Kim Elizabeth, Zhang Kevin, Abdi Miski, Li Wei Tse, Xin Ruomin, Wang-Rodriguez Jessica, Ongkeko Weg M
Department of Otolaryngology-Head and Neck Surgery, University of California, La Jolla, San Diego, CA 92093, USA.
Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA.
Biomedicines. 2025 Jun 19;13(6):1508. doi: 10.3390/biomedicines13061508.
Alzheimer's disease (AD) is a progressive neurodegenerative condition whose growing prevalence has become an increasingly important public health concern as the population ages. The lack of a definitive cure elevates the importance of identifying risk factors that are crucial for prevention efforts. Hypertension (HTN) and obesity have emerged as two highly widespread, interrelated conditions that have independently been associated with AD risk. Despite extensive research into AD pathology, the impact of obesity in a hypertensive population is not well explored. This study aims to investigate how obesity and blood pressure control within a hypertensive population may interact with genomic risk and environmental factors to influence AD incidence. A retrospective cohort of matched AD and normal patients diagnosed with HTN and taking anti-HTN drugs ( = 1862) from the All of Us database was analyzed. In this hypertensive cohort, obesity was significantly associated with increased AD risk. Genome-wide association studies (GWASs) were conducted on hypertensive AD individuals ( = 1030) and identified six single nucleotide variants (SNVs) that were associated with AD development in this population. Obesity and Area Deprivation Index, a measure of socioeconomic status, were significantly associated with elevated AD risk within the hypertensive cohort. GWAS analysis identified six SNVs significantly associated with AD development among the hypertensive cohort. Our findings suggest that among hypertensive individuals, comorbid obesity and the Area Deprivation Index confer greater AD risk. These results highlight the critical need for obesity prevention and management strategies as part of Alzheimer's risk reduction efforts.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,随着人口老龄化,其患病率不断上升,已成为日益重要的公共卫生问题。由于缺乏确切的治愈方法,识别对预防工作至关重要的风险因素变得更加重要。高血压(HTN)和肥胖已成为两种广泛存在且相互关联的疾病,它们各自都与AD风险相关。尽管对AD病理学进行了广泛研究,但肥胖在高血压人群中的影响尚未得到充分探索。本研究旨在调查高血压人群中的肥胖和血压控制如何与基因组风险及环境因素相互作用,从而影响AD发病率。对来自“我们所有人”数据库的1862例诊断为HTN并正在服用抗高血压药物的AD患者和正常患者进行回顾性队列匹配分析。在这个高血压队列中,肥胖与AD风险增加显著相关。对1030例高血压AD患者进行全基因组关联研究(GWAS),并确定了6个与该人群AD发生相关的单核苷酸变异(SNV)。肥胖和作为社会经济地位衡量指标的地区贫困指数与高血压队列中AD风险升高显著相关。GWAS分析在高血压队列中确定了6个与AD发生显著相关的SNV。我们的研究结果表明,在高血压个体中,合并肥胖和地区贫困指数会带来更高的AD风险。这些结果凸显了作为降低阿尔茨海默病风险努力的一部分,预防和管理肥胖策略的迫切需求。