Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
Department of Epidemiology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
Brain. 2023 Jan 5;146(1):337-348. doi: 10.1093/brain/awac354.
Higher vascular disease burden increases the likelihood of developing dementia, including Alzheimer's disease. Better understanding the association between vascular risk factors and Alzheimer's disease pathology at the predementia stage is critical for developing effective strategies to delay cognitive decline. In this work, we estimated the impact of six vascular risk factors on the presence and severity of in vivo measured brain amyloid-beta (Aβ) plaques in participants from the population-based Rotterdam Study. Vascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, physical inactivity and smoking) were assessed 13 (2004-2008) and 7 years (2009-2014) prior to 18F-florbetaben PET (2018-2021) in 635 dementia-free participants. Vascular risk factors were associated with binary amyloid PET status or continuous PET readouts (standard uptake value ratios, SUVrs) using logistic and linear regression models, respectively, adjusted for age, sex, education, APOE4 risk allele count and time between vascular risk and PET assessment. Participants' mean age at time of amyloid PET was 69 years (range: 60-90), 325 (51.2%) were women and 190 (29.9%) carried at least one APOE4 risk allele. The adjusted prevalence estimates of an amyloid-positive PET status markedly increased with age [12.8% (95% CI 11.6; 14) in 60-69 years versus 35% (36; 40.8) in 80-89 years age groups] and APOE4 allele count [9.7% (8.8; 10.6) in non-carriers versus 38.4% (36; 40.8) to 60.4% (54; 66.8) in carriers of one or two risk allele(s)]. Diabetes 7 years prior to PET assessment was associated with a higher risk of a positive amyloid status [odds ratio (95% CI) = 3.68 (1.76; 7.61), P < 0.001] and higher standard uptake value ratios, indicating more severe Aβ pathology [standardized beta = 0.40 (0.17; 0.64), P = 0.001]. Hypertension was associated with higher SUVr values in APOE4 carriers (mean SUVr difference of 0.09), but not in non-carriers (mean SUVr difference 0.02; P = 0.005). In contrast, hypercholesterolaemia was related to lower SUVr values in APOE4 carriers (mean SUVr difference -0.06), but not in non-carriers (mean SUVr difference 0.02). Obesity, physical inactivity and smoking were not related to amyloid PET measures. The current findings suggest a contribution of diabetes, hypertension and hypercholesterolaemia to the pathophysiology of Alzheimer's disease in a general population of older non-demented adults. As these conditions respond well to lifestyle modification and drug treatment, further research should focus on the preventative effect of early risk management on the development of Alzheimer's disease neuropathology.
更高的血管疾病负担增加了发展为痴呆症（包括阿尔茨海默病）的可能性。更好地理解血管危险因素与痴呆前阶段阿尔茨海默病病理之间的关联，对于制定延迟认知能力下降的有效策略至关重要。在这项工作中，我们估计了六个血管危险因素对来自基于人群的鹿特丹研究中参与者体内测量的脑淀粉样蛋白-β（Aβ）斑块的存在和严重程度的影响。血管危险因素（高血压、高胆固醇血症、糖尿病、肥胖、身体活动不足和吸烟）在 635 名无痴呆症的参与者中分别在进行 18F-氟比他滨 PET（2018-2021 年）之前的 13 年（2004-2008 年）和 7 年（2009-2014 年）进行评估。使用逻辑回归和线性回归模型，分别将血管危险因素与二元淀粉样蛋白 PET 状态或连续 PET 读数（标准摄取值比，SUVr）相关联，调整了年龄、性别、教育程度、APOE4 风险等位基因数和血管危险因素与 PET 评估之间的时间。参与者进行淀粉样蛋白 PET 时的平均年龄为 69 岁（范围：60-90 岁），325 名（51.2%）为女性，190 名（29.9%）至少携带一个 APOE4 风险等位基因。经过调整后，淀粉样蛋白阳性 PET 状态的患病率估计值随着年龄的增长而显著增加[60-69 岁年龄组为 12.8%（95%CI 11.6%；14），80-89 岁年龄组为 35%（36%；40.8%）]和 APOE4 等位基因数[非携带者为 9.7%（8.8%；10.6%），携带者为 38.4%（36%；40.8%）至 60.4%（54%；66.8%）]。PET 评估前 7 年的糖尿病与阳性淀粉样蛋白状态的风险增加相关[比值比（95%CI）=3.68（1.76；7.61），P<0.001]和更高的标准摄取值比，表明 Aβ 病理学更严重[标准化β=0.40（0.17；0.64），P=0.001]。高血压与 APOE4 携带者的 SUVr 值升高相关（平均 SUVr 差值为 0.09），但与非携带者无关（平均 SUVr 差值为 0.02；P=0.005）。相比之下，高胆固醇血症与 APOE4 携带者的 SUVr 值降低相关（平均 SUVr 差值为-0.06），但与非携带者无关（平均 SUVr 差值为 0.02）。肥胖、身体活动不足和吸烟与淀粉样蛋白 PET 测量无关。目前的研究结果表明，糖尿病、高血压和高胆固醇血症在老年非痴呆成年人的一般人群中对阿尔茨海默病的病理生理学有一定的影响。由于这些情况对生活方式改变和药物治疗反应良好，因此进一步的研究应集中在早期风险管理对阿尔茨海默病神经病理学发展的预防作用上。
