The prevalence, severity, and association with HbA1c and fibrinogen of cognitive impairment in chronic kidney disease
2013; Elsevier BV; Volume: 85; Issue: 3 Linguagem: Inglês
10.1038/ki.2013.366
ISSN1523-1755
AutoresUlla K. Seidel, Janine Gronewold, Michaela Volsek, Olga Todica, Andreas Kribben, Heike Bruck, Dirk M. Hermann,
Tópico(s)Chronic Kidney Disease and Diabetes
ResumoCognitive impairment is a frequent finding in patients with chronic kidney disease (CKD). We examined cognitive performance in a prospective study of 119 patients with CKD stages 3–5 (including dialysis) and 54 control patients of the same age without CKD but with similar vascular risk profiles. Analysis included a comprehensive test battery evaluating memory, information processing speed, executive function, language, and visuoconstructive function, in addition to depression and anxiety. Thirty percent of patients with CKD had cognitive deficits (one or more s.d. below control patient performance). Cognitive deficits (T-value related to published norm values) were mild but significantly decreased to 48.8 in patients with stage 3–5 CKD not requiring hemodialysis and 47.2 in patients with stage 5D disease requiring hemodialysis, compared with 51.5 in control patients. Linear regressions among patients with CKD (forced entry strategy) showed that age (β=-0.50 per s.d.), HbA1c (β=-0.18 per s.d.), and fibrinogen (β=-0.18 per s.d.) predicted cognitive performance. Interestingly, HbA1c discriminated cognition in all age groups, while fibrinogen differentiated cognition particularly in patients over 70 years of age. Thus, our cross-sectional study suggests the severity of cognitive impairment in CKD is mild. As such, longitudinal studies are required to further characterize the role of cognitive deficits in CKD. Cognitive impairment is a frequent finding in patients with chronic kidney disease (CKD). We examined cognitive performance in a prospective study of 119 patients with CKD stages 3–5 (including dialysis) and 54 control patients of the same age without CKD but with similar vascular risk profiles. Analysis included a comprehensive test battery evaluating memory, information processing speed, executive function, language, and visuoconstructive function, in addition to depression and anxiety. Thirty percent of patients with CKD had cognitive deficits (one or more s.d. below control patient performance). Cognitive deficits (T-value related to published norm values) were mild but significantly decreased to 48.8 in patients with stage 3–5 CKD not requiring hemodialysis and 47.2 in patients with stage 5D disease requiring hemodialysis, compared with 51.5 in control patients. Linear regressions among patients with CKD (forced entry strategy) showed that age (β=-0.50 per s.d.), HbA1c (β=-0.18 per s.d.), and fibrinogen (β=-0.18 per s.d.) predicted cognitive performance. Interestingly, HbA1c discriminated cognition in all age groups, while fibrinogen differentiated cognition particularly in patients over 70 years of age. Thus, our cross-sectional study suggests the severity of cognitive impairment in CKD is mild. As such, longitudinal studies are required to further characterize the role of cognitive deficits in CKD. Chronic kidney disease (CKD) is a worldwide growing health problem that is found in 23–35% of adults above 64 years.1.Zhang Q.L. Rothenbacher D. Prevalence of chronic kidney disease in population-based studies: systematic review.BMC Public Health. 