Dementia risk increases with poorer kidney function, faster decline of kidney function

Decreased kidney function, as well as a sharper decline in kidney function, correlated with the development of dementia in older adults, according to results from a 5-year study of a health care use cohort published in Neurology.

“Even a mild reduction in kidney function, as defined by estimated glomerular filtration rate (eGFR), is associated with a markedly increased risk of comorbidities, such as [cardiovascular] and cerebrovascular disease, infections, anemia and possibly dementia. There is indeed growing evidence of a relationship between the kidneys and the brain,” the researchers wrote. “Some studies have shown an association between [chronic kidney disease (CKD)], a higher prevalence of cognitive impairment and faster decline in cognitive function.”

Previous research found “conflicting results” regarding the relationship between kidney function and the rate of dementia diagnoses, according to Hong Xu, MD, PhD, a postdoctoral researcher in the department of neurobiology, care sciences and society and the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, and colleagues. As a result, they examined the risk for dementia “across the full spectrum of kidney function” in a large group of Swedish participants aged 65 years and older.

Xu and colleagues examined data from the Stockholm CREAtinine Measurements (SCREAM) project, a health care use cohort from Stockholm that included all residents receiving serum creatinine tests between 2006 and 2011. The SCREAM study collected more than 90% of the complete census population of individuals aged 65 years and older in the region due to “the commonness of creatinine testing among the elderly,” the researchers wrote.

The researchers examined the relationship between eGFR and the risk for dementia — which they defined as a new dementia diagnosis or the start of dementia treatments — among 329,822 residents from Stockholm who used health care between 2006 and 2011 and were aged 65 years and older. Participants had no history of dementia and were receiving kidney replacement therapy. Xu and colleagues also estimated the rate of eGFR decline in 205,622 participants for whom repeated eGFR measurements during the first year of observation were available to examine its relationship with ensuing risk for dementia.

During a median follow-up period of 5 years, the researchers identified 18,983 cases of dementia (5.8% of participants). Xu and colleagues found that dementia incidence progressively increased as eGFR decreased, from 6.56 per 1,000 person-years among individuals with an eGFR level of 90 to 104 mL per minute to 30.28 per 1,000 person-years among individuals with an eGFR level below 30 mL per minute. Following multivariable adjustment, lower eGFR correlated with a greater risk for dementia in eGFR levels of 30 to 59 mL per minute (HR = 1.71; 95% CI, 1.54-1.91) and less than 30 mL per minute (HR = 2.62; 95% CI, 1.91-3.58) compared with an eGFR rate of 90 to 104 mL per minute.

A sharper decline in eGFR status (>2 mL/minute/1.73m²/year) within 1 year correlated with an increased risk for dementia, according to the study results. Xu and colleagues found that the risk magnitudes were greater for vascular dementia than for Alzheimer’s disease. Additionally, as many as 10% of dementia cases were attributable to an eGFR level of less than 60 mL per minute per 1.73 m².

“Assuming a direct association, our analysis suggest[s] that 10% of the dementia cases could be attributed to CKD, a proportion higher than that observed for other well-established dementia risk factors such as cardiovascular disease and diabetes,” Xu and colleagues wrote.

The study’s primary finding, which demonstrated an inverse linear relationship between baseline kidney function and the rate of dementia among more than 325,000 participants, is “to our knowledge, the largest study to date on the matter, exceeding by several fold the sample size of all previous studies combined and evaluating the whole spectrum of kidney function,” according to the researchers. While Xu and colleagues noted that these results “are not novel,” they added that their findings “may help reconcile the disagreement in previous literature” that could be related to small sample sizes and dichotomization of kidney function.

The results of the present study could assist health care policymakers create and put into place strategies for dementia screening in persons with CKD, in addition to assisting with planning for health services, according to Xu and colleagues.

“On one hand, we speculate that estimating kidney function at dementia screening visits may help in risk stratification, provision of lifestyle recommendations and perhaps consideration of cholinesterase inhibitors over other anti-dementia medications given their potential kidney function sparing effect,” the researchers wrote. “On the other hand, because awareness of CKD is still very low among patients and physicians, such testing may allow early identification of CKD cases that can benefit from nephrologist referral and initiation of anti-proteinuric therapies (ie, renin-angiotensin system inhibitors).”

Xu and colleagues also noted that lifestyle habits that help prevent cardio-cerebral vascular disease may help decrease the risk for dementia and reduce the risk for progression of CKD.