Can This Common Class Of Drugs Alleviate Cognitive Impairment?

Research indicates that midlife hypertension is linked to dementia and cognitive impairment. But, whether primary or secondary antihypertensive treatment can help curb such neurocognitive syndromes remains to be elucidated, with various meta-analyses and randomized clinical trials demonstrating mixed results.

In an attempt to determine the true relationship between blood pressure control and risk of dementia and cognitive impairment, researchers publishing in JAMA performed a meta-analysis, with 12 randomized clinical trials (n=92,135) making the cut for inclusion.

Here's a closer look at the issue.

Recent clinical trials

Findings on the role of antihypertensive treatment in dementia and cognitive decline can be murky, as demonstrated by the results of two recent clinical trials.

In the SPRINT MIND randomized clinical trial, researchers examined antihypertensive treatment target blood pressures of less than 120 mmHg vs 140 mmHG in 9,361 adults with hypertension and found no significant difference in dementia risk. The researchers did find, however, that targeting blood pressures with drugs may help decrease the risk of mild cognitive impairment (MCI), which is defined as a liminal state between normal cognitive aging and dementia.

“There is some indication that intensive BP [blood pressure] control may be beneficial,” the authors wrote. “This is the first trial, to our knowledge, to demonstrate an intervention that significantly reduces the occurrence of MCI, a well-established risk factor for dementia, as well as the combined occurrence of MCI or dementia.”

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On the other hand, results of the HOPE-3 clinical trial indicated that in 2,361 patients, long-term blood pressure control randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg), rosuvastatin (10 mg), or placebo failed to lower cognitive decline in the elderly.

Meta-analysis findings

The JAMA meta-analysis, with 12 randomized clinical trials detailing the incidence of dementia, found that lowering blood pressure with antihypertensive agents, compared with control, was associated with a composite dementia or cognitive impairment outcome in 7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years—a statistically significant difference.

The average age of participants was 69 years, with 42.2% of the study population women. The average systolic blood pressure and diastolic blood pressure readings at baseline were 154 mmHg and 83.3 mmHg, respectively.

Therapeutic reductions in blood pressure were significantly related to a decreased risk of dementia or cognitive impairment. Specifically, absolute risk reduction of dementia was 0.39%, and absolute risk reduction of cognitive decline was 0.71%. Cognitive test scores, however, did not change with reductions in blood pressures via drugs. Overall, during an average followup of 4.1 years, the overall risk of developing dementia/cognitive impairment was 7.0% on antihypertensive treatment vs 7.5% with the control group—a small but statistically significant difference.

The researchers stressed that the benefit of lowering blood pressure with antihypertensives with regard to dementia or cognitive impairment in clinical trials is minimal—especially when compared with that of stroke risk reduction.

“The causes of neurocognitive syndromes are more heterogeneous than stroke, including Alzheimer disease and other causes, and the population-attributable fraction of hypertension for dementia is lower than that reported for stroke based on indirect comparison of studies,” wrote the authors. “In addition, the association of hypertension with neurocognitive syndromes, mediated through chronic covert vascular damage (ischemia, microhemorrhage, or atrophy), appears to have an extended time lag between cause and clinical consequence, although dementia may be a complication of acute stroke.”

As for why treatment for hypertension did not affect cognitive test scores, the investigators hypothesized that none of the clinical trials reported dementia as a primary endpoint. To determine the effect, high-powered, simple trials with clinically important outcomes need to be performed to determine the benefit of preventive interventions.

The investigators wrote that the results of the current study could translate into a public health benefit. “Effective screening for and management of hypertension is essential for reducing premature dependence from dementia,” they concluded. “Although the lower risk associated with blood pressure treatment is modest for an individual, the effect at a population level, given the incidence of dementia in an aging population, may be considerable. Rates of blood pressure control are low, even in high-income countries, but especially in middle- and low-income countries, which carry the largest burden of dementia,” they added.

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