2008; 8: 117Crossref PubMed Scopus (712) Google Scholar CKD is frequently associated with cognitive deficits. In previous studies, 17–50% of CKD patients exhibited impairments in memory, executive functioning, information processing, or language abilities, depending on CKD stage.2.Kurella M. Chertow G.M. Luan J. et al.Cognitive impairment in chronic kidney disease.J Am Geriatr Soc. 2004; 52: 1863-1869Crossref PubMed Scopus (349) Google Scholar, 3.Thornton W.L. Shapiro R.J. Deria S. et al.Differential impact of age on verbal memory and executive functioning in chronic kidney disease.J Int Neuropsychol Soc. 2007; 13: 344-353Crossref PubMed Scopus (47) Google Scholar, 4.Nulsen R.S. Yaqoob M.M. Mahon A. et al.Prevalence of cognitive impairment in patients attending pre-dialysis clinic.J Ren Care. 2008; 34: 121-126Crossref PubMed Scopus (16) Google Scholar, 5.Abdel-Kader K. Dew M.A. Bhatnagar M. et al.Numeracy skills in CKD: correlates and outcomes.Clin J Am Soc Nephrol. 2010; 5: 1566-1573Crossref PubMed Scopus (43) Google Scholar In end-stage renal disease requiring hemodialysis, >85% of patients had memory, executive function, or language deficits.6.Murray A.M. Tupper D.E. Knopman D.S. et al.Cognitive impairment in hemodialysis patients is common.Neurology. 2006; 67: 216-223Crossref PubMed Scopus (497) Google Scholar A major problem in CKD studies is the definition of normal cognitive performance, in which age- and education-matched control subjects3.Thornton W.L. Shapiro R.J. Deria S. et al.Differential impact of age on verbal memory and executive functioning in chronic kidney disease.J Int Neuropsychol Soc. 2007; 13: 344-353Crossref PubMed Scopus (47) Google Scholar or norm values from healthy subjects2.Kurella M. Chertow G.M. Luan J. et al.Cognitive impairment in chronic kidney disease.J Am Geriatr Soc. 2004; 52: 1863-1869Crossref PubMed Scopus (349) Google Scholar,4.Nulsen R.S. Yaqoob M.M. Mahon A. et al.Prevalence of cognitive impairment in patients attending pre-dialysis clinic.J Ren Care. 2008; 34: 121-126Crossref PubMed Scopus (16) Google Scholar,5.Abdel-Kader K. Dew M.A. Bhatnagar M. et al.Numeracy skills in CKD: correlates and outcomes.Clin J Am Soc Nephrol. 2010; 5: 1566-1573Crossref PubMed Scopus (43) Google Scholar were used. Only in a few studies, controls were recruited from a medical clinic.6.Murray A.M. Tupper D.E. Knopman D.S. et al.Cognitive impairment in hemodialysis patients is common.Neurology. 2006; 67: 216-223Crossref PubMed Scopus (497) Google Scholar, 7.Pliskin N.H. Yurk H.M. Ho L.T. et al.Neurocognitive function in chronic hemodialysis patients.Kidney Int. 1996; 49: 1435-1440Abstract Full Text PDF PubMed Scopus (86) Google Scholar, 8.Umans J.G. Pliskin N.H. Attention and mental processing speed in hemodialysis patients.Am J Kidney Dis. 1998; 32: 749-751Abstract Full Text PDF PubMed Scopus (36) Google Scholar In two studies, cognitive performance of CKD subjects did not differ from controls.7.Pliskin N.H. Yurk H.M. Ho L.T. et al.Neurocognitive function in chronic hemodialysis patients.Kidney Int. 1996; 49: 1435-1440Abstract Full Text PDF PubMed Scopus (86) Google Scholar,8.Umans J.G. Pliskin N.H. Attention and mental processing speed in hemodialysis patients.Am J Kidney Dis. 1998; 32: 749-751Abstract Full Text PDF PubMed Scopus (36) Google Scholar These observations raised doubts about the validity of existing neuropsychological data. CKD patients exhibit high loads of vascular risk factors and morbidities.9.Collins A.J. Kasiske B. Herzog C. et al.US Renal Data System: excerpts from the USRDS 2002 Annual Data Report: atlas of end-stage renal disease in the United States.Am J Kidney Dis. 2003; 41: S1-S260Abstract Full Text PDF PubMed Scopus (143) Google Scholar The presence of cardiovascular diseases causes a predisposition to cognitive deficits.10.Weiner D.E. Scott T.M. Giang L.M. et al.Cardiovascular disease and cognitive function in maintenance hemodialysis