Cerebral metabolite alterations and cognitive dysfunction in chronic kidney disease: a systematic review of proton magnetic resonance spectroscopy studies

Abstract

Abstract Introduction Cognitive impairment is common in chronic kidney disease (CKD), particularly among patients with advanced disease and dialysis dependence, yet the underlying mechanisms remain incompletely understood. Proton magnetic resonance spectroscopy ( 1 H-MRS) enables non-invasive assessment of cerebral metabolites and may provide insight into metabolic pathways associated with cognitive dysfunction. This systematic review evaluated the relationship between brain metabolic alterations detected by 1 H-MRS and cognitive impairment in CKD. Methods A PRISMA 2020-compliant systematic review was conducted using the Cochrane Library, PubMed, ScienceDirect, Google Scholar, and supplementary backward and forward citation-searching methods through May 2026. Observational studies reporting both 1 H-MRS brain metabolite measurements and standardized cognitive assessments in CKD patients were included. Methodological quality was evaluated using the Newcastle–Ottawa Scale. Results Five studies involving 231 CKD patients met inclusion criteria. Cognitive impairment was reported across all studies, affecting intelligence, memory, attention, executive function, and processing speed. Recurrent directional metabolic abnormalities were reported in advanced CKD and dialysis populations, including reduced creatine concentrations, decreased N-acetylaspartate-to-creatine (NAA/Cr) ratios, and increased myo-inositol-to-creatine (mI/Cr) ratios, although substantial heterogeneity in populations, brain regions, acquisition protocols, and quantification methods limited direct quantitative comparability. An isolated inverse correlation between mI/Cr and performance IQ ( r = − 0.895) was reported in a single pediatric cohort but has not been independently replicated and should therefore be considered hypothesis-generating. Importantly, some studies demonstrated metabolic abnormalities without corresponding metabolite–cognition correlations, suggesting that additional vascular, inflammatory, or uremic mechanisms may contribute to cognitive decline. Overall study quality ranged from poor to good. Conclusion Cerebral metabolic abnormalities have been reported in advanced CKD and dialysis populations, frequently alongside cognitive impairment; however, direct metabolite–cognition associations remain inconsistent and insufficiently replicated. Current evidence does not establish causality or support routine clinical use of MRS-based biomarkers.

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