Cognitive Impairments and Dysexecutive Behavioral Disorders in Chronic Kidney Disease
Abstract
Methods
Design and Setting
Patients
Assessments at Baseline
Clinical variables.
Neuropsychological assessment.
MRI.
Laboratory tests.
Data Analyses
Results
Characteristic | N | % | Mean | SD |
---|---|---|---|---|
Demographic and clinical data | ||||
Age (years) | — | — | 62.58 | 11.01 |
Male gender | 22 | 55.0 | — | — |
Educational level (years) | — | — | 10.7 | 3.2 |
Right-handedness | 39 | 97.5 | — | — |
Chronic kidney disease stage: 2, 3, 4, 5a | 7, 19, 8, 6 | 17.5, 47.5, 20.0, 15.0 | — | — |
Hypertension | 33 | 84.6 | — | — |
Weight (kg) | — | — | 76.3 | 14.84 |
Body mass index (kg/m2) | — | — | 27.5 | 5.92 |
Diabetes | 16 | 41.0 | — | — |
Hypercholesterolemia | 25 | 64.1 | — | — |
Smoker | 14 | 43.8 | — | — |
Pulse-wave velocity (m/s) | — | — | 9.9 | 3.37 |
MRI features | ||||
Normalized brain tissue volume (cm3) | — | — | 1,414.2 | 66.5 |
Stroke volume (mm3) | — | — | 3,678.9 | 2,0265 |
Total hippocampal atrophy | — | — | 2b | 1–4b |
White matter hyperintensities burdenc | 12, 19, 4, 5 | 30, 47.5, 10, 12.5 | — | — |
Presence of microbleeds | 6 | 15 | — | — |
Infarct and hemorrhage | 9 | 22.5 | — | — |
Metabolic data | ||||
Estimated glomerular filtration rate (mL/min/1.73 m2)d | — | — | 42.48 | 17.71 |
Creatinine (µmol/L) | — | — | 219.29 | 168.01 |
Anion gap (mmol/L) | — | — | 12.34 | 3.1 |
Prothrombin time | — | — | 93.3 | 16.64 |
C-reactive protein (mg/L) | — | — | 4.22 | 2.96 |
Albuminemia (g/L) | — | — | 42.4 | 3.88 |
Leukocyte count (103/mm) | — | — | 7.13 | 1.9 |
Hemoglobin (g/dL) | — | — | 12.92 | 1.64 |
Hematocrit (%) | — | — | 38.98 | 4.5 |
Erythrocyte count (103/mm) | — | — | 4.28 | 0.61 |
Cholesterol (mmol/L) | — | — | 4.44 | 1.22 |
Low-density lipoprotein cholesterol (mmol/L) | — | — | 2.31 | 0.93 |
Triglycerides (mmol/L) | — | — | 1.72 | 1.43 |
High-density lipoprotein cholesterol (mmol/L) | — | — | 1.38 | 0.39 |
Parathyroid hormone (pg/mL) | — | — | 145.18 | 162.6 |
Calcitriol 1.25(OH)vitamin D3 (pg/mL) | — | — | 36.70 | 21.14 |
Calcidiol 25(OH)vitamin D3 (pg/mL) | — | — | 26.276 | 10.818 |
Glycemia (mmol/L) | — | — | 6.065 | 2.306 |
Calcium (mmol/L) | — | — | 2.34 | 0.156 |
Uric acid (µmol/L) | — | — | 475.33 | 131.395 |
Indole–3-acetic acid (µmol/L) | — | — | 1.52 | 0.81 |
P-cresyl sulfate (µmol/L) | — | — | 81.34 | 84.47 |
Indoxyl sulfate (µmol/L) | — | — | 25.08 | 32.9 |
Cognitive Impairments and Behavioral Disorders
Measure | Cohen’s d | 95% CI | p |
---|---|---|---|
