Month: April 2021

By 2050, 13.8 million people in the US will likely have Alzheimer’s disease, and two-thirds will be women. The economic cost is staggering, as it is estimated to rise to more than $2 trillion. Women are at the epicenter of this because the economic threat is especially dire for women, given they are an increasingly powerful element of our global economy and the vast majority of unpaid caregivers. Thus, maintaining intact memory starting early in midlife with the transition to menopause is critical not only for women themselves, but also for their families, society, and our economic health.

Preventing memory decline starts in early midlife

The decline in cognitive ability is not limited to neurodegenerative diseases like Alzheimer’s disease (AD), but also part of healthy aging, with consequences for our quality of life. Most studies of aging and cognitive decline, particularly studies of AD, begin in people in their 70s. However, understanding factors that happen earlier in life, and how they impact age-related brain changes, is critical for developing prevention strategies for one of the major public health challenges of our time.

What happens to women’s brains through the transition into menopause?

In addition to chronological aging, women undergo reproductive aging in early midlife: menopause, during which they experience a depletion over time of ovarian hormones such as estradiol, the primary form of estrogen that works in the brain. Our research team and others have demonstrated that estradiol directly relates to changes in memory performance and reorganization of our brain circuitry that regulates memory function. Thus, women and men undergo different aging processes, especially in early midlife when reproductive aging is more critical for women than chronological aging. However, cognitive aging is rarely considered a women’s health issue. This is essential, because viewing brain aging as beginning in early midlife, and understanding the impact of menopause on the brain, will allow for development of strategies to prevent memory loss for women.

On average, women perform better than men on measures of verbal memory, beginning as early as post-puberty. However, women’s advantage for verbal memory performance is reduced with menopause. Many women report increased forgetfulness and “brain fog” during the menopausal transition. All women eventually undergo menopause, but there is a large age range for when it begins (from late 40s to early 60s), and substantial variation in women’s experience of its impact.

Over the last 15 years, an increasing number of studies are mapping out the intricate ways in which menopause affects the brain and what helps maintain intact memory. For example, menopause can affect how brain cells are generated, connect with each other, and even die, and these processes impact brain regions that are critical for memory. Menopause also lowers the level of glucose in the brain, the primary fuel used by brain cells. The brain then looks to other metabolic sources to provide the necessary fuel to function — that is, the brain adapts to a new hormonal environment in order to maintain functioning.

Further, women with other medical conditions like diabetes and hypertension are at increased risk for cognitive decline. Research into understanding this is focusing, in part, on how the brain and body share similar processes to produce energy to function (metabolism), and how blood pressure and other aspects of the vascular system function similarly in the brain and body.

Can hormone replacement treatment help?

Research shows that timing matters. Initiation of hormone replacement (HR) in perimenopause (roughly four to eight years before menopause) or early menopause may have positive effects on brain activity and memory function, although systematic HR trials have not been conducted during perimenopause. Initiation of HR in late menopause may have adverse effects on the brain, and increase risk of disorders like Alzheimer’s disease. Research is critically needed to establish the most effective timing of administration, hormonal formula, dose, route of administration (for example, orally or by skin patch), and duration.

Further, to date much of the HR research has been conducted in healthy women, and little is known about its impact in women with chronic diseases such as diabetes and hypertension. Finally, there may be differences in responses in women who are genetically at high risk for brain disorders, like AD, that show increased benefits for using HR. Research shows us that one size does not fit all, and precision medicine is needed to identify which women may benefit the most. One example is for women with bilateral removal of the ovaries, particularly at a young age, for whom HR has been found to be very beneficial for brain function. In some women HR may not be an option, and alternative mechanisms may need to be identified, such as targeting levels of glucose and other effects associated with estradiol regulation of the brain.

What can women do to maintain brain health?

There are three major pillars for maintaining intact memory: effortful physical activity, effortful cognitive activity, and social contact. Research shows that the first two of these have direct beneficial effects on the brain, even at the level of cellular function. Social contact is another form of keeping our brains active by external stimuli, novel experiences, and perspectives outside of ourselves. Dietary habits (such as the Mediterranean diet, or intake of omega-3 fatty acids like in fish oil) have also had beneficial effects on memory function. The good news is that these are modifiable lifestyle habits, which may be particularly important for women with hypertension or diabetes who are at higher risk for cognitive decline.

