Role of autoantibodies and blood–brain barrier leakage in cognitive impairment in systemic lupus erythematosus

Abstract

ObjectiveCognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood–brain barrier (BBB) leakage in patients with SLE with and without cognitive impairment. In addition, we determined whether the relationship between SLE autoantibodies, other biomarkers and cognitive impairment differed depending on the presence or absence of concurrent extensive BBB leakage.MethodsConsecutive patients with SLE, recruited from a single academic medical centre, underwent formal neuropsychological testing for assessment of cognitive function. On the same day, BBB permeability was determined using dynamic contrast-enhanced MRI scanning. SLE autoantibodies and other serological biomarkers were measured. Regression modelling was used to determine the association between cognitive impairment, extensive BBB leakage and autoantibodies/biomarkers.ResultsThere were 102 patients with SLE; 90% were female and 88% were Caucasian, with a mean±SD age of 48.9±13.8 years. The mean±SD SLE disease duration was 14.8±11.0 years. Impairment in one or more cognitive tests was present in 47 of 101 (47%) patients and included deficits in information processing speed (9%), attention span (21%), new learning (8%), delayed recall (15%) and executive abilities (21%). Extensive BBB leakage was present in 20 of 79 (25%) patients and was associated with cognitive impairment (15 of 20 (75%) vs 24 of 59 (41%); p=0.01) and shorter disease duration (median (IQR): 7 (8–24 years) vs 15 (2–16 years); p=0.02). No serological parameters were associated with extensive BBB leakage and there was no statistically significant association between cognitive impairment and circulating autoantibodies even after adjusting for BBB leakage.ConclusionsExtensive BBB leakage alone was associated with cognitive impairment. These findings suggest that BBB leakage is an important contributor to cognitive impairment, regardless of circulating SLE-related autoantibodies.

Cognitive dysfunction in patients with systemic lupus erythematosus. A cross-sectional study in a Brazilian sample

“…While anticardiolipin antibodies have been positively linked to cognitive deterioration in adults with SLE 41 and in normal elderly individuals, 42 others could not prove this association. Hanly et al, 7 who have used dynamic contrast-enhanced MRI scanning, found that cognitive impairment in SLE was associated with blood–brain barrier leakage independently of the circulating autoantibody profile (including antiphospholipid).…”

“…5,6 Patients with SLE who experience a stroke and seizure may have CD in up to 50% of the cases, but patients without neurological manifestations or an active disease may also complain of these symptoms. 3 CD is considered one of the most common manifestations of neuropsychiatric lupus 7 ; however, because the numbers change, it is difficult to assess its exact prevalence, according to studies. This is because the studied samples are varied, there is no biomarker available, and it is difficult to attribute CD to the lupus itself, as several medications and complications may be implicated in this context.…”

Association between systemic rheumatic diseases and dementia risk: A meta-analysis

“…Increasing evidence has shown an essential factor for IL-1b overexpression and the deterioration of tau phosphorylation function and tangle formation ( 50 ). Moreover, a higher level of IL-1b can hamper the amyloid-beta (Aβ) clearance functions of microglia ( 51 ) and increase blood-brain barrier permeability, which is mainly responsible for the accumulation of Aβ in the brain ( 19 , 52 , 53 ). Pro-inflammatory cytokines, such as TNF, IL-1, IL-6, and IL-17 in SRDs may increase the risk of dementia through cell apoptosis and neuronal damage ( 54 ).…”

“…Regarding the current evidence of SRDs, little information can be gathered if SRDs are related to dementia. Thus, we examined the relationship between SRDs and dementia risk through an updated systematic review of evidence ( 19 ).…”

Neuropsychiatric Systemic Lupus Erythematosus: Molecules Involved in Its Imunopathogenesis, Clinical Features, and Treatment

“…Anti-NR2 antibodies cross-react with anti-double-stranded DNA antibodies [ 82 ]. Anti-NR2 antibodies can enter the CNS via intrathecal IgG synthesis or by breaching the BBB [ 83 ]. The severity of BBB damage plays a significant role in diffuse NPSLE syndromes, including the potential acute confusional state, because it allows large titers of anti-NR2 to enter the CNS [ 84 ].…”