The Impact Of Chronic Kidney Disease On Cognitive Function In The Elderly: A Systematic Review

Aim and objectives of the research

The current study focuses on the aspect of a systematic review of chronic kidney disease and its effect on the cognitive function.

Research question

What is the impact of chronic kidney disease on the cognitive function?

 Aim and objectives of the research

The research aims at finding out a plausible link between impaired glomerular filtration rate in people with chronic kidney disease and its effect on the cognitive function

What is the effect of estimated glomerular filtration rate of cognitive decline in people with chronic kidney disease?

The research has aimed to decipher an association between estimated glomerular filtration rate (eGFR) and its effects on the cognitive function of individuals. It could be further  supported by neuro-imaging tests and results. It supports that individuals with defective glomerular filtration have increased risk of brain infarctions or incidents of cerebral micro bleeds. The brain images of the ones suffering from lower eGFR have shown increased white lesions due to cellular necrosis (O’Lone et al. 2016).

Lowered eGFR levels increase the level of uremic toxins such as creatinine, guanidine, which activates N-methyl-D-aspartate receptors, which further inhibits the function of gamma-amino butyric acid receptors as an effect of competitive inhibition (Hill et al. 2016). This could affect the cognition by blocking the effective functioning of the neurotransmitters.

The data have been collected through secondary methods of data collection. Thus, the data have been gathered from existing journals or  secondary databases.  The secondary data has been collected from a number of peers reviewed journals, government reports and official statistics. Moreover, linking with cohort journals helps in arriving at a potential agreement regarding the problem.

In this respect, the data has been gathered through peer-reviewed journals mostly focusing on cohort studies. The latter aims at, drawing relationship between health risk and its  possible outcome. Moreover, the journal publishes in English within the last 10 years have only been considered for the purpose of the review.

In order to gather data, peer reviewed journals estimating present health conditions from eGFR rates were gathered. The data were gathered from participants from different medical backgrounds. The elderly people of 65 years old and above were chosen for data generation. In this regard, the ones with no history of dementia and cardiovascular diseases were also taken into consideration for comparative analysis.

A number of intervention strategies were undertaken in order to provide suitable care and treatment to the ones suffering from chronic kidney diseases. Some of the basic intervention policies, which could be undertaken over here  are controlling the blood pressure along with blood glucose levels. The patients with CKD are at 15% risk of contracting cardiovascular diseases which g further raises to 20% in the presence of reported diabetes (Walker et al. 2014). Thus, some of the effective medications, which could be provided to the patients in order to prevent the origination of cardiovascular diseases, are stain and aspirin.

Moreover, community-based care strategies led by nurse driven teams could also help in the prevention and control of chronic kidney diseases in one fourth of the population (Macedo et al. 2014). Additionally, audit and patient recall calls could also be used in order to gather data regarding the present health conditions and situations of the ones receiving care.

Eligibility criteria

A number of programs were implemented in order to provide care for chronic kidney diseases. Some of the national and governmental policies could have been highlighted over here, such as the Rand Corporations Prominent quality Care Assessment tools. The test undertakes regular screening for CKD of the ones affected by diabetes and hypertension.  The National Committee for Quality Assurances Healthcare Effectiveness Data and information states that non-steroidal medications or COX-2 inhibitors could be used for the prevention and treatment of the ones suffering from lower estimated glomerular filtration rate.

A number of factors were taken into consideration for making the relevant searches, based on the factors, which were either included or excluded in the process. Thus, peer reviewed journals related to the topic were only chosen for the purpose the study.  Additionally, the data had been collected from a number of secondary databases and resources such as EMBASE, MEDLINE, CINAHL, SIGLE being some of the few.   During the search hits, the data, which were in languages other than English, were eliminated. Moreover, the journal published only over the last ten years had been taken into consideration.

For further study and research tools such as Prisma model could be used which consists of six major components based upon the coordination among services,  the point of entry, management of the specified case and analysis through unique tools, accessing service plans of individuals and gaining relevant information through tools.

For the purpose of review secondary methods of data collection has been chosen where sufficient data had been gathered from peer reviewed journals along with different other databases. The selection had been restricted to peer-reviewed journals where data had been collected from participants possessing chronic kidney disease and the ones with (or without any) forms of cardiovascular disease. This was done in order to find out the relation between CKD and its effect in producing other associated physical conditions along with cognitive decline.

