Rosacea Linked to Increased Risk for Alzheimer's

April 28, 2016

Individuals with the skin condition rosacea appear to be at increased risk for dementia, a new study suggests.

The risk was highest in older patients and in those in whom rosacea was diagnosed by a hospital dermatologist. The Danish researchers conclude that "increased focus on symptoms of cognitive dysfunction in patients with rosacea may be warranted."

The study, published online April 28 in the Annals of Neurology, was conducted by a group led by Alexander Egeberg, MD, University of Copenhagen, Denmark.

"We found a slightly increased risk of dementia, in particular Alzheimer's disease, in patients with rosacea," Dr Egeberg commented to Medscape Medical News. "However, it is important for patients to remember that having rosacea does not necessarily mean that they will develop Alzheimer's disease.

"In fact, while the risk in rosacea patients may be slightly increased compared with the general population, the absolute risk is still quite low," he added. "In our study we looked at retrospectively collected data, and while we show an association, this does not necessarily mean that a causal link exists."

Nationwide Study

Dr Egeberg explained that single-case reports have previously described a possible association between rosacea and Alzheimer's disease (AD) and that certain subtypes of rosacea have been associated with other neurologic symptoms, including burning and stinging pain in the skin, migraines, and neuropsychiatric symptoms. His group has also recently reported an association between rosacea and Parkinson's disease.

In addition, certain inflammatory mediator proteins, such as matrix metalloproteinases (MMPs) and antimicrobial peptides (AMPs), have been found in increased levels in the skin of patients with rosacea, and these have also been linked to dementia, in particular AD, Dr Egeberg noted.

Because of these observations, the researchers decided to investigate whether there was an association between rosacea and AD in a population-based cohort using nationwide registers.

"This is the first comprehensive investigation of Alzheimer's disease in a large population of patients with rosacea," Dr Egeberg said.

For this analysis, the researchers linked data from national registries that included all Danish citizens aged 18 years or older between 1997 and 2012 with details of all hospital contacts and pharmacy-dispensed medicines.

Of a total of 5,591,718 individuals in the database, 82,439 had rosacea and 99,040 individuals developed dementia in the study period, of whom 29,193 were diagnosed with Alzheimer's.

The incidence rates of dementia per 1000 person-years were 1.47 in the reference population and 2.03 in patients with rosacea. Incidence rates of AD were 0.43 in the reference population and 0.79 in those with rosacea.

After adjustment for potential confounding factors, including baseline age, sex, socioeconomic status, alcohol abuse, smoking, statin and antidepressant use, hypertension, and diabetes, patients with rosacea had small but significantly increased risks for dementia (hazard ratio [HR], 1.07) and AD (HR, 1.25), with a slightly stronger association in women than in men.

When results were stratified by age at study entry, the risk for AD was only significantly increased in individuals aged 60 years old or older (HR, 1.20).

The highest risks were seen in patients who had a hospital dermatologist diagnosis of rosacea; these patients had an HR for dementia of 1.42 and for AD of 1.92.

Emerging data from his team and other research groups around the world suggest a link between rosacea and neurologic disorders, Dr Egeberg noted. "While it is too early to suggest possible treatment options based on these findings, it will be interesting to see if treatment of rosacea may impact the dementia risk and vice versa."

Tetracycline: Possible Treatment for AD?

On the possible role of inflammatory mediator proteins, including MMPs and AMPs, in both conditions, the researchers point out in the Annals paper that tetracycline, a commonly used oral therapy for rosacea, acts through inhibition of MMP expression in endothelial cells, and that it has also been associated with suppressed β-amyloid and tau protein expression, as well as neuroprotective effects.

"This suggests that tetracycline may have therapeutic potential in patients with dementia, including AD, although this is hypothesis-generating and requires further study," the authors write.

"Additionally, although involvement of AMPs is well-established in rosacea, β-amyloid (which itself is an AMP with proinflammatory abilities) is central to the pathology of Alzheimer's disease," they report.

"The current sum of evidence suggests that certain forms of dementia, in particular AD, have prominent inflammatory components, and MMPs and AMPs may provide mechanistic links for the observed association between rosacea and dementia," they add.

They suggest that other proinflammatory mediators, including T cells and interleukin-17, may also play a role.

The authors have disclosed no relevant financial relationships.

Ann Neurol. Published online April 28, 2016. Abstract

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