Zsolt Huszár, Alina Solomon, Marie Anne Engh, Vanda Koszovácz, Tamás Terebessy, Zsolt Molnár, Péter Hegyi, András Horváth, Francesca Mangialasche, Miia Kivipelto, Gábor Csukly
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Vascular risk factors were summarized with the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score, dichotomized into higher versus lower risk. Depression and smoking (yes/no) were categorised according to medical history or current symptoms. Analyses were stratified by beta-amyloid negative (A-) and positive (A +), p-tau negative (T-) and positive (T +), or beta-amyloid and p-tau negative (A-T-) and positive (A + T +) biomarker status. Cox proportional hazard models were adjusted for age, sex, education, baseline MMSE score, baseline hippocampal volume and ApoE4 carrier status.</p><p><strong>Results: </strong>Higher CAIDE score was associated with increased risk of progression to all-cause dementia in most MCI subgroups: adjusted hazard ratios (aHR) [95% CI] were 3.1 [1.43; 6.53] in the A- subgroup, 1.7 [1.20-2.27] in T + , 2.6 [1.06-6.59] in A-T-, and 1.6 [1.15-2.22] in the A + T + subgroup. Smoking (yes/no) was associated with increased dementia aHR in the A + MCI subgroup: 1.6 [1.07-2.34]. Depression increased dementia aHR in the T + MCI subgroup: 1.5 [1.06-2.02]. No significant associations were found in the CU biomarker subgroups.</p><p><strong>Conclusion: </strong>Addressing modifiable risk factors carries an important potential for reducing the risk of dementia even after the onset of Alzheimer's pathology. 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引用次数: 0
摘要
背景：针对多种可改变风险因素的痴呆症预防干预是一种很有前景的方法。然而，在存在β-淀粉样蛋白或磷酸化-tau（p-tau）病理的情况下，可改变的风险因素的影响尚不明确：本研究的目的是研究阿尔茨海默病神经影像学倡议（ADNI）数据库中的434名认知功能未受损者（CU）和611名MCI患者中，可改变的风险因素（血管因素、抑郁和吸烟）在进展为轻度认知障碍（MCI）或痴呆症过程中的作用。血管风险因素通过心血管风险因素、衰老和痴呆（CAIDE）评分进行总结，并分为高风险和低风险。抑郁和吸烟（是/否）根据病史或当前症状进行分类。根据β-淀粉样蛋白阴性（A-）和阳性（A +）、p-tau阴性（T-）和阳性（T +）或β-淀粉样蛋白和p-tau阴性（A-T-）和阳性（A + T +）生物标记物状态进行分层分析。Cox比例危险模型对年龄、性别、教育程度、基线MMSE评分、基线海马体积和载脂蛋白E4携带者状态进行了调整：在大多数MCI亚组中，CAIDE评分越高，发展为全因痴呆的风险越高：A-亚组的调整后危险比（aHR）[95% CI]为3.1[1.43; 6.53]，T +为1.7[1.20-2.27]，A-T-为2.6[1.06-6.59]，A + T +亚组为1.6[1.15-2.22]。在 A + MCI 亚组中，吸烟（是/否）与痴呆 aHR 的增加有关：1.6 [1.07-2.34].抑郁会增加 T + MCI 亚组中痴呆症的 aHR：1.5 [1.06-2.02].在CU生物标记物亚组中没有发现明显的关联：结论：即使在阿尔茨海默病发病后，解决可改变的风险因素也有可能降低痴呆症的风险。了解生物标志物的状态可以进一步优化预防策略。
Association of modifiable risk factors with progression to dementia in relation to amyloid and tau pathology.
Background: Dementia preventive interventions targeting multiple modifiable risk factors are a promising approach. However, the impact of modifiable risk factors in the presence of beta-amyloid or phosphorylated-tau (p-tau) pathology is unclear.
Methods: The objective of the study was to examine the role of modifiable risk factors (vascular factors, depression, and smoking) in the progression to mild cognitive impairment (MCI) or dementia among 434 cognitively unimpaired (CU) and 611 individuals with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Vascular risk factors were summarized with the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score, dichotomized into higher versus lower risk. Depression and smoking (yes/no) were categorised according to medical history or current symptoms. Analyses were stratified by beta-amyloid negative (A-) and positive (A +), p-tau negative (T-) and positive (T +), or beta-amyloid and p-tau negative (A-T-) and positive (A + T +) biomarker status. Cox proportional hazard models were adjusted for age, sex, education, baseline MMSE score, baseline hippocampal volume and ApoE4 carrier status.
Results: Higher CAIDE score was associated with increased risk of progression to all-cause dementia in most MCI subgroups: adjusted hazard ratios (aHR) [95% CI] were 3.1 [1.43; 6.53] in the A- subgroup, 1.7 [1.20-2.27] in T + , 2.6 [1.06-6.59] in A-T-, and 1.6 [1.15-2.22] in the A + T + subgroup. Smoking (yes/no) was associated with increased dementia aHR in the A + MCI subgroup: 1.6 [1.07-2.34]. Depression increased dementia aHR in the T + MCI subgroup: 1.5 [1.06-2.02]. No significant associations were found in the CU biomarker subgroups.
Conclusion: Addressing modifiable risk factors carries an important potential for reducing the risk of dementia even after the onset of Alzheimer's pathology. Knowledge of biomarker status can further optimize prevention strategies.
期刊介绍：
Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.
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