The Brain and the Heart: Understanding How to Prevent and Treat Alzheimer’s Disease

In the United States, one in three people 65 and older die with Alzheimer’s disease or another form of dementia. Today, there are more than 6 million people in the country living with the disease. Experts predict that number will rise to almost 13 million by 2050.

For Dr. Michelle Mielke, these numbers motivate the questions she has devoted her career toward answering. Questions like: Can we predict who will develop Alzheimer’s disease (AD) and other dementias? Can we identify biomarkers to predict disease development early? What are the most promising treatment targets?

And importantly, how do sex and gender affect risk factors, symptom onset, and disease progression? In the United States, two-thirds of adults with AD are women, and experts still ponder how much of this gender difference can be attributed to the average longer lifespan of women compared with men and how much stems from biological or environmental factors.

“As we have learned with many diseases and conditions, women and men can have different risk factors, different mechanisms underlying disease, and different responses to treatments,” said Mielke, chair of the Department of Epidemiology and Prevention and a professor of epidemiology, gerontology and geriatric medicine, and neurology at Wake Forest University in North Carolina. “We need to continue studying sex-and-gender differences in Alzheimer’s disease to uncover what’s best for women and men.”

Women’s Health Research at Yale Director Carolyn M. Mazure, PhD, invited Dr. Mielke to discuss her research on this topic at a virtual Grand Rounds presentation in April sponsored by the Women’s Behavioral Health Division of Yale School of Medicine’s Department of Psychiatry.

Raised Risks for Some Women

Before leaving her faculty position at the Mayo Clinic in March, Dr. Mielke was the senior author of a study published in the journal Neurology, finding that the link between cardiovascular conditions, risk factors for cardiovascular disease (CVD), and cognitive decline in mid-life was stronger for women than for men. This was true even though men generally have more heart conditions and cardiovascular risk factors in mid-life, such as high blood pressure, diabetes, and obesity.

“There is still a lot of work to be done about the mechanistic, biological underpinnings of Alzheimer’s disease,” Mielke said. “But what our study and prior research are telling us is that what’s good for the heart is good for the brain. And this might be even more true for women.”

Reasons for this difference could include the influence of sex hormones on heart health and cognition as well as social differences that often vary between women and men, such as exercise and education. Women are also more likely than men to have types of CVD that decrease small vessel blood flow to the heart without a co-occurring cholesterol blockage in the larger arteries. Such sex differences in the biology underlying CVD might affect cognition differently for women and men.

Dr. Mielke said the data increasingly point toward a need to treat cardiovascular-related conditions early and to more closely follow women with these conditions over time to optimize both heart and brain health. For example, women with preeclampsia, a condition of high blood pressure in pregnancy that can damage organs and threaten the pregnancy and the life of the mother, often have worse cognition in their 60s and 70s.

“If we know that these associations exist between heart health and cognition, even if we do not yet know the precise biological connection, we can follow women with these conditions more closely,” she said. “And see if by treating their cardiovascular disease, maybe the cognitive issues can be prevented.”

The Role of Hormones

Similarly, Dr. Mielke’s team has demonstrated how the surgical removal of a woman’s ovaries — and thus the hormones they produce — before natural menopause is associated with poorer cognition and dementia. She cautioned against the unnecessary removal of ovaries for women without ovarian cancer or who are not at high risk of developing the disease. She also pointed to a larger lesson about how to perceive hormonal fluctuations across the lifespan.

“Some have said that menopause is a risk factor for dementia, but I don’t believe that is correct,” she said. “All cisgender women go through menopause. To blame menopause would be like saying puberty is a risk factor for heart disease.”

Instead, Mielke likens menopause to a “stress test” in which evidence is starting to show that women with more severe menopause symptoms, such as intense hot flashes, are more susceptible to developing cardiovascular disease and potentially at a higher risk for AD or vascular dementia.

Screening for Signs

Mielke’s work also focuses on identifying blood-based biomarkers for AD that can aid diagnosis through primary care as opposed to the more expensive, harder-to-access visits to specialists with more expensive tests, such as neuroimaging or a lumbar puncture.

At the same time, Mielke wants medical providers to understand how such a test could be effectively utilized in the general population, particularly as other diseases and conditions might affect the levels of certain biomarkers and how to interpret the results.

For example, experts have long focused on proteins called beta-amyloids that can collect between brain cells and form plaques that disrupt brain function. Another target protein called tau can form tangles inside neurons that prevent proper communication between the cells. Although previously not feasible, with new technology beta-amyloids and tau can now be measured in the blood. However, recent evidence suggests that people with chronic kidney disease have higher levels of beta-amyloids and tau than people without kidney disease, even though they do not appear to have a greater risk for AD. Similarly, other groups of people develop high levels of these blood markers but no symptoms of cognitive dysfunction.

In addition, if an accurate predictor of AD were to be established, Mielke stressed the importance of understanding how to present the results of such a test given the implications of a positive biomarker. For example, how might this new knowledge affect an individual’s mental health or their ability to obtain life insurance?

“It would be phenomenal if we could eventually develop an effective method for screening potential susceptibility to Alzheimer’s disease, as this could lead to possible preventive strategies,” she said. “But, in any event, we would definitely need to educate health care providers about the meaning of a positive biomarker, so they understand how to discuss with patients what this means.”

Beyond Biology

Research has identified differences in the way Alzheimer’s disease affects the brains of women and men. For example, the women who develop AD experience higher neurodegeneration, a condition in which brain cells become damaged or die at accelerating rates. Dr. Mielke also stresses the importance of discussing how environment and experience filtered through gender contribute to disease.

