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Hughes D, Judge C, Murphy R, et al. Association of Blood Pressure Lowering With Incident Dementia or Cognitive Impairment: A Systematic Review and Meta-analysis. JAMA. 2020 May 19;323(19):1934-1944. doi: 10.1001/jama.2020.4249. (Systematic review)
Abstract

Importance: The benefit of blood pressure lowering for the prevention of dementia or cognitive impairment is unclear.

Objective: To determine the association of blood pressure lowering with dementia or cognitive impairment.

Data Sources and Study Selection: Search of PubMed, EMBASE, and CENTRAL for randomized clinical trials published from database inception through December 31, 2019, that evaluated the association of blood pressure lowering on cognitive outcomes. The control groups consisted of either placebo, alternative antihypertensive agents, or higher blood pressure targets.

Data Extraction and Synthesis: Data were screened and extracted independently by 2 authors. Random-effects meta-analysis models were used to report pooled treatment effects and CIs.

Main Outcomes and Measures: The primary outcome was dementia or cognitive impairment. The secondary outcomes were cognitive decline and changes in cognitive test scores.

Results: Fourteen randomized clinical trials were eligible for inclusion (96 158 participants), of which 12 reported the incidence of dementia (or composite of dementia and cognitive impairment [3 trials]) on follow-up and were included in the primary meta-analysis, 8 reported cognitive decline, and 8 reported changes in cognitive test scores. The mean (SD) age of trial participants was 69 (5.4) years and 40 617 (42.2%) were women. The mean systolic baseline blood pressure was 154 (14.9) mm Hg and the mean diastolic blood pressure was 83.3 (9.9) mm Hg. The mean duration of follow-up was 49.2 months. Blood pressure lowering with antihypertensive agents compared with control was significantly associated with a reduced risk of dementia or cognitive impairment (12 trials; 92?135 participants) (7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years; odds ratio [OR], 0.93 [95% CI, 0.88-0.98]; absolute risk reduction, 0.39% [95% CI, 0.09%-0.68%]; I2 = 0.0%) and cognitive decline (8 trials) (20.2% vs 21.1% of participants over a mean trial follow-up of 4.1 years; OR, 0.93 [95% CI, 0.88-0.99]; absolute risk reduction, 0.71% [95% CI, 0.19%-1.2%]; I2 = 36.1%). Blood pressure lowering was not significantly associated with a change in cognitive test scores.

Conclusions and Relevance: In this meta-analysis of randomized clinical trials, blood pressure lowering with antihypertensive agents compared with control was significantly associated with a lower risk of incident dementia or cognitive impairment.

Ratings
Discipline Area Score
Family Medicine (FM)/General Practice (GP) 7 / 7
General Internal Medicine-Primary Care(US) 7 / 7
Internal Medicine 6 / 7
Geriatrics 6 / 7
Neurology 6 / 7
Public Health 6 / 7
Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

This meta-analysis sheds more light on the benefit of lowering blood pressure in older patients to reduce onset of cognitive decline and dementia. Although the follow-up was relatively short (about 4 years) after initiating anti-hypertensive treatment, these results are promising. Clinicians should consider lowering blood pressure in older patients while observing potential adverse effects such as hypotension.

Geriatrics rater

A meta-analysis looking at blood pressure control in late life and the development of dementia. A clinically very small statistically significant effect was found with no difference in actual cognitive scores. The take-home message: In our older patients, we should control their blood pressure for reasons other than dementia prevention. Whether or not blood pressure control is helpful for preventing dementia if started in midlife was not addressed in this study. I do not think the results of this study will change our practice or our expectations.

Geriatrics rater

Frail elderly persons rarely participate in BP-lowering trials, so not generalizeable to all groups. Perhaps the biggest benefit occurs midlife.

Geriatrics rater

So, lowering BP reduces the risk for dementia, but how much to lower? This well done analysis demonstrates a bias toward reducing cognitive decline, but leaves us unclear as to how aggressively to treat. Studies relating to `non dippers` (individuals whose BP does not reduce at night) have demonstrated increased white matter lesions, supporting the adverse effect of hypertension on the brain. So treat we should, but we need to look elsewhere for answers to how aggressively to lower BP, particularly in the elderly.

Geriatrics rater

Meta-analysis suggesting very small effect size on risk for dementia or cognitive impairment (NNT=256) or cognitive decline (NNT=141) with anti-hypertensive therapy. To facilitate meaningful shared decision-making, it would have been helpful for the authors to also provide potential harms and costs with these small benefits. Understanding the dementia subtypes (AD, vascular, etc) would also be illuminating as one would expect a larger effect size in reducing vascular dementia. With a myriad other cardiovascular and cerebrovascular benefits for anti-HTN therapy, however, these results are unlikely to alter current blood pressure management prescribing patterns.

Internal Medicine rater

Studies of the effect of BP control on dementia are conflicting. This large meta-analysis found that the preponderance of evidence suggests that treating HTN has a modest but statistically significant reduction in dementia and cognitive impairment.

Internal Medicine rater

This meta-analysis, although it included high-quality placebo-controlled trials, does not yield additional value to the medical community. The vast majority of included trials did not achieve statistically significant results. Testing for cognitive impairment and dementia was not universal. Clinicians understand the role of blood pressure and vascular dementia, and this did not suggest any additional new insight.

Internal Medicine rater

It looks like the benefit is real but small.

Neurology rater

The epidemiologic association of hypertension and dementia and hypertension treatment and dementia are known. This meta-analysis adds RCT evidence about the reduction of incident cognitive decline and dementia with blood pressure lowering.

Neurology rater

An important meta-analysis that will raise further questions and possibly change treatment re hypertension management and cognitive impairment.

Public Health rater

Almost all providers are seeing patients with hypertension, most of whom are taking medications that are not without risks and adverse effects. We base all of this on the effects of blood pressure on organ damage. One of the effects of hypertension is earlier onset dementia. It is re-assuring to see that a literature review shows that BP-lowering reduces the risk for dementia and cognitive impairment.

Public Health rater

This review points out another possible reason to control blood pressure. Readers should be aware that the average starting blood pressure was over 150. So this review, like many of the trials, does not support lower blood pressure goals. Also, there was no change in cognitive scores, reducing some evidence for a causal mechanism.
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