Treating high blood pressure with medicines to prevent future dementia or problems with memory and thinking

Why this review is important

Observational studies following participants over many years have suggested that high blood pressure is associated with subsequent dementia or new problems with memory and thinking (cognitive impairment). It is important to establish if treating high blood pressure can reduce the risk of dementia and problems with memory and thinking. There is already clear evidence to support the treatment of high blood pressure after stroke. The evidence for treating high blood pressure in the absence of stroke was not as well established when this review protocol was written.

Main findings of the review

We included 12 trials, with a total of 30,412 participants, in this review. Treating high blood pressure with medicines may reduce the risk of dementia and problems with memory and thinking, but we were unable to confirm this using the data we have available. This may be due to shortcomings in the evidence available.

Some participants had side effects from medications, such as falls, that led to them stopping the medications. This is also an important consideration.

Limitations of the review

We were unable to find evidence to confirm that treating high blood pressure with medicines will prevent future dementia or problems with memory and thinking. Based on the evidence available, all we can say is that the methods used in the studies we looked at were not sufficient to answer our study question. In practice, we want to know if treating high blood pressure in mid-life reduces dementia and problems with memory and thinking in later life. These studies were too short in duration to answer this question. They tended to be designed to investigate heart attack and stroke as outcome measures, with memory and thinking tests added on, which means they were less likely to include the numbers of people with problems with memory and thinking necessary to reliably answer the question. In the studies comparing active medicines and placebo (inactive medicine), many people in the placebo groups ultimately did receive active medicine which further complicated the results.

Antihypertensive treatment may prevent new problems with memory and thinking, or dementia, or both, despite the findings of this review. To be more confident in our conclusions, we would need studies that have more distinct treatment and placebo groups, and that treat participants starting at a younger age and with a longer follow-up.

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.

Read the full abstract...
Background: 

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.

Objectives: 

To assess whether pharmacological treatment of hypertension can prevent cognitive impairment or dementia in people who have no history of cerebrovascular disease.

Search strategy: 

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.

Selection criteria: 

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.

Data collection and analysis: 

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.

Main results: 

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.