https://orcid.org/0009-0004-1763-6803
Figures
Abstract
Rationale & objective
Cognitive impairment is commonly associated with chronic kidney disease (CKD. A number of intervention approaches have the potential to improve cognitive performance in CKD. Our objective was to characterize interventions studied to improve cognitive performance for adults with CKD across all categories of severity, including kidney failure.
Selection criteria for studies
We searched 5 electronic databases for studies published up to April 5, 2024. Eligible sources were primary research studies that investigated any intervention targeting cognition in adults (≥18 years) with CKD or kidney failure. Full-text article screening was performed in duplicate.
Results
Seventy-one studies were included. Over half (n = 37, 52%) were conducted within the past five years, and most studies (n = 47, 66%) targeted people on maintenance hemodialysis therapy. Just over one-third of studies investigated pharmacological interventions, with much of the pharmacological or medical research focusing on anemia management or dialysis adequacy. Although recent research has expanded in focus, many other purported mechanisms of cognitive dysfunction in CKD remain understudied in interventional research. Exercise training (n = 14) was the most common nonpharmacological approach studied, but few studies have explored other promising nonpharmacological approaches such as cognitive rehabilitation interventions.
Conclusion
Research into cognitive interventions for people with kidney disease has primarily focused on the hemodialysis population and investigated erythropoietin stimulating agents, frequent or prolonged dialysis, and exercise, although there has been recent growth of research activity into other interventions. Future research should aim to address a broader range of purported pathophysiological mechanisms of cognitive impairment in CKD, investigate interventions for predialysis and peritoneal dialysis patients, and explore the impacts of established cognitive rehabilitation approaches.
Citation: Farragher J, Khan UK, Yau K, Stewart KE, Harrison TG, Engel L, et al. (2025) Interventions to improve cognitive performance in chronic kidney disease: A scoping review. PLoS One 20(8): e0329815. https://doi.org/10.1371/journal.pone.0329815
Editor: Jordan Llego, University of Luzon, PHILIPPINES
Received: December 20, 2024; Accepted: July 22, 2025; Published: August 7, 2025
Copyright: © 2025 Farragher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: CKD, chronic kidney disease; CI, cognitive impairment; JBI, Joanna briggs institute; PRISMA-ScR, preferred reporting items for systematic reviews and meta-analyses – scoping reviews
Introduction
Cognitive impairment is a common complication of chronic kidney disease (CKD) [1,2] that has been recognized as a serious public health issue [1]. Characterized by changes or declines in cognitive functions such as memory, executive functions, or judgment/decision making, an estimated 20–50% of people with chronic kidney disease (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² for >3 months or presence of albuminuria) experience cognitive impairment [3], which often worsens as CKD progresses [4] and affects approximately 50% of people with kidney failure (eGFR < 15 mL/min/1.73 m2) on hemodialysis and 40% of people on peritoneal dialysis [5]. However, cognitive impairment has historically been underrecognized and unaddressed in kidney disease, with one landmark multicenter study from 2004 finding that only 5% of patients on hemodialysis had ever undergone cognitive screening and/or referral to an appropriate specialist [1]. Although developments in certain parts of the world (e.g., mandated cognitive screening for Medicare Part B beneficiaries during annual wellness visits in the U.S.A.) have since aimed to improve detection of cognitive issues, gaps in screening protocols in both CKD and dialysis clinics remain. Potential barriers include time constraints in busy clinical settings, lack of staff training, and uncertainty about which tools are appropriate and clinically meaningful in this population, while patient fatigue, sensory impairments, and the fluctuating cognitive state associated with the dialysis cycle also complicate both the timing and interpretation of assessments [6,7].
