"Golgi Cenci" Foundation, Corso San Martino 10, 20081, Abbiategrasso, Italy.
Department of Business Economics, Health and Social Care Centre of Competence on Ageing, University of Applied Sciences and Arts of Southern Switzerland, Stabile Piazzetta, Via Violino 11, CH-6928, Manno, Switzerland.
Alzheimers Res Ther. 2020 Aug 7;12(1):94. doi: 10.1186/s13195-020-00661-y.
Preventing dementia onset is one of the global public health priorities: around 35% of dementia cases could be attributable to modifiable risk factors. These estimates relied on secondary data and did not consider the concurrent effect of non-modifiable factors and death. Here, we aimed to estimate the potential reduction of dementia incidence due to modifiable risk factors elimination, controlling for non-modifiable risk factors and for the competing risk of death.
Participants from the InveCe.Ab population-based prospective cohort (Abbiategrasso, Italy) without a baseline dementia diagnosis and attending at least one follow-up visit were included (N = 1100). Participants underwent multidimensional assessment at baseline and after 2, 4, and 8 years, from November 2009 to January 2019. Modifiable risk factors were low education, obesity, hypertension, diabetes, depression, smoking, physical inactivity, hearing loss, loneliness, heart disease, stroke, head injury, and delirium. Non-modifiable risk factors were age, sex, and APOE ε4 genotype. The primary endpoint was dementia diagnosis within the follow-up period (DSM-IV criteria). We performed competing risk regression models to obtain sub-hazard ratio (SHR) for each exposure, with death as competing risk. The exposures associated with dementia were included in a multivariable model to estimate their independent influence on dementia and the corresponding population attributable fraction (PAF).
Within the study period (mean follow-up, 82.3 months), 111 participants developed dementia (10.1%). In the multivariable model, APOE ε4 (SHR = 1.89, 95% CI 1.22-2.92, p = 0.005), diabetes (SHR = 1.56, 95% CI 1.00-2.39, p = 0.043), heart disease (SHR = 1.56, 95% CI 1.03-2.36, p = 0.037), stroke (SHR = 2.31, 95% CI 1.35-3.95, p = 0.002), and delirium (SHR = 8.70, 95% CI 3.26-23.24, p < 0.001) were independently associated with increased dementia risk. In the present cohort, around 40% of dementia cases could be attributable to preventable comorbid diseases.
APOE ε4, diabetes, heart disease, stroke, and delirium independently increased the risk of late-life dementia, controlling for the competing risk of death. Preventive intervention addressed to these clinical populations could be an effective approach to reduce dementia incidence. Further studies on different population-based cohort are needed to obtain more generalizable findings of the potential of dementia prevention in the real-world setting.
ClinicalTrials.gov, NCT01345110 .
预防痴呆症发病是全球公共卫生的重点之一：大约 35%的痴呆症病例可能归因于可改变的危险因素。这些估计依赖于二级数据，并未考虑不可改变因素和死亡的并发影响。在这里，我们旨在估计消除可改变的危险因素对痴呆症发病率的潜在降低作用，同时控制不可改变的危险因素和死亡的竞争风险。
我们纳入了来自 InveCe.Ab 基于人群的前瞻性队列（意大利 Abbategrasso）中没有基线痴呆症诊断且至少参加过一次随访的参与者（N=1100）。参与者在基线和 2、4 和 8 年后接受了多维评估，时间为 2009 年 11 月至 2019 年 1 月。可改变的危险因素包括低教育程度、肥胖、高血压、糖尿病、抑郁、吸烟、身体活动不足、听力损失、孤独、心脏病、中风、头部损伤和谵妄。不可改变的危险因素包括年龄、性别和 APOE ε4 基因型。主要终点是在随访期间发生痴呆症（DSM-IV 标准）。我们使用竞争风险回归模型来获得每个暴露因素的亚危险比（SHR），以死亡为竞争风险。在多变量模型中，将与痴呆症相关的暴露因素纳入，以估计它们对痴呆症的独立影响及其相应的人群归因分数（PAF）。
在研究期间（平均随访 82.3 个月），有 111 名参与者患上了痴呆症（10.1%）。在多变量模型中，APOE ε4（SHR=1.89，95%CI 1.22-2.92，p=0.005）、糖尿病（SHR=1.56，95%CI 1.00-2.39，p=0.043）、心脏病（SHR=1.56，95%CI 1.03-2.36，p=0.037）、中风（SHR=2.31，95%CI 1.35-3.95，p=0.002）和谵妄（SHR=8.70，95%CI 3.26-23.24，p<0.001）与痴呆症风险增加独立相关。在本队列中，约 40%的痴呆症病例可能归因于可预防的合并症。
APOE ε4、糖尿病、心脏病、中风和谵妄独立增加了晚年痴呆症的风险，同时考虑了死亡的竞争风险。针对这些临床人群的预防干预可能是减少痴呆症发病率的有效方法。需要对不同的基于人群的队列进行进一步研究，以获得在现实环境中预防痴呆症的潜在效果的更具普遍性的发现。
ClinicalTrials.gov，NCT01345110。
