Lieke Scheepers (1), Mats Dehlin (1), Lennart Jacobsson (1), Lena Johansson (2), Ingmar Skoog (2)
Affiliation(s):
1. Department of rheumatology and inflammation research, Sahlgrenska Academy, University of Gothenburg, Sweden
2. Department of psychiatry and neurochemistry, Sahlgrenska Academy, University of Gothenburg, Sweden
Background-Purpose: The role of serum uric acid (sUA) in the development of dementia is controversial. Low levels of sUA has been suggested a risk factor for dementia because of reduced antioxidant capacity while high levels of sUA are associated with cardiovascular morbidity which also is a risk factor for dementia. We therefore examined the possible association of sUA with the risk of Alzheimer’s disease (AD) and vascular dementia (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 possible predictors for dementia. Re-examination occurred in 1974, 1980, 1992, 2000, 2005, 2009, and 2012 (sUA collected in 1968 and 1992). Subjects with dementia or stroke before baseline were excluded (n=38). Dementia was diagnosed according to Diagnostic and Statistical Manual (DSM – III). 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, BMI, alcohol consumption, smoking, 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. 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) 0.65 to 0.94) and for VaD (HR 0.71; 95% CI 0.49 to 0.97). Women in the highest sUA tertile had a decreased risk for developing both AD (HR 0.61; CI 0.37 to 0.98) and VaD (HR 0.44; CI 0.21 to 0.93) compared to women in the lowest tertile.
Conclusion: In a population-based cohort study we found that a lower sUA level was associated with an increased risk for developing AD and VaD in women. If these findings are confirmed in men and other populations the inverse association between AD and sUA should be addressed in treatment of hyperuricemia.