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Alopecia areata (AA), an autoimmune disease that causes hair loss, including baldness, prednisone cause hot flashes has been linked to a significantly increased risk for dementia, new research shows.

After controlling for an array of potential confounders, investigators found a threefold higher risk of developing any form of dementia and a fourfold higher risk of developing Alzheimer’s disease in those with AA vs the controls.

“AA shares a similar inflammatory signature with dementia and has great psychological impacts that lead to poor social engagement,” lead author Cheng-Yuan Li, MD, MSc, of the Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.

“Poor social engagement and shared inflammatory cytokines might both be important links between AA and dementia,” said Li, who is also affiliated with the School of Medicine and the Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei.

The study was published online October 26 in the Journal of Clinical Psychiatry.

Significant Psychological Impact

Patients with AA often experience anxiety and depression, possibly caused by the negative emotional and psychological impact of the hair loss and partial or even complete baldness associated with the disease, the authors note.

However, AA is also associated with an array of other atopic and autoimmune diseases, including psoriasis and systemic lupus erythematosus (SLE).

Epidemiologic research has suggested a link between dementia and autoimmune diseases such as psoriasis and SLE, with some evidence suggesting that autoimmune and inflammatory mechanisms may “play a role” in the development of AD.

Dementia in general and AD in particular, “have been shown to include an inflammatory component” that may share some of the same mediators seen in AA (eg, IL-1β, IL-6, and tumor necrosis factor-a [TNF-a]).

Moreover, “the great negative psychosocial impact of AA might result in poor social engagement, a typical risk factor for dementia,” said Li. The investigators sought to investigate whether patients with AA actually do have a higher dementia risk than individuals without AA.

The researchers used data from the Taiwan National Health Insurance Research Database, comparing 2534 patients with AA to 25,340 controls matched for age, sex, residence, income, dementia-related comorbidities, systemic steroid use, and annual outpatient visits. Participants were enrolled between 1998 and 2011 and followed to the end of 2013.

The mean age of the cohort was 53.9 years, and a little over half (57.6%) were female. The most common comorbidity was hypertension (32.3%), followed by dyslipidemia (27%) and diabetes (15.4%).

Dual Intervention

After adjusting for potential confounders, those with AA were more likely to develop dementia, AD, and unspecified dementia, compared with controls. They also had a numerically higher risk for vascular dementia, compared with controls, but it was not statistically significant.

Table. Risk for dementia and Alzheimer’s disease among patients with alopecia areata.

ConditionAdjusted hazard ratio (95% CI)
Any dementia3.24 (2.14 – 4.90)
Alzheimer’s disease4.34 (1.45 – 12.97)
Unspecified dementia3.36 (2.06 – 5.48)
Vascular dementia2.05 (0.64 – 6.63)*

* not statistically significant

When participants were stratified by age, investigators found a significant association between AA and higher risk for any dementia as well as unspecified dementia in individuals of all ages and an increased risk for AD in patients with dementia age at onset of 65 years and older.

The mean age of dementia diagnosis was considerably younger in patients with AA vs controls (73.4 vs 78.9 years, P = .002). The risk for any dementia and unspecified dementia was higher in patients of both sexes, but the risk for AD was higher only in male patients.

Sensitivity analyses that excluded the first year or first 3 years of observation yielded similar and consistent findings.

“Intervention targeting poor social engagement and inflammatory cytokines may be beneficial to AA-associated dementia,” said Li.

“Physicians should be more aware of this possible association, help reduce disease discrimination among the public, and encourage more social engagement for AA patients,” he said.

“Further studies are needed to elucidate the underlying pathophysiology between AA and dementia risk,” he added.

No Cause and Effect

Commenting on the study for Medscape Medical News, Heather M. Snyder, PhD, vice president of medical and scientific affairs, Alzheimer’s Association, said, “We continue to learn about and better understand factors that may increase or decrease a person’s risk of dementia.”

“While we know the immune system plays a role in Alzheimer’s and other dementia, we are still investigating links between, and impact of, autoimmune diseases — like alopecia areata, rheumatoid arthritis, and others — on our overall health and our brains, [which] may eventually give us important information on risk reduction strategies as well,” said Snyder, who was not involved in the research.

She cautioned that although the study did show a correlation between AA and dementia risk, this does not equate to a demonstration of cause and effect.

At present, “the message for clinicians is that when a patient comes to your office with complaints about their memory, they should, number one, be taken seriously; and, number two, receive a thorough evaluation that takes into account the many factors that may lead to cognitive decline,” Snyder said.

The study was supported by a grant from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. Li, co-authors, and Snyder have disclosed no relevant financial relationships.

J Clin Psychiatry. Published online October 26, 2021. Abstract

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