Uric acid and dementia
Why is hyperuricaemia associated with a lower risk of Alzheimer's disease?
Life is metabolism and therefore most diseases will be associated with some form of metabolic dysfunction. The question is always is metabolic dysfunction upstream and hence potentially part of the causal pathway or downstream and a consequence of disease in question. Even if it is upstream doesn’t immediately imply causation. Therefore the association between raised uric acid levels and a lower risk of Alzheimer’s disease is surprising, but what is surprising is that this association did not extend to all-cause dementia or there was not an increased risk of dementia with hyperuricaemia.
Hyperuricaemia is arguably a metabolic integrator of a component of our metabolism linked to diet. In addition, uric acid is metabolic active and induces inflammation as well as being a putative antioxidant. Hyperuricaemia and/or a history of gout is a well-established, albeit a relatively weak, risk factor for cardiovascular disease. Therefore not finding it to be associated with all-cause dementia is surprising. We also know from recent GWAS studies that hyperuricaemia/gout is linked to variants in urate transporters. In view of the results of this study, we should look to see if these variants are associated with a lower risk of Alzheimer’s disease?
What is important is that to tackle heart health metabolically we will need to include normauricaemia as part of the metabolic profile. One way is non-pharmacologically with a diet that reduces your carbohydrate, red meat and alcohol intake; obviously easier said than done. However, will this be good for the brain or the brain that is primed to develop Alzheimer’s disease?
Objectives: Gout, characterised by hyperuricaemia with monosodium urate crystal formation and inflammation, is the most common inflammatory arthritis in adults. Recent studies have found that elevated uric acid levels are related to the occurrence of dementia. We conducted a study to investigate the association between dementia and gout or hyperuricaemia.
Design: Systematic review and meta-analysis of cohort studies.
Data sources: Studies were screened from inception to 28 June 2019 by searching Medline, Embase and the Cochrane Library databases.
Eligibility criteria: Cohort studies comparing the risk of dementia in patients with gout and hyperuricaemia versus non-gout and non-hyperuricaemia controls were enrolled.
Data extraction and analysis: Two reviewers separately selected studies and extracted data using the Medical Subject Headings without restriction on languages or countries. The adjusted HRs were pooled using the DerSimonian and Laird random effects model. Sensitivity analyses were conducted to evaluate the stability of the results. Publication bias was evaluated using Egger's and Begg's tests. Quality assessment was performed according to the Newcastle-Ottawa Scale.
Results: Four cohort studies that met the inclusion criteria were included in our meta-analysis. We found that gout and hyperuricaemia did not increase the risk of dementia, with a pooled HR of 0.94 (95% CI 0.69 to 1.28), but might decrease the risk of Alzheimer's disease (AD), with a pooled HR of 0.78 (95% CI 0.64 to 0.95). There was little evidence of publication bias. Quality assessment of the included studies was high (range: 6-8 points).
Conclusions: Our study shows that gout and hyperuricaemia do not increase the risk of dementia. However, gout and hyperuricaemia might have a protective effect against AD. Due to the limited number of research articles, more investigations are needed to demonstrate the potential relationship between dementia and gout or hyperuricaemia.
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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.
Very interesting, I’m from a family of long-lived gout and RA sufferers on one side and shorter-lived Alzheimer’s/dementia sufferers on the other. Would be nice if they cancelled each other out!