Centre for Public Health, Queen's University Belfast, Belfast, UK.
Care of the Elderly Medicine, Western Health and Social Care Trust, Londonderry, UK.
Cochrane Database Syst Rev. 2021 May 24;5(5):CD004034. doi: 10.1002/14651858.CD004034.pub4.
This is an update of a Cochrane Review first published in 2006 (McGuinness 2006), and previously updated in 2009 (McGuinness 2009). Hypertension is a risk factor for dementia. Observational studies suggest antihypertensive treatment is associated with lower incidences of cognitive impairment and dementia. There is already clear evidence to support the treatment of hypertension after stroke.
To assess whether pharmacological treatment of hypertension can prevent cognitive impairment or dementia in people who have no history of cerebrovascular disease.
We searched the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group, CENTRAL, MEDLINE, Embase, three other databases, as well as many trials registries and grey literature sources, most recently on 7 July 2020.
We included randomised controlled trials (RCTs) in which pharmacological interventions to treat hypertension were given for at least 12 months. We excluded trials of pharmacological interventions to lower blood pressure in non-hypertensive participants. We also excluded trials conducted solely in people with stroke.
Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected information regarding incidence of dementia, cognitive decline, change in blood pressure, adverse effects and quality of life. We assessed the certainty of evidence using GRADE.
We included 12 studies, totaling 30,412 participants, in this review. Eight studies compared active treatment with placebo. Of the four non-placebo-controlled studies, two compared intensive versus standard blood pressure reduction. The two final included studies compared different classes of antihypertensive drug. Study durations varied from one to five years. The combined result of four placebo-controlled trials that reported incident dementia indicated no evidence of a difference in the risk of dementia between the antihypertensive treatment group and the placebo group (236/7767 versus 259/7660, odds ratio (OR) 0.89, 95% confidence interval (CI) 0.72 to 1.09; very low certainty evidence, downgraded due to study limitations and indirectness). The combined results from five placebo-controlled trials that reported change in Mini-Mental State Examination (MMSE) may indicate a modest benefit from antihypertensive treatment (mean difference (MD) 0.20, 95% CI 0.10 to 0.29; very low certainty evidence, downgraded due to study limitations, indirectness and imprecision). The certainty of evidence for both cognitive outcomes was downgraded on the basis of study limitations and indirectness. Study durations were too short, overall, to expect a significant difference in dementia rates between groups. Dementia and cognitive decline were secondary outcomes for most studies. Additional sources of bias include: the use of antihypertensive medication by the placebo group in the placebo-controlled trials; failure to reach recruitment targets; and early termination of studies on safety grounds. Meta-analysis of the placebo-controlled trials reporting results found a mean change in systolic blood pressure of -9.25 mmHg (95% CI -9.73, -8.78) between treatment (n = 8973) and placebo (n = 8820) groups, and a mean change in diastolic blood pressure of -2.47 mmHg (95% CI -2.70, -2.24) between treatment (n = 7700) and placebo (n = 7509) groups (both low certainty evidence downgraded on the basis of study limitations and inconsistency). Three trials - SHEP 1991, LOMIR MCT IL 1996 and MRC 1996 - reported more withdrawals due to adverse events in active treatment groups than placebo groups. Participants on active treatment in Syst Eur 1998 were less likely to discontinue treatment due to side effects, and participants on active treatment in HYVET 2008 reported fewer 'serious adverse events' than in the placebo group. There was no evidence of a difference in withdrawals rates between groups in SCOPE 2003, and results were unclear for Perez Stable 2000 and Zhang 2018. Heterogeneity precluded meta-analysis. Five of the placebo-controlled trials provided quality of life (QOL) data. Heterogeneity again precluded meta-analysis. SHEP 1991, Syst Eur 1998 and HYVET 2008 reported no evidence of a difference in QOL measures between active treatment and placebo groups over time. The SCOPE 2003 sub-study (Degl'Innocenti 2004) showed a smaller drop in QOL measures in the active treatment compared to the placebo group. LOMIR MCT IL 1996 reported an improvement in a QOL measure at twelve months in one active treatment group and deterioration in another.
AUTHORS' CONCLUSIONS: High certainty randomised controlled trial evidence regarding the effect of hypertension treatment on dementia and cognitive decline does not yet exist. The studies included in this review provide low certainty evidence (downgraded primarily due to study limitations and indirectness) that pharmacological treatment of hypertension, in people without prior cerebrovascular disease, leads to less cognitive decline compared to controls. This difference is below the level considered clinically significant. The studies included in this review also provide very low certainty evidence that pharmacological treatment of hypertension, in people without prior cerebrovascular disease, prevents dementia.
