IGF1 and Alzheimer disease: Conversely, AD-related neurodegeneration disrupts bone homeostasis to aggravate periodontitis via multiple mechanisms: (1) Aβ-mediated osteoclast activation through RAGE/NF-κB signaling and suppression of osteoblastogenesis; (2) autonomic nervous system dysregulation, where sympathetic hyperactivity promotes RANKL-dependent bone resorption; and (3) endocrine dysfunction, including HPA axis hyperactivation (chronic hypercortisolism), sex hormone deficiency, insulin resistance, and growth hormone/IGF-1 insufficiency, all of which perturb the balance between bone formation and resorption.