Impacts of Kidney Dysfunction and Cerebral Cortical Thinning on Cognitive Change in Elderly Population

Article type: Research Article

Authors: Chen, Chih-Hao^{a; b; 1} | Chen, Ya-Fang^{c; 1} | Tsai, Ping-Huan^{a; 1} | Chiou, Jeng-Min^d | Lai, Liang-Chuan^e | Chen, Ta-Fu^b | Hung, Hung^a | Chen, Jen-Hau^{a; f; *} | Chen, Yen-Ching^{a; g; *}

Affiliations: [a] Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan | [b] Department of Neurology, National Taiwan University Hospital, Taiwan | [c] Department of Medical Imaging, National Taiwan University Hospital, Taiwan | [d] Institute of Statistical Science, Academia Sinica, Taiwan | [e] Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan | [f] Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taiwan | [g] Department of Public Health, College of Public Health, National Taiwan University, Taiwan

Correspondence: [*] Correspondence to: Dr. Yen-Ching Chen, Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Tel.: +886 2 3366 8019; Fax: +886 2 2351 1955; E-mail: [email protected]; Dr. Jen-Hau Chen, Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan. Tel.: +886 2 2312 3456 ext. 67095; Fax: +886 2 2391 0615; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Cerebral cortical thickness is a neuroimaging biomarker to predict cognitive decline, and kidney dysfunction (KD) is associated with cortical thinning. Objective:This study aimed to investigate the effects of KD and cortical thinning on cognitive change in a prospective cohort study. Methods:A total of 244 non-demented participants were recruited from elderly health checkup program and received cognitive exams including Montreal Cognitive Assessment (MoCA) and different cognitive domains at baseline and three biannual follow-ups afterwards. KD was defined as having either glomerular filtration rate <60 ml/min/1.73 m2 or proteinuria. Cortical thickness of global, lobar, and Alzheimer’s disease (AD) signature area were derived from magnetic resonance imaging at baseline, and cortical thinning was defined as the lowest tertile of cortical thickness. Generalized linear mixed models were applied to evaluate the effects of KD and cortical thinning on cognitive changes. Results:KD was significantly associated with the decline in attention function (β= –0.29). Thinning of global (β= –0.06), AD signature area (β= –0.06), temporal (β= –0.06), and parietal lobes (β= –0.06) predicted poor verbal fluency over time, while temporal lobe thinning also predicted poor MoCA score (β= –0.19). KD modified the relationship between thinning of global, frontal, and limbic, and change of logical memory function (pinteraction < 0.05). When considering jointly, participants with both KD and cortical thinning had greatest decline in attention function compared with those without KD or cortical thinning (β= –0.51, ptrend = 0.008). Conclusions:KD and cortical thinning have joint effect on cognitive decline, especially the attention function. Reverse associations may exist between cortical thinning and memory function in participants with KD, though the results should be interpreted cautiously as an exploratory analysis.

Keywords: Cerebral cortex, cognition, glomerular filtration rate, proteinuria

DOI: 10.3233/JAD-200053

Journal: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 225-236, 2020