Due to the under-recognition of cognitive challenges in this population,interventions that can address cognitive impairment in CKD are unclear. Unaddressed cognitive dysfunction can lead to functional dependence, reduced quality of life, caregiver burden, and long-term care admission [8–11], health outcomes that have been identified as top priorities of people living with CKD. Severe cognitive impairment or dementia among people with kidney failure on hemodialysis is also associated with an approximately 2-fold increased risk of mortality [12], further emphasizing its profound impact on patients. Investigating the range of interventions with the potential to reduce cognitive dysfunction and promote quality of life for people with CKD should thus be a priority for research.
In CKD, the underlying mechanisms of cognitive impairment are believed to be multifactorial and complex [6,13] (Fig 1). People with CKD often have traditional cardiovascular risk factors such as diabetes and hypertension, which can contribute to the risk for cerebrovascular disease [6,14]. Uremic metabolites begin to accumulate in CKD before the onset of kidney failure and increase as kidney function declines, and while high-flux, high-efficiency dialysis membranes reduce severe uremic encephalopathy in those on dialysis, many middle molecules are inadequately cleared by conventional dialysis and could have deleterious effects on cognitive functioning [6,15] Anemia is a common complication of CKD that has been associated with cognitive impairment in some studies [6,13], while polypharmacy is common in people with CKD who frequently receive medications that may affect cognition, such as opioids, psychotropics, antivirals, and drugs with anticholinergic properties [16]. Depression and sleep disorders are also highly prevalent in people with CKD and may further interfere with cognitive functioning [6], while factors such as electrolyte disturbances, hyperparathyroidism, and vitamin D deficiencies might also contribute to cognitive deficits [13]. Importantly, hemodialysis treatment can induce hemodynamic instability and itself lead to ischemic cerebral injury in those with kidney failure [17,18]. Given its complexity, the optimal management of cognitive impairment in people with CKD should be holistic, seeking to prevent, mitigate or reverse its underlying mechanisms while also supporting people with cognitive impairments and their caregivers using evidence-based approaches to maximize their quality of life.
A variety of interventions to mitigate cognitive dysfunction in CKD have previously been proposed. These include addressing cardiovascular risk factors; using ACE, ARBs, and lipid-lowering drugs; improving blood pressure control; treating depression; improving sleep; and implementing medication deprescribing protocols [6,13,15,16]. For those on dialysis, improving dialytic clearance and using intradialytic cooling have also been proposed [6,13,15,16]. The International Federation on Ageing Think Tank on Dementia further recommends nonpharmacological approaches to support people with cognitive impairments, including addressing its impact on disability and functioning (e.g., through physical or cognitive rehabilitation programs); employing targeted rehabilitation interventions after acute illness or injury; supplying assistive technology to aid functioning; and providing caregiver support and education [19]. Each of these approaches represent potential opportunities to improve outcomes for people with CKD and cognitive impairment, and thus warrant exploration in the research literature.
Given that cognitive impairment has been historically underappreciated in kidney disease [20], it is unclear to what extent the range of interventions to support patients in optimizing their cognitive functioning and quality of life have been explored. The primary objective of this scoping review was therefore to identify and describe interventions studied to improve cognitive performance across the spectrum of chronic kidney disease, with a view to identify key knowledge gaps and opportunities for further research and clinical intervention.
Materials and methods
We used scoping review methodology, as it enables a broad and comprehensive examination of literature to identify knowledge gaps, clarify concepts, and inform directions for future research [21]. Our review was guided by the JBI guidance on scoping reviews [22], follows a published protocol [23], and adheres to the reporting guidelines from the PRISMA Extension for Scoping Reviews (PRISMA-ScR) [24].
Article eligibility criteria
Types of participants.
Eligible studies investigated adults (≥18 years) with CKD (defined as an estimated GFR < 60mL/min/1.73m2 for >3 months or presence of albuminuria [25]), including adults with kidney failure treated with all dialysis modalities. Studies focusing on children or people living with kidney transplants were excluded, as their needs for cognitive interventions may be distinct from patients with CKD or kidney failure on dialysis.
Concept.
