Relationship between Level of 25 (OH) D Vitamins and Cognitive Impairment in Chronic Kidney Disease (CKD) in Dialysis and Non-Dialysis Patients Using Trial Making Test B View PDF

Cognitive impairment (CI) and deficiency in vitamin D always together detected in CKD patients. Meanwhile in CNS regulatory and neuroprotective roles were played by vitamin 25(OH) D.  These factors draining are effective clues lead to CI and complicate through related processes which important causes for mortality in addition to morbidity. Deficiency in vitamin D and cognitive decline have both together important effect on CKD patients, where the periodical determination of status of D vitamin and its supplementation, with continuous screening for neuropsychological state must be achieved in of clinical care units for CKD patients [1]. Cognitive impairment have been accelerated with deficiency of vitamin D in CKD patients, in spite of this fact little previous studies achieved in this side [2]. The sources of vitamin D are photosynthesis, vitamin enriched diet, and oral supplementation with tow formula one is 25(OH) D and the other 1,25(OH)2D where the second one is the active form which derived from1α-hydroxylation of the first form where occur in kidney and other tissues like brain [3]. Other function of vitamin D is to regulate the levels of phosphorous and calcium and keeping the bones healthy [4-7]. All ages are affected by deficiency in the level vitamin D and consider a risk factor resulted from CKD, deficiency of sun exposure, obesity, and inadequate diet [8]. Pollutions of the air is a risk factor for deficiency of vitamin D according to low level of UV light [9]. Level of vitamin D also affected by genetic variation within populations according to changes in polymorphism of 1α-hydroxylase enzyme and expression of vitamin D binding protein [10-13], So that this study was aimed to assess cognitive function by using one validated score: trial making test B in patients with CKD in both dialysis and non-dialysis.

The study archived in the campus of Baghdad Medical city, the study extended during the period from May 2019 to February 2020. Hemodialysis center received ESRD patients three times weekly, with period of 3-4 hrs. for each treatment. A trained nephrologists screened all the participants, and assess their eligibility criteria for CKD, in which CKD was defined as eGFR <60 mL/min on at least two occasions during the period of study (calculated using six-variable in the Modification of Diet in Renal Disease (MDRD) study). In ESRD patients the recording of laboratory data occur periodically in each month, And the values of cognitive function testing recorded within 1 month (parameters other than cholesterol and parathyroid hormone recorded within 6 months)  

Trail making Test B (Trails B)

Visuospatial scanning, executive function (duties which in need for self-shifting and memory)  were evaluated by this test as well as to concentration, all that values used to estimate the time required to link sequential series of lettered and numbers circles. Better performance indicated by completion within short time out of 300 second maximum [14].

Cognitive Impairment

Consistent with prior studies, the function that is impaired executive considered to be a Trails B score of >300 sec [15].

Vitamin D Assessment

Vitamin D [25(OH) D] levels assessed from each participant, using a direct enzyme immunoassay method [16]. With assay range 4.0-110 ng/mL (product code: IS-2520N).

Statistical Analysis

For comparison between two categorical variable chi-square tests used, while for two continuous independent t-tests used. Linear regression analysis used for assessment of the correlation between vitamin D and serum creatinine with cognitive function score. All analyses carried out using SPSS version 23.1, p-value considered to be significant <0.05.

A total of 63 CKD and 68 patients with ESRD for dialysis that enrolled in present study, for assessment of the baseline no significantly differences in age, gender, hypertension history, and the coronary artery disease (CAD), accordingly the history of diabetic, and serum creatinine was significant higher in patients on dialysis, while serum hemoglobin was significantly lower in dialysis patients compared to CKD patients as illustrated in table 1.

Table 1: Baseline characteristics.

For CKD patients, 27.0 ± 6.7 had deficient 25 (OH) D levels, 40.4% insufficient, while 0 (0%) had sufficient levels of 25 (OH) D levels. According to vitamin D levels in patients with dialysis only 27 (39.7%) had sufficient amount level, while 25 (36.7%) deficient level of vitamin and only 20 (29.4%) recorded in serum level ≥20 ng/mL, serum had significant level of 25 (OH) vitamin D lower in patients on dialysis compared to those with CKD, as illustrated in table 2.

Table 2: Assessment of vitamin D.

Mean Trails B was higher significantly in dialysis patients compared with CKD, as illustrated in table 3 and figure 1.

Table 3: Numbers and Mean of Tests on Performance and Reports of Self- Questionnaire for Subjects with ESRD and CKD.

There was a significant correlation between various cognitive function tests (Trials B) with vitamin D, as illustrated in table 4 and figure 2.

Table 4: The relationship between 25 (OH) D with various cognitive functions in dialysis patients.

There was a significant correlation between various cognitive function tests (Trials B) with creatinine, as illustrated in table 5.

Table 5: Relationship between serum creatinine with various cognitive functions in dialysis patients.

In our study, the mean age patients was (52.0 ± 9.1) years for dialysis patients and (49.0 ± 9.5) years for CKD patients, which related to other studies like, Jovanovich AJ, et al. (2014) (a study carried out in the USA involved 247 CKD patients, 358 ESRD on dialysis patients) mean age was 69 ± 12 years for CKD patients and 66 ± 11 years for ESRD patients [17], Liu GL, et al. (2015) study (study carried out in China involved 273 peritoneal dialysis patients) mean age was similar to our 53.58 ± 14.06 years [18]. In the present study, there was a direct significant correlation between serum creatinine with Trails B score. This indicates poor cognitive function associated with lower creatinine in ESRD patients on dialysis. In our study the correlation was significant between 25 (OH) D and Trails B score (r = -0.890, p-value <0.001).Other study for 858 elderly Italian patients more than 65 years old were the relative risk was significantly higher cognitive decline in patient with level lower than 10 ng/ml of vitamin D, associated with patients higher than 30ng/ml of vitamin over period of 6-years [19,20]. The European men for elderly people is less than 14 ng/ml which mostly related to low performance on tests which evaluated the rapidity of information processes but not memory [21]. Mechanisms by which vitamin D related to CI are more varies, in one study 255 U.S. patients with hemodialysis by mean of  62.9 ± 16.9 over the period of 2004-2012, reported that 139(49%) of patients had level of vitamin D between 12-20 ng/ml, and 36(14%) had level lower than 12 ng/ml, while 80(31%) recorded more than 20 ng/ml [22]. The higher global cognitive score is associated independently with level lower higher than 20 ng/ml of vitamin D, while lower levels are related to impaired executive function nevertheless not for global function [23-26]. Study include 36 patients in the Veterans Affairs Medical Centers between 2001-2006, all with CKD patients with dialysis and non-dialysis the result show that there is no relationship for level of vitamin D with cognitive function [17]. Conversely, vitamin D levels in the blood measured between 2002 and 2004, years before processing cognitive tests in 2005-2006, the result not completely explain there is an effect on cognitive study period by the level of vitamin D, and still remain the same level with first period of study. Within phone calls for 20 min the test done, and lead to selection bias. The result shows that most of the patients had not well physically feeling, with several point of cognitive impairment; they were having no tolerance a conversation in the phone for 20 min. This types of patients not involved in the current study. Then the selection of patients could be directed toward null hypothesis and healthier patient population. This study used to a different battery of instruments for cognitive capacity measuring. Therefore, it is not fair to equate current study with the studies of Shaffi K, et al. (2013) and Liu GL, et al. (2015) s[18,22].

Prevalence of vitamin 25 (OH) D deficiencies in CKD especially cognitive decline associated with hemodialysis patients

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