A large population-based study in Sweden found that individuals who experienced acute kidney injury had a significantly higher risk of developing dementia, including specific dementia subtypes.
The research, published in Neurology, analyzed data from 305,122 adults aged 65 years and older in Stockholm between 2006 and 2019. During a median follow-up of 12.3 years, 26% of participants experienced at least one episode of acute kidney injury (AKI), and 16% developed incident dementia.
The study utilized data from the Stockholm CREAtinine Measurements project. AKI episodes were identified using laboratory data based on Kidney Disease Improving Global Outcomes criteria. Dementia diagnoses were ascertained through the Swedish registry of cognitive/dementia disorders, clinical diagnoses, and medication records.
Researchers employed Cox proportional hazard regression models, treating AKI as a time-varying exposure. Models were adjusted for age, sex, estimated glomerular filtration rate, comorbidities, and medications.
Key Findings
The study reported that AKI was associated with a 49% higher rate of subsequent all-cause dementia (adjusted hazard ratio [HR] = 1.49; 95% confidence interval [CI] = 1.45-1.53).
Risk of dementia increased with AKI severity: stage 1 AKI (HR = 1.45; 95% CI = 1.41-1.50) vs stages 2 and 3 (HR= 1.61; 95% CI = 1.53-1.68).
Hospital-acquired AKI carried a higher risk of dementia development (HR = 1.54; 95% CI = 1.47-1.61) than community-acquired/community-managed AKI (HR = 1.31; 95% CI = 1.26-1.37).
AKI was associated with increased risk across dementia subtypes: dementia with Lewy bodies and Parkinson's disease dementia (HR = 1.88; 95% CI = 1.53-2.32), vascular dementia (HR = 1.47; 95% CI = 1.38-1.56), and Alzheimer's disease (HR = 1.31; 95% CI = 1.25-1.38).
Additional Data
Baseline characteristics of the study participants included:
- Mean age: 75 ± 8 years
- 56.6% women
- Most common comorbidity: hypertension (35.9%)
- Diabetes prevalence: 11.1%
- Atrial fibrillation prevalence: 10.1%
- Use of β-blockers: 29.7%
- Use of ACEi/ARBs: 25.0%
- Chronic kidney disease (CKD) stages 3-5 prevalence: 19.7%.
AKI incidence and characteristics:
- Overall AKI incidence: 24.71 per 1,000 person-years (95% CI = 24.54-24.88)
- Mean age at AKI occurrence: 77 ± 8 years
- Proportion of women among AKI cases: 53.2%
- Hypertension prevalence at time of AKI: 69.3%
- CKD stages 3-5 prevalence at time of AKI: 64.1%.
Dementia incidence:
- Total dementia events: 47,938 (15.7% of participants)
- Incidence rate before AKI: 17.34 per 1,000 person-years (95% CI = 17.17-17.52)
- Incidence rate after AKI: 36.99 per 1,000 person-years (95% CI = 36.23-37.75).
Specific dementia types:
- Alzheimer's disease: 17,663 cases (65.7% of specific dementia types)
- Vascular dementia: 7,971 cases (29.7%)
- Dementia with Lewy bodies and Parkinson's disease dementia: 975 cases (3.6%)
- Frontotemporal dementia: 270 cases (1%).
AKI recurrence data:
- First AKI event: HR = 1.47 (95% CI = 1.43-1.52)
- Second AKI event: HR = 1.48 (95% CI = 1.41-1.56)
- Third or more AKI events: HR = 1.39 (95% CI = 1.31-1.48).
Subgroup analyses revealed a stronger association between AKI and dementia in people without depression and hearing loss compared to those with these conditions (p for interaction <0.05). The risk of dementia with Lewy bodies and Parkinson's disease dementia was higher in individuals older than 85 years (HR = 4.15; 95% CI = 1.81-9.54).
Sensitivity analyses excluding early dementia events (within 90 days of AKI) yielded an HR of 1.21 (95% CI = 1.17-1.24). Accounting for death as a competing risk resulted in an HR of 1.18 (95% CI = 1.16-1.21). During follow-up, 111,096 individuals (44.7%) died.
The study also reported negative control outcomes, showing no significant association between AKI and psoriasis (HR = 0.94; 95% CI = 0.87-1.02) or cataracts (HR = 1.01; 95% CI = 0.99-1.03). A positive control outcome demonstrated a significant association between AKI and heart failure (HR = 4.10; 95% CI = 4.02-4.18).
The study's strengths included its large sample size, long follow-up period, and use of laboratory data to identify AKI events; limitations included potential outcome misclassification bias and lack of information on lifestyle factors and cognitive function at baseline.
The study authors concluded, "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."
Conflict of interest disclosures were not made available at time of publishing.