Kidney function and risk of dementia: Observational study, meta-analysis, and two-sample mendelian randomization
Alisa D Kjaergaard1, Christina Ellervik2,3,4, Daniel R Witte5
1Steno Diabetes Center Aarhus, Aarhus University Hospital, Palle Juul-Jensens Blvd. 11, Indgang A, Aarhus, Denmark. alisa.kjaergaard@auh.rm.dk.
European Journal of Epidemiology
|November 5, 2022
Summary
Impaired kidney function is linked to a modestly increased dementia risk. However, genetic analyses did not support a causal link, suggesting further research is needed.
Area of Science:
- Nephrology
- Neurology
- Epidemiology
Background:
- The relationship between kidney function and dementia risk remains unclear.
- Investigating this association is crucial for understanding dementia's multifactorial origins.
Purpose of the Study:
- To investigate the association between estimated glomerular filtration rate (eGFR) and the risk of developing dementia.
- To explore potential causal links using genetic approaches.
Main Methods:
- A triangulation approach combining a prospective cohort study (Copenhagen General Population Study), a meta-analysis of Scandinavian populations, and a Mendelian randomization study using European genome-wide association study data.
- Analysis included over 90,000 individuals in the prospective study and up to 1 million in genetic analyses.
Main Results:
- The prospective study and meta-analysis indicated a modestly increased risk of dementia with declining eGFR, particularly with severe impairment.
- However, Mendelian randomization analyses did not find a causal association between eGFR and dementia risk.
- No association was found in observational or genetic analyses when using specific eGFR measures.
Conclusions:
- Impaired kidney function shows a modest association with increased dementia risk, but evidence for a causal link is not supported by current genetic data.
- Further research with stronger genetic instruments and larger datasets, especially for vascular dementia, is warranted to re-evaluate causality.
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