Association Between Acute Kidney Injury and Dementia in the Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Rationale & objective: Acute kidney injury (AKI) causes biochemical changes in the brain in animal models and is associated with adverse neurological complications in hospitalized patients. This study tested the association between AKI and incident dementia in a community-based cohort.

Study design: Prospective cohort study.

Setting & participants: Adult participants in the Atherosclerosis Risk in Communities (ARIC) study who experienced hospitalized AKI compared with participants hospitalized for other reasons (primary analysis, mean follow-up period 4.3 years) or participants without hospitalized AKI (secondary analysis).

Predictors: Incident AKI, defined by ICD codes from hospital records.

Outcome: Incident dementia, diagnosed based on a combination of neurocognitive testing, informant interviews, ICD codes, and death certificates.

Analytical approach: In the primary analysis, we estimated the propensity for hospitalized AKI and matched these participants with those hospitalized for another reason to examine the association of AKI with subsequent onset of dementia (N = 1,708). In the secondary analysis, we estimated the association between time-varying hospitalized AKI and subsequent onset of dementia using multivariable Cox proportional hazards regression models, adjusted for age, sex, race/center, education, smoking status, body mass index, baseline estimated glomerular filtration rate, baseline urinary albumin-creatinine ratio, systolic blood pressure, coronary heart disease, diabetes, hypertension, apolipoprotein E (APOE) ε4 allele, and C-reactive protein.

Results: The mean age in the propensity-matched cohort was 76.1 ± 6.5 (SD) years, and 53.2% of the participants were women. People who were hospitalized with AKI had a higher risk of dementia (HR, 1.25 [95% CI, 1.02-1.52]; P = 0.03) compared with those without a hospitalization for AKI. The associations were slightly stronger in the time-varying analysis (HR, 1.69 [95% CI, 1.48-1.92]; P < 0.001). Other risk factors for dementia included older age, male sex, higher albuminuria, diabetes, current smoker status, and presence of the APOE risk alleles.

Limitations: Observational study, with AKI identified through diagnosis codes.

Conclusions: Participants who experienced a hospitalization for AKI were at increased risk of dementia.

Keywords: Acute kidney injury (AKI); albuminuria; apolipoprotein E (APOE); brain; cognitive function; dementia; estimated glomerular filtration rate (eGFR); hospitalization; memory; renal function; ε4 genotype.

Figure 1:

Covariate balance before and after propensity matching.

Figure 2:

Cumulative incidence for dementia among patients with and without AKI hospitalization in the propensity-matched analysis. Analysis time 0 is the time of hospitalization.