Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study

Abstract

ObjectivesIn patients with gout, maintaining too low serum uric acid (SUA) level with urate-lowering therapy is a concern because uric acid is thought to be neuroprotective. However, the relation between SUA and dementia remains debated. This study aimed to investigate the impact of SUA level on the incidence of dementia.MethodsWe assessed the longitudinal association between SUA level and incident dementia (Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV) criteria) in a large cohort of healthy older people from the community (Three-City Dijon cohort). Additionally, we investigated the relation between SUA level and MRI markers of brain ageing (white matter hyperintensity volume (WMHV), lacunes and hippocampal volume).ResultsThe study sample comprised 1598 people (mean (SD) age 72.4(4.1) years, 38.3% male). During the 13,357 person-years of follow-up (median duration: 10.1 years), dementia developed in 110 participants (crude incidence rate: 8.2/1000 person-years). After multiple adjustments, the multivariate HR with the highest (≥75th percentile) versus lowest SUA level was 1.79 (95% CI 1.17 to 2.73; p=0.007). The association was stronger with vascular or mixed dementia (HR=3.66 (95% CI 1.29 to 10.41), p=0.015) than Alzheimer’s disease (HR=1.55 (95% CI 0.92 to 2.61), p=0.10). There was a non-significant trend towards an association between high SUA level and extensive WMHV (p=0.10), a biomarker of small vessel disease, but not hippocampal volume (p=0.94) or lacunes (p=0.86). The association between SUA level and vascular or mixed dementia might be affected by interim strokes.ConclusionsRisk of dementia, especially vascular or mixed dementia, may be increased with high SUA levels in elderly people.

Uric acid and incident dementia: a population-based cohort study

“…The results reported by Latourte et al differ from those of another prospective population-based cohort study,2 which demonstrated that higher SUA levels are associated with a decreased risk of dementia and better cognitive function later in life, suggesting a possible protective role for uric acid as an antioxidant. First, traditional cardiovascular risk factors, such as age, hypertension, and diabetes mellitus , had a much higher incidence in the group with high SUA levels than in the group without high SUA levels 1. A positive association between cardiovascular risk factors and dementia has been extensively reported 3 4.…”

“…We read with great interest the article by Latourte and colleagues,1 regarding the effect of serum uric acid (SUA) level on the incidence of dementia. This large population-based prospective cohort study with 12 years of follow-up demonstrated that high SUA levels were associated with increased risk of dementia, especially vascular or mixed dementia.…”

Role of serum urate in neurocognitive function and dementia: new evidence contradicts old thinking

“…The current cohort study draws our attention to the association of the sUA level (hyperuricaemia) with the risk of dementia in the elderly using a population-based sample of the French elderly 1. The current study reported an association opposite to what has been a past concern, by showing a significant association of the highest baseline sUA quartile with a 1.8-times higher risk of dementia with up to 12-year follow-up.…”

“…The current study reported an association opposite to what has been a past concern, by showing a significant association of the highest baseline sUA quartile with a 1.8-times higher risk of dementia with up to 12-year follow-up. The study showed that the association of higher sUA level was stronger with vascular or mixed dementia compared with Alzheimer’s disease, hinting at different pathogenic mechanisms for these types of dementia as it relates to sUA levels 1. The lack of association of sUA levels and MRI markers of cerebrovascular disease is an equally interesting negative finding.…”

“…In ARD, Latourte et al used the data from a community-based prospective French cohort study of healthy 4931 elderly people 65 years or older, examined at six clinical visits (including cognitive examinations) over 12 years, and analysed 1598 participants with a baseline serum urate level (serum uric acid (sUA)), no diagnosis of dementia, a Mini-Mental State Examination (MMSE) score of >24 and at least one follow-up visit 1. Dementia was diagnosed in a 3-step process, screening using the MMSE and the Isaacs Set Test by trained psychologists, additional neuropsychological testing by a physician, and adjudication based on criteria by an independent committee of neurologists.…”