Immune-mediated mechanisms of cognitive memory dysfunction: From autoimmune diseases to therapeutic neuromodulation.

Abstract

Cognitive memory is fundamental to how humans adapt, form identity, and retain experiences. Recent research highlights that memory processes are modulated by the immune system. Here, we review both preclinical and clinical findings to examine how dysregulated immunity impairs memory processes. This review discusses broad immune-memory dynamics to disease-specific disruptions in autoimmune disorders, including intervention strategies aimed at mitigating immune-related cognitive dysfunction. We emphasize the roles of cytokines, autoantibodies, and neuroinflammation in affecting memory-related brain regions. Infectious diseases are also discussed as potential triggers and modulators of immune-mediated cognitive impairment, expanding the scope of relevant etiological factors. Addressing these specific pathways could offer more targeted therapeutic opportunities for cognitive deficits in immune-mediated conditions. Autoimmune diseases such as systemic lupus erythematosus (SLE), autoimmune encephalitis (AE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) are examined, with attention to studies that disentangle memory impairments from comorbid factors like depression and fatigue. In addition to neurological autoimmune syndromes, we also review psychiatric autoimmune syndromes, emphasizing their shared impact on memory dysfunction. Additionally, Fibromyalgia (FM), increasingly conceptualized as having autoimmune features, is discussed as a chronic pain syndrome with emphasis on its cognitive dysfunction aspects. Memory deficits are frequently reported in FM, suggesting immune-mediated disruption of higher-order cognitive processes. Finally, we explore emerging non-invasive neuromodulation techniques, including transcranial Direct Current Stimulation (tDCS), and transcranial Alternating Current Stimulation (tACS), as tools for restoring cognitive function in FM.