Zohara Sternberg, PhD, Clinical Associate Professor of Neurology, Buffalo Medical Center, Buffalo, NY, 14203, Tel: 716-8597540, Fax: 716-8592430, 859-7573, Email:
J Prev Alzheimers Dis. 2024;11(6):1634-1646. doi: 10.14283/jpad.2024.156.
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.
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.
We have used the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS).
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.
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.
动脉高血压会导致阿尔茨海默病（AD）和血管病理学的痴呆发展和进展。然而，不同类别的抗高血压药物（AHTs）对痴呆进展速度和脑神经病理学的影响尚不清楚。
研究每种 AHT 类别的效果，包括单一和联合使用，对痴呆进展速度的影响。此外，我们还分析了 AHTs 对 AD 患者脑神经病理学的影响，通过 Braak 分期、海马萎缩以及基线 CSF 中 A-β42、总（T）tau 和 P-181 tau 的水平来评估。
我们使用了国家阿尔茨海默病协调中心（NACC）统一数据集（UDS）。
AHTs 与 10 年随访期间 CDR-SOB 评分每年增加 1.025 相关（P<0.001）。与非使用者相比，AHT 使用者的总生存率更高[HR：0.912：0.860，0.967，P=0.002]。当按年龄、性别和 APOE4 等位基因对参与者进行分层时，这些趋势仍在继续。未使用 AHTs 的参与者的 CDR-SOB 评分每年平均增加 1.71±1.7。这一数值降低到使用βB 和 A.R.B.s 的参与者分别为 1.48±1.6（P=0.006）和 1.45±1.6（P=0.024）。将利尿剂与α1-AB 或 ACEI 联合使用可产生协同作用，降低 CDR-SOB 评分的上升。与非使用者相比，使用 AHTs 的参与者中被诊断为 AD 且 Braak 分期严重的比例显著降低。在>70 岁和<70 岁的男性和女性参与者中，Braak 分期和海马萎缩的严重程度存在差异。海马萎缩与 Braak 分期之间以及海马萎缩与基线 CSF 中 P-181 tau 水平之间存在显著相关性。
无论病因与 AD 还是血管病理学有关，我们的结果都可能对阻止痴呆进展产生影响。AHT 治疗联合方案的选择还应考虑到可带来最佳减缓痴呆进展效果的联合方案。此外，我们的结果强调了一个比之前认为的更复杂的 AD 疾病模型，这为新的治疗选择开辟了道路。
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