Kidney Function, Kidney Function Decline, and the Risk of Dementia in Older Adults: A Registry-Based Study

Abstract

Objective: Community-based reports regarding the association between the estimated glomerular filtration rate (eGFR) and dementia risk show conflicting results. The aim of this study is to investigate the links among kidney function, kidney function decline, and dementia incidence.

Methods: We analyzed the association of eGFR with the risk of dementia (defined as a new dementia diagnosis or initiation of dementia treatments) among 329,822 residents of Stockholm who accessed health care during 2006 to 2011, were ≥65 years of age, had no history of dementia, or underwent kidney replacement therapy. We also estimated the rate of eGFR decline among 205,622 residents with repeated eGFR measurements during the first year of observation and investigated its association with subsequent dementia risk.

Results: We detected 18,983 cases of dementia (5.8% of participants) over a median follow-up of 5 years. Dementia incidence rates were progressively higher with lower eGFR: from 6.56/1,000 person-years in those with eGFR of 90 to 104 mL/min to 30.28/1,000 person-years in those with eGFR <30 mL/min. After multivariable adjustment, lower eGFR was associated with a higher dementia risk (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.54-1.91 in eGFR 30-59 mL/min; HR 2.62, 95% CI 1.91-3.58 in eGFR <30 mL/min) compared with eGFR of 90 to 104 mL/min. A steeper decline in eGFR (decline >2 mL/min/1.73 m²/y) within 1 year was associated with higher dementia risk. Risk magnitudes were stronger for vascular dementia than for Alzheimer dementia. As many as 10% (95% CI 6%-14%) of dementia cases could be attributed to eGFR <60 mL/min/1.73 m², a proportion higher than that attributed to other dementia risk factors such as cardiovascular disease and diabetes.

Conclusions: Both lower kidney function and steeper kidney function decline are associated with the development of dementia.

Figure 1. Risk of Dementia Associated With Baseline eGFR

(A) Hazard ratios (HRs) for all-cause dementia risk by estimated glomerular filtration rate (eGFR; per 1–ml/min/1.73 m² increase, continuous variable) using linear splines. Model adjusted for sex, chronic smoking, alcohol abuse, diagnosed obesity, comorbid conditions (hypertension, diabetes, congestive heart failure, myocardial infarction, stroke, atrial fibrillation, cancer history, depression, and hearing loss), and medications (use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, β-blocking agents, calcium channel blockers, nonsteroidal anti-inflammatory drugs, and statins). Knots were set every 15 mL/min/1.73 m² of eGFR, rendering the same eGFR categories as in table 1. Data were reported as HRs and 95% confidence intervals (dashed lines). (B) Percentage of participants (n = 329,822) across eGFR levels.

Figure 2. Risk of Dementia Associated With Rate of Kidney Function Decline

(A) Hazard ratios (HRs) for all-cause dementia risk by the rate of kidney function decline (estimated glomerular filtration rate [eGFR] slope per ml/min/1.73 m², continuous variable) using linear splines. Model adjusted for baseline eGFR, sex, chronic smoking, alcohol abuse, diagnosed obesity, comorbid conditions (hypertension, diabetes, congestive heart failure, myocardial infarction, stroke, atrial fibrillation, cancer history, depression, and hearing loss), and medications (use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, β-blocking agents, calcium channel blockers, nonsteroidal anti-inflammatory drugs, and statins). Knots were set at −3, −1, 0, and 1 mL/min/y. Data were reported as HRs and 95% confidence intervals (dashed lines). (B) Percentage of participants (n = 205,622) across eGFR slope values.