Mini-Mental State examination | 0.792 | 0.468–1.116 | 0.0001 |
Montreal Cognitive Assessment | 0.597 | 0.279–0.915 | 0.0100 |
Boston Naming Test | 0.729 | 0.359–1.099 | 0.0001 |
Complex figure (copying) | 0.523 | 0.206–0.840 | 0.0012 |
Free and Cued Selective Recall Test | |||
Free recall sum | 0.446 | 0.123–0.770 | 0.0068 |
Total recall sum | 0.188 | –0.139–0.516 | 0.2588 |
Recognition | 0.033 | –0.287–0.353 | 0.8391 |
Delayed free recall | 0.169 | –0.153–0.492 | 0.3022 |
Delayed total recall | –0.098 | –0.420–0.224 | 0.5513 |
Baddeley Doors test | 0.158 | –0.163–0.479 | 0.3339 |
Complex figure (recall) | 0.136 | –0.186–0.459 | 0.4071 |
Trail-Making Test | |||
Part A completion time | 0.682 | 0.361–1.002 | 0.0001 |
Part B completion time | 1.147 | 0.820–1.474 | 0.0001 |
Test errors B–A | 0.786 | 0.453–1.118 | 0.0062 |
Digit Symbol Substitution Test | 0.939 | 0.620–1.258 | 0.0001 |
Letter fluency | 0.809 | 0.495–1.123 | 0.0001 |
Category fluency | 0.631 | 0.320–0.942 | 0.0001 |
Behavioral Dysexecutive Syndrome Inventory | 0.825 | 0.610–1.041 | 0.0002 |
Risk Factors of Cognitive Impairment
Features | Cognitive Impairment Present (N=13) | Cognitive Impairment Absent (N=27) | p | ||||||
---|---|---|---|---|---|---|---|---|---|
N | % | Mean | SD | N | % | Mean | SD | ||
Demographic and clinical data | |||||||||
Age (years) | — | — | 62.08 | 14.14 | — | — | 62.81 | 9.45 | 0.84 |
Male gender | 7 | 53.9 | — | — | 15 | 55.6 | — | — | 1 |
Education level (years) | — | — | 10.54 | 2.2 | — | — | 10.74 | 3.59 | 0.85 |
Right handedness | 13 | 100 | — | — | 26 | 96.3 | — | — | 1 |
Hypertension | 12 | 92 | — | — | 21 | 77.8 | — | — | 0.20 |
Weight (kg) | — | — | 70.46 | 10.97 | — | — | 79.92 | 13.17 | 0.06 |
Body mass index (kg/m2) | — | — | 25.39 | 3.41 | — | — | 28.46 | 6.61 | 0.16 |
Diabetes | 4 | 33.3 | — | — | 12 | 44.4 | — | — | 0.77 |
Hypercholesterolemia | 8 | 66.7 | — | — | 17 | 63.0 | — | — | 1 |
Smoker | 4 | 40.0 | — | — | 10 | 45.4 | — | — | 1 |
Pulse wave velocity (m/s) | — | — | 9.23 | 1.31 | 10.24 | 4.01 | 0.42 | ||
MRI features | |||||||||
Normalized brain tissue volume (cm3) | — | — | 1,364.4 | 68.2 | — | — | 14,379.4 | 51.6 | 0.0005 |
Stroke volume (mm3) | — | — | 11,302.7 | 35233.3 | — | — | 8.16 | 24.34 | 0.0048 |
Total hippocampal atrophy | — | — | 2a | 0–5a | — | — | 2a | 1–3a | 0.83 |
White matter hyperintensities burdenb | — | — | 1a | 1–1a | — | — | 1a | 0–1a | 0.93 |
Presence of microbleeds | 2 | 15.4 | — | — | 4 | 14.8 | — | — | 1 |
Metabolic data | |||||||||