Studies were included if they investigated an intervention stated to be targeting cognitive functioning, broadly defined as all forms of knowing and awareness (e.g., perceiving, conceiving, remembering, reasoning, judging, imagining, and problem solving [26]). Studies were also included if the intervention targeted one or more specific cognitive domains included in the “mental function” component of the World Health Organization International Classification of Functioning [27] inclusive of consciousness, orientation, intellectual function, attention, memory, perception, thought functions, higher-level cognition, mental functions of language, calculation, and/or experience of self and time. In addition, studies were included if they investigated the effect of an intervention on cognition or more than one of the aforementioned cognitive domains, irrespective of the inherent nature or focus of the intervention. Studies were excluded if they investigated interventions not specifically targeting cognitive functioning, such as cognitive-behavioural interventions designed to target mood or psychosocial well-being, but not cognition, or self-management interventions not aimed at specifically addressing cognitive impairment.
Context.
Studies from any year, countries, or practice settings were considered. Studies that were not available in English were excluded.
Types of sources.
Information sources included full-text, primary research articles. Primary studies using qualitative, quantitative, or mixed methods designs (including randomized controlled trials, quasi-experimental studies, pre-post studies, observational studies, pilot studies, single-case experiments, qualitative studies) were included, with no limits placed on publication date. We excluded case series, case studies, clinical practice guidelines, theoretical papers, theses and opinion-driven reports (editorials, non-systematic or literature/narrative reviews). Reference lists of relevant scoping and systematic reviews from the initial search were examined to identify additional articles.
Search strategy & article selection.
The screening process is outlined in the PRISMA diagram in Fig 2. We worked with an information specialist to select search terms that represent the target population (CKD), concept (cognition), and intervention (Table 1). Our selection of cognition search terms was informed by prior reviews on cognitive interventions [28,29]. We searched the following six electronic databases up to April 2024 to identify relevant literature: Medline (OVID), EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL Plus, and SCOPUS. A search was also conducted using the Canadian Agency for Drugs and Technologies in Health (CADTH) guidelines to search online search engines (Google Canada/US/UK), relevant Health Technology Assessment agencies, and Clinical Trials databases. In addition, we performed backward citation searching, examining reference lists of included studies and relevant systematic/scoping reviews to identify literature.
Adapted from Kelly & Rothwell (2022), Frontiers in Neurology, under CC BY 4.0 license.
Following the initial search, results were imported into Rayyan [30], an online tool for eligibility screening. Screening was conducted independently by three reviewers after excellent inter-rater agreement (κ = 0.92) was established for 10% of the titles/abstracts. Full-text screening was conducted independently in duplicate for all articles. Disagreements about eligibility were resolved by discussion with a third reviewer to obtain consensus.
Charting, collating and summarizing data.
A data extraction spreadsheet was developed a priori and piloted with five articles before data extraction was undertaken. Once piloted, two reviewers performed independent data extraction for each included study, and disagreements were resolved by discussion to reach consensus. Data extracted included article characteristics (e.g., authors, date, journal, country, and study design), population characteristics (e.g., age, sex, CKD category and definition, and screening criteria), cognitive intervention characteristics (e.g., aims, theoretical background, design, dose/duration, materials, location, provider(s)), and study outcomes (e.g., outcomes assessed, outcome measures used, results reported). A narrative summary of the characteristics of the literature was completed, with counts and percentages used to describe patterns in the literature. Reported findings of intervention outcomes were categorized as positive, unchanged, or negative for each study to describe general trends, with no critical examination of evidence quality.
Results
The initial search strategy generated 26,717 results. After duplicates were removed and articles were screened and selected for eligibility, 71 studies were included in the review (Fig 2).