patients.Am J Kidney Dis. 2011; 58: 773-781Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar Although the epidemiological relevance of CKD-related cognitive deficits is possibly large, the underlying mechanisms are largely unknown. It is well established that cognitive deficits are most pronounced in advanced CKD stages.11.Yaffe K. Ackerson L. Kurella Tamura M. et al.Chronic kidney disease and cognitive function in older adults: findings from the chronic renal insufficiency cohort cognitive study.J Am Geriatr Soc. 2010; 58: 338-345Crossref PubMed Scopus (213) Google Scholar,12.Lee J.J. Chin H.J. Byun M.S. et al.Impaired frontal executive function and predialytic chronic kidney disease.J Am Geriatr Soc. 2011; 59: 1628-1635Crossref PubMed Scopus (10) Google Scholar It has been hypothesized that cognitive impairment results from microvascular dysfunction that is related to the patients' vascular risk profiles.13.Pereira A.A. Weiner D.E. Scott T. et al.Cognitive function in dialysis patients.Am J Kidney Dis. 2005; 45: 448-462Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar, 14.Monk R.D. Bennett D.A. Reno-cerebrovascular disease? The incognito kidney in cognition and stroke.Neurology. 2006; 67: 196-198Crossref PubMed Scopus (10) Google Scholar, 15.Murray A.M. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden.Adv Chronic Kidney Dis. 2008; 15: 123-132Abstract Full Text Full Text PDF PubMed Scopus (287) Google Scholar To characterize neuropsychological deficits in CKD, we prospectively and comprehensively studied cognitive performance in 119 patients with CKD stages 3–5 and compared the results with 54 control patients of the same age without CKD with similar vascular risk profile. In this cohort, we then examined predictors of cognitive deficits. The characteristics of The New Tools for the Prevention of Cardiovascular Disease in the CKD study (NTCVD) cohort are summarized in Table 1. CKD patients in this study had a mean age of 61.5±15.7 years, with a predominance of men (63%) in the whole sample. The age and gender profile of all CKD patients did not differ from control patients (mean 62.3±10.1 years, 74.1% men). Compared with CKD stage 3–5 patients who did not receive hemodialysis, stage 5D patients on hemodialysis were younger and more often men. Educational status did not differ between the groups.Table 1Characteristics of control patients and CKD patients, the latter also split into stages 3–5 and stage 5DControls (n=54 patients)CKD all (n=119 patients)CKD stages 3–5 (n=84 patients)CKD stage 5D (n=35 patients)MeasurementsMeasurementsP-value compared with controlsMeasurementsP-value compared with controlsMeasurementsP-value compared with controlsP-value compared with stages 3–5Age (years)62.3±10.161.5±15.70.68964.5±13.50.53354.6±18.40.0640.015Gender (male)40 (74.1)75 (63.0)0.15448 (57.1)0.04327 (77.1)0.7430.039Highest academic degree0.1210.1120.4150.668 No degree1 (1.9)10 (8.4)8 (9.5)2 (5.7) Secondary school40 (74.1)94 (79.0)66 (78.6)28 (80.0) Baccalaureate7 (13.0)9 (7.6)5 (6.0)4 (11.4) University degree6 (11.1)6 (5.0)5 (6.0)1 (2.9)Arterial hypertension47 (87.0)112 (94.9)0.86278 (94.0)0.83334 (97.1)0.9690.887Dyslipidemia41 (75.9)95 (79.8)0.68870 (83.3)0.35925 (71.4)0.6360.180Diabetes17 (31.5)46 (38.5)0.41433 (39.3)0.55913 (37.1)0.4060.771Smoking8 (15.1)16 (13.6)0.80913 (15.7)0.9163 (8.6)0.5160.389BMI (kg/m2)28.3±5.127.2±5.00.20827.8±5.11.00026.0±4.50.1040.226Waist circumference (cm)101.2±14.5103.2±14.30.459103.4±14.41.000102.6±14.41.0001.000Coronary heart disease23 (42.6)46 (38.7)0.55130 (35.7)0.31116 (45.7)0.7090.197Myocardial infarction12 (22.2)16 (13.8)0.17511 (13.4)0.1915 (14.7)0.3851.000Peripheral artery disease2 (3.7)12 (10.2)0.2297 (8.4)0.4815 (14.3)0.1020.319Stroke/transient ischemic attack07 (5.9)0.1027 (8.4)0.04301.0000.100Systolic blood pressure (mmHg)140.6±21.5140.7±25.50.992142.2±25.01.000137.2±26.71.0001.000Diastolic blood pressure (mmHg)74.6±11.871.5±11.60.10271.3±11.60.30472.0±11.60.8851.000Total cholesterol (mg/dl)200.8±42.1201.1±56.20.966204.2±61.41.000193.7±40.91.0001.000LDL cholesterol (mg/dl)119.7±33.6107.1±35.80.303110.0±37.70.343100.2±30.30.0340.503HDL cholesterol (mg/dl)52.2±15.252.2±18.00.99452.1±18.21.00052.5±17.81.0001.000Triglycerides (mg/dl)140.7±72.7177.7±317.10.399188.0±375.60.911153.3±69.90.3020.242HbA1c (%)6.2±1.26.2±1.20.9486.3±1.21.0005.9±1.00.9050.293Glucose (mg/dl)115.1±40.1118.5±44.30.632117.2±40.21.000121.4±53.11.0001.000BNP (pg/ml)25.8 (11.8; 48.0)71.5 (31.3; 169.6)<0.00161.4 (26.3; 120.5)<0.001141.7 (46.0; 558.1)<0.0010.001eGFR (ml/min per 1.73m2)70.9±9.6n.a.n.a.35.2±16.0<0.001n.a.n.a.n.a.Creatinine (mg/dl)1.1±0.23.6±2.7<0.0012.5±1.9<0.0016.2±2.3<0.001<0.001Hemoglobin (g/dl)14.1±1.312.5±1.7<0.00112.5±1.6<0.00112.5±1.9<0.0010.998Potassium (mmol/l)4.2±0.34.7±0.7<0.0014.4±0.60.0055.1±0.8<0.0010.001Fibrinogen (mg/dl)329.6±64.3421.8±116.2<0.001406.9±116.4<0.001457.3±109.3<0.0010.077IMT (mm)1.3±0.31.3±0.30.3911.3±0.31.0001.3±0.31.0001.000ABI1.7±0.31.7±0.40.7741.7±0.31.0001.8±0.51.0001.000Urine albumin (mg/l)0.0 (0.0; 0.0)102.4 (6.6; 520.1)<0.00156.0 (0.0; 301.1)0.003548.3 (214.1; 1778.4)aPatients with anuria (n=14) could not be considered.0.0030.003Urine protein (mg per g creatinine)6.0 (4.0; 20.0)20.0 (5.0; 155.0)0.00213.0 (5.0; 95.0)0.00988.0 (11.0; 243.0)aPatients with anuria (n=14) could not be considered.0.0030.127Time since first dialysis (months)n.a.n.an.a.n.a.n.a.21.0 (5.3; 42.4)n.a.n.a.Time since last dialysis (h)n.a.n.an.a.n.a.n.a.28.0 (22.5; 35.5)n.a.n.a.Abbreviations: ABI, ankle-brachial index; BMI, body mass index; BNP, brain–derived natriuretic peptide; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; IMT, intima-media thickness of common carotid artery; LDL, low-density lipoprotein; n.a., not applicable.Data are means±s.d. for normally distributed continuous data or median (25th, 75th percentile) for non-normally distributed continuous data, and categorical data are presented as n (%). Statistical comparisons were performed as appropriate with tests described in the Materials and Methods section. In post hoc tests, Bonferroni corrections were made for three group comparisons between control patients, CKD stage 3–5 patients, and CKD stage 5D patients.a Patients with anuria (n=14) could not be considered. Open table in a new tab Abbreviations: ABI, ankle-brachial index; BMI, body mass index; BNP, brain–derived natriuretic peptide; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; IMT, intima-media thickness of common carotid artery; LDL, low-density lipoprotein; n.a., not applicable. Data are means±s.d. for normally distributed continuous data or median (25th, 75th percentile) for non-normally distributed continuous data, and categorical data are presented as n (%). Statistical comparisons were performed as appropriate with tests described in the Materials and Methods section. In post hoc tests, Bonferroni corrections were made for three group comparisons between control patients, CKD stage 3–5 patients, and CKD stage 5D patients. As expected, CKD patients exhibited a high prevalence of arterial hypertension (94.9%), dyslipidemia (79.8%), and diabetes (38.5%). The mean body mass index was 27.2±5.0kg/m2. Of these CKD patients, 38.7% had a history of coronary heart disease, 13.8% had a history of myocardial infarcts, and 10.2% had a history of peripheral artery disease. Only 5.9% reported strokes or transitory ischemic attacks (TIAs). The history of strokes or TIAs was more prevalent in stage 3–5 (8.4%) than in control (0%) patients (P=0.043). Low-density lipoprotein cholesterol was lower in stage 5D (100.2±30.3mg/dl) than in control (119.7±33.6mg/dl) patients (P=0.034). No additional significant differences of risk factors and vascular diseases were observed between the groups. Brain–derived natriuretic peptide was elevated in CKD, more strongly in stage 5D (median [Q1;Q3]=141.7 [46.0;558.1] pg/ml) than in stage 3–5 (61.4[26.3;120.5] pg/ml; controls: 25.8[11.8;48.0]) patients (P=0.001). The mean estimated glomerular filtration rate (eGFR) in stage 3–5 patients was 35.2±16.0ml/min per 1.73m2, compared with 70.9±9.6ml/min per 1.73m2 in control patients. Fibrinogen, an acute-phase protein and inflammation marker, was elevated in CKD patients (stage 5D: 457.3±109.3mg/dl; stage 3–5: 406.9±116.4mg/dl; controls: 329.6±64.3mg/dl). Intima-media thickness (IMT) and ankle-brachial index (ABI), which are the markers of macroangiopathy, did not differ between the groups. Neuropsychological results, which were obtained using a battery of 10 tests that evaluated memory, information processing speed, executive function, language, and visuoconstructive abilities, are summarized in Table 2. In this cohort, stage 3–5 patients performed worse than control patients in all tests except the backward condition of the digit span and the forward condition of the block span of the revised Wechsler memory scale and the subtest 'animals' of the Regensburg word fluency test. In most tests, stage 3–5 and stage 5D patients revealed very similar performance, except for the block span (backward condition) of the Wechsler memory scale and the trail–making test (TMT) part A, in which stage 5D patients achieved better results than stage 3–5 patients.Table 2Neuropsychological data of control patients and CKD patients, the latter also split into patients not requiring (stages 3–5) and requiring hemodialysis (stage 5D)Controls (n=54 patients)CKD all (n=119 patients)CKD stages 3–5 (n=84 patients)CKD stage 5D (n=35 patients)MeasurementsMeasurementsP-value compared with controlsMeasurementsP-value compared with controlsMeasurementsP-value compared with controlsP-value compared with stages 3–5Digit span, forward (correct responses)7.9±1.66.9±1.70.0016.9±1.70.0066.9±1.90.0461.000Digit span, backward (correct responses)6.2±1.65.6±1.90.0535.5±1.90.0965.7±1.70.4990.819Block span, forward (correct responses)7.4±1.47.7±1.50.2347.8±1.50.2857.4±1.60.9760.568Block span, backward (correct responses)7.0±1.66.4±1.80.0246.1±1.70.0087.0±2.01.0000.032TMT part A (seconds)38.9±16.247.8±22.80.00550.6±25.00.00441.1±14.60.7890.033TMT part B (seconds)92.4±35.8124.2±59.7<0.001127.8±63.8<0.001115.4±48.10.0600.510Stroop test, interference (seconds)90.0±17.5100.0±28.80.007101.8±30.10.01595.7±25.20.4990.524Word fluency, 'animals' (correct responses)31.3±8.328.5±9.30.06428.9±8.20.22927.5±11.81.0000.245Word fluency, 's-words' (correct responses)20.5±6.616.2±6.9<0.00116.6±6.30.00515.2±8.10.0020.966Rey–Osterrieth complex figure test (raw value)32.7±2.430.2±5.0<0.00130.4±5.00.00229.6±5.10.0040.688HADS, depression scale (score)5.0 (2.0; 6.5)4.0 (2.0;8.0)0.6974.0 (2.0; 7.0)1.0006.0 (2.0; 13.0)0.2430.090HADS, anxiety scale (score)5.0 (3.0; 8.0)5.0 (2.0; 7.0)0.7405.0 (2.0; 7.0)0.7776.0 (4.0; 12.0)0.5520.066Abbreviations: CKD, chronic kidney disease; HADS, Hospital Anxiety and Depression Scale; TMT, trail–making test.Data are means±s.d. for normally distributed continuous data or median (25th; 75th percentile) for non-normally distributed continuous data, and categorical data are presented as n (%). Statistical comparisons were performed as appropriate