Objective: Community-based reports regarding the association between the estimated glomerular filtration rate (eGFR) and dementia risk show conflicting results. This study aims is to investigate the links between 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 healthcare during 2006-2011, were ≥65 years, 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: 18,983 cases of dementia (5.8% of participants) were detected over a median follow-up of 5 years. Dementia incidence rates (IR) were progressively higher with lower eGFR: from 6.56/1000 person-years in persons with eGFR 90-104ml/min to 30.28/1000 person-years in those with eGFR<30ml/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 30-59ml/min and HR 2.62, 1.91-3.58 in eGFR<30ml/min] compared with eGFR of 90-104ml/min. A steeper decline in eGFR (decline>2ml/min/1.73m²/year) within one year was associated with higher dementia risk. Risk magnitudes were stronger for vascular dementia than for Alzheimer. As many as 10% (95% CI 6-14%) of dementia cases could be attributed to eGFR<60ml/min/1.73m², 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.

SUPPLEMENT MATERIALS

KIDNEY FUNCTION, KIDNEY FUNCTION DECLINE AND THE RISK OF DEMENTIA IN OLDER ADULTS: A REGISTRY-BASED STUDY

TABLE OF CONTENTS

Supplement Table e-1. List of ICD-10 and ATC codes used to define comorbidities and ongoing medications

Supplement Table e-2. List of ICD-10 codes for dementia

Supplement Table e-3. Proportion of dementia cases and subtypes identified during follow up, overall and by eGFR strata.

Supplement Table e-4. Adjusted hazards ratio and population attributable fraction (PAF) with incident of all-cause dementia risk with medications.

Supplement Table e-5. Sensitivity analysis of incident dementia during follow up, excluding events occurring within the first 2 years

Supplement Table e-6. Subgroup of hazard ratios for all-cause dementia risk by eGFR strata and age and sex.

Supplement Table e-7. Subgroup of hazard ratios for all-cause dementia risk by eGFR strata and comorbidities.

Supplement Table e-8. eGFR slope, number of available eGFR measurements per individual within the first year of observation, and number of events.

Supplement Table e-9. Hazard Ratio (and 95% CI) between annual eGFR slope and dementia risk.

Supplement Figure e-1. Flow chart of study participants and study design.

Supplement Figure e-2. Incidence rate of dementia (all-cause, vascular and Alzheimer’s dementia) by eGFR strata.

Supplement Figure e-3. The time to incident (all-cause) dementia by eGFR strata as assessed with the Kaplan–Meier estimation.