Deoxycholic Acid and Cognitive Impairment and Decline in the Chronic Renal Insufficiency Cohort (CRIC)

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. Study Design: Cross-sectional and longitudinal multivariable-adjusted regression analyses. Setting & Participants 2,836 CRIC Study participants; 699 CRIC Cognitive (COG) Study participants. Exposure: Fasting serum DCA levels measured at visit 5 (ie, baseline). Outcomes: 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. Results: 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). Limitations: No adjustment for inflammation, no stool DCA, 3MS may lack specificity. Conclusion: 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.