Study characteristics
Most studies were conducted recently, with more than half (n = 37, 52%) published since 2020 and 73% (n = 52) published within the last 10 years (Fig 3). Studies were most frequently conducted in Asia (n = 30, 42%), North America (n = 23, 32%) or Europe (n = 14, 20%), with two studies from South America, one study from Africa and one study from Australia. Most studies (n = 47, 69%) specifically targeted people with kidney failure on hemodialysis therapy. Thirty-seven percent of studies (n = 26) were randomized controlled trials, with a range of other study designs that include quasi-experiments (n = 10, 14%), uncontrolled pre-post studies (n = 10, 14%), retrospective cohort studies (n = 6, 8%), study protocols (n = 5, 7%), pilot studies (n = 5, 7%), observational studies (n = 4, 6%), a case-series study, a case-control study, and a secondary analysis of a randomized controlled trial. Cognitive functions were the primary outcome in 43 (61%) studies and a secondary outcome in 27 (39%) studies.
Interventions
Dialysis.
The majority of studies (n = 49) exclusively targeted people on hemodialysis therapy, with only six studies including people on PD and only two studies specifically targeting the PD population. For the hemodialysis population, there were 13 studies of pharmacological interventions, 12 studies of dialysis-related interventions, and 24 studies of nonpharmacological interventions. Erythropoietin stimulating agents (ESAs) were the most frequently studied pharmacological approach (n = 6). The other seven studies investigated six different pharmacologic interventions, including two studies of L-carnitine, and one study each of donepezil, melatonin, vitamin D, thiamine and folic acid, and valerian. Dialysis-related interventions included more frequent hemodialysis (n = 5), hemodiafiltration (n = 3), cooled dialysate (n = 1), incremental hemodialysis (n = 1), AKST1210 beta-2-microglobulin removal (n = 1), and ultrafiltration with a low-salt diet (n = 1). Nonpharmacological interventions consisted of several types of exercise programs such as home or community-based exercise programs (n = 2), intradialytic exercise programs (n = 3), and exercise programs combined with computerized cognitive training activities (n = 4). Six studies explored self-management education programs, and two studies investigated generalized, multimodal inpatient rehabilitation programs. The remaining nonpharmacological approaches were diverse, including approaches such as remote ischemic pre-conditioning, virtual reality for PD training, guided meditation, and aromatherapy. The two studies investigating interventions for people on peritoneal dialysis included one study of rHuEPO therapy and one study of a virtual reality program to support PD training. The four studies including people on either type of dialysis examined home-based exercise programs (n = 2), treatment for secondary hyperparathyroidisim, and a self-care dialysis model. Cognitive outcome trends reported for each intervention are depicted in Fig 4.
Predialysis.
Twelve studies investigated interventions to mitigate cognitive impairment for people with predialysis CKD, which included 8 pharmcological and 4 nonpharmacological interventions. Pharmacological interventions studied for this population included rHuEPO therapy, daprodustat, angiotensin receptor blockers, rivastigmine, AST120, NaHC03, and statin therapy. Nonpharmacological interventions included three light-intensity exercise programs, and one nutritional counselling intervention. See Fig 5 for an overview of cognitive outcome trends reported for each intervention.
All CKD (Predialysis and Dialysis)
Four studies investigated interventions to mitigate cognitive impairment for predialysis and/or dialysis patients. The interventions included rHuEPO therapy, the influenza vaccination, high-dose vitamins, and a dedicated nephrology care environment.
Outcome measurement
Most intervention studies (n = 43, 61%) measuring cognitive outcomes in CKD used one or more objective cognitive performance tests. Of these, seventeen studies used a global cognitive screening tool, with the MMSE (n = 19) and the MoCA (n = 12) the most commonly-used cognitive outcome measures. Twenty-five studies used one or more domain-specific neurocognitive tests, with memory (n = 19), executive function (n = 14), and attention (n = 10) the most frequently measured cognitive outcome domains. Fifteen studies assessed cognition subjectively, with the cognitive subscale from the KDQOL-36 the most commonly-used subjective cognitive tool (n = 10). Other subjective cognitive outcome measures included the problem-solving subscale from the self-management scale for hemodialysis patients (n = 2); the retrospective and prospective memory scale (n = 1); the cognitive subscale from the CKD anemia questionnaire (n = 1); and diary self-ratings of alertness, awareness and clarity of thought. No studies combined subjective cognitive measures with objective performance-based cognitive tests. Other cognitive outcome measurement approaches that were used include the incidence of dementia (n = 6), or were not specified (n = 3) (Fig 6).
