Cognition in chronic kidney disease: a systematic review and meta-analysis

Background Cognitive impairment is common in people with chronic kidney disease (CKD) and associated with increased morbidity and mortality. Subtle changes can impact engagement with healthcare, comprehension, decision-making, and medication adherence. We aimed to systematically summarise evidence of cognitive changes in CKD. Methods We searched MEDLINE (March 2016) for cross-sectional, cohort or randomised studies that measured cognitive function in people with CKD (PROSPERO, registration number CRD42014015226). The CKD population included people with eGFR < 60 mL/min/1.73 m2, not receiving renal replacement therapy, in any research setting. We conducted a meta-analysis using random effects, expressed as standardised mean differences (SMD) with 95% confidence intervals (CI). Outcomes were performance in eight cognitive domains. Bias was assessed with the Newcastle-Ottawa Scale (NOS). Results We identified 44 studies reporting sufficient data for synthesis (51,575 participants). Mean NOS score for cohort studies was 5.8/9 and for cross-sectional 5.4/10. Studies were deficient in NOS outcome and selection due to poor methods reporting and in comparison group validity of demographics and chronic disease status. CKD patients (eGFR < 60 mL/min/1.73 m2) performed worse than control groups (eGFR ≥ 60 mL/min/1.73 m2) on Orientation & Attention (SMD –0.79, 95% CI, –1.44 to –0.13), Language (SMD –0.63, 95% CI, –0.85 to –0.41), Concept Formation & Reasoning (SMD –0.63, 95% CI, –1.07 to –0.18), Executive Function (SMD –0.53, 95% CI, –0.85 to –0.21), Memory (SMD –0.48, 95% CI, –0.79 to –0.18), and Global Cognition (SMD –0.48, 95% CI, –0.72 to –0.24). Construction & Motor Praxis and Perception were unaffected (SMD –0.29, 95% CI, –0.90 to 0.32; SMD –1.12, 95% CI, –4.35 to 2.12). Language scores dropped with eGFR (<45 mL/min/1.73 m2 SMD –0.86, 95% CI, –1.25 to –46; 30 mL/min/1.73 m2 SMD –1.56, 95% CI, –2.27 to –0.84). Differences in Orientation & Attention were greatest at eGFR < 45 mL/min/1.73 m2 (SMD –4.62, 95% CI, –4.68 to –4.55). Concept Formation & Reasoning differences were greatest at eGFR < 45 mL/min/1.73 m2 (SMD –4.27, 95% CI, –4.23 to –4.27). Differences in Executive Functions were greatest at eGFR < 30 mL/min/1.73 m2 (SMD –0.54, 95% CI, –1.00 to –0.08). Conclusions Cognitive changes occur early in CKD, and skills decline at different rates. Orientation & Attention and Language are particularly affected. The cognitive impact of CKD is likely to diminish patients’ capacity to engage with healthcare decisions. An individual’s cognitive trajectory may deviate from average