Exercise and Blood Pressure Control Help the Brain, But Results May Take Years

Conventional wisdom says what’s good for the heart is good for the brain. Scientists estimate that approximately 45 percent of dementia cases are potentially attributed to modifiable risk factors like high blood pressure or physical inactivity. 

Research shows that getting blood pressure under control may reduce the risk of developing mild cognitive impairment and dementia, while exercise itself boosts cognitive function in older adults. 

Rong Zhang, a professor at UT Southwestern, who studies the impact of exercise and other cardiovascular risk factors on brain aging and Alzheimer’s disease, wanted to know how combining these two interventions would affect cognitive function and brain structure. 

The first results from his randomized trial, published in JAMA Neurology, revealed that two years of controlling blood pressure and cholesterol with medications alongside exercise isn’t enough time to see a boost in cognitive health. His team is  analyzing data to see how these interventions affected brain structure.

Exercise and getting blood pressure and cholesterol under control boost heart health and prevent stroke, ultimately lowering the risk of dementia. “We know that cardiovascular health is essential,” Zhang told Being Patient, adding it takes time for the improvements in heart health to manifest in the brain. “We simply don’t have that time window to observe that.“

Putting exercise to the test

Zhang’s team recruited 513 physically inactive older adults, aged 60 to 85, without dementia who had high blood pressure and a family history of the disease. Some had self-reported cognitive decline, which didn’t reach the threshold for mild cognitive impairment.

Researchers randomized study participants into four different groups: one that received 160 minutes per week of moderate-to-vigorous exercise, another that received medications to control high blood pressure and cholesterol, an exercise and medications group, and a group that continued following the recommendations of their primary care doctor.

Over two years, the participants stuck with their treatments 85 to 91 percent of the time. Zhang’s team measured the Preclinical Alzheimer’s Cognitive Composite Score, which detects slight changes in overall cognitive ability in healthy older adults, as the main measure to test whether the treatment led to cognitive improvements.

When the researchers compared the treatments to the usual care group, there were no enhanced overall cognitive benefits. The results were consistent across eight other memory and thinking tests — no group showed a clear advantage. All the participants, even those in the control group, showed similar small improvements in cognitive function. 

Zhang said that people in all the treatment arms may have improved over time simply because they had practice taking the cognitive tests. In the long run, he would expect all the older participants to experience some level of cognitive decline. In a longer study, he believes, the individuals receiving exercise and medications longer would score higher. “They probably will maintain that cognitive function,” he said, while the standard care group starts to decline.

Less surprisingly, the participants that received blood pressure lowering medications and statins showed a larger drop in blood pressure and cholesterol than the usual care group. 

Some people may experience muscle pain as a side effect from statins, raising concerns that it may impact their ability to exercise. The results of this trial provide some assurance, Zhang said, as they didn’t see any adverse effects from people taking high doses of statins while they exercised.

Why didn’t this trial find a benefit?

Rather than suggesting that exercise doesn’t matter, these findings suggest that preserving and improving brain health might require longer interventions or targeting multiple lifestyle factors together.

Since they didn’t use biomarkers of Alzheimer’s, some participants in their study — including those reporting subjective cognitive decline — may not actually be at high risk of developing Alzheimer’s or other dementias. 

“People are notoriously not great about actually knowing how much decline they’ve had,” Dr. Patrick J. Smith, a clinical psychologist and associate professor at the University of North Carolina at Chapel Hill, who wasn’t involved in the study, told Being Patient. Reporting subjective cognitive decline is “oftentimes more associated with your mood than it is with your actual level of functioning.” 

Still, he lauded the study for the trial design. Using various treatment arms allows researchers to tease out the specific effects of interventions. Even when studies show that targeting exercise or another risk factor alone doesn’t provide a cognitive boost, multidomain interventions, such as FINGER and POINTER, show more success. 

Unlike those studies, this trial zeroed in on how individual interventions worked and whether combining them proved more beneficial. Applying this to multidomain trials could help scientists figure out what components work best together, and design better interventions. 

The researchers suggested that the study was too small to detect subtle changes in cognitive decline. While there wasn’t a measurable benefit across the treatment group, individuals varied widely in their responses. “We may just be glossing over some big differences between people in terms of how much they benefit,” Smith said.

Dr. Jessica Caldwell, a neuropsychologist and one of the principal investigators of the Wisconsin Registry for Alzheimer’s Prevention study, told Being Patient that physical inactivity and high blood pressure are midlife risk factors that need to be addressed decades earlier to see more cognitive benefit. 

Even if there aren’t immediate cognitive benefits, all the experts who spoke with Being Patient agreed that exercise is still worthwhile and has clear benefits that pay dividends for dementia risk later in life, including reducing the risk of stroke, a major risk factor for cognitive decline and dementia.

Future studies need to follow people over a longer period to see if the treatment leads to a long-term reduction in mild cognitive impairment or Alzheimer’s risk. Perhaps other factors, related to exercise, are really driving cognitive decline. 

“It’s possible that it’s really metabolic functioning,” Smith said, “like your insulin sensitivity and other related factors, as opposed to your cardiovascular fitness.”

Even though the two-year study found no change in cognitive outcomes, Zhang’s confident a longer study would show benefits. As his team continues to analyze imaging data from the study, Zhang is optimistic about what they might discover.