Related Factors and Predictors of Cognitive Dysfunction in Chronic Kidney Disease on Maintenance Hemodialysis in Nigeria

INTRODUCTION

Chronic kidney disease (CKD) is a substantial public health problem.[1] Epidemiologic data increasingly show that individuals at all stages of CKD have a higher risk of developing cognitive dysfunctions.[2] In patients on maintenance hemodialysis, the prevalence of cognitive dysfunctions ranges between 30% and 60% and twice that of the age-matched control.[34] Cognitive impairment (CI) is important because it is also likely to become more of a problem as the dialysis population ages.[5]

Deficits in a number of domains of cognition including concentration, judgment, abstraction, memory, and executive function may occur in patients with CKD and have implication for patients’ capability ranging from impaired ability to participate in adequate care of their condition,[4] to difficulty with requisite provision of informed consent in relation to dialysis initiation or maintenance, and ultimately, renal transplantation.[36] In spite of the huge influence of CI on the quality of life of patients with CKD, it is poorly recognized by nephrologists.[7]

Prior studies have reported an association of CKD with cognitive performance, incident dementia, and functioning cognitive capabilities in relation[7] to verbal learning, visual attention, mental flexibility, and executive functioning.[389] In some of these studies, CI assessment was based on short screening tests, such as the mini-mental state examination,[1011] which is adjudged to have limited sensitivity for cognitive function evaluation.[912] Besides, some of the cognitive tests were administered during a hemodialysis session. However, Murray et al. have shown that global cognitive function varies significantly over the course of the dialysis session with the performance worst during the session itself and best shortly before the session or on the day after.[913]

Moreover, there is small number of published studies of predictors of cognitive dysfunctions patients with CKD from the developing countries, where CKD constitutes a major public health problem. Consequently, there is a need for information about CI and its associated factors among CKD patients which will draw attention to early evaluation, diagnosis, follow-up, and treatment.

Against this background, this study was designed to determine the factors associated with CI and factors that independently predict CI in CKD patients on maintenance hemodialysis using a computer-based neuropsychological test battery.

MATERIALS AND METHODS

RESULTS

During the study period, eighty patients comprising 45 (56.2%) males and 35 (43.8%) females were evaluated. The mean age ± SD of the patients was 49.85 ± 10.58. The median duration of CKD from diagnosis was 2 years (range 0.2–5 years) [Table 1].

Table 1 Sociodemographic, clinical, and laboratory characteristics of the study participants

Considering the etiological factors of CKD in the patients, 35 (43.8%) had chronic glomerulonephritis, 29 (36.2%) patients had hypertension only, 9 (11.2%) had type 2 diabetes mellitus only, 6 (7.6%) had hypertension and diabetes, and 1 (1.2%) patient had unidentified etiology.

The reference values obtained from 100 apparently healthy volunteers for ART D, ART ND, VRT D, VRT ND, BCT, CVST, RMT (words), RMT (figure), taping test D, taping test ND were 149.7–338.8, 158.6–290.4, 86.4–275.5, 86.4–275.5 ms, 49.8%–92.2%, 4.0–10.4 ms, 39.62%–97.11%, 17.62%–88.42%, 39.8%–82.19%, 36.39–78.77, respectively. Table 1 shows sociodemographic, clinical, and laboratory characteristics of the patients.

Forty-one (51.3%) and 43 (53.8%) CKD patients had abnormal scores on ART dominant (D) and nondominant (ND) sides, respectively. Forty (50%) and 42 (52.5%) patients had abnormal scores on VRT D and ND sides, respectively. Twenty-one (26.3%) and 68 (85%) had abnormal scores on BCT and CVST, respectively. Sixty-four (80%) and 65 (81.3%) had abnormal scores on RMT (words) and RMT (figure), respectively. Fifty-two (65%) and 48 (60%) patients had abnormal scores on D and ND sides of tapping test, respectively.

Factors associated with psychomotor speed impairment were duration of CKD from diagnosis (P = 0.0001 and 0.043 in D and ND ART testing, respectively), duration of dialysis use (P = 0.0001 across board in D and ND ART testing as well as in D and ND VRT testing, respectively), and plasma urea (PU) and plasma creatinine (PCr) levels (P < 0.05).

