Gout and the risk of Alzheimer's disease: a population-based, BMI-matched cohort study.
OBJECTIVE
While gout is associated with cardiovascular (CV)-metabolic comorbidities and their sequelae, the antioxidant effects of uric acid may have neuroprotective benefits. We evaluated the potential impact of incident gout on the risk of developing Alzheimer's disease (AD) in a general population context.


METHODS
We conducted an age-matched, sex-matched, entry-time-matched and body mass index (BMI)-matched cohort study using data from The Health Improvement Network, an electronic medical record database representative of the UK general population, from 1 January 1995 to 31 December 2013. Up to five non-gout individuals were matched to each case of incident gout by age, sex, year of enrolment and BMI. We compared incidence rates of AD between the gout and comparison cohorts, excluding individuals with prevalent gout or dementia at baseline. Multivariate hazard ratios (HRs) were calculated, while adjusting for smoking, alcohol use, physician visits, social deprivation index, comorbidities and medication use. We repeated the same analysis among patients with incident osteoarthritis (OA) as a negative control exposure.


RESULTS
We identified 309 new cases of AD among 59 224 patients with gout (29% female, mean age 65 years) and 1942 cases among 238 805 in the comparison cohort over a 5-year median follow up (1.0 vs 1.5 per 1000 person-years, respectively). Univariate (age-matched, sex-matched, entry-time-matched and BMI-matched) and multivariate HRs for AD among patients with gout were 0.71 (95% CI 0.62 to 0.80) and 0.76 (95% CI 0.66 to 0.87), respectively. The inverse association persisted among subgroups stratified by sex, age group (<75 and ≥75 years), social deprivation index and history of CV disease. The association between incident OA and the risk of incident AD was null.


CONCLUSIONS
These findings provide the first general population-based evidence that gout is inversely associated with the risk of developing AD, supporting the purported potential neuroprotective role of uric acid.
Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Na
N
Lu
Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA Section of Rheumatology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
Maureen
M
Dubreuil
Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA.
Yuqing
Y
Zhang
Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA.
Tuhina
http://orcid.org/0000-0002-9515-1711
T
Neogi
Arthritis Research Centre of Canada, University of British Columbia, Vancouver, British Columbia, Canada.
Sharan K
SK
Rai
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Alberto
A
Ascherio
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Miguel A
MA
Hernán
Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Hyon K
HK
Choi
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology*; D015992:Body Mass Index; D015331:Cohort Studies; D015897:Comorbidity; D016208:Databases, Factual; D005260:Female; D006073:Gout / Q000453:epidemiology*; D006801:Humans; D033461:Hyperuricemia / Q000453:epidemiology*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology*; D010003:Osteoarthritis / Q000453:epidemiology; D016016:Proportional Hazards Models; D065840:Protective Factors; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
Arthritis; Epidemiology; Gout