Population-Based Study Finds Link Between CKD, Dementia

A new analysis supports the case that changes in kidney function could be warning signs of the development of dementia.

The report, published in the journal Neurology, is based on data from more than 300,000 people in Sweden. It adds to earlier evidence from community-based reports suggesting a link between dementia and estimated glomerular filtration rate (eGFR).

Both dementia and chronic kidney disease (CKD) are most prevalent in older patients, and changes in eGFR have already been linked with a number of other ailments, including cardio- and cerebrovascular disease, infections, and anemia. What is not yet clear is the extent to which kidney decline and cognitive decline are related, if at all.

To better understand potential links, investigators from the Karolinska Institute in Sweden decided to conduct a population-level analysis that looked at rates of dementia across the full spectrum of kidney function.

Corresponding author Hong Xu, MD, PhD, and colleagues used a database of 329,822 residents of Stockholm in search of patients with a new dementia diagnosis or who began treatments for dementia between 2006-2011. All of the patients in the study were at least 65 years old and the investigators excluded patients who had a history of dementia or who had undergone kidney replacement therapy. Within that population, a subgroup of 205,622 patients had repeated eGFR measurements (at least 2) during the first year of observation. Those data were also included in the analysis.

Among the more than 300,000 patients, 5.8% (n=18,983) went on to develop cases of dementia (median follow-up was 5 years). The data showed a link between eGFR and dementia, with dementia rates rising among patients with lower eGFR readings. Among patients with an eGFR reading of 90-104 ml/min, the rate of dementia was 6.56 per 1000 person-years. However, among patients with eGFR readings below 30 ml/min, the incidence of dementia was 30.28 per 1000 person-years.

Those data translated—following multivariate adjustment—to a higher dementia risk hazard ratio (HR) of 1.71 (95% CI, 1.54-1.91) in patients with eGFR measurements of 30-59 ml/min and an HR of 2.62 (95% CI, 1.91-3.58) in patients with eGFRs below 30 ml/min when compared with patients with eGFR readings of 90-104 ml/min.

The investigators further found that patients who underwent a steep decline in eGFR (defined as >2ml/min/1.73m /year) in a single year had higher risks of dementia. The risk was greater for vascular dementia than Alzheimer’s disease, they added.

Though their findings contradict some other studies on the question, the investigators said they believe their results are strong, in part because of the large population studied.

As for the reasons for the apparent link between CKD and dementia, Xu and colleagues pointed out a number of potential explanations, including that CKD and dementia both share traditional vascular risk factors, such as hypertension and diabetes. They added that CKD can lead to chronic inflammation, oxidative stress, and other conditions that are associated with ischemic cerebrovascular lesions.

Though those and other causes would require more study to verify, the investigators said their analysis should prompt doctors and policy makers to consider strategies to detect dementia among patients with CKD. They said that could involve kidney function testing at dementia screening visits. Such a policy would also allow doctors to catch CKD early, an important factor given that awareness of CKD is still relatively low, they noted.

Reference:

Xu H, Garcia-Ptacek S, Trevisan M, et al. Kidney function, kidney function decline, and the risk of dementia in older adults: a registry-based study. Neurology. Published online May 5, 2021. 2021. doi:10.1212/WNL.0000000000012113