Mortaji Parisa, Cai Xuan, Oh Ester, Frazier Rebecca, Srivastava Anand, Fischer Michael, Ricardo Ana, He Jiang, Mills Katherine, Wolfrum Katherine, Anderson Amanda, Feldman Harold I, Miyazaki Makoto, Chonchol Michel, Tamura Manjula Kurella, Nowak Kristen, Isakova Tamara, Jovanovich Anna
Department of Internal Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
Division of Nephrology and Hypertension, Department of Medicine, Northwestern University, Chicago, IL.
Kidney Med. 2025 Apr 25;7(7):101018. doi: 10.1016/j.xkme.2025.101018. eCollection 2025 Jul.
RATIONALE & OBJECTIVE: Cognitive impairment is common in chronic kidney disease (CKD). The secondary bile acid, deoxycholic acid (DCA), is associated with cognitive impairment and Alzheimer's dementia among older adults without CKD. Whether DCA is associated with cognitive impairment and decline in CKD is unknown.
Cross-sectional and longitudinal multivariable-adjusted regression analyses.
SETTING & PARTICIPANTS: 2,836 CRIC Study participants; 699 CRIC Cognitive (COG) Study participants.
Fasting serum DCA levels measured at visit 5 (ie, baseline).
Modified Mini-Mental State Examination (3MS) in the main CRIC cohort and domain-specific cognitive tests in the CRIC COG cohort: Trail Making Test Parts A and B, Category Fluency, Buschke Selective Reminding, and Boston Naming. Cognitive impairment was defined as test score >1 standard deviation worse than the mean test score.
Mean age 59 ± 10 years, 45% female, and 39% Black. In the overall cohort, in cross-sectional analyses, there was no association between DCA and cognitive impairment by 3MS in after adjustment for demographics and clinical factors (prevalence ratio doubling DCA, 1.00; 95% CI, 0.95-1.06; n = 2,836). In longitudinal analyses, DCA was associated with decline (mean annual percent change in 3MS per doubling DCA, -0.13; 95% CI, -0.28 to -0.02) but not with incident impairment (n = 2,836; follow-up of 8.6 ± 3.9 years). Among CRIC COG Study participants, in cross-sectional analyses, DCA was associated with cognitive impairment based on Category Fluency (prevalence ratio per doubling DCA, 1.14; 95% CI, 1.02-1.27) but not with other specific-domain cognitive tests (n = 698-699). In CRIC COG longitudinal analyses, DCA was not associated with decline or incident cognitive impairment (n = 538-574).
No adjustment for inflammation, no stool DCA, 3MS may lack specificity.
Among individuals with CKD stages 2-4, higher DCA levels were independently associated with prevalent cognitive impairment in Category Fluency. The association between DCA and progressive cognitive impairment assessed by 3MS was small and likely not clinically significant.
认知障碍在慢性肾脏病（CKD）中很常见。次级胆汁酸脱氧胆酸（DCA）与无CKD的老年人的认知障碍和阿尔茨海默病性痴呆有关。DCA是否与CKD中的认知障碍及衰退相关尚不清楚。
横断面和纵向多变量校正回归分析。
2836名慢性肾脏病预后研究（CRIC）参与者；699名CRIC认知（COG）研究参与者。
在第5次访视（即基线）时测量的空腹血清DCA水平。
主要CRIC队列中的改良简易精神状态检查表（3MS）以及CRIC COG队列中的特定领域认知测试：连线测验A和B部分、类别流畅性、Buschke选择性提醒测验以及波士顿命名测验。认知障碍定义为测试分数比平均测试分数差超过1个标准差。
平均年龄59±10岁，45%为女性，39%为黑人。在整个队列中，横断面分析显示，在对人口统计学和临床因素进行校正后，DCA与3MS评估的认知障碍之间无关联（DCA加倍时的患病率比，1.00；95%CI，0.95 - 1.06；n = 2836）。纵向分析显示，DCA与衰退相关（DCA每加倍时3MS的平均年变化百分比，-0.13；95%CI，-0.28至-0.02），但与新发障碍无关（n = 2836；随访8.6±3.9年）。在CRIC COG研究参与者中，横断面分析显示，基于类别流畅性，DCA与认知障碍相关（DCA每加倍时的患病率比，1.14；95%CI，1.02 - 1.27），但与其他特定领域认知测试无关（n = 698 - 699）。在CRIC COG纵向分析中，DCA与衰退或新发认知障碍均无关（n = 538 - 574）。
未对炎症进行校正，未检测粪便DCA，3MS可能缺乏特异性。
在2 - 4期CKD患者中，较高的DCA水平与类别流畅性方面的现患认知障碍独立相关。DCA与3MS评估的进行性认知障碍之间的关联较小，可能无临床意义。
