Acute Kidney Injury and Its Association With Dementia and Specific Dementia Types: Findings From a Population-Based Study in Sweden

Abstract

Background and objectives: Preclinical studies suggest that acute kidney injury (AKI) results in biochemical and pathologic changes in the brain. We aimed to explore the association between experiencing AKI and subsequent risks of developing dementia.

Methods: We conducted a study involving individuals aged 65 years and older in Stockholm from 2006 to 2019, who were free from dementia diagnosis and had data on kidney function. The exposure was an episode of AKI (time varying), ascertained by issued clinical diagnoses and transient creatinine elevations according to Kidney Disease Improving Global Outcomes criteria. The outcome was all-cause dementia and specific types of dementia, ascertained by clinically confirmed cases in the Swedish registry of cognitive/dementia disorders, the presence of 2 issued dementia diagnoses in outpatient care, or initiation of specific antidementia medications. We investigated associations with dementia through Cox proportional hazard regression by AKI, severity levels of AKI, AKI recurrence, and setting (community-acquired or hospital-acquired AKI).

Results: We included 305,122 individuals with a median age of 75 ± 8 years (56.6% women). During a median follow-up of 12.3 (interquartile range 8.7-13.3) years, there were 79,888 individuals (26%) suffering from at least 1 episode of AKI and 47,938 incident cases (16%) of dementia. The rate of dementia cases was 37.0 per 1,000 person-years (95% CI 36.2-37.8) after developing AKI, which was approximately 2 times higher than the rate observed during the periods before AKI (17.3, 95% CI 17.2-17.5). After multivariable adjustment, developing AKI was associated with a 49% higher rate of subsequent dementia (adjusted hazard ratio hazard ratio [HR] 1.49, 95% CI 1.45-1.53). This pattern was consistent across dementia types, with HRs of 1.88 (95% CI 1.53-2.32), 1.47 (1.38-1.56), and 1.31 (1.25-1.38) for dementia with Lewy bodies and Parkinson disease with dementia, vascular dementia, and Alzheimer dementia, respectively. Risk associations were stronger in magnitude across more severe AKIs and in hospital-acquired vs community-acquired AKI.

Discussion: Individuals who experienced an AKI were at increased risk of receiving a diagnosis of dementia.

Figure 1. Subgroup Analyses Regarding the Association Between Developing AKI and Risk of All-Cause Dementia

ACEi = angiotensin-converting enzyme inhibitor; AKI = acute kidney injury; ARB = angiotensin II receptor blocker; eGFR = estimated glomerular filtration rate; HR = hazard ratio; NSAID = nonsteroidal anti-inflammatory drug; PY = person-years. ^†Adjusted for age, sex, baseline or reference eGFR (the first available outpatient creatinine measurement was considered the baseline eGFR and eGFR within a year before the AKI was considered the reference eGFR), selected comorbidities (tobacco abuse, alcohol abuse, obesity, hypertension, diabetes, congestive heart failure, myocardial infarction, stoke, atrial fibrillation, cancer, depression, hearing loss, and traumatic brain injury), and medications (ACEi/ARB, β-blocking agents, calcium channel blockers, NSAIDs, and statins).