Background/Purpose: Elevated serum uric acid (sUA) is an established risk factor for gout. Its role in the development of dementia is controversial, low levels of sUA has been suggested to increase the risk for dementia because of its reduction impairs antioxidants capacity, on the other hand, high levels of sUA are associated with increased cardiovascular risk which might increase the risk for vascular dementia (VaD). We therefore examined the possible association of sUA with the risk of Alzheimer’s disease (AD) and VaD in a population-based cohort of women.

Methods:  Longitudinal analyses were conducted in the Prospective Population Study of Women in Gothenburg, Sweden. In 1968, 1462 women 38–60 years old randomly selected from the population census, were examined with a wide range of possible predictors for dementia. Re-examination occurred in 1974, 1980, 1992, 2000, 2005, 2009, and 2012 (with sUA being collected only in 1968 and 1992). Subjects with dementia or stroke before baseline were excluded (n=38). Follow-up was defined from baseline to either the date of developing dementia, date of death, or end of data collection (31^st of December 2012), whichever came first. Dementia was diagnosed according to Diagnostic and Statistical Manual (DSM – III) of Mental Disorders criteria based on information from neuropsychiatric examinations, informant interviews, hospital records and registry data. Multivariate proportional-hazards analyses were used to asses sUA in a time-dependent fashion as a predictor for AD and VaD in separate models, since the effect may differ between dementia subtypes. Analyses were adjusted for socioeconomic status and level of education at baseline and for age, body mass index (BMI), alcohol consumption, smoking status, triglycerides, cholesterol and hypertension in a time-dependent fashion.

Results:  At baseline, women were on average 46.8 (SD 6.2) years old and had a mean sUA of 234.5 µmol/L (SD 75.5). During the 44-year follow-up, 153 women developed AD and 48 developed VaD. Women in higher sUA tertiles (compared to lower) were older and had a worse metabolic profile, with a higher BMI, blood pressure, cholesterol and triglycerides concentration. Table 1 shows the results of the age and fully adjusted analyses. In fully adjusted analyses, an increase in sUA concentration (per SD) was associated with a decreased risk for AD (HR 0.78; 95% Confidence Interval (CI) 0.63 to 0.96). For VaD, women in the lowest and highest tertiles had an increased risk for VaD (HR 3.41; CI 1.36 to 8.54) and (HR 2.61; CI 1.00 to 6.88), respectively, compared to women in the middle tertile.

Conclusion:  In a population-based cohort study we found that a lower sUA level was associated with an increased risk for developing AD in women. For VaD, we found an increased risk among women with low and high sUA levels. If these findings are confirmed in men and other populations the inverse association between AD and sUA should be addressed in treatment of hyperuricemia.