Factors found to be associated with short-term memory impairment included the age (P = 0.045 and 0.025 on words and figures RMT testing, respectively), PU (P = 0.002 and 0.005 on words and figures RMT testing, respectively), and serum creatinine (P = 0.012 and 0.040 on words and figures RMT testing, respectively). Duration of dialysis use (P = 0.032) and serum creatinine (P = 0.001) were associated with attention and concentration in the patients. Tables 2 and 3 show the detail of factors associated with performance on the various neuropsychological tests. Following adjustment for confounders, out of the entire cognitive domains assessed, only psychomotor speed was independently predicted by duration of CKD [Figure 1].

Table 2 Factors associated with cognitive impairment in end-stage renal dise

Table 3 Factors associated with cognitive impairment in end-stage renal disease (continued)

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Figure 1

Odd ratio plot showing an independent predictor of psychomotor speed: Auditory (a), visual (b)

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DISCUSSION

On the basis of this cross-sectional observation conducted in CKD patient on maintenance hemodialysis, we showed that majority of the CKD patients had performance on neuropsychological test batteries that were below the normative values generated from the same population. The high frequency of CI is not dissimilar to the previous reports of 30%–70% among hemodialysis patients.[1718] This study extends the findings of previous cross-sectional and longitudinal studies that reported a close association between CKD and CI.[31920] In a prospective cohort study conducted in a multiethnic stroke-free population by Khatri et al., CKD was found to be associated with cognitive decline and the relationship extended to those with mildly reduced estimated glomerular filtration rate.[17] Several mechanisms underlying CI in persons with CKD have been hypothesized; one of them proposed that mediators of relations between kidney function and cognitive functions are similar to those that have been advanced to explain relations between cardiovascular risk factors and cognition,[8] and this has paved the way for investigations of CKD in relation to diseases where cardiovascular risk factors may play a causal role.[17] A plausible potential mechanism is that CKD, through its adverse effects on the cerebral vasculature, potentiates vascular CI.[212223] A systematic review of structural and functional neuroimaging findings in patients with CKD concluded that cerebral atrophy and cerebral density change, cerebral vascular disease, including deep white matter hyperintensities, silent cerebral infarction and cortical infarction, white matter lesions, and cerebral microbleeds,[24] which are known to be associated with depression and CI,[25] are frequently seen in patients with CKD.

Our data showed that longer CKD duration is associated with an increased likelihood of poor performance on auditory and visual reaction testing, the tests that assessed psychomotor speed in the participants. This observation was supported by both univariate analysis and multiple logistic regression. However, we did not demonstrate a similar effect on attention, memory, motor activation and fluency, and processing and perceptual-mental strategies. Our current finding is concordant with the work of the previous workers.[56726]

Besides cerebrovascular changes, a direct uremic neuronal toxicity supports additional neurodegenerative pathways.[2] In the current study, urea, creatinine, and duration on dialysis were also found to be significantly associated with cognitive dysfunction in the patients but were not strong enough to predict impairment in the study. Unlike in the general population and contrary to expectation, age was not established as a strong factor and determinant of impaired cognitive function in patients with CKD on maintenance dialysis. The significant relationship that was found to exist between age and performance on auditory reaction testing was not sustained on adjusting for other associated factors. This finding is in conformity with the reports from studies elsewhere.[56726]

A major constraint in CI in CKD studies is the definition of normal cognitive performance in the study population; the current study obtained the baseline normative values from age, sex, and level of education-matched apparently healthy individuals in the study population, which were subsequently used in categorization of the cognitive performance in the selected sample of patients. This, in our view, is one of the strengths of the current study.

Nonetheless, the current study has some limitations; the presence of some other coexisting conditions that our analysis did not reveal but which may have impacted cognition could not be completely excluded. The cross-sectional study design of this study limits ability to make inferences regarding the cause of the poor performance observed in some of the participants. It would have been more instructive to track this relationship over time; hence, the need for a longitudinal study on the subject matter cannot be overemphasized.

In spite of these limitations, the findings in our study help raise awareness in respect to the reality of the high frequency of CI, factors associated with impaired cognitive domains, and determinants of CI in CKD patients. It is high time the physicians in charge of CKD patients respond by ensuring early screening for CI, using simple instruments, and ultimately reflect the screening results in the management of patients as well as in discussions with their caregivers.

CONCLUSION

We showed that the factors associated with psychomotor speed impairment were duration of CKD, duration on dialysis use, and PU and PCr levels. Factors found to be associated with short-term memory impairment included the age, PU, and serum creatinine levels. Duration on dialysis and serum creatinine were associated with attention and concentration in the patients, and only psychomotor speed was independently predicted by duration of CKD.