A large register-based study from Sweden identified chronic kidney disease as a risk factor for dementia in older adults

29 Jun 2021

Chronic kidney disease (CKD), defined as the persistent reduction in kidney function, is a growing health concern in the elderlies with an estimated global mean prevalence of 34.3% for populations over the age of 70-years-old.1 Associated with multiple comorbidities, reduced kidney function is a strong predictor of hospitalization, poor quality-of-life, and most importantly, cognitive dysfunction.1 In a recent large-scale study in Sweden, the link between dementia incidence and kidney function, as defined by estimated glomerular filtration rate (eGFR), was identified in a large population of older adults over the age of 65-years-old.2 

Currently, identifying potential risk factors is one of the viable strategies in preventing dementia.3 Where some studies showed an association between CKD and a higher prevalence of cognitive impairment and faster decline in cognitive function, epidemiologic data also suggested that individuals at all stages of CKD had a higher risk of developing dementia and cognitive disorders than those without CKD.3,4 To evaluate the possibility of using CKD as a predictor to dementia, a study was conducted to explore the risk of dementia across the full spectrum of kidney function, with serial measures of eGFR, in a large Sweden population aged 65-years-old and above.3

The study analyzed the association between eGFR and the risk of dementia, defined as a new dementia diagnosis or initiation of dementia treatments, among more than 329,000 older residents of Stockholm who accessed healthcare during 2006 to 2011, were at least 65-years-old and had no history of dementia or underwent kidney replacement therapy.3 During a median follow-up of 5 years, 5.8% of participants were diagnosed with dementia with higher incidence rates (IRs) observed among those with lower eGFR or CKD at stage 3 or above.3 The IRs rose progressively from 6.56 per 1,000 patient-years (py) in participants with an eGFR of 90-104mL/min/1.73m2 to 30.3 per 1,000py in those with an eGFR below 30mL/min/1.73m2.3 Notably, participants with moderate CKD (eGFR 30-59mL/min/1.73m2) had a 71% higher risk of developing dementia (HR=1.71; 95% CI: 1.54-1.91; p<0.001) that increased to 162% higher risk (HR=2.62; 95% CI: 1.91-3.58; p<0.001) among those with severe kidney dysfunction (eGFR below 30mL/min/1.73m2) when compared to those with normal kidney function (eGFR 90-104mL/min/1.73m2).3

In addition, the study also estimated the rate of eGFR deterioration in a subgroup of over 205,000 participants.3 Through repeated eGFR measurements during the first year of observation, a steeper eGFR decline of over 2mL/min/1.73m2/year within one year was found to infer a higher risk of all-cause dementia, and in particular, vascular dementia.3 A similar but less clear association was also observed between the rate of eGFR decline and the risk of Alzheimer’s dementia.3 Assuming a direct association, up to 10% (95% CI: 6-14%) of dementia cases could be attributed to CKD, which was proportionally higher than that attributed to other dementia risk factors such as cardiovascular disease (CVD) and diabetes.3

Given the increase in life expectancy and the aging population in industrialized countries, the burden of dementia associated with CKD is expected to worsen.4 With this study concluding the inverse linear association between kidney function and dementia, a rapid decline in kidney function can now be used as a significant predictor to dementia similar to CVD.3 By raising the awareness of the association between these two conditions, appropriate strategies for dementia screening can be developed in patients with CKD, as well as healthcare service planning to ease the burden of both CKD and dementia and improve the quality-of-life of these elderly patients.3

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