For the current study, a positivist research methodology has been chosen, which focuses on collection of data through well-represented facts and theories. Moreover, the role of the researcher is restricted to the collection and interpretation of the data  through an objective approach. A deductive approach has been used for the research methodology were well-published case studies have been used to gather the data.

The design chosen over here is an exploratory research design, which serves as a precursor to quantitative data collection. The data was further extracted with the help of thematic analysis.  For choosing the sample, a screening procedure had been applied to select journals. Thus, journals, which have reviewed people of age groups above 65 and above possessing lower levels of estimated glomerular filtration rate were only taken.  

Domain	Key items
Title of the journal	1.Anemia and risk for cognitive decline in chronic kidney disease; 2. Kidney function is associated with the rate of cognitive decline in the elderly.
Authors	Kurella et al. (2016); Buchman et al. (2009)
Type of study and design	Quantitative study with cross sectional design
Participants	905 total numbers of participants with renal inefficiencies and chronic kidney impairments were selected. They were also found to suffer from decline in basic cognitive abilities.
Population	Here, 825 participants aged between 21- 70 years showing renal disorders were selected from African American centre of Kidney disease and some other cohort study centres. For the second method, 80 subjects with CKD III and IV, put on dialysis along with the ones receiving haemo-dialysis or in the terminal stage of renal impairment. Some other criteria used for exclusion over here were the ones aged above 55 and possessing HIV infections, stage III or IV heart failure, cirrhosis, renal carcinoma, among the few.
Index tests (data collection)	The test conducted here was Chronic Renal inefficiency Cohort (CRIC) and baseline serum test (BSA) to check the progress of chronic kidney disease in adults with mild to the moderate condition of CKD.
Variables	Independent variable : eGFR levels Dependent variable : Cognitive function
Sample size	Here, the target size of the sample taken was 75, with equal number of people participating from the four clinical centers.
Missing data	For the management of missing data complete and detailed case analysis along with imputation and other methods.
Model development	A Geo-scientific model development (GMD) had been used over here, which is different from the otherwise used normal scientific journals. Here, the potential of the internet has been  tampered to encourage scientific discussion and allow the publication of journals.
Statistical  evaluation	The model was evaluated through, statistical analyses where the association between lower levels of eGFr and cognitive decline were tested, using logistic regression model. Moreover, the normally distributed and continuous data were evaluated with the help of ANOVA, chi-square tests were used to evaluate categorical data. The model took into consideration a number of factors such as age, sex, education and the centre of the participants along with other factors such as the presence of other associated conditions such as hypertension, depression, diabetes, coronary heart disease along with eGFR.
Results	Out of the 905 patients selected for the study, 27% has shown Hb levels less than the threshold value. Out of the other co-variations, Anemia was present in 46 % of the participants who were also low in their overall educational attainment.
Conclusion	The study focused on the fact that decreased levels of eGFR or defective function of the kidney could be associated with lower cognitive functions. Moreover, the chronic kidney diseases have often been found to have a strong correlation with some other co-morbid conditions such as hypertension and cardiovascular disease. These are often predominant in old age, however, further study and research in the following area is needed.
Limitations	The representation of the link between CKD and cognitive decline is only suggestive of the sub-cortical vascular disease. Thus, the scope of the research is limited in evaluating the effect of low eGFR in cognitive decline. Thus, the same could be evaluated only with the help of proper tests and brain imaging.
Strength	Thus, recruiting large number of patients with different co-morbid conditions and severities helped in accessing the link between eGFR levels and cognitive function. Additionally, diverse tests have been employed to authenticate the data further.

Table: Data extraction tool

(Source:  Researcher )

Analysis :

For the purpose of gathering and extraction of the data, a methodical approach was followed. The study was conducted at a number cohort study centers including the African American Centre for Kidney Disease. Here, a number of participants were selected suffering from renal impairments. Moreover, CKD patients with type III, IV, and V were also included in the cohort study group. Moreover, the data were grouped and analyzed using simple ANOVA and Chi-square tests. The test further helped in the establishment of a relationship between renal impairment and cognitive decline.

