Cognitive profile and inflammatory markers in children and adolescents with specific learning disorder: a cross-sectional study

Background: Specific learning disorder (SLD) is frequently characterized by weaknesses in working memory and processing speed; however, its biological correlates remain unclear. In this study, we investigate whether inexpensive, blood count-derived inflammation composites and micronutrients are related to cognitive variation in SLD. Methods: In this cross-sectional study, participants in the SLD group underwent Wechsler Intelligence Scale for Children-Fourth Edition assessment to characterize their cognitive profile, yielding a Full-Scale IQ (FSIQ) and four index scores: Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed. Fasting blood samples were obtained from all participants for routine hematology/biochemistry, vitamin B12 and folate, C-reactive protein (CRP), and the composite indices, the systemic immune-inflammation index (SII), the systemic inflammation response index (SIRI), and the pan-immune-inflammation value (PIV). Results: = 0.025), whereas CRP, SII, SIRI, and folate levels did not differ significantly. Within the SLD group, higher cell-based inflammatory indices correlated with poorer cognitive performance, most consistently for the PIV in relation to processing speed and working memory, while vitamin B12 correlated positively with FSIQ, working memory, and processing speed. In the adjusted analyses of the full case-control sample, a higher PIV was independently associated with an increased likelihood of SLD, whereas a higher vitamin B12 level was independently associated with a decreased likelihood of SLD. SII and SIRI exhibited positive trend-level associations, whereas folate showed no association with group membership. Conclusions: In this case-control study, SLD was associated with lower vitamin B12 levels and higher PIV values than healthy controls. Within the SLD group, higher inflammatory composite indices and lower vitamin B12 levels were associated with poorer cognitive performance, particularly in processing speed and working memory. These findings should be interpreted as associations within a case-control framework and warrant further longitudinal and mechanistic studies.