这是一篇发表于 2006 年的 Cochrane 综述更新版（McGuinness 2006），之前曾于 2009 年更新（McGuinness 2009）。高血压是痴呆的一个危险因素。观察性研究表明，降压治疗与认知障碍和痴呆的发生率降低有关。已有明确的证据支持在中风后进行抗高血压治疗。
评估在没有脑血管疾病病史的人群中，药物治疗高血压是否可以预防认知障碍或痴呆。
我们检索了 Cochrane 痴呆症和认知改善组的专业注册库、CENTRAL、MEDLINE、Embase、另外三个数据库以及许多试验注册库和灰色文献来源，最近一次检索是在 2020 年 7 月 7 日。
我们纳入了随机对照试验（RCTs），其中药物干预高血压的治疗时间至少为 12 个月。我们排除了在非高血压参与者中进行降压药物干预的试验。我们还排除了仅在中风患者中进行的试验。
两位作者独立评估了试验质量并提取了数据。我们联系了研究作者以获取更多信息。我们收集了关于痴呆、认知下降、血压变化、不良反应和生活质量的信息。我们使用 GRADE 评估证据的确定性。
我们纳入了 12 项研究，共 30412 名参与者，对这些研究进行了综述。八项研究比较了积极治疗与安慰剂。在四项非安慰剂对照研究中，两项比较了强化降压与标准降压。最后纳入的两项研究比较了不同类别的降压药物。研究持续时间从一年到五年不等。四项报告痴呆发生率的安慰剂对照试验的综合结果表明，降压治疗组与安慰剂组在痴呆风险方面没有差异（236/7767 与 259/7660，比值比（OR）0.89，95%置信区间（CI）0.72 至 1.09；极低确定性证据，因研究局限性和间接性而降级）。五项报告 Mini-Mental State Examination（MMSE）变化的安慰剂对照试验的综合结果可能表明降压治疗有适度益处（平均差异（MD）0.20，95%CI 0.10 至 0.29；极低确定性证据，因研究局限性、间接性和不精确性而降级）。由于研究局限性和间接性，两种认知结局的证据确定性都降级了。总的来说，研究持续时间太短，无法期望两组之间痴呆发生率有显著差异。痴呆和认知下降是大多数研究的次要结局。其他偏倚来源包括：安慰剂对照试验中安慰剂组使用降压药物；未能达到招募目标；以及出于安全考虑提前终止研究。报告结果的安慰剂对照试验的荟萃分析发现，治疗组（n = 8973）与安慰剂组（n = 8820）之间的收缩压平均变化为-9.25mmHg（95%CI-9.73，-8.78），舒张压平均变化为-2.47mmHg（95%CI-2.70，-2.24）（均为低确定性证据，因研究局限性和不一致性而降级）。三项试验 - SHEP 1991、LOMIR MCT IL 1996 和 MRC 1996 - 报告称，活性治疗组的不良反应导致更多的停药，而安慰剂组则更少。Syst Eur 1998 中接受积极治疗的参与者因副作用而停止治疗的可能性较小，而 HYVET 2008 中接受积极治疗的参与者报告的“严重不良事件”比安慰剂组少。SCOPE 2003 中没有证据表明两组之间的停药率有差异，而 Perez Stable 2000 和 Zhang 2018 的结果则不清楚。由于存在异质性，无法进行荟萃分析。五项安慰剂对照试验提供了生活质量（QOL）数据。由于存在异质性，同样无法进行荟萃分析。SHEP 1991、Syst Eur 1998 和 HYVET 2008 报告称，在没有脑血管疾病病史的人群中，降压治疗与安慰剂治疗相比，在整个研究期间，QOL 指标没有差异。SCOPE 2003 的子研究（Degl'Innocenti 2004）显示，与安慰剂组相比，积极治疗组的 QOL 指标下降幅度较小。LOMIR MCT IL 1996 报告称，在 12 个月时，一组活性治疗的 QOL 指标有所改善，而另一组则有所恶化。
关于高血压治疗对痴呆和认知能力下降的影响，还没有高质量的随机对照试验证据。本综述纳入的研究提供了低确定性证据（主要因研究局限性和间接性而降级），表明在没有先前脑血管疾病的人群中，药物治疗高血压与对照组相比，认知能力下降程度较小。这种差异低于临床认为有意义的水平。本综述纳入的研究还提供了非常低确定性证据，表明在没有先前脑血管疾病的人群中，药物治疗高血压可以预防痴呆。
