Cognitive dysfunction in SLE: An understudied clinical manifestation

Neuropsychiatric lupus (NPSLE) is a debilitating manifestation of SLE which occurs in a majority of SLE patients and has a variety of clinical manifestations. In the central nervous system, NPSLE may result from ischemia or penetration of inflammatory mediators and neurotoxic antibodies through the blood brain barrier (BBB). Here we focus on cognitive dysfunction (CD) as an NPSLE manifestation; it is common, underdiagnosed, and without specific therapy. For a very long time, clinicians ignored cognitive dysfunction and researchers who might be interested in the question struggled to find an approach to understanding mechanisms for this manifestation. Recent years, however, propelled by a more patient-centric approach to disease, have seen remarkable progress in our understanding of CD pathogenesis. This has been enabled through the use of novel imaging modalities and numerous mouse models. Overall, these studies point to a pivotal role of an impaired BBB and microglial activation in leading to neuronal injury. These insights suggest potential therapeutic modalities and make possible clinical trials for cognitive impairment.