Poor Kidney Function Significantly Linked With Dementia Incidence

Results of a 10-year follow up of a cohort study revealed poor and declining kidney function in older adults is associated with a higher risk of dementia. Findings, published in Age and Aging, also showed the association is not attributable to stroke and persists after accounting for major cardiometabolic conditions, authors wrote.

Previous research has indicated cognitive impairment is common among patients with end-stage renal disease undergoing hemodialysis, while a graded association exists between chronic kidney disease (CKD) severity and cognitive impairment.

“The kidneys and the brain, both being end organs, are thought to be susceptible to vascular damage due to similar anatomic and hemodynamic features,” the researchers explained, proposing one possible common underlying mechanism.

Globally, CKD prevalence is increasing due in part to increasing rates of hypertension, diabetes, and obesity.

To better elucidate the relationship between estimated glomerular filtration rate (eGFR) and dementia, the investigators assessed data that were compiled for over 10 years in a large community dwelling as part of the Whitehall II cohort study. This study was established in 1985 and originally included data on 10,308 individuals. Since the study’s inception, follow-up clinical examinations have taken place every 4 to 5 years, while in the current analysis, baseline data on kidney function measured between 2007 and 2009 were utilized.

Data were also linked with electronic health records of the United Kingdom National Health Service and all-cause dementia was identified based on International Classification of Diseases, 10th Revision codes. Individuals were followed until the recorded date of dementia, death, or March 31, 2019.

Changes in eGFR were measured at follow-up appointments that took place between 2012 and 2013. A total of 6050 adults with a mean age of 65.8 (5.9) years were included in the current analysis.

The researchers found:

• 306 cases of dementia were recorded over a mean follow-up of 10 years
• Baseline eGFR < 60 was associated with an HR for dementia of 1.37 (95% CI, 1.02-1.85) in analysis adjusted for sociodemographic factors, hypertension, obesity, stroke, diabetes and cardiovascular disease/medication
• Removing stroke cases at baseline and censoring them over the follow-up yielded an HR of 1.42 (95% CI, 1.00-2.00) for the association between CKD and dementia
• Decline of eGFR ≥ 4 between 2007 to 2009 and 2012 to 2013 was associated with incidence of dementia over a 6.3-year mean follow-up (HR, 1.37; 95% CI, 1.02-1.85), with somewhat stronger associations when analyses were restricted to those with eGFR ≥ 60 in 2007 to 2009 (HR, 1.56; 95% CI, 1.12-2.19)

Mean (SD) age at dementia diagnosis was 78.1 (5.3) years and these individuals tended to have worse sociodemographic and health profiles at baseline.

Overall, the researchers noted 3 key findings:

• The eGFR < 60 threshold, used to denote risk of CKD, is also valid for risk of dementia
• A robust association of eGFR < 60 with incidence of dementia that was not attributable to stroke and persisted after adjustment for other major cardiometabolic conditions
• Declining eGFR, even when confined to analysis on persons with eGFR ≥ 60 at baseline, was associated with higher incidence of dementia

Current results are in accordance with previously published research, but the exact underlying mechanisms linking the 2 conditions remain unclear.

In the Whitehall II analysis, the researchers were only able to adjust for traditional risk factors, marking a limitation to the study. Participants included were also more likely to be healthier than those with advanced kidney disease, while the follow-up period employed “is not long enough to rule out reverse causations where estimates can be biased due to the long preclinical phase of dementia affecting multiple processes,” the authors wrote.

Cost of care, increasing rates of CKD prevalence, and poor outcomes warrant the prioritization of CKD surveillance from a public health standpoint, the researchers concluded. “While cardiovascular disease and reduction in life expectancy are recognized adverse outcomes of CKD, it is possible that dementia is also part of the risk associated with CKD.”

Reference

Singh-Manoux A, Oumarou-Ibrahim A, Machado-Fragua MD, et al. Association between kidney function and incidence of dementia: 10-year follow-up of the Whitehall II cohort study. Age Aging. Published online January 17, 2022. doi:10.1093/ageing/afab259