Discussion
In this review, we sought to characterize interventions that have been studied to address cognitive impairment in people with CKD. The majority of studies were preliminary and targeted people on hemodialysis, using a widely heterogeneous set of interventions among which ESAs, frequent or prolonged hemodialysis, and exercise training were the most common approaches. We found a relative dearth of research investigating cognitive interventions for people on peritoneal dialysis and people with predialysis CKD, and a widespread lack of research into supportive nonpharmacological interventions, such as cognitive rehabilitation, that can improve quality of life and participation in people with cognitive impairments [19,28,29,102]. We also found few studies incorporated patient perspectives in the design of interventions or captured subjective cognitive functioning as an outcome. Our findings collectively highlight a number of underexplored opportunities for supporting people in managing the cognitive complications of chronic kidney disease.
Dialysis
A diverse set of pharmacological interventions have been studied for people on dialysis, which reflects the complex and multifactorial etiology of cognitive decline in this population [6]. That ESAs are the most widely-studied pharmacological approach for cognitive management reflects an early research boom into their impacts in the 1980’s, rather than strong potential to affect cognitive outcomes, which has not been conclusively demonstrated [6]. Outside of the ESA literature, there has recently been an increased exploration of alternative pharmacological strategies for cognitive management, but the evidence base remains largely preliminary. For example, we found few studies have targeted vascular contributions to cognitive impairment, despite strong evidence for cerebral small vessel disease in this population [103]. There have been no clinical trials or preliminary studies of approaches such as antihypertensives, oral anticoagulation therapies or antiplatelet therapies. While single studies addressed other possible mechanisms of cognitive impairment (e.g., electrolyte disturbances, hyperparathyroidism, vitamin D deficiency [41,47,61,63], this research is early-phase and larger trials with replication are needed. Meanwhile, pharmacologic interventions to target depression and sleep disorders have been neglected, and the cognitive impacts of reducing polypharmacy are unexplored. For the hemodialysis population, there has been some investigation into the cognitive impacts of interventions that reduce vascular insults caused by uremic metabolites and hemodynamic instability during hemodialysis. For example, increasing the frequency or duration of hemodialysis has received considerable attention, but studies in this area have generally not reported positive impacts on cognitive performance [67,69–71]. The impact of removing more middle-molecular weight solutes during dialysis through hemodiafiltration has also been explored, but evidence is currently based on small studies [64–66], and definitive trials are required. Cooled dialysate has also been proposed to address the circulatory stress associated with dialysis [6] with a previous study having demonstrated positive effects of cooled dialysate on brain white matter microstructure [104], but data showing an impact on cognitive performance has yet to be produced. Collectively, these findings highlight a number of knowledge gaps on pharmacological or dialysis-related cognitive management in the dialysis population.