Finally, adequate sleep (currently suggested as seven hours a night) is critical for brain health. Research has shown that during certain periods of sleep, learning is consolidated; that is, sleep plays a key role in storing and maintaining what we learned during the day, and even helps in clearing the brain of amyloid, one of the markers of potential AD pathology. More research is required to fully understand the beneficial impacts of these modifiable lifestyle factors. However, the time to start incorporating them into your life is now.

What can you add to a wide variety of foods, from cereals to salads, that’s crunchy, filling, and flavorful — and good for your heart? The answer is nuts. While all varieties of nuts are chock full of important nutrients, walnuts may be especially good for protecting cardiovascular health, according to a recent study in the journal Circulation that supports earlier research in this realm.

What is the study?

The Walnuts and Healthy Aging study is a randomized controlled trial supported by a grant from the California Walnut Commission that tracked healthy older adults living in two communities. For the study, researchers recruited 708 adults ages 63 to 79 living in Loma Linda, California, or Barcelona, Spain, and split them into two groups. One group added about a quarter-cup to a half-cup of walnuts to their daily diet for two years, while the other group ate no walnuts.

After two years, average levels of harmful low-density lipoprotein (LDL) cholesterol were modestly lower in the walnut group. Of note: nearly a third of the participants were taking cholesterol-lowering statins, so the average cholesterol levels of both groups were already in a normal range. The researchers speculate that the cholesterol-lowering benefits from walnuts might be more pronounced in people with elevated cholesterol levels. There is no way to know from the current data if this is true.

“This recent trial confirms what earlier studies have found, namely, that that adding walnuts to your diet appears to improve your cholesterol levels,” says Dr. Deirdre Tobias, an obesity and nutritional epidemiologist at Harvard-affiliated Brigham and Women’s Hospital. The new trial also lasted much longer than past walnut studies. However, it’s not clear what foods were being replaced by the walnuts in the participants’ diets, which might affect the magnitude of benefits the researchers saw. For example, replacing unhealthful, ultra-processed snacks with walnuts would presumably have a greater benefit than a lateral move from healthy options to walnuts, Dr. Tobias explains.

Lower levels of harmful blood fats, no additional weight

The researchers also analyzed the concentration and size of the LDL particles. Smaller, more dense LDL particles are more likely to trigger atherosclerosis, the buildup of fatty plaque inside arteries that’s the hallmark of most cardiovascular disease that results in heart attacks or strokes.

The walnut eaters had lower levels of these smaller particles. They also had decreased levels of intermediate-density lipoproteins (IDL), which are also linked to a rise in cardiovascular-related risks. And even though a quarter-cup of chopped walnuts is about 190 calories (and a half-cup is about 380 calories), the walnut eaters did not pack on any extra pounds.

Earlier research has found that people who eat nuts regularly are less likely to have heart disease, and many studies have focused specifically on walnuts. In 2018, Dr. Tobias and colleagues published a meta-analysis and systematic review of studies that examined how eating walnuts affects a person’s blood lipids and other heart-related risks. The review included 26 controlled trials involving a total of more than 1,000 people. It found that walnut-enriched diets led to lower total cholesterol, LDL cholesterol, and triglycerides, the most common form of fat in the bloodstream.

What’s special about walnuts?

Although all nuts are good sources of healthy unsaturated fats, walnuts are especially rich in alpha-linolenic acid (ALA). This is a precursor to the omega-3 fatty acids EPA and DHA found in fatty fish that are known for their heart-protecting powers. Our bodies convert ALA to EPA and DHA, although the efficiency of this varies from person to person.

What’s more, walnuts are usually eaten raw. So they have greater antioxidant abilities than nuts that are usually eaten roasted. (Antioxidants help prevent or reduce the artery-damaging oxidation that contributes to heart disease).

Adding walnuts to your diet

It’s worth noting that the FDA allows a qualified health claim on some nuts (including walnuts). Foods made with them are permitted to include the following statement: “Eating a diet that includes one ounce of nuts daily can reduce your risk of heart disease.” An ounce of walnuts is about a handful, or one-quarter cup.

