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Dementia Tied to Most Common Form of Lupus, Study Finds


While an association was found between dementia and the most common form of lupus, links to other autoimmune diseases—rheumatic arthritis, Sjögren’s syndrome, and Behcet’s disease—were not found.

A new study has found a significant association between dementia and the most common form of lupus, and that patients with the autoimmune disease are at high risk for early vascular dementia (VaD) and should be screened to prevent occurrence.

Researchers from Korea also looked at other autoimmune diseases—rheumatic arthritis (RA), Sjögren’s syndrome (SS), and Behcet’s disease (BD)—but found no association with dementia.

The study, published in PLoS One, determined that a diagnosis of systemic lupus erythematosus (SLE) resulted in being 2.4 times more likely to have dementia even after excluding other comorbidities.

The study was conducted using a database consisting of individuals who submitted medical claims from 2002-2013. Of the 6028 patients with dementia, 261 (4.3%) had RA, 108 (1.6%) had SS, 12 (0.2%) had SLE, and 6 (0.1%) had BD. Only the rate of SLE was significantly higher in dementia patients compared to the control group.

SLE significantly increased dementia risk regardless of type (Alzheimer’s disease: odds ratio [OR], 2.29; 95% CI, 1.06–4.91; VaD: OR, 4.54; 95% CI, 1.36–5.15), results showed. The associations did not hold up for the group with relatively lesser comorbidities or the elderly.

However, study results suggest the risk for SLE patients is 15 times higher for early VaD. “We believe that providing treatment to control disease activity, along with risk factor management, may help prevent dementia in SLE patients,” the authors wrote.

SLE has a history of being linked to dementia. In 1999, the American College of Rheumatology labeled it “neuropsychiatric SLE.” The authors noted that possible mechanisms include the passage of brain-reactive autoantibodies and inflammatory cells through the blood brain barrier, resulting in damage to the brain as well as diffuse blood clotting and a buildup of plaque in the arteries.

VaD is the second-most common cause of dementia. It is generally linked to cardiovascular risk factors, but with immunological damage to brain blood vessels and neuronal cells also involved, the authors said.

Previous studies also have suggested that the characteristic inflammation of the nerves and blood vessels seen in AD is an important factor in its origin. Accumulation of amyloid β (Aβ) deposits reduce cerebral blood flow and causes chronic shortages of oxygen supply and nerve damage. Transport and accumulation of Aβ in the brain are accelerated through the blood brain barrier in AD. Such results indicate the causes of AD and VaD may well be related.

Anti-N-methyl-D-aspartate (NMDA) antibodies may also be a mechanism. NMDA receptors are expressed in the hippocampus, amygdala, and hypothalamus of the brain, and anti-NMDA antibodies are known to be found in 14–35% of SLE patients, researchers said.

Prior studies reported an increased risk of AD in those with SS, but the new study showed otherwise. The researchers believed they were more accurate in labeling which patients had the disease by only analyzing patients who took acetylcholinesterase inhibitors for the condition.


Park H, Yim Dh, Ochirpurev B, et al. (2021) Association between dementia and systemic rheumatic disease: A nationwide population-based study. PLoS One. 2021;16(3). Published online March 12, 2021. doi:10.1371/journal.pone.0248395

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