Jaramillo Ramos Julio Joel, Galindo Pupo Néstor Manuel, Mena Diego, Solis Ricardo Perez, Bedoya Jaramillo Julian Eduardo, Vega Solano Manrique
Internal Medicine, Hospital Santo Tomás, Panama City, PAN.
Internal Medicine, Universidad Cooperativa de Colombia, Florencia, COL.
Cureus. 2025 Jul 21;17(7):e88397. doi: 10.7759/cureus.88397. eCollection 2025 Jul.
Chronic inflammatory diseases (CIDs), such as rheumatoid arthritis (RA), obesity, type 2 diabetes mellitus (T2DM), systemic lupus erythematosus (SLE), fibromyalgia (FM), and chronic infection, are risk factors for neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). This review synthesizes evidence from longitudinal cohort studies and clinical trials, highlighting the contrasting evidence to explain the complex association between systemic inflammation and neurodegeneration. These important mechanisms are disruption of the blood-brain barrier, microglial activation, cytokine-related neurotoxicity (e.g., IL-6, TNF-alpha), lysosomal maladaptation, and metabolic imbalance (e.g., insulin resistance, hyperglycemia). Disease-specific correlations present study outcomes that are paradoxical, including that RA has genetic protection against PD but an increased risk of AD, whereas obesity and T2D associations are the same across studies, persistent associations of these terms with worsened cognitive decline. The risk of dementia is worsened by autoimmune diseases, such as SLE and FM, involving neuroinflammation caused by autoantibodies and central sensitization in the latter, respectively. The new markers, such as glial fibrillary acidic protein (GFAP) (neuroinflammation) and neurofilament light (NfL) (axonal injury), have prospects in early detection, but there is a need for validation in future studies. Therapeutic approaches emphasize the need for immunomodulation (e.g., disease-modifying antirheumatic drugs {DMARDs} in RA), glycemic control in T2DM, and lifestyle interventions, with a lack of targeting the non-amyloid pathways. New studies should emphasize longitudinal studies, multiome-based methods, and clinical trials in an attempt to create precision treatment. Considering the inflammatory risk stratification in the prevention of neurodegeneration, this review sheds light on the possibility of early preventative action that may offset the progressive cognitive decline in especially vulnerable groups.
慢性炎症性疾病（CIDs），如类风湿性关节炎（RA）、肥胖症、2型糖尿病（T2DM）、系统性红斑狼疮（SLE）、纤维肌痛（FM）和慢性感染，是神经退行性疾病的危险因素，如阿尔茨海默病（AD）和帕金森病（PD）。本综述综合了纵向队列研究和临床试验的证据，突出了相互矛盾的证据，以解释全身炎症与神经退行性变之间的复杂关联。这些重要机制包括血脑屏障破坏、小胶质细胞激活、细胞因子相关神经毒性（如白细胞介素-6、肿瘤坏死因子-α）、溶酶体适应不良和代谢失衡（如胰岛素抵抗、高血糖）。疾病特异性相关性呈现出矛盾的研究结果，包括RA对PD有遗传保护作用，但患AD的风险增加，而肥胖和T2D的关联在各研究中是相同的，这些因素与认知功能下降加剧持续相关。自身免疫性疾病，如SLE和FM，分别通过自身抗体引起的神经炎症和后者的中枢敏化作用，使痴呆风险增加。新的标志物，如胶质纤维酸性蛋白（GFAP）（神经炎症）和神经丝轻链（NfL）（轴突损伤），在早期检测方面具有前景，但未来研究需要进行验证。治疗方法强调免疫调节的必要性（如RA中的改善病情抗风湿药{DMARDs}）、T2DM中的血糖控制和生活方式干预，而缺乏针对非淀粉样蛋白途径的治疗。新的研究应强调纵向研究、基于多组学的方法和临床试验，以尝试实现精准治疗。考虑到预防神经退行性变中的炎症风险分层，本综述阐明了早期预防行动的可能性，这可能会抵消特别脆弱群体中逐渐加重的认知功能下降。