The nonpharmacological literature in dialysis has been dominated by studies examining the impacts of exercise on cognitive function, which aligns with evidence from other populations that aerobic exercise can have a small beneficial effect on cognitive functioning [105,106]. Exercise also has other demonstrated benefits for people on dialysis [107,108], and there is little doubt that it should be viewed as a key aspect of care for this population. Family support, goal setting and accessibility of local facilities are important determinants of physical activity levels [109], while staff encouragement and support and use of a routine have also been identified as facilitators to intradialytic exercise [110]. Meanwhile, a focus on enjoyable activities, predictability, simplified instructions, and collaborative problem-solving around obstacles can help to engage people with cognitive impairments in physical activity [111]. Beyond exercise, there has been a widespread lack of research into other evidence-based nonpharmacological approaches for cognitive management in the hemodialysis population, such as cognitive rehabilitation, caregiver support, or environmental modifications. In particular, systematic reviews from multiple sclerosis, Alzheimer’s disease, and traumatic brain injury have outlined large evidence bases for cognitive rehabilitation interventions [19,28,29,102] but there has been almost no research into such approaches for people on dialysis. Such approaches often focus on promoting outcomes such as life participation and quality of life, which are prioritized by people living with kidney disease [112,113], and should thus receive greater focus in the research literature. We also note that no nonpharmacological intervention explicitly incorporated patient or caregiver input in their design or selection. This is concerning because individuals with cognitive impairment may face unique challenges with adherence, comprehension, and engagement [114,115] that can ultimately affect the feasibility and success of interventions. Caregivers often play a central role in managing these challenges, particularly in advanced CKD, and their perspectives can offer valuable insight into how cognitive changes impact daily life and care routines. Incorporating patient and caregiver voices is therefore essential to ensure that interventions are not only clinically effective, but also tailored to the practical realities, preferences, and priorities of those living with or supporting someone with cognitive impairment.
Despite a high prevalence of cognitive impairment in people on peritoneal dialysis, we found a wide discrepancy in the attention paid to cognitive management between hemodialysis and peritoneal dialysis, with only six studies in total including PD patients and just two studies examining cognitive interventions specifically for the PD population. PD patients face many of the same cognitive risks as those on HD, including toxin accumulation, vascular pathology, and inflammation [7,17], but also have distinct patterns of uremic toxin clearance, inflammatory burden, and oxidative stress, which may influence the mechanisms underlying cognitive impairment and the effectiveness of pharmacological treatments [116–118]. People on PD also experience unique stressors such as increased self-management responsibilities and less frequent contact with healthcare teams [114,119] (Griva et al., 2016; Walker et al., 2015) that might require specialized approaches tailored to their needs, routines, and care settings. Future studies into cognitive management should thus explicitly include PD populations, ideally through stratified designs or PD-specific trials, to evaluate the feasibility, acceptability, and effectiveness of interventions for this group. Qualitative research exploring the lived experience of cognitive challenges in PD are also warranted to offer important insights that can inform intervention development.
Predialysis
Compared to the dialysis population, we found that considerably fewer interventions have been studied to address cognitive impairment in individuals with predialysis CKD, reflecting a major gap in the literature despite growing recognition that cognitive decline often begins in the early stages of kidney disease. Among the eight pharmacological interventions identified, most mirrored those studied in dialysis patients, targeting anemia, vascular dysfunction, uremic toxin accumulation, acidosis, and neurotransmitter dysfunction. However, these interventions were largely evaluated in single studies with minimal replication. Only four nonpharmacological interventions were studied, consisting of light-intensity exercise [43–45] and nutritional counselling [46], with no studies exploring approaches such as cognitive rehabilitation, psychosocial interventions, or combined strategies. The scarcity of interventions in this group is notable, given the potential to prevent or delay cognitive deterioration before the onset of dialysis. Research in predialysis CKD should prioritize early, multimodal intervention trials targeting the known drivers of cognitive impairment—including vascular health, systemic inflammation, and lifestyle factors—and assess both cognitive and functional outcomes over time. Three large multidomain trials (FINGER, MAPT and PreDIVA) have been completed in the past several years to prevent cognitive impairment in non-CKD populations [120–122], with the FINGER trial showing that a multidomain lifestyle intervention can benefit cognition in elderly people with an elevated risk of dementia [120]. Such multimodal approaches should be studied in people with predialysis CKD to help mitigate early cognitive decline in this population.