with tests described in the Materials and Methods section. In post hoc tests, Bonferroni corrections were made for three group comparisons between control patients, CKD stage 3–5 patients and CKD stage 5D patients. Open table in a new tab Abbreviations: CKD, chronic kidney disease; HADS, Hospital Anxiety and Depression Scale; TMT, trail–making test. Data are means±s.d. for normally distributed continuous data or median (25th; 75th percentile) for non-normally distributed continuous data, and categorical data are presented as n (%). Statistical comparisons were performed as appropriate with tests described in the Materials and Methods section. In post hoc tests, Bonferroni corrections were made for three group comparisons between control patients, CKD stage 3–5 patients and CKD stage 5D patients. Global cognitive performance, which was evaluated using z-scores computing means for all 10 tests, was significantly worse in stage 3–5 (-0.6±0.8) and stage 5D (-0.5±0.9) patients compared with control (0.0±0.6) patients, both when evaluated by one-way analysis of variance followed by Bonferroni tests (P<0.001 and P=0.020 for stage 3–5 and stage 5D compared with control, respectively) and nonparametric exact tests (P<0.001 and P=0.007 for stage 3–5 and stage 5D compared with control, respectively). Depression and anxiety scores, evaluated by the Hospital Anxiety and Depression Scale, did not differ between the groups. To evaluate the prevalence of cognitive impairment in the CKD cohort, we examined the number and percentage of patients performing more than one s.d. worse than control patients by means of z-scores (Table 3). These analyses revealed that 30.3% of CKD patients had a poor global cognitive performance, 18.5% had memory deficits, 26.1% had deficits in information processing, 37.8% had executive dysfunction, 35.3% had language deficits, and 38.7% had visuoconstruction deficits. Compared with control patients, cognitive impairment in stage 3–5 patients was more prevalent in all five neuropsychological domains. Compared with control patients, cognitive impairment in stage 5D patients was more prevalent in the domains' executive function, language, and visuoconstruction. Stage 5D patients showed a higher prevalence of language impairment (51.4%) compared with stage 3–5 patients (28.6%). In all other domains, no significant differences were found between stage 3–5 and stage 5D patients.Table 3Frequencies of cognitive impairment in patients with CKD and also split into patients not requiring (stages 3–5) and requiring hemodialysis (stage 5D)CKD all (n=119 patients)CKD stages 3–5 (n=84 patients)CKD stage 5D (n=35 patients)MeasurementsP-value compared with controlsMeasurementsP-value compared with controlsMeasurementsP-value compared with controlsP-value compared with stages 3–5Global cognitive performance36 (30.3)<0.00126 (31.0)<0.00110 (28.6)0.0030.767Memory22 (18.5)<0.00117 (20.2)0.0165 (14.3)0.2550.430Information processing speed31 (26.1)0.01226 (31.0)0.0035 (14.3)0.5070.055Executive function45 (37.8)0.02434 (40.5)<0.00111 (31.4)0.0070.335Language42 (35.3)<0.00124 (28.6)0.00118 (51.4)<0.0010.012Visuoconstruction46 (38.7)0.00231 (36.9)0.00515 (42.9)0.0040.608Abbreviations: CKD, chronic kidney disease.Data are numbers (%) of patients scoring more than one s.d. below control subjects. Statistical comparisons were performed with the χ2- or Fisher's exact test as appropriate. Global cognitive performance: all neuropsychological tests; memory: digit and block span (forwards and backwards); information processing speed: trail–making test, part A; executive function: Stroop (interference) and trail–making test, part B; language: Regensburger Wortflüssigkeitstest ('animals' and 's-words'); visuoconstruction: Rey–Osterrieth complex figure (copy task). Open table in a new tab Abbreviations: CKD, chronic kidney disease. Data are numbers (%) of patients scoring more than one s.d. below control subjects. Statistical comparisons were performed with the χ2- or Fisher's exact test as appropriate. Global cognitive performance: all neuropsychological tests; memory: digit and block span (forwards and backwards); information processing speed: trail–making test, part A; executive function: Stroop (interference) and trail–making test, part B; language: Regensburger Wortflüssigkeitstest ('animals' and 's-words'); visuoconstruction: Rey–Osterrieth complex figure (copy task). To further characterize cognitive performance in CKD patients, we also related neuropsychological test results to age- and education-matched norm values obtained from the literature (summarized for 60-year-old subjects with secondary school graduation in Supplementary Table S1 online), calculating T-values for the global cognitive performance. This analysis revealed that stage 3–5 patients (T=48.8±5.4) and stage 5D patients (T=47.2±7.1) exhibited a significantly worse global cognitive performance, when compared with control patients from our own cohort (51.5±5.4; P=0.026 and P=0.003, respectively) (Figure 1). Yet, this group difference of 2.7–4.3 T-values was small, equivalent to <0.5 s.d. in the published reference cohorts. Download .doc (.1 MB) Help with doc files Supplementary Tables To evaluate predictors of neuropsychological deficits, univariate and multivariable linear regressions were computed for the whole cohort (both control and CKD patients), in which the factors age, gender, education, CKD stage, systolic blood pressure, dyslipidemia, glycated hemoglobin (HbA1c), smoking, body mass index, brain–derived natriuretic peptide, fibrinogen, depression, anxiety, IMT, ABI, and history of coronary heart disease, stroke/TIA, and peripheral vascular disease were inserted either alone or in different combinations (Table 4). In univariate regressions (unadjusted model in Table 4), the factors age, education, HbA1c, fibrinogen, depression, IMT, and history of coronary heart disease and stroke/TIA predicted global cognitive performance.Table 4Predictors for global cognitive performance in all patients (n=173 subjects)Global cognitive performanceModel 2Model 3Model 4Model 5Model 6UnadjustedCorrected R2=0.354Corrected R2=0.414Corrected R2=0.407Corrected R2=0.404Corrected R2=0.372β or B95% CIPβ or B(95% CI)Pβ or B95% CIPβ or B95% CIPβ or B95% CIPβ or B95% CIPAge-0.49-0.62; -0.36<0.001-0.48-0.61; -0.34<0.001-0.49-0.63; -0.34<0.001-0.49-0.63; -0.34<0.001-0.56-0.75; -0.40<0.001-0.49-0.63; -0.32<0.001Gender (male vs. female)-0.21-0.46; 0.050.111-0.130.34; -0.080.222-0.11-0.10; 0.320.301-0.11-0.11; 0.320.330-0.12-0.35; 0.110.289-0.14-0.37; 0.090.231Education0.400.27; 0.55<0.0010.230.10; 0.370.0010.220.08; 0.350.0020.200.06; 0.350.0060.180.03; 0.330.0180.210.05; 0.370.011CKD stage-0.14-0.29; 0.010.073-0.24-0.37; -0.12<0.001-0.24-0.40; -0.070.006-0.23-0.40; -0.050.011-0.33-0.48; -0.17<0.001-0.29-0.44; -0.120.001Systolic blood pressure-0.11-0.26; 0.040.1460.03-0.10; 0.150.6780.02-0.11; 0.150.7930.02-0.11; 0.160.7410.03-0.11; 0.180.673Dyslipidemia (yes vs. no)-0.27-0.56; 0.030.075-0.05-0.20; 0.300.703-0.08-0.19; 0.340.562-0.02-0.25; 0.290.887-0.10-0.19; 0.380.508HbA1c-0.25-0.40; -0.110.001-0.16-0.29; -0.020.022-0.15-0.28; -0.010.031-0.15-0.32; 0.000.052-0.19-0.32; -0.040.011Smoking (yes vs. no)-0.06-0.29; 0.410.756-0.23-0.54; 0.070.135-0.22-0.53; 0.090.165-0.25-0.56; 0.060.115-0.21-0.53; 0.110.197BMI-0.12-0.27; 0.030.1190.00-0.14; 0.130.984-0.01-0.15; 0.130.907-0.04-0.19; 