OBJECTIVE: Rosacea is a common chronic inflammatory skin disorder where upregulation of matrix metalloproteinases (MMPs) and antimicrobial peptides (AMPs) is observed. Notably, inflammation, MMPs, and AMPs are also involved in the etiopathogenesis of neurodegenerative disorders including certain forms of dementia such as Alzheimer disease (AD). Based on several clinical observations, we investigated the association between rosacea and dementia, including AD in Danish registers.

METHODS: All Danish citizens aged ≥18 years between January 1, 1997 and December 31, 2012 were linked at the individual level through administrative registers. Cox regression was used to calculate unadjusted and adjusted hazard ratios (HRs).

RESULTS: The study comprised a total of 5,591,718 individuals, including 82,439 patients with rosacea. A total of 99,040 individuals developed dementia (any form) in the study period, of whom 29,193 were diagnosed with AD. The adjusted HRs of dementia and AD were 1.07 (95% confidence interval [CI] = 1.01-1.14), and 1.25 (95% CI = 1.14-1.37), respectively, in patients with rosacea. Stratified by sex, the HRs of AD were 1.28 (95% CI = 1.15-1.45) and 1.16 (95% CI = 1.00-1.35) in women and men, respectively. When results were stratified by age at study entry, the risk of AD was only significantly increased in individuals ≥60 years old (adjusted HR = 1.20, 95% CI = 1.08-1.32). When analyses were limited to patients with a hospital dermatologist diagnosis of rosacea only, the adjusted HRs of dementia and AD were 1.42 (95% CI = 1.17-1.72) and 1.92 (95% CI = 1.44-2.58), respectively.

INTERPRETATION: Rosacea is significantly associated with dementia, particularly AD. Increased focus on symptoms of cognitive dysfunction in older patients with rosacea may be relevant. Ann Neurol 2016;79:921-928.