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Are patients with rheumatic diseases at high risk of dementia?

Jairia Dela Cruz
08 Jan 2018

Rheumatic diseases, particularly rheumatoid arthritis, Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), and osteoarthritis (OA), appear to pose an increased risk of dementia, a study has reported.

In a cohort of 10,180 rheumatic disease patients with newly diagnosed dementia and 61,080 matched controls without the brain disease, the risk of developing dementia was substantially higher in patients with RA (odds ratio [OR], 1.11; 95 percent CI, 1.10–1.22; p<0.05), SS (OR, 1.28; 1.11–1.47; p<0.01), SLE (OR, 1.55; 1.16–2.07; p<0.01), OA (OR, 1.47; 1.40–1.54; p<0.01), or PsA (OR, 2.10; 1.20–3.62; p<0.01). [Int J Rheum Dis 2017;doi:10.1111/1756-185X.13246]

On the other hand, the risk found in patients with ankylosing spondylitis (p>0.05) was not statistically significant.

Subgroup analyses showed that the increased dementia risk was especially pronounced in female patients with SLE (OR, 1.60; p<0.05), male patients with PsA (OR, 5.72; p<0.05), and patients of either gender with SS (females: OR, 1.26; p<0.05; males: OR, 1.34; p<0.01) or OA (females: OR, 1.42; p<0.01; males: OR, 1.51; p<0.05).

Additionally, the risk was more evident in SLE among younger patients (aged 40–64 years; OR, 2.46; p<0.01), in SS among older patients (aged ≥65 years; OR, 1.25; p<0.01), and in OA among patients in both age groups (young: OR, 1.48; old: OR, 1.47; p<0.01 for both).

The authors postulated that inflammation and medications might explain the connection between dementia and rheumatic diseases.

“First, both rheumatic diseases and Alzheimer’s disease [AD] involve inflammation caused by inflammatory mediators,” they said. The overwhelming inflammatory response will drive microglia cells to overreact and release chemokines, which can (1) lead to cell apoptosis and therefore result in massive loss of neurons (2) or cause great damage to the beta-amyloid clearance functions of microglia and consequently speed up the accumulation of beta-amyloid in the brain—the hallmark of AD. [N Engl J Med 2010;362:329–344; PLoS One 2014:9:e110024]

“Second, anti-inflammatory drugs may play a role in deteriorating cognitive status in patients with rheumatic disease,” the authors continued. Glucocorticoids, commonly used in the treatment of rheumatic diseases, have some adverse effects that contribute to a decrease in the volume of the hippocampus, which therefore results in cognitive impairment.

Corticosteroid-induced dementia occurs in patients receiving 30–60 mg doses daily and is usually accompanied by a decline in verbal memory and loss of concentration. This effect can be reversed by reducing the dose. [Psychiatry Clin Neurosci 2011;65:549–560]

Despite the presence of several limitations in the study, the authors expressed increased confidence that their findings would bring forth a far-reaching perspective of the association between rheumatic diseases and dementia. This is in light of a sample size that was large enough to avoid selection bias. Moreover, the 10-year population data were extracted from the Longitudinal Health Insurance Database, making the results more comprehensive.

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