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A study in 650 elderly men and women reported that the risk of elevated plasma homocysteine levels was significantly higher in those with lower cognitive function scores (72)

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Additionally, significant associations were observed between single nucleotide variants in the NNMT gene and energy metabolism, obesity, T2D, hyperlipidemia, and hypertension (Zhu et al., 2016

Key pathophysiologic mechanisms include: Mucosal barrier dysfunction: Impaired epithelial tight junctions allow bacterial translocation, triggering innate immune activation T-helper cell dysregulation: Predominantly Th1 and Th17 pathways drive chronic inflammation via TNF-, IL-12, IL-23 the basis for biologic therapy targets Transmural inflammation: Unlike UC (mucosal only), CD involves all layers: mucosa submucosa muscularis propria serosa Granuloma formation: Non-caseating granulomas are pathognomonic but present in only ~3050% of biopsies Fibrosis and stricture: Chronic inflammation activates myofibroblasts collagen deposition luminal narrowing obstructive symptoms Fistula formation: Transmural ulcers penetrate serosa form sinus tracts connect to adjacent bowel, bladder, vagina, or skin 7