Midlife Hypertension Linked to Late-Life Cognitive Decline

Sufficient evidence exists to show that hypertension in middle age is associated with cerebrovascular damage later in life, but data from clinical trials on whether antihypertensive treatment can improve cognition are lacking, according to a statement issued by the American Heart Association yesterday in Hypertension.

“Dementia is going to be a major threat to world health in the next several decades and currently, about 40 million people worldwide are living with dementia at a cost of $600 billion,” Constantino Iadecola, MD (Weill Cornell Medicine, New York, NY), chair of the document’s writing committee, told TCTMD. “By 2050, this number is going to grow to $2 to $3 trillion.”

In the scientific statement, Iadecola and colleagues review multiple studies and provide an overview of current evidence about how hypertension influences the development of stroke, vascular cognitive impairment, and Alzheimer’s disease.

Structure and Function

The majority of evidence in the review was observational, including cross-sectional and longitudinal studies. However, looking across these studies there was consistent evidence that elevated blood pressure in midlife is associated with altered cognitive function later in life, according to Iadecola.

Studies looking at blood pressure in midlife include:

• The CARDIA study, in which patients had a mean age of 25 at baseline, showed that a higher burden of systolic blood pressure over 25 years was associated with worse performance over several cognitive tests including verbal memory, processing speed, and executive function when the cohort was a mean of 50 years.
• The Honolulu-Asia Aging Study showed that a systolic blood pressure of 160 mm Hg or greater in midlife doubled the risk for poor cognitive function 25 years later.
• The Maine-Syracuse Longitudinal Study found that higher baseline blood pressure was linked to worse cognitive function and a decline in visualization and fluid abilities up to 20 years later.

Hypertension can have a terrible effect on the brain because it is one of the few things that affects both the structure and function of cerebral blood vessels, according to Iadecola. Blood pressure alters the physical structure of vessels and enhances atherosclerosis, making vessels stiffer and less able to conduct blood in a normal fashion. Once blood flow is altered, vessels are no longer able to regulate flow to the areas of the brain that need it, for example, when speaking or having conversations.

“The brain needs a constant delivery of blood flow,” Iadecola said. “If you block blood flow you have a stroke, but if you starve the brain of blood flow . . . you make it insufficient, then you have cognitive impairment.”

Knowledge in Infancy

“It is very well established that if you have high blood pressure in midlife you will do worse cognitively in late life,” Iadecola said. “What we do not know, at least at the standard of evidence-based medicine, is if we treat blood pressure with drugs if it will end up reducing risk for dementia later in life.”

One study that may begin to provide answers is the SPRINT-MIND trial, which is designed to determine the effects of reducing systolic blood pressure on cognitive function. The study hypothesizes that over a period of 5 years, the incidence of all-cause dementia will be lower in participants whose blood pressure is reduced to a lower goal than currently recommended—intensive treatment—compared with patients assigned to standard blood pressure treatment.

“We are looking at high-risk patients to see if intensive blood pressure control for people who already have a lot of cardiovascular risk factors can slow the progression to dementia or even to early mild cognitive impairment,” SPRINT-MIND researcher Jeff D. Williamson, MD (Wake Forest Baptist Health, Winston-Salem, NC), told TCTMD.

However, Williamson said that because this area of research is in its infancy, there are many other areas of important work to be done. For example, research should examine which antihypertensive agents might be best for lowering blood pressure in the context of also reducing cognitive impairment.

“We have done work like this in chronic kidney disease, but there have not been any clinical trials in what I would consider a more important organ, the brain, for which blood pressure lowering agents might be most efficacious at reducing the rate of cognitive decline,” Williamson said.

Both Williamson and the authors of the AHA statement acknowledged that unlike looking at typical cardiovascular outcomes, examining cognitive outcomes is more difficult because these take so long to materialize.

“Many cardiovascular trials were stopped once a cardiovascular endpoint was reached and were not designed with an extension in mind at the beginning that could help address brain function,” Williamson said. That means that results from long-term studies addressing the questions of when to start treatment, what blood pressure levels to achieve, and which medications are best may still be many years away.

Until then, Iadecola said, clinicians must carefully consider each patient on a case-by-case basis.

“In the era of personalized medicine, we need to take into account each patient when considering how much we should reduce blood pressure. The number is not going to be the same for everyone and we must consider how their heart is doing, their kidneys, their brain vessels, and based on those considerations determine how much to lower blood pressure,” Iadecola said. “Precise parameters are not yet available.”

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