Zheng Ming
Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China; Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Apr 2;138:111316. doi: 10.1016/j.pnpbp.2025.111316. Epub 2025 Mar 5.
Alzheimer's disease (AD) is a leading neurodegenerative disorder, characterized by progressive cognitive decline and memory impairment, with a complex etiology involving genetic, environmental, and lifestyle factors. Traditionally, AD has been studied in isolation, but emerging evidence highlights its interconnectedness with various comorbidities across multiple organ systems. This study introduces a Disease-Wide Association Study (DWAS) approach to explore the disease continuum centered around AD. Using the FinnGen cohort, which includes over 392,000 participants, this study systematically analyzed the comorbidities associated with AD, spanning cardiovascular, metabolic, musculoskeletal, digestive, and oncological conditions. These findings reveal that AD is part of a much broader, systemic disease continuum, with shared pathophysiological mechanisms, including chronic inflammation, metabolic dysregulation, and vascular health, which may influence AD onset and progression. Temporal analysis of pre- and post-AD comorbidities identifies modifiable risk factors such as hypertension, atherosclerosis, and type 2 diabetes that may not only precede AD but also exacerbate its progression. The study emphasizes the importance of an integrated care approach for AD patients, addressing both neurological and systemic health to improve outcomes. Furthermore, by identifying modifiable risk factors, this research opens new avenues for early interventions aimed at delaying or preventing AD. These findings challenge the traditional view of AD as an isolated disease and provide insights into the shared etiology of AD and its comorbidities, offering potential targets for personalized therapeutic strategies and public health policies.
阿尔茨海默病（AD）是一种主要的神经退行性疾病，其特征为进行性认知衰退和记忆障碍，病因复杂，涉及遗传、环境和生活方式等因素。传统上，AD一直是孤立地进行研究，但新出现的证据凸显了它与多个器官系统的各种合并症之间的关联性。本研究引入了一种全疾病关联研究（DWAS）方法，以探索围绕AD的疾病连续谱。利用包含超过39.2万名参与者的芬兰基因队列，本研究系统地分析了与AD相关的合并症，涵盖心血管、代谢、肌肉骨骼、消化和肿瘤疾病。这些发现表明，AD是一个更为广泛的全身性疾病连续谱的一部分，具有共同的病理生理机制，包括慢性炎症、代谢失调和血管健康，这些机制可能影响AD的发病和进展。对AD前后合并症的时间分析确定了可改变的风险因素，如高血压、动脉粥样硬化和2型糖尿病，这些因素不仅可能先于AD出现，还可能加剧其进展。该研究强调了对AD患者采取综合护理方法的重要性，既要关注神经健康，也要关注全身健康，以改善治疗效果。此外，通过确定可改变的风险因素，本研究为旨在延缓或预防AD的早期干预开辟了新途径。这些发现挑战了将AD视为孤立疾病的传统观点，并为AD及其合并症的共同病因提供了见解，为个性化治疗策略和公共卫生政策提供了潜在靶点。
