be stratified based on age, sex, educational levels, and regions to underscore the significance of cognitive frailty. Additionally, it is recommended that future research should prioritize interventional randomized controlled trials targeting both CF and comorbidities simultaneously as a proactive strategy to prevent, delay, or manage poor health outcomes among older adults.

Conclusions

In conclusion, the findings of our study highlights the synergistic effects of CF and comorbidities, such as OA, HD, depressive symptoms, and diabetes mellitus, heightening the risk of disability in later life. Early identification of individuals at risk for both CF and comorbidities is crucial for preventing or mitigating disability in older populations. In addition, implementing interdisciplinary interventions targeting CF and associated comorbidities can delay disability onset, emphasizing the importance of integrated care models and community-based support systems to enhance the well-being of older adults.