Types of studies

The data has been synthesized using mixed statistical methods such as Pearson correlation and logistics regression model. The Pearson correlation had been used to access the bivariate relation of kidney with cognition and some other co-variants such as high blood pressure and diabetes. Moreover, the continuous variables selected for the test were further expressed in means +/- standard deviation. The variables were further compared using t-tests and chi-square tests for grouping similar and dissimilar categories.

For the present study, two different tests were conducted such as Chronic Renal inefficiency Cohort and Baseline serum tests. The tests were conducted across different centers with a number of participants. For the CRIC tests, participants of different age groups were selected across different regions of the United States, where the mean eGFR levels of the participants of various age groups was recorded. The study, however, depicted a strong correlation between low eGFR and decreased cognition.

The other methods adopted for the selected study was the Basal Serum Test, which was conducted upon 886 elderly women of the Chicago region. The test was conducted using the modification of diet in renal disease formula. Here, the 19 cognitive tests were used to relate kidney impairment with eGFR levels below or more than 60ml/min. Thus, here 60 ml/min was maintained as the threshold value.   

The CHARMS checklist has been used for the purpose of critically appraising and data extraction in systematic reviews. There are total 11 parameters based upon which evaluation and appraisals were done. It includes the source of the data, the participants, the outcomes predicted. It explains the method used for arriving at a suitable result based upon the tests performed. Additionally, the model development, performance, has also been presented in the checklist. Thus, the systematic review is important due to the increase in the number of measurement tools particularly in the field of health. The methodological quality is of utmost importance for reviewing a particular problem. Here, the appropriateness of the method further guarantees the validity of the gathered data based on, which future analysis could be done. However, in the context of inappropriate or faulty data misleading results can be generated.

The evaluation of the results justified that impaired kidney function was associated with the loss of semantic memory, working memory among the few. Moreover, the lowering of the cognitive abilities could be associated with lowered estimated glomerular filtration rate. An eGFR of less than 30 ml/min could result in 47% increase in the chances of decline in the cognition power of an individual.  The participants of the test were made to undergo through, a Modified Mini Mental State Exam (3 MS) to test a few of the basic cognitive abilities. Some of the testing parameters listed here being concentration, orientation, memory, language, praxis. Thus, lowered EGFr levels were found to interfere with the decision-making skills of the patients receiving the health care (Kurella Tamura et al. 2016).

Baseline serum test

The second test adopted over here was the baseline serum test, which measures the amount of creatinine present in the blood of an individual. The test has pointed at the presence of anomalies in the accepted normal standards. Here, the reports have shown that almost 38% of the adults aged above 65 have been found, to be possessing eGFR levels less than 60ml /min.  However, reports and studies have shown a substantial correlation between the malfunctioning of kidneys with that of the gradual cognitive decline (Kurella et al. 2004).

Types of participants

The presence of creatinine level of more than 1.2 women and more than 1.4 in men signifies the presence of anomalies with the proper functioning of the kidney. The glomerular filtration rate helps in understanding the rate at which the kidneys can remove the waste products. Thus, eGFR content of less than 60 is a sign that clinical intervention is required. Moreover, the falling of the level below 15 can point towards fatal incidents such as kidney failure.

In this respect, almost 20% of women having eGFr levels within the range of 45-59 ml were found to suffer from cognitive decline. Here, a correlation was drawn between multiple tests of similar domains testing the cognition levels of patients with CKD.  On analysis, there was a revelation that the ones possessing lower eGFR levels had invariably high creatinine levels, which could result in lethal conditions such as  brain shocks (Lamb, 2014).  Additionally, higher toxin concentration such as creatinine can block the enzymatic activity of neurotransmitters such as gamma-amino butyric acid.

In this context, the study was conducted with the aid of peer-reviewed journals. However, a number of the journals being paid resulted in accessibility issues. The availability of the journals in languages other than English also possessed a problem.

Conclusions 

The study helps in understanding that a strong relationship exists between low levels of estimated glomerular filtration rate and decline in the cognitive abilities of a person. This could be explained, with the help of the increased concentration in the rate of the uremic acid such as creatinine and guanidine, which act as acid block receptors. This could further affect nervous stimulation and signal transmission.

