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Patients with Autoimmune Diseases May Be at Greater Risk for Dementia

VBCR - June 2017, Vol 6, No 2 - Rheumatic Diseases
Anne Rowe

Individuals with certain autoimmune disorders may be more likely to develop dementia than those without them, according to the results of a recent retrospective cohort study (Wotton CJ, Goldacre MJ. J Epidemiol Community Health. 2017;71:576-583). These findings add to existing evidence that inflammatory and autoimmune mechanisms may be linked to dementia and Alzheimer’s disease (AD) in some patients.

Clare J. Wotton, MSc, Epidemiologist, Cancer Epidemiology Unit, University of Oxford, United Kingdom, and Michael J. Goldacre, BM, BCh, MA, MSc, FFPH, FRCP, Director, Unit of Health-Care Epidemiology, University of Oxford, collected national hospital care and mortality administrative data from 1,833,827 patients who were admitted to National Health Service hospitals in England with various autoimmune diseases between April 1, 1998, and March 31, 2012. They also created a control cohort of approximately 7 million individuals who were admitted to the same hospitals with a wide range of other medical conditions (eg, varicose veins, upper respiratory tract infections, dislocations, sprains, tooth disorders) during the same time period. Ms Wotton and Dr Goldacre then analyzed the data to determine the percentage of patients in each cohort who were readmitted to the hospital at a later date for dementia.

“The objectives of the study were to determine whether hospital admission with an autoimmune disease is associated with future admission with dementia more often than expected by chance,” they explained.

Results showed that, overall, patients who were admitted to the hospital with an autoimmune disease were 20% more likely to develop dementia than those who were admitted to the hospital for a condition other than an autoimmune disease (rate ratio [RR], 1.20; 95% confidence interval [CI], 1.19-1.21).

“The associations with vascular dementia may be one component of a broader association between autoimmune diseases and vascular damage,” Ms Wotton and Dr Goldacre stated.

Patients with multiple sclerosis were among those with autoimmune disorders who were at the highest risk for developing dementia (RR, 1.97; 95% CI, 1.88-2.07). Increased risk for dementia compared with controls was also high in patients with Addison’s disease (RR, 1.48; 95% CI, 1.34-1.64), systemic lupus erythematosus (RR, 1.46; 95% CI, 1.32-1.61), and psoriasis (RR, 1.29; 95% CI, 1.25-1.34).

Ms Wotton and Dr Goldacre noted that, although the type of dementia was frequently not included in the hospital records they analyzed, they were able to determine that, on the whole, the RR for AD was slightly lower (1.06) than the RR for vascular dementia (1.28) in patients hospitalized for autoimmune diseases. The risk for vascular dementia was higher in patients hospitalized for idiopathic thrombocytopenia purpura, pemphigus, polyarteritis nodosa, scleroderma, Sjögren’s syndrome, and systemic lupus erythematosus; whereas the risk for AD was higher in those hospitalized for Addison’s disease, myxedema, pemphigoid, pernicious anemia, psoriasis, and thyrotoxicosis.

Interestingly, although patients with rheumatoid arthritis had an increased risk for vascular dementia, they had a significantly decreased risk for AD (RR, 1.16 vs 0.89, respectively; P <.001). Ms Wotton and Dr Goldacre speculated that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis may have contributed to these findings.

“Although evidence that NSAIDs reduce the risk of AD is not conclusive, our findings might add circumstantial evidence to the data supporting the hypothesis that NSAIDs protect against AD....A recent case-control study found that NSAID use was positively associated with vascular dementia....Thus, it seems possible that NSAID use may reduce the risk of AD but increase the risk of vascular dementia,” they said.

The researchers also noted that the correlation between certain autoimmune diseases and vascular dementia may suggest associations between autoimmune disease and risk factors for coronary heart disease and cerebrovascular conditions, such as stroke. Citing a separate but similar analysis, they reported that patients with autoimmune disease had RRs of 1.53 and 1.46 for coronary heart disease and ischemic stroke, respectively.

The researchers asserted that, although their study was very large in size, the effect sizes were small, and further research needs to be conducted. “The findings may be relevant to furthering understanding of the pathogenesis of AD and of vascular dementia. Studies should be considered to confirm or refute our findings; and, if confirmed, to explore possible mechanisms mediating the associations,” they concluded.

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