抗高血压药可降低阿尔茨海默病的进展速度:与遗传学和神经病理学分析相关的队列研究

Zohara Sternberg, R. Podolsky, J. Yu, S. Hua, S. Halvorsen, D. Hojnacki, B. J. Schaller
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引用次数: 0

摘要

背景由于阿尔茨海默病(A.D.)和血管病变,动脉高血压会导致痴呆症的发生和发展。然而,不同类别的抗高血压药(A.H.T.s)对痴呆症进展速度和脑神经病理学的影响尚不清楚。目的 研究各类抗高血压药(包括单药和联合用药)对痴呆症进展速度的影响。此外,我们还分析了A.H.T.对AD患者脑神经病理学的影响,具体表现为布拉克分期、海马萎缩以及A-β42、总(T)tau和P-181 tau的基线CSF水平。方法我们使用了国家阿尔茨海默氏症协调中心(NACC)的统一数据集(UDS)。结果A.H.T.患者的CDR-SOB评分在10年随访期间每年增加1.025分(P<0.001),而A.H.T.患者的CDR-SOB评分每年增加1.025分(P<0.001)。A.H.T.使用者的总生存率高于非使用者[HR:0.912:0.860, 0.967) P=0.002]。按年龄、性别和 APOE4 等位基因对参与者进行分层后,这些趋势依然存在。未使用A.H.T.s的参与者的CDR-SOB评分平均每年增加1.71±1.7分。有记录显示使用βB和A.R.B.s的参与者的这一数值分别降至1.48±1.6(P=0.006)和1.45±1.6(P=0.024)。将利尿剂与α1-AB或ACEI结合使用可产生协同效应,降低CDR-SOB评分的上升。A.H.T.使用者在死后被诊断为AD并伴有严重Braak分期的比例明显低于非使用者。70岁与70岁的男女参与者的布拉克分期严重程度和海马萎缩程度不同。海马萎缩与布拉克分期之间、海马萎缩与P-181 tau的基线CSF水平之间存在明显关系。在选择A.H.T.疗法的组合时,还应考虑能在延缓痴呆症进展方面产生最佳疗效的组合。此外,我们的研究结果还强调了一种比以前认为的更为复杂的急性髓性白血病疾病模型,这为我们提供了新的治疗方案。
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Anti-Hypertensives Reduce the Rate of Alzheimer’s Disease Progression: A Cohort Study Linked with Genetic and Neuropathological Analyses

Background

Arterial hypertension contributes to both the development and progression of dementia due to both Alzheimer’s disease (A.D.) and vascular pathology. However, the effects of different classes of anti-hypertensives (A.H.T.s), on the rate of dementia progression and brain neuropathology are unknown.

Objective

To investigate the effect of each class of A.H.T., both as single and combined, on the rate of dementia progression. In addition, we analyzed the effect of A.H.T.s on brain neuropathology in AD participants, indicated by Braak staging, hippocampal atrophy, and baseline CSF levels of A-β42, total (T) tau, and P-181 tau.

Methods

We have used the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS).

Results

A.H.T.s were associated with reduced yearly increase in the CDR-SOB scores of 1.025 during a 10-year follow-up (P<0.001). The overall survival rate was higher in A.H.T. users than non-users [HR: 0.912: 0.860, 0.967) P=0.002]. These trends continued when stratifying participants by age, gender, and APOE4 allele. Participants who did not use A.H.T.s had a mean yearly increase of 1.71±1.7 in the CDR-SOB scores. This value was reduced to 1.48±1.6, P=0.006 and 1.45±1.6, P=0.024 for participants with documented use of βB and A.R.B.s, respectively. Combining diuretics with α1-AB or ACEI led to synergistic effects in reducing the rise in CDR-SOB scores. The proportion of participants who were diagnosed having AD postmortem with severe Braak staging was significantly lower in A.H.T.-users than non-users. The severity of Braak staging, and hippocampal atrophy differed in participants >70 vs. <70 years old, in both males and females. A significant relationship was observed between hippocampal atrophy and Braak staging; and between hippocampal atrophy and baseline CSF levels of P-181 tau.

Conclusion

Our results could have implications for halting the progression of dementia regardless of the etiology being related to AD or vascular pathology. The choice of combination of A.H.T. therapy should also consider the combination which would lead to an optimum benefit in slowing the progression of dementia. Additionally, our results underline a more complex A.D. disease model than previously thought, which opens new treatment options.

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The Journal of Prevention of Alzheimer's Disease
The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health
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期刊介绍: The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.
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