The escalating prevalence of dementia worldwide necessitates preventive strategies to mitigate its extensive health, psychological, and social impacts. As the prevalence of dementia continues to rise, gaining insights into its risk factors and causes become paramount, given the absence of a definitive cure. Cardiovascular disease has emerged as a prominent player in the complex landscape of dementia. Preventing, dyslipidaemia, unhealthy Western type diets, hypertension, diabetes, being overweight, physical inactivity, smoking, and high alcohol intake have the potential to diminish not only cardiovascular disease but also dementia. The purpose of this review is to present our current understanding of cardiovascular risk factors for Alzheimer's disease (AD) and vascular dementia (VaD) by using clinical human data from observational, genetic studies and clinical trials, while elaborating on potential mechanisms. Hypertension and type 2 diabetes surface as significant causal risk factors for both AD and VaD, as consistently illustrated in observational and Mendelian randomization studies. Antihypertensive drugs and physical activity have been shown to improve cognitive function in clinical trials. Important to note is, that robust genome wide associations studies are lacking for VaD, and indeed more and prolonged clinical trials are needed to establish these findings and investigate other risk factors. Trials should strategically target individuals at the highest dementia risk, identified using risk charts incorporating genetic markers, biomarkers, and cardiovascular risk factors. Understanding causal risk factors for dementia will optimise preventive measures, and implementation of well-known therapeutics can halt or alleviate dementia symptoms if started early. Needless to mention is that future health policies should prioritise primordial prevention from early childhood to prevent risk factors from even occurring in the first place. Together, understanding the role of cardiovascular risk factors in dementia, improving GWASs for VaD, and advancing clinical trials are crucial steps in addressing this significant public health challenge.

中文翻译：

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痴呆的致病心血管危险因素 – 来自观察和遗传研究的见解


全球痴呆症的患病率不断上升，需要制定预防策略来减轻其广泛的健康、心理和社会影响。随着痴呆症的患病率持续上升，鉴于缺乏明确的治愈方法，了解其风险因素和原因变得至关重要。心血管疾病已成为痴呆复杂环境中的重要参与者。预防、血脂异常、不健康的西式饮食、高血压、糖尿病、超重、缺乏运动、吸烟和高酒精摄入量不仅有可能减少心血管疾病，而且有可能减少痴呆症。本综述的目的是通过使用来自观察性、遗传研究和临床试验的临床人类数据，展示我们目前对阿尔茨海默病 （AD） 和血管性痴呆 （VaD） 的心血管危险因素的理解，同时详细说明潜在机制。高血压和 2 型糖尿病是 AD 和 VaD 的重要致病危险因素，这在观察性和孟德尔随机化研究中一致说明。临床试验显示，抗高血压药物和身体活动可以改善认知功能。需要注意的是，缺乏针对 VaD 的稳健全基因组关联研究，确实需要更多和长期的临床试验来确定这些发现并调查其他风险因素。试验应战略性地针对痴呆风险最高的个体，使用包含遗传标志物、生物标志物和心血管危险因素的风险图表进行识别。了解痴呆的致病风险因素将优化预防措施，如果及早开始，实施众所周知的治疗方法可以停止或缓解痴呆症状。 毋庸置疑，未来的卫生政策应优先考虑从儿童早期开始的原始预防，以从一开始就防止风险因素的发生。总之，了解心血管危险因素在痴呆中的作用，改善VaD的GWASs，以及推进临床试验，是应对这一重大公共卫生挑战的关键步骤。