The unexpected link between Alzheimer’s disease and cardiovascular health

An estimated 55 million people worldwide are affected by dementia, of which Alzheimer’s disease is the most common type. As the world’s population ages, the World Health Organization projects that the prevalence of Alzheimer’s will increase fourfold in the next 50 years — eventually, one in 45 Americans will be affected by this devastating and progressive form of cognitive impairment, which can lead to profound memory loss, decline of motor skills, and difficulty reasoning, communicating, and performing basic daily functions.

In the fight to prevent Alzheimer’s disease, a growing body of research has underscored the surprising connection between cardiovascular health and our cognitive function. As research progresses, understanding and addressing cardiovascular risk factors may offer new pathways for Alzheimer’s prevention and treatment.

In 2023, the Alzheimer’s Association and the National Institutes on Aging worked to update the diagnostic and staging criteria for Alzheimer’s to include accumulation of amyloid plaques and tau protein tangles as the primary catalyst for the development of Alzheimer’s disease. Amyloid proteins are naturally occurring in the brain, but in people with Alzheimer’s, they clump together to form plaques. Similarly, tau proteins, also normally present in the brain, become tangled in people with Alzheimer’s.

As these plaques and protein tangles accumulate in the brain over time, they interfere with communication between brain cells, particularly those involved in memory and thinking. This progressive damage leads to the cognitive decline characteristic of Alzheimer’s, affecting memory, reasoning, and other mental functions. “The way we think is by chemical transmission between neurons,” explains Dr. Carl Sadowsky, director of research at Palm Beach Neurology. “The amyloid impairs the neurons’ ability to communicate. That impairment of synaptic function directly relates to cognitive loss. The fewer synapses we have working, the less horsepower the brain has to think — it’s like going from a 250 horsepower car to a 150 horsepower car.”

The presence of amyloid plaques and tau protein tangles in the brain is required to make a diagnosis of Alzheimer’s disease, Sadowsky says. “If a person has memory loss without amyloid or tau proteins in the brain, they may have another form of dementia — but the etiology is not Alzheimer’s disease. Alzheimer’s disease is, specifically, a form of dementia associated with amyloid plaques and tau tangles in the brain.”

However, these components may not tell the full story of how the disease develops. A growing body of research indicates there is also a correlation between cardiovascular health and cognitive health.

Studies suggest that conditions which contribute to cardiovascular disease — like hypertension, diabetes, obesity, high cholesterol, and atherosclerosis — can also raise the risk of cognitive decline and Alzheimer’s disease. A recent meta-analysis of 214 medical studies found that high blood pressure is associated with the development of Alzheimer’s. One such study, by the National Institute on Aging, found that 47 percent of individuals with Alzheimer’s disease also have high blood pressure. The World Health Organization also lists hypertension and diabetes as two conditions which can increase the risk of developing dementia — in fact, having two or more cardiovascular risk factors like high blood pressure and diabetes increases the risk of dementia, including Alzheimer’s, by threefold.

There is also evidence that vascular damage — which can occur as the result of chronic conditions like hypertension, diabetes, atherosclerosis, and high cholesterol — can increase the risk of Alzheimer’s disease. A Neurology study revealed that 80 percent of individuals with Alzheimer’s also had microvascular damage: that is, damage to small blood vessels like arterioles and capillaries which regulate blood flow to various organs, including the brain.

Cardiovascular conditions like hypertension, diabetes, and atherosclerosis, can also result in reduced blood flow throughout our bodies. This can present another potential risk factor for Alzheimer’s disease: According to research published in Vascular Health and Risk Management, individuals with Alzheimer’s experience a 20 percent reduction in blood flow, or often much worse, to specific brain regions compared to healthy individuals.

So, what drives the link between cognitive and cardiovascular health? The connection lies in the cardiovascular system’s role in delivering oxygen and nutrients to the brain. The heart pumps oxygen-rich blood through arteries to all parts of the body, including the brain. Within the brain, a network of blood vessels, known as the cerebral vasculature, branches out to supply oxygen and nutrients to neurons and other cells. This continuous supply of oxygen and nutrients is essential for the brain’s energy metabolism and overall function, supporting activities such as thinking, memory, and movement.

