Acute Kidney Injury May Increase Risk for Various Forms of Dementia

Acute kidney injury (AKI) is associated with an increased risk for a dementia diagnosis, according to study findings published in the journal Neurology.

A team of researchers aimed to determine the effect of AKI, as well as its severity, type, and recurrence, on risk of developing dementia.

Eligible participants were enrolled in the Stockholm Creatinine Measurement (SCREAM) project, aged 65 and older, and had available their first outpatient creatinine measurement (index date) that was used to estimate glomerular filtration rate (eGFR).

Study exposure was an AKI episode, defined as index creatinine of 1.5 times or higher than the reference creatinine; 26.5 μmol/L (0.3 mg/dL) or higher than the reference creatinine; and/or initiation of dialysis. AKI severity (stages 1-3 and/or dialysis) and AKI type (community-acquired and -managed, community-acquired and hospital-managed, and hospital-acquired) were also determined.

Primary study outcome was the clinical diagnosis of dementia, based on the International Classification of Diseases, Tenth Revision (ICD-10), codes. Secondary outcomes included specific dementia types (Alzheimer disease [AD], vascular, dementia with Lewy bodies [DLB] and Parkinson disease with dementia [PDD], frontotemporal, alcohol-related, and unspecified).

A total of 305,122 older adults (mean age, 75; women, 56.6%) were included in the analysis. The most common comorbidity was hypertension and the most frequently used medication was β-blockers and angiotensin-converting enzyme (ACE) inhibitors. Overall, 60,109 patients (19.7%) had chronic kidney disease (CKD) stages 3 to 5.

Of the total cohort, 79,888 patients (26.2%; mean age, 77; women, 53.2%) had at least 1 episode of AKI, with an incidence of 24.71 per 1000 person-years, during a median follow-up of 12.3 years. Hypertension and use of ACE inhibitors and angiotensin II receptor blockers (ARBs), as well as rates of CKD stages 3 to 5 (64.1%), were higher in the AKI vs non-AKI group.

The researchers observed a total of 47,938 (15.7%) all-cause dementia events, the incidence of which was 2 times higher after vs before an AKI episode (incidence, 36.99 vs 17.34 per 1000 person-years).

After adjusting for covariates including age, sex, medications, comorbidities, and reference eGFR, patients with an AKI episode had approximately a 1.5-fold higher risk of developing subsequent all-cause dementia (hazard ratio [HR], 1.49; 95% CI, 1.45-1.53).

The researchers noted a higher risk for dementia with more severe AKIs (HR, 1.45 [95% CI, 1.41-1.50] and HR, 1.61 [95% CI, 1.53-1.68] after AKI stage 1 and stages 2 and 3, respectively) and after community-acquired and hospital-managed AKI (HR, 1.56; 95% CI, 1.51-1.62) and hospital-acquired AKI (HR, 1.54; 95% CI, 1.47-1.61) vs community-acquired and -managed AKI (1.31; 95% CI, 1.26-1.37). However, dementia risk after recurrent AKI episodes was similar between all patients.

The most common specific dementia type was AD, occurring in 17,663 patients (65.7%), with incidence rates of all dementia types increased after an AKI episode.

Results of the subgroup and sensitivity analyses were consistent with those of the primary analysis.

Study limitations included the lack of establishing a causal relationship between AKI and dementia; the date of dementia diagnosis did not match the actual date that the disease started; the lack of inclusion of lifestyle habits; possible inaccuracies in dementia diagnoses; and lack of generalizability to other populations and countries.

“As a clinical application, this study thus identifies individuals with AKI as a population in which monitoring for dementia and potential preventive and therapeutic strategies may be indicated,” the researchers concluded.