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

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 (ß= -0.29). Thinning of global (ß= -0.06), AD signature area (ß= -0.06), temporal (ß= -0.06), and parietal lobes (ß= -0.06) predicted poor verbal fluency over time, while temporal lobe thinning also predicted poor MoCA score (ß= -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 (ß= -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.

Effect of Kidney Dysfunction on Cerebral Cortical Thinning in Elderly Population.

Chronic kidney disease has been linked to cognitive impairment and morphological brain change. However, less is known about the impact of kidney functions on cerebral cortical thickness. This study investigated the relationship between kidney functions and global or lobar cerebral cortical thickness (CTh) in 259 non-demented elderly persons. Forty-three participants (16.7%) had kidney dysfunction, which was defined as either a glomerular filtration rate (GFR) of <60 ml/min/1.73 m2 or presence of proteinuria. Kidney dysfunction was associated with lower global (ß = -0.05, 95% CI = -0.08 to -0.01) as well as frontal, parietal, temporal, occipital, and insular lobar CTh. In the stratified analysis, the associations were more pronounced in women, APOEε4 non-carriers, and participants with a lower cognitive score. Besides, kidney dysfunction significantly increased the risk of cortical thinning, defined as being the lowest CTh tertile, in the insular lobe (adjusted odds ratio = 2.74, 95% CI = 1.31-5.74). Our results suggested that kidney dysfunction should be closely monitored and managed in elderly population to prevent neurodegeneration.

Association of DNA methyltransferases 3A and 3B polymorphisms, and plasma folate levels with the risk of urothelial carcinoma.

BACKGROUND: Interindividual genetic variations of human DNA methyltransferases (DNMTs), which involve the methyl donor from the folate-related one-carbon metabolism pathway, are hypothesized as a risk factor for urothelial carcinoma (UC). Therefore, we evaluated the role of gene-environment interaction in UC carcinogenesis. METHODS: A hospital-based case-control study was conducted by recruiting 192 patients with UC and 381 controls. Their plasma folate levels were measured using a competitive immunoassay kit. In addition, DNMT3A -448A>G and DNMT3B -579G>T genotyping was evaluated using a polymerase chain reaction-restriction fragment length polymorphism technique. Multivariate logistic regression and 95% confidence intervals (CIs) were applied to estimate the UC risk. RESULTS: We observed that patients with UC exhibited a higher prevalence rate of folate insufficiency (folate levels ≤6 ng/mL) compared with the controls (35.94% and 18.37%, respectively). Furthermore, folate levels were higher in the prevalent UC patients than in the incident UC patients. However, folate insufficiency was similarly associated with a nearly two-fold increase in the risk of UC regardless of the UC patient group. In addition, the frequencies of the variant alleles for DNMT3A and DNMT3B were 0.80 and 0.92, respectively, and no association was observed with UC risk. However, participants with a variant homozygous genotype of DNMT3B -579G>T and folate insufficiency or with high cumulative cigarette smoking exhibited an increased risk of UC. CONCLUSION: Overall, environmental factors may contribute more significantly to UC carcinogenesis compared with genetic susceptibility. Future studies should investigate other polymorphisms of DNMT3A and DNMT3B to determine genetic susceptibility.