Background/Purpose: While gout is associated with cardiovascular (CV)-metabolic comorbidities and their sequelae, uric acid’s anti-oxidant effects may have neuroprotective benefits.  Several studies have found an inverse association between a history of gout and the future risk of Parkinson’s disease, but no such evidence is available for the risk of Alzheimer’s disease (AD). To that effect, a Rotterdam study has found an inverse association between prior serum uric acid levels and the risk of AD. Thus, we evaluated the potential impact of incident gout on the risk of developing AD in a general population context.

Methods: We conducted a matched cohort study using data from The Health Improvement Network (THIN), an electronic medical records database representative of the UK general population. Study population included individuals aged ≥ 40 who had at least 1 year of active enrollment with the general practice during 1 January 1995 to 31 May 2010. For each case of incident gout patient, up to 5 non-gout individuals were selected and matched on age, sex, date of study entry and year of enrollment. Gout diagnoses, outcomes, and dementia risk factors were identified from electronic medical records. We compared incidence rates (IRs) of AD between the gout and comparison cohorts, excluding individuals with prevalent gout or dementia at baseline.  Cox proportional hazards models were used to estimate the hazard ratio (HR), adjusting for body mass index (BMI), smoking, alcohol use, prior comorbid conditions, and use of CV medicines.

Results: Among 55,471 individuals with gout (28% female, mean age 63 years), we identified 179 new cases of AD over a 4-year median follow up. The IR of AD was 0.7 per 1000 person-years (PY) vs. 1.3 per 1000 PY in the comparison cohort, and the multivariate HR of AD among those with gout was 0.69 (95% CI, 0.58 to 0.81). The inverse association was similarly present among men and those < vs ≥ 75 years, but was stronger among those with CV disease (i.e., ischemic heart disease or stroke) than those without (HRs, 0.37 [95% CI, 0.24 to 0.58] vs. 0.76 [95% CI, 0.61 to 0.93]) (p for interaction, 0.02).

Conclusion: These findings provide the first general population-based evidence that gout is associated with a protective effect against developing AD and support the purported potential neuro-protective role of uric acid.  These associations may be more evident among those with CV disease.