Heart Function Tied to Brain Function

Pauline Anderson

November 08, 2017

Lower cardiac output has been tied to poorer cerebral blood flow (CBF) in the temporal lobes of older adults without heart failure, a finding that adds to a growing body of research linking heart health to brain health.

The associations were statistically independent of key covariates, including vascular risk factors, cardiovascular disease (CVD), atrial fibrillation, and atrophy.

The study is part of a growing body of research demonstrating the strong connection between heart and brain health.

"Researchers know a lot about preventing and managing most forms of heart disease, but not how to prevent Alzheimer's disease and dementia," Angela Jefferson, PhD, professor of neurology, and director of the Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, told Medscape Medical News

Dr Angela Jefferson

"This research, which links heart function to brain function, is especially important because it suggests that we can use knowledge about managing heart health to treat risk factors for memory loss in older adults, perhaps before memory loss or other cognitive symptoms develop."

The study was published online November 8 in Neurology.

First Evidence

The brain accounts for only 2% of total body weight but receives 12% of cardiac output. Prior research shows patients with severe heart failure have poor cardiac function and lower blood flow in the brain.

However, it's believed that blood flow to the brain is preserved in those without heart failure because of a complex autoregulatory control system that maintains constant blood supply to the brain in both resting and acute conditions.

"Our results are among the first evidence in aging adults who don't have heart failure that these complex regulation processes may be vulnerable and less effective as we get older," said Dr Jefferson.

The analysis included 314 persons  (mean age, 73 years; 59% men) who participate in the Vanderbilt Memory & Aging Project, a longitudinal study investigating vascular health and brain aging. Study participants did not have heart failure, clinical dementia, or stroke.

Of the 314 participants, 39% had mild cognitive impairment (MCI), which increases the risk of developing dementia or Alzheimer's disease, while the remaining participants had normal cognitive function.

Researchers measured the cardiac index — the amount of blood flowing out of the heart, adjusted for body size — by using echocardiography. They measured blood flow in the brain with MRI.

They adjusted for age; education; race/ethnicity; Framingham stroke risk profile score, which includes systolic blood pressure, antihypertensive medication use, diabetes mellitus, smoking status, left ventricular hypertrophy, CVD, and atrial fibrillation; APOE ε4 allele status; cognitive diagnosis; and regional tissue volume.

The researchers found that in the entire cohort, lower cardiac index was associated with lower resting CBF in the left (β = 2.4; P = .001) and right (β = 2.5; P =0.001) temporal lobes, areas critical for memory processing. The magnitude of effects for the left and right temporal lobes corresponded to an estimated 15 to 20 years of advancing age, respectively.

"This estimate was determined by first defining how 1 year of aging relates to blood flow in the brain," said Dr Jefferson. "Next, we compared the effect of 1 year of aging to the effect of lower cardiac index."

The investigators found that cardiac index was unrelated to CBF in other brain regions (P  > .10).

Impact on the Brain

Researchers then analyzed the MCI and normal cognition groups separately. They found that in the MCI group, the effects were not statistically significant whereas in the cognitively normal group, the effects were significant in several brain areas.

"We saw significant results throughout the brain, including the left and right hemisphere, the frontal lobe, and the occipital lobe, but the largest, most robust effects were in the left and right temporal lobes, the region of the brain where Alzheimer's disease first develops," said Dr Jefferson.

The brain has a network of small vessels that are integral to brain function, supplying oxygen and nutrients to brain cells and removing waste products and toxins. It could be that this network in the temporal lobes is more vulnerable to reductions in cardiac blood flow, said Dr Jefferson.

"We speculate that the intricate microcirculatory network of very small blood vessels in this region might be vulnerable to subtle, chronic reductions of blood flow from the heart."

In sensitivity analyses excluding participants with atrial fibrillation or prevalent CVD, associations persisted between cardiac index and CBF in the left (β = 2.3; P = .003) and right (β = 2.5; P = .003) temporal lobes.

The null findings persisted in the remaining brain regions (P > .20).

The results underscore the potential importance of maintaining optimal cardiac output. Several interventions will boost cardiac output, including physical exercise and some medications. However, Dr Jefferson cautioned that more information is needed before clinical recommendations to raise cardiac output can be made.

 "We need to explore in more detail whether it's feasible to raise cardiac output in a healthy way, and then we can assess whether such increases have a positive impact on brain health, whether that's improved cognition or blood flow in the brain," she said.

These results won't have a major impact on general recommendations for patients, except to emphasize the importance of healthy lifestyle habits.

"Managing blood pressure and diabetes, maintaining a healthy weight, and regular physical activity are all important for good heart health, which may have important implications for maintaining good brain health," said Dr Jefferson.

New Research Frontier

Commenting on the findings for Medscape Medical News, Dean M. Hartley, PhD, director of science initiatives, Medical and Scientific Relations Division, Alzheimer's Association, said  the investigators are exploring a new line of research that is "highly important."

Dr Jefferson and her colleagues have taken on "a technological challenge," said Dr. Hartley. "They have pushed the envelope in thinking about cardiac MRIs, thinking about multimodel brain imaging, and connecting the two."

Dr Hartley talked about the "cross-talk" between the disciplines of cardiology and neurology being "critical" in moving this field forward.

But he noted some limitations of the research. For example, he said, the study was cross-sectional and the cohort included mostly white men.

Dr Hartley also stressed that the study participants were relatively healthy.

"They did not have cardiovascular disease, which is important. The researchers think there may be alternative mechanisms driving this brain injury, or damage, over time, especially to the temporal lobes, which we know is important for memory."

The researchers pointed to many ways that systemic blood flow might be linked to CBF, although the exact mechanism is still unclear, said Dr Hartley.

One possibility is that the connection between lower cardiac output and lower CBF is due to a compromised sympathetic nervous system, which is responsible for hemodynamic control throughout the body. However, said Dr Hartley, this hypothesis requires further study.

"This study does start to set the ground rules for thinking about this alternative pathway," he said.

The study was funded by the Alzheimer's Association, National Institute on Aging, National Institute of Neurological Disorders and Stroke, American Heart Association, Paul B. Beeson Career Development Award in Aging, Vanderbilt Clinical Translational Science Award, and Vanderbilt Memory & Alzheimer's Center. Dr Jefferson has disclosed no relevant financial relationships.

Neurology. Published online November 8, 2017. Abstract

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