0.110.570-0.03-0.18; 0.120.706BNP-0.07-0.22; 0.080.3670.06-0.08; 0.190.4130.06-0.08; 0.190.4130.11-0.04; 0.340.1250.06-0.09; 0.200.466Fibrinogen-0.29-0.44; -0.14<0.001-0.12-0.27; 0.040.142-0.12-0.29; 0.050.151HADS, depression scale-0.19-0.34; -0.040.012-0.03-0.21; 0.150.758-0.06-0.24; 0.130.539-0.04-0.23; 0.150.693HADS, anxiety scale-0.11-0.26; 0.040.142-0.01-0.19; 0.170.9080.03-0.15; 0.200.7700.01-0.17; 0.200.938IMT-0.35-0.49; -0.20<0.0010.04-0.13; 0.210.631ABI0.09-0.06; 0.250.239-0.02-0.15; 0.110.798Coronary heart disease (yes vs. no)-0.39-0.63; -0.150.0020.00-0.26; 0.260.994Stroke/TIA (yes vs. no)-0.74-1.34; -0.150.015-0.49-1.04; 0.070.085Peripheral vascular disease (yes vs. no)-0.39-0.81; 0.040.076-0.11-0.30; 0.510.608Abbreviations: ABI, ankle-brachial index; BMI, body mass index; BNP, brain–derived natriuretic peptide; CI, confidence interval; CKD, chronic kidney disease; HADS, Hospital Anxiety and Depression Scale; HbA1c, glycated hemoglobin; IMT, intima-media thickness of common carotid artery; TIA, transitory ischemic attack.For model 1 (unadjusted model), univariate linear regressions were calculated; for models 2–6, multivariable linear regressions were calculated (using simultaneous inclusion (i.e., forced entry) strategy). Model 2: adjusted for age, gender, education (years), and CKD stage. Model 3: adjusted for age, gender, education (years), CKD stage, systolic blood pressure, dyslipidemia, HbA1c, smoking, BMI, BNP, and fibrinogen. Model 4: adjusted for age, gender, education (years), CKD stage, systolic blood pressure, dyslipidemia, HbA1c, smoking, BMI, BNP, fibrinogen, HADS (depression scale), and HADS (anxiety). Model 5: adjusted for age, gender, education (years), CKD stage, systolic blood pressure, dyslipidemia, HbA1c, smoking, BMI, BNP, HADS (depression scale), HADS (anxiety scale), ABI, and IMT. Model 6: adjusted for age, gender, education (years), CKD stage, systolic blood pressure, dyslipidemia, HbA1c, smoking, BMI, BNP, HADS (depression scale), HADS (anxiety scale), coronary heart disease, stroke/ TIA, and peripheral vascular disease. Open table in a new tab Abbreviations: ABI, ankle-brachial index; BMI, body mass index; BNP, brain–derived natriuretic peptide; CI, confidence interval; CKD, chronic kidney disease; HADS, Hospital Anxiety and Depression Scale; HbA1c, glycated hemoglobin; IMT, intima-media thickness of common carotid artery; TIA, transitory ischemic attack. For model 1 (unadjusted model), univariate linear regressions were calculated; for models 2–6, multivariable linear regressions were calculated (using simultaneous inclusion (i.e., forced entry) strategy). Model 2: adjusted for age, gender, education (years), and CKD stage. Model 3: adjusted for age, gender, education (years), CKD stage, systolic blood pressure, dyslipidemia, HbA1c, smoking, BMI, BNP, and fibrinogen. Model 4: adjusted for age, gender, education (years), CKD stage, systolic blood pressure, dyslipidemia, HbA1c, smoking, BMI, BNP, fibrinogen, HADS (depression scale), and HADS (anxiety). Model 5: adjusted for age, gender, education (years), CKD stage, systolic blood pressure, dyslipidemia, HbA1c, smoking, BMI, BNP, HADS (depression scale), HADS (anxiety scale), ABI, and IMT. Model 6: adjusted for age, gender, education (years), CKD stage, systolic blood pressure, dyslipidemia, HbA1c, smoking, BMI, BNP, HADS (depression scale), HADS (anxiety scale), coronary heart disease, stroke/ TIA, and peripheral vascular disease. In a multivariable regression (forced entry strategy), in which the factors age, gender, education, and CKD stage were included (model 2 in Table 4), the factors age (β=-0.48 per
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