The present study was conducted to draw a link between the anomalous eGFR levels and its relation to cognitive decline. However, much research has not been conducted in this particular area before. Moreover, the study could contribute a lot more by presenting through its sources, that there exists a clear link between the eGFR and cognition. The importance of the study lies in the fact that the other co-variants have also been considered. In this context, anomalies present in the concentration of blood could also be related to the malfunctioning of the kidney.

The study conducted here being of interpretive and exploratory research design leaves a lot of scope for future research and analysis. It tries to satisfy both the further development of theories and the validation of already established concepts. However, there are always limitations and more research needs to be conducted in future in order to elaborate the matter further.

References

Hill, N. R., Fatoba, S. T., Oke, J. L., Hirst, J. A., O’Callaghan, C. A., Lasserson, D. S., & Hobbs, F. R. (2016). Global prevalence of chronic kidney disease–a systematic review and meta-analysis. PLoS One, 11(7), p.1587.

Lamb, E. J., Brettell, E. A., Cockwell, P., Dalton, N., Deeks, J. J., Harris, K., … & Ottridge, R. S. (2014). The eGFR-C study: accuracy of glomerular filtration rate (GFR) estimation using creatinine and cystatin C and albuminuria for monitoring disease progression in patients with stage 3 chronic kidney disease-prospective longitudinal study in a multiethnic population. BMC Nephrology, 15(1), p.13.

Macedo, A. F., Taylor, F. C., Casas, J. P., Adler, A., Prieto-Merino, D., & Ebrahim, S. (2014). Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC medicine, 12(1), p.51.

Murray, A. M., Bell, E. J., Tupper, D. E., Davey, C. S., Pederson, S. L., Amiot, E. M., … & Foley, R. N. (2016). The Brain in Kidney Disease (BRINK) Cohort Study: design and baseline cognitive function. American Journal of Kidney Diseases, 67(4), 593-600.

O’Hare, A. M. (2009). The Management of Elderly People With a Low eGFR: Moving Toward an Individualised Approach. American Journal of Kidney Diseases?: The Official Journal of the National Kidney Foundation, 53(6), 925–927. Retrieved from https://doi.org/10.1053/j.ajkd.2009.02.013.

O’Lone, E., Connors, M., Masson, P., Wu, S., Kelly, P. J., Gillespie, D., … & Craig, J. C. (2016). Cognition in people with end-stage kidney disease treated with hemodialysis: a systematic review and meta-analysis. American Journal of Kidney Diseases, 67(6), 925-935.

Walker, S. R., Wagner, M., & Tangri, N. (2014). Chronic kidney disease, frailty, and unsuccessful ageing: a review. Journal of Renal Nutrition, 24(6), 364-370.

Murray AM. Cognitive impairment in the ageing dialysis and chronic kidney disease populations: an occult burden. Adv Chronic Kidney Dis 2008;15:123–32.

Kurella M, Chertow GM, Fried L, Cummings SR, Harris T, Simonsick E, et al. Chronic kidney disease and cognitive impairment in the elderly: the Health, Ageing and Body Composition Study. J Am Soc Nephrol 2005;16:2127–33

Odden MC, Chertow GM, Fried LF et al. Cystatin C and measures of physical function in elderly adults: The Health, Aging, and Body Composition (HABC) Study. Am J Epidemiol 2006;164:1180–1189.

 Fried LF, Lee JS, Shlipak M et al. Chronic kidney disease and functional limitation in older people: Health, ageing and body composition study. J Am Geriatr Soc 2006;54:750–756.

Anderson AH, Yang W, Hsu CY, Joffe MM, Leonard MB, Xie D, et al. Estimating GFR among participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2012;60(2):250–61.

Slinin Y, Paudel ML, Taylor BC, Fink HA, Ishani A, Canales MT, Yaffe K, Barrett-Connor E, Orwoll ES, Shikany JM, Leblanc ES, Cauley JA, Ensrud KE: 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology 74: 33– 41, 2010

Kurella Tamura et al. (2016, January 28) Anaemia and risk of cognitive decline in Chronic Kidney Disease. Retrieved from: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-016-0226-6.