Estimated glomerular filtration ratec (mL/min/1.73cm2) | — | — | 41.3 | 21.71 | — | — | 43 | 16.21 | 0.81 |
Creatinine (µmol/L) | — | — | 229.36 | 144.82 | — | — | 215.19 | 179 | 0.82 |
Anion gap (mmol/L) | — | — | 12.36 | 2.34 | — | — | 12.33 | 3.43 | 0.97 |
Albuminemia (g/L) | — | — | 44.18 | 3.58 | — | — | 41.64 | 3.79 | 0.07 |
Prothrombin time | — | — | 88.92 | 22.92 | — | — | 95.4 | 12.66 | 0.27 |
C-reactive protein (mg/L) | — | — | 3.59 | 1.04 | — | — | 4.48 | 3.44 | 0.41 |
Parathyroid hormone (pg/mL) | — | — | 222.33 | 249.01 | — | — | 109.58 | 87.59 | 0.04 |
Calcium (mmol/L) | — | — | 2.25 | 0.22 | — | — | 2.38 | 0.1 | 0.015 |
Calcitriol 1.25(OH)vitamin D3 (pg/mL) | — | — | 35.18 | 20.23 | — | — | 37.43 | 21.97 | 0.78 |
Calcidiol 25(OH) vitamin D3 (pg/mL) | — | — | 23.63 | 9.5 | — | — | 27.45 | 11.33 | 0.32 |
Leukocytes (103/mm) | — | — | 6.44 | 1.26 | — | — | 7.44 | 2.07 | 0.13 |
Hemoglobin (g/dL) | — | — | 12.64 | 1.73 | — | — | 13.26 | 1.69 | 0.07 |
Low-density lipoprotein cholesterol (mmol/L) | — | — | 1.93 | 0.58 | — | — | 2.14 | 0.99 | 0.13 |
Triglycerides (mmol/L) | — | — | 2.0 | 2.3 | — | — | 1.58 | 0.77 | 0.42 |
High-density lipoprotein cholesterol (mmol/L) | — | — | 1.34 | 0.38 | — | — | 1.4 | 0.4 | 0.68 |
Glycemia (mmol/L) | — | — | 4.55 | 0.4 | — | — | 6.77 | 2.49 | 0.004 |
Uric acid (µmol/L) | — | — | 521.36 | 126.83 | — | — | 439.48 | 98.88 | 0.03 |
Indole–3-acetic acid (µmol/L) | — | — | 1.69 | 1.03 | — | — | 1.44 | 0.69 | 0.38 |
P-cresyl sulfate (µmol/L) | — | — | 75.43 | 59.19 | — | — | 84.30 | 95.58 | 0.76 |
Indoxyl sulfate (µmol/L) | — | — | 21.68 | 17.59 | — | — | 26.79 | 38.56 | 0.65 |
Potential Predictor | Regression Coefficient (Estimated) | Standard Error of the Regression Coefficient | p | Bootstrap (%) (N=1,000 Permutations) |
---|---|---|---|---|
Weight (kg) | 7.251×10–3 | 7.514×10–3 | 0.34 | 45 |
Stroke volume (mm3) | –7.221×10–2 | 3.074×10–2 | 0.026 | 87 |
Brain tissue volume (mm3) | 1.485×10–6 | 1.619×10–6 | 0.367 | 41 |
Parathyroid hormone (pg/mL) | –1.655×10–3 | 5.673×10–4 | 0.007 | 86 |
Glycaemia (mmol/L) | 1.059×10–1 | 4.780×10–2 | 0.035 | 90 |
Uric acid (µmol/L) | –1.815×10–3 | 7.230×10–4 | 0.018 | 88 |
Discussion
Cognitive Impairments and Behavioral Disorders
Risk Factors of Cognitive Impairment
Vascular hypothesis of cognitive impairment.
Metabolic hypothesis of cognitive impairment: hyperparathyroidism, neuronal toxicity of the uremic state, and hypoglycemia.
Conclusions
Acknowledgments
References
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