You can sprinkle walnuts onto oatmeal or other hot or cold cereals; stir them into pancakes, muffins, or other quick breads; or toss them with vegetables or into salads. If high cholesterol is a health concern for you, there are other foods that may help lower your LDL cholesterol and boost your heart health.

All parents want their children to be successful in life — and by successful, we mean not just having a good job and a good income, but also being happy. And all parents wonder how they can make that happen.

According to Harvard’s Center on the Developing Child, it’s less about grades and extracurricular activities, and more about a core set of skills that help children navigate life’s challenges as they grow. These skills all fall under what we call executive function skills that we use for self-regulation. Developing strong executive function skills, and finding ways to strengthen those skills, can help people feel successful and happy in life.

What are five important core skills?

• Planning: being able to make and carry out concrete goals and plans
• Focus: the ability to concentrate on what’s important at a given time
• Self-control: controlling how we respond to not just our emotions but stressful situations
• Awareness: not just noticing the people and situations around us, but also understanding how we fit in
• Flexibility: the ability to adapt to changing situations.

While these are skills that children (and adults) can and do learn throughout their lifetimes, there are two time periods that are particularly important: early childhood (ages 3 to 5) and adolescence/early adulthood (ages 13 to 26). During these windows of opportunity, learning and using these skills can help set children up for success. In this post, we’ll talk about that first window of early childhood.

The best way to learn any skill is by practicing — and we are all more likely to want to practice something if it is fun and we feel motivated. Here are some ways that parents can help their children learn and strengthen executive function skills.

Planning

It’s natural for parents and caregivers to do the planning for young children, but there are absolutely ways to get them involved, such as:

• Planning the day’s activities with them, whether it be a school day or a play day. Talk about all the day’s tasks, including meals, dressing, bathing, and other things; help them see it as part of a whole, and something that they can help manage.
• Cook or bake something together. Put together the shopping list, go shopping, go over the recipe together, and help them understand all the steps.
• When getting ready for a holiday or a party, include them in thinking about what everyone would like to do and how to do it.

Focus

The explosion of device use has definitely caused all sorts of problems with focus in both children and adults. There is an instant gratification to screens that makes it hard to put them aside and focus on less stimulating tasks. Now, more than ever, it’s important to:

• Enforce screen-free time, even if they complain (parents need to abide by this too).
• Have the materials on hand to make or build things. Find projects that will take an hour or two. Do it with them!
• Read print books out loud together, including chapter books. Having to picture things themselves rather than seeing it on a screen helps children learn to focus.

Self-control

This is one where being mindful of your own reactions to situations is important. How do you react to anger and frustration? Is road rage a problem for you? Remember that children always pay more attention to what we do than what we say. To help your child learn self-control, you can:

• Talk about feelings, and about strategies for managing strong emotions — like taking a deep breath, stepping away from the situation, screaming into a pillow, etc.
• Help them understand how their behavior affects others, and why it’s important to be mindful of that (which also teaches awareness).
• Debrief after tantrums or upsets. What could everyone have done differently?

Awareness

This one can be fun to teach.

• Go for walks. Visit places together. Listen and watch. Imagine together what people might be doing or thinking.
• Join community service activities; show children that anyone can make a difference.
• Have rituals of checking in as a family, like at dinner. Give people a chance to talk about the best and worst parts of their day, and talk about ways you can work better as a family and treat each other well.

Flexibility

We tend to cater to our children and their needs, making our schedules and plans around them. Some of that is pure parenting survival. But ultimately, it’s not always helpful; life has a way of messing up even the most careful plans. Kids need structure, sure, but they also need to be able to adjust to the inevitable curve balls.

• Don’t always say no to something that might happen during a naptime or mealtime. It’s okay if schedules occasionally vary.
• Be spontaneous when you can. Go for an unplanned outing, and otherwise make last-minute plans sometimes.
• When plans change or fall through, be upbeat about it and make the most of it. Be a role model.

In helping your children learn these skills, you might just learn something about yourself — and learn some new skills too.