The cardiovascular system also has a critical role in helping to remove carbon dioxide and other waste products from the brain — including the amyloid and tau proteins that characterize Alzheimer’s disease. “Amyloid can be cleared from the brain through the vascular and the glymphatic system, which is sort of like the immune system of the brain,” Sadowsky says. In a healthy person, the glymphatic system works during sleep to move waste products like amyloid and tau proteins out of the brain and into the blood vessels, where they are carried away and metabolized. The vascular system is critical to this process, Sadowsky says: “Without a healthy, functioning vascular system, your body cannot clear amyloid out of the brain.”

In addition to the buildup of amyloid and tau proteins, another defining characteristic of Alzheimer’s is reduced blood flow to the brain, says Dr. Jack Juni, nuclear physician and medical advisor to Stage 2 Innovations and Renew Research. “We can see this with imaging — early on, people start losing blood flow in the temporo-parietal lobes, the area of the brain associated with your sense of identity, place, and time. Then we see reduced blood flow to the frontal lobes, which are associated with advanced thinking, planning, and executive function.” Eventually, says Juni, the whole brain has reduced blood flow. In fact, he says, “by the time a person shows symptoms of Alzheimer’s disease, they may have already gone 15 years with abnormalities or a reduction of blood flow in their brain.”

Far from contradicting the amyloid theory, experts believe that the cardiovascular system’s link to cognitive health can provide a complementary theory of how Alzheimer’s disease develops and advances.

“I am a huge believer of the amyloid hypothesis — but it’s only half of the equation,” says Sadowsky. “The vascular component is critical. When we do pathology on patients who meet the classical definition of Alzheimer’s disease, we find that they all have plaques and tangles. But 90 percent of them also have vascular disease.”

The reduction in blood flow to the brain cited by Juni is also closely linked with the accumulation of amyloid and tau proteins. “There is debate about which happens first,” he says. “But we know that as the amyloid proteins and tau tangles accumulate in the brain, they cause reduced blood flow, which causes further accumulation. It’s a vicious cycle where the protein buildup causes the blood flow to be reduced, and the reduced blood flow causes the protein buildup. In the end, it doesn’t matter which comes first because they both come.”

Sadowsky explains that cardiovascular factors like hypertension, diabetes, high cholesterol, and atherosclerosis are risk factors for dementia that layer over the plaque and tangle pathology of Alzheimer’s.

“There’s a famous study of nuns out of Chicago which showed that if you have plaque and tangle pathology in the brain, you need much less plaque and tangle [to develop Alzheimer’s] if you also have vascular pathology in the brain,” he says. “These are additive pathologies. We know that if we can treat the vascular side of it, we can lessen the impact of the plaque and tangle.”

The link between cardiovascular and cognitive health could provide a beacon of hope, in that it offers us more avenues for intervention. It turns out, what’s good for the heart is also good for the brain.

“We try to get our patients to focus on managing all the risk factors that we know can slow cognitive aging,” says Sadowsky. “Controlling hypertension, controlling diabetes, improving the vascular system, adopting the Mediterranean diet, exercise — all are important to reduce the vascular components of the underlying cognitive loss.” Avoiding smoking, limiting alcohol intake, and taking steps to manage stress and improve sleep can also help lower the risk.

While those lifestyle modifications can help reduce the risk of Alzheimer’s disease, Juni believes it’s also worth considering the need for treatments which directly target blood flow to the brain. “Eating the right diet and exercising — those can help Alzheimer’s disease,” says Juni, “but they are not nearly enough.”

On the other hand, he says, there is evidence that drugs that cause the blood vessels to open up, like statins, can help. “When we talk about cardiovascular risk factors, there’s a tendency to think in terms of lifestyle changes — but I think there needs to be a treatment aspect of this as well,” Juni says. “We need to find ways to affect the small blood vessels and make people aware that they need to get the blood flowing in their head, not just their heart beating.”

As researchers continue to explore the link between cardiovascular health and cognitive function, it could open a promising frontier in Alzheimer’s prevention and treatment, offering renewed hope for millions.