Outcome measurement
Our review highlights several considerations for cognitive outcome measurement across the various CKD subgroups. First, we found that brief cognitive screens like the MMSE and MOCA were the most commonly-used outcome measures in existing CKD research. While these tools offer feasibility due to their brief length, their further validation as outcome measures in CKD is needed, given minimal evidence of their responsiveness to change in other populations [123,124]. In addition, these brief tools do not provide a fulsome assessment of cognition, and do not always accurately reflect real-world functioning as they do not assess a person performing learned, habitual tasks in their usual environment. Although executive functioning is a major cognitive domain affected by CKD, we found it was only specifically measured in ten studies. Executive functions are integral to independent living and community functions, and in turn, related to improved life satisfaction, health, and wellbeing [125–127]. Including more outcome measures of executive functioning to replace or augment global cognitive assessments might help to improve detection of meaningful cognitive changes in the CKD population. We also found that most studies relied on objective cognitive outcome measures, with only a limited number of studies capturing subjective cognitive functioning as an outcome. Although subjective cognitive tools alone are vulnerable to reporting biases and errors, they can provide additional insight into the impacts of cognitive impairment on real-world functioning when paired with objective tests. Subjective measures can help contextualize cognitive test results, identify functionally meaningful impairments, and capture concerns that might otherwise go undetected—particularly in early or subtle stages of cognitive decline (Jessen et al., 2014; Rabin et al., 2017). Such discrepancies can inform hypotheses about compensatory strategies, fatigue, mood, or contextual barriers that influence cognitive function (Vaughan et al., 2020). Integrating both perspectives is therefore essential for developing interventions that are not only statistically effective, but clinically relevant and aligned with patient priorities. As such, subjective cognitive assessments should be viewed as a critical complement to objective testing, and future intervention studies in the CKD population should incorporate both objective and subjective outcome measures to gain a more holistic understanding of treatment impact and real-world cognitive change.
Strengths and limitations
This review has several methodological strengths. We followed the gold-standard JBI guidance [22] on scoping review conduct to maximize its quality and thoroughness, and both the protocol and the final manuscript adhere to the PRISMA-SCr reporting guidelines [24]. Our review used a comprehensive and systematic literature search refined by an information specialist. We also conducted duplicate full-text screening and data extraction of eligible articles. The limitations of this review include those inherent to scoping review methodology, such as a lack of critical appraisal of included articles, which makes it impossible to draw conclusions about the effectiveness of the interventions discussed. However, scoping review methodology lays the necessary groundwork for future systematic reviews by identifying research gaps and charting a course for knowledge advancement. Further, due to the large number of initial search results, and resource limitations among our team, we were unable to perform full duplication of title and abstract screening as is recommended by JBI scoping review guidelines. Not using two independent reviewers for all screening and selection poses a limitation through possible screening errors of one person. However, we conducted inter-rater validation for a subset of articles to ensure consistency among our screeners before independent screening was undertaken. We also excluded non-English studies from the review, which may have omitted relevant articles that reported results in other languages and may limit the generalizability of our findings to non-English populations.
Conclusion
Research into interventions to improve cognitive performance for people with chronic kidney disease has primarily focused on the hemodialysis population and on investigating ESAs, frequent or prolonged dialysis, and exercise, although there has been an increase in the amount and scope of research activity in this area in recent years. Notable research gaps include the lack of research into promising nonpharmacological approaches such as cognitive rehabilitation and multimodal approaches; a lack of research into interventions targeting the diverse purported mechanisms of cognitive impairment in CI, such as cardiovascular disease, polypharmacy and depression; and a lack of research into cognitive interventions for people on peritoneal dialysis. Future research should continue to target a broader range of purported pathophysiological mechanisms of cognitive impairment in CKD; use RCTs and other robust methodologies to further establish efficacy; investigate cognitive rehabilitation approaches; include patient perspectives to improve the uptake and implementation of exercise training in cognitively impaired populations; and investigate interventions to promote cognitive functioning in PD.
Acknowledgments
The authors are grateful for the contributions made by Diane Lorenzetti, who provided guidance on the search strategy for the review.
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