A 2019 study from UCLA found that mothers between the ages of 60 and 70 who never participated in the wage-base labor force showed far more rapid declines in memory than women who worked. This was true for married women and single women who experienced a prolonged period without paid employment.

The authors suggested that mental stimulation and financial and social benefits could have contributed to the observed difference. With such factors in mind, Dr. Mielke has helped form a group on sex and gender at the Alzheimer’s Association to take a global perspective on whether and how sociocultural factors contribute to the disease.

“We have had so many changes in society over the last 50 years,” Mielke said. “It’s important to understand what effect these social transitions might have, so we can better protect people from this disease.”

In our book, Running All Over the World, Our Race Against Early Onset Alzheimer’s I talk about the relationship between the heart and the brain.  Here is a chapter for your reading pleasure.

RunningwithCat.com

Chapter 14

Does Running Slow Down Alzheimer’s?

What is good for the heart is also good for the brain. —Robert Roca

As we were running all over the world, dealing with physical, logistical, and financial issues, sometimes I couldn’t help asking myself, “Is this really helping Catherine?”

Before I answer that question, here’s some context. According to the Alzheimer’s Association, an estimated 5.8 million Americans have the disease. Alzheimer’s doesn’t just cause dementia: It kills more Americans than breast cancer and prostate cancer combined. Since 2000, deaths from the biggest killer, heart disease, have gone down 7.8 percent while deaths from Alzheimer’s have gone up 146 percent.

Many people think of Alzheimer’s as genetic bad luck, but scientists have also been studying associations between Alzheimer’s and a variety of lifestyle choices. In the report, “Dementia and Risk Reduction: An Analysis of Protective and Modifiable Factors,” Alzheimer’s Disease International identified four categories of risk factors: developmental, psychological, lifestyle, and cardiovascular- all of which have been repeatedly linked to Alzheimer’s.

Most doctors and nurses who treat Alzheimer’s patients now believe that common-sense lifestyle adjustments can help people avoid the disease or slow its progression. As Robert Roca, vice president of medical affairs at Baltimore’s Sheppard Pratt Health System said in an interview with the Woman’s Brain Health Initiative, “The good news is that if you take simple steps that are beneficial for your overall health, you can reduce your risk.”

We’ve all seen the PSAs about quitting smoking and the ads telling us to eat this or that “heart-healthy” food, but partly because we know less about it, There has been less public education about Alzheimer’s. As it turns out, some of the same choices and habits that protect against heart disease (including regular exercise) also protect against Alzheimer’s. “What is good for the heart,” Roca said, “is also good for the brain.”

Ann McKee, the associate director of Boston University Alzheimer’s Disease Center, agreed. “The brain and the heart actually have a lot in common. Both organs are responsive to what is going on in the rest of the body—and to our life experiences.”

When it comes to treating the symptoms of Alzheimer’s, there are five FDA-approved drugs. Unfortunately, according to Robert Stern, director of the clinical core at Boston University’s Alzheimer Center, “Medications can bring about some improvement for some people some of the time, but they don’t modify the course of the disease.”

In fact, according to David Bennett, director of the Alzheimer’s Disease Center at the Rush University Medical School, “The best current tool involves not taking medication but building up resilience.”

Bennett said that people who got more education early in life have a greater amount of “cognitive reserve” a technical term for a variety of cognitive skills which can help them compensate for the damage to their brains. And no matter how educated someone is, they can improve their resilience by learning new skills. In an article for Scientific American Mind called “Banking Against Alzheimer’s,” Bennett wrote steps that we can all take to age-proof our brains to make them more resistant to dementia: remaining socially and intel- lectually active, achieving goals that we set for ourselves, and even helping others. I would say that our nomadic lifestyle forces us to do all those things.

It’s hard to say exactly how much benefit Catherine got from our constant flow of new experiences, but Yaakov Stern, a professor of neuropsychology at Columbia University’s Taub Institute for Research on Alzheimer’s Disease and the Aging Brain who has published several papers on cognitive reserve, has said that “…experiences acquired over a lifetime can stave off dementia—often for several years.”

What’s easier to say is the benefit she got from regular cardiovascular exercise. Aerobic exercise protects against Alzheimer’s through its impact on the heart, but it can also slow down the deterioration of the brain. In a neuroimaging study published in the Annals of the New York Academy of Sciences in 2007, Bonita L. Marks, a professor in the department of exercise and sport science at the University of North Carolina at Chapel Hill, showed that greater aerobic fitness was associated with more white matter integrity in several regions of the brain. A 2016 paper published in Alzheimer’s Dementia, by Dane Cook (not the comedian), but a professor of kinesiology at the University of Wisconsin at Madison) showed that regular physical activity can protect against temporal lobe atrophy.

What does “regular physical activity” mean? One book I read called Cured has an entire section on Alzheimer’s and exercise. It turns out that merely exercising several times a week is not enough. It’s great to get your ten thousand steps a day, but to reap the true benefits, you need to participate in intensive exercise for at least thirty minutes at least four times a week. Other articles I read recommended an hour day at least six days a week.

The science behind the need for this much exercise is complicated, but the bottom line is that you need to get your heart rate up, you need to sweat, and you need to be worn out when you’re finished. They say that it reduces the inflammation in the brain, which they feel is the root of the problem. As time goes on, I have read more and more about inflammation, and I have adjusted Catherine’s supplements to help with that issue. Since I’m not doing a clinical trial, I can’t give a scientific answer as to whether running helps, but it certainly doesn’t hurt.

Our travels, coupled with our exercise routine, have given us the ability to run marathons and other various race distances so far. It will give us the ability to continue this lifestyle as long as feasible.

During our latest stay in ATL, Catherine gave another 8 tubes of blood for a study to see if they will be able to use ones own blood to foresee the possibility of someone getting ALZ later in life.