Cognition in end-stage renal disease: prevalence, determinants, and clinical implications of cognitive complaints and cognitive impairments

Abstract

There is long-established evidence that cognitive impairments (CIs) are present in early renal dysfunction, persist throughout the progression of chronic kidney disease, and are challenging to reverse with renal replacement therapies. The exact mechanisms are not fully understood but are thought to involve a mix of traditional (e.g., older age, diabetes) and kidney-specific risk factors (e.g., accumulation of uraemic toxins, intradialytic hypotension). In end-stage renal disease (ESRD) patients undergoing haemodialysis (HD), severe CIs is more than three times more likely than age-matched healthy controls. CIs in ESRD patients have also been associated with adverse health outcomes including dialysis withdrawal, hospitalisation, and mortality. This is typically thought to be due to CIs interfering with patients’ decision-making capacity and treatment adherence, however empirical evidence is scarce.

Although the cognitive burden of ESRD is well-established, currently we have very limited understanding of how these impairments manifest in patients’ everyday lives and what it implicates for the clinical management of ESRD. Most prior work focused on diagnosing CIs in this population using traditional neuropsychological tests (or objective tests). Neuropsychological tests, while sensitive in detecting CIs, may not fully capture the real-world cognitive challenges faced by patients. In contrast, everyday cognition, the ability to tackle real-world problems, has been overlooked in ESRD research but is crucial for patient-centred care and early intervention. Research in other populations (e.g., Alzheimer’s disease, cancer) has shown that everyday cognitive difficulties (assessed using self-reports or performance-based tasks) are early markers of cognitive decline, and stronger predictors of functional outcomes compared to traditional tests. It is therefore pivotal to advance our understanding of this often neglected aspect of cognitive health in ESRD patients to facilitate early identification and timely cognitive support in renal settings.

The overarching theme of this PhD project is the investigation of cognitive health in ESRD patients, with a particular focus on the aspect of everyday cognition in the population undergoing HD treatment. A mixed-methods approach was employed, including systematic review, cross-sectional and longitudinal survey studies, and qualitative interviews and focus group discussion.

Study 1 synthesised evidence from 221 studies on self-reported everyday cognitive difficulties in ESRD patients, revealing high prevalence of these complaints and consistent associations with hospitalisation, depression, anxiety, fatigue, and poor quality of life. It is of note however that over 90% of the included studies measured cognitive complaints using a three-item subscale from a quality-of-life questionnaire and included cognitive complaints only as a secondary outcome. Results from this systematic review are therefore by no means conclusive hence further empirical work was deemed necessary.

Study 2 and Study 3 were based on data from two previous studies that assessed cognitive complaints and a range of behavioural and clinical outcomes in HD patients. Cross-sectional (Study 2) and longitudinal (Study 3) analyses showed self-reported cognitive difficulties as a potential barrier hindering self-management, as these complaints were associated with lower self-efficacy, worse self-management skills, and poorer treatment adherence (indicated by both self-report and clinical markers).

In Study 4 and Study 5, I adopted a more comprehensive set of tools for measuring cognitive difficulties (i.e., neuropsychological test, self-report, scenario-based task) and conducted a cross-sectional observational study including 268 HD patients in 10 dialysis centres in Singapore. Study 4 revealed distinct cognitive profiles within the recruited sample and identified determinants of different profiles. Notably, only a quarter of the sample had intact cognitive function, while the rest exhibited either objective impairments or subjective complaints, or both. Study 5 adopted structural equation modelling analysis and revealed complex relations between different aspects of cognition, functionality, and clinical outcomes. Everyday cognitive indicators were found to be stronger predictors of treatment nonadherence and functional interference compared to traditional cognitive indicators.

A qualitative study was then conducted (Study 6) to obtain an in-depth understanding of cognitive difficulties and their clinical implications from both patients’ and healthcare providers’ perspectives. Interviews and focus groups with these two stakeholders uncovered several modifiable individual- and system-level barriers to the identification and management of cognitive impairments in renal settings that could be targeted with interventions.

Finally, Study 7 was conducted as an initial attempt to address one of the clinical gaps in current renal settings, which is the lack of a rapid cognitive screening tool. Data collected from Study 4 and 5 were used. Network analysis was performed to identify central cognitive symptoms among HD patients. The central symptoms were then combined to form a five-item self-reported screener, which showed good reliability and validity, as well as acceptable sensitivity and specificity in identifying clinically significant cognitive complaints. Patients’ scores on the self-reported screener was also found to be associated with their performance on objective tests after controlling for sociodemographic and clinical confounders, suggesting its potential clinical utility for routine administration in renal care settings.

In summary, this PhD project provides a multifaceted examination of cognitive health in ESRD patients, emphasizing the significance of everyday cognition and its implications for self-management, functional independence, and clinical outcomes. Through a systematic review, surveys, and qualitative research, the project has shed light on the prevalence and consequences of everyday cognitive difficulties, identified barriers to care, and proposed a novel screening tool. The findings underscore the need for a patient-centred approach that integrates cognitive health into the routine management of ESRD, paving the way for improved early detection, intervention, and ultimately, enhanced quality of life for patients.