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A calcium ‘leak’ in brain cells may be part of the mechanism involved in heart failure-related cognitive decline. Image credit: shunli zhao/Getty Images.
  • More than 64 million people globally have heart failure.
  • Cognitive impairment is a common complication in people with heart failure.
  • Researchers from Columbia University believe a small calcium leak inside the brain’s neurons is why heart failure may lead to cognitive decline.
  • Scientists have also developed an experimental drug aimed at ‘plugging’ the calcium leak to help slow heart failure progression.

Over 64 million people worldwide are impacted by heart failure — an incurable cardiovascular condition where the heart cannot efficiently pump blood throughout the body.

People with heart failure are at a higher risk for certain complications, including shortness of breath, arrhythmia, kidney issues, and fluid build-up in the lungs, abdomen, feet, and legs.

Additionally, cognitive impairment is a common complication in people with heart failure.

Now, researchers from Columbia University believe a small calcium leak inside the brain’s neurons may be why heart failure could lead to cognitive decline.

Additionally, scientists have developed an experimental drug to “plug” the calcium leak and potentially slow the progression of heart failure.

This study was recently published in the journal Nature Neuroscience.

According to Dr. Andrew R. Marks, chair of the Department of Physiology & Cellular Biophysics at Columbia University Vagelos College of Physicians and Surgeons and lead researcher of this study, the team decided to study a potential correlation between heart failure and cognitive decline based on what they already knew about the ryanodine receptor type 2 (RyR2)/intracellular Ca2+ (calcium) release channel.

“The RyR2 channel is present in both [the] heart and brain, so I reasoned that since the channel is leaky in the heart due to systemic stress of heart failure it might also be leaky in the brain,” he explained for Medical News Today.

RyR2 is an encoded protein found in cardiac muscle. As part of the intracellular calcium channel, it helps supply that particular mineral to the muscles in the heart.

“Calcium is required to activate muscle contraction in the heart and for signaling in the brain, so calcium is fundamental to both heart and brain function,” Dr. Marks pointed out.

In this study, Dr. Marks and his team used a mouse model to research their hypothesis. Researchers found in mice with heart failure, calcium leaks in the brain’s neurons led to cognitive impairment.

Additionally, scientists examined the brains of deceased people with heart failure. Upon examination, they found those brains also contained leaky calcium channels, suggesting the leak may have caused cognitive impairment in those individuals.

“Importantly, based on our findings, doctors may want to carefully examine their heart failure patients for cognitive impairment and follow this since heart failure is progressive,” Dr. Marks said. “The doctors could assess whether cognitive impairment in their patients is affecting their ability to follow doctors’ orders and take their medications.”

During the study, Dr. Marks and his team also found that an experimental drug called Rycals designed by Marks’ laboratory could be used to “plug” the calcium leak and potentially slow heart failure progression.

“Rycals fix the leak in RyR channels and are in clinical trials at the Mayo Clinic and at the AMC in Amsterdam for an inherited form of exercise-induced sudden death,” Dr. Marks said. “Depending on the results of this trial they could be available in a year or two.”

MNT also spoke with Dr. Richard Wright, a cardiologist at Providence Saint John’s Health Center in Santa Monica, CA, not involved in the research, about this study.

He commended the investigators on finally coming up with a grand unifying theory of different disease states, which has been in the works for decades.

“It’s been known for many years that people with chronic heart failure are weak and they have trouble breathing,” Dr. Wright explained. “And, as was pointed out in this article, frequently they have cognitive dysfunction compared to their peers.”

“Here Dr. Marks’ team is trying to come up with a unifying theory to explain all these different changes that occur in heart failure patients and I think they’ve struck the mark. I think this concept that calcium overload is a unifying mechanism to explain not only the heart’s dysfunction, but skeletal muscle dysfunction, diaphragm dysfunction, and as the point of the article, brain dysfunction as well, I buy into it.”

– Dr. Richard Wright

Dr. Wright commented he was very excited to hear about a compound developed in the research team’s laboratory that has been shown to beneficially affect these changes.

“We’re at the dawn of a new era and that era is what I would call designer molecules,” he said. “We’ve already seen it now in amyloidosis, we’ve seen it in hypertrophic cardiomyopathy, where you can design molecules that alter pathologic changes of proteins.“

“They have these substances developed in their lab that help circumvent these changes that help avert the calcium overload inside the neurons in the brain and inside the heart cells and inside skeletal muscle cells that could make a huge impact on the outcomes of our patients.”

However, Dr. Wright did state more research still needs to be conducted as most of the data in this article was from a mouse model.

“Sometimes we get misled because humans are not mice,” he added. “But they’ve done a very good job of trying to circumvent that and going to the trouble of using pieces of brains from autopsies to prove their point, which I think is very real.”

Other study limitations include the fact that the sample of human brains analyzed by the researchers was small, and that the control group in this study was made out of participants much younger than the individuals who had experienced heart failure and cognitive decline.

Cognitive impairment — also called mild cognitive impairment — occurs when a person has trouble completing everyday tasks requiring brain-related skills like memory and thinking.

Examples of cognitive impairment include:

  • forgetfulness
  • missing calendared events
  • not knowing how to get to places you go all the time
  • trouble following a conversation
  • difficulty making decisions
  • inability to finish tasks or follow instructions

Those with mild cognitive impairment may also experience mental health changes, including depression, anxiety, and anger.

There are a number of different causes for cognitive impairment, including certain diseases, prescription medications, and infections.

People with mild cognitive impairment are also at a higher risk for developing different types of dementia, such as Alzheimer’s disease.