Follow me on Twitter @drClaire

In the US, breast cancer is the most commonly diagnosed cancer in women, and the second leading cause of cancer-related deaths. Each year, an estimated 270,000 women — and a far smaller number of men — are diagnosed with it. When caught in early stages, it’s usually highly treatable.

A promising new form of targeted treatment may expand options available to some women with early-stage breast cancer linked to specific genetic glitches. (Early-stage cancers have not spread to distant organs or tissues in the body.)

The BRCA gene: What does it do?

You may have heard the term BRCA (BReast CAncer) genes, which refers to BRCA1 and BRCA2genes. Normally, BRCA genes help repair damage to our DNA (genetic code) that occurs regularly in cells throughout the human body.

Inherited BRCA mutations are abnormal changes in these genes that are passed on from a parent to a child. When a person has a BRCA mutation, their body cannot repair routine DNA damage to cells as easily. This accumulating damage to cells may help pave a path leading to cancer. Having a BRCA1 or BRCA2 mutation — or both — puts a person at higher risk for cancer of the breast, ovaries, prostate, or pancreas; or for melanoma. A person’s risk for breast cancer can also be affected by other gene mutations and other factors.

Overall, just 3% to 5% of all women with breast cancer have mutations in BRCAgenes. However, BRCA mutations occur more often in certain groups of people, such as those with triple negative breast cancer (TNBC), Ashkenazi Jewish ancestry, a strong family history of breast and/or ovarian cancer, and younger women with breast cancer.

Inherited BRCA mutations and breast cancer types

Certain types of breast cancer are commonly found in women with BRCA gene mutations.

• Estrogen receptor-positive, HER2-negative cancer: Women with a BRCA2 mutation usually develop ER+/HER2- breast cancer — that is, cancer cells that are fueled by the hormone estrogen but not by a protein known as HER2 (human epidermal growth factor 2).
• Triple negative breast cancer: Women with a BRCA1 mutation tend to develop triple negative breast cancer (ER-/PR-/HER2-) — that is, cancer cells that aren’t fueled by the hormones estrogen and progesterone, or by HER2.

Knowing what encourages different types of breast cancer to grow helps scientists develop new treatments, and helps doctors choose available treatments to slow or stop tumor growth. Often this involves a combination of treatments.

A new medicine aimed at early-stage BRCA-related breast cancers

The OlympiA trial enrolled women with early-stage breast cancer and inherited BRCA1/BRCA2 mutations. All were at high risk for breast cancer recurrence despite standard treatments.

Study participants had received standard therapies for breast cancer:

• surgery (a mastectomy or lumpectomy)
• chemotherapy (given either before or after surgery)
• possibly radiation
• possibly hormone-blocking treatment known as endocrine therapy.

They were randomly assigned to take pills twice a day containing olaparib or a placebo (sugar pills) for one year.

Olaparib belongs to a class of medicines called PARP inhibitors. PARP (poly adenosine diphosphate-ribose polymerase) is an enzyme that normally helps repair DNA damage. Blocking this enzyme in BRCA-mutated cancer cells causes the cells to die from increased DNA damage.

Results from this study were published in the New England Journal of Medicine. Women who received olaparib were less likely to have breast cancer recur or metastasize (spread to distant organs or tissues) than women taking placebo. Follow-up at an average of two and a half years showed that slightly more than 85% of women who had received olaparib were alive and did not have a cancer recurrence, or a new second cancer, compared with 77% of women treated with placebo.

Further, the researchers estimated that at three years:

• The likelihood that cancer would not spread to distant organs or tissues was nearly 88% with olaparib, compared to 80% with placebo.
• The likelihood of survival was 92% for the olaparib-treated group and 88% for the placebo group.

The side effects of olaparib include low white cell count, low red cell count, and tiredness. The chances of developing these were low.

The bottom line

Olaparib is already approved by the FDA to treat BRCA-related cancers of the ovaries, pancreas, or prostate, and metastatic breast cancer. FDA approval for early-stage breast cancer that is BRCA-related is expected soon based on this study. These findings suggest taking olaparib for a year after completing standard treatment could be a good option for women who have early-stage breast cancer and an inherited BRCA gene mutation who are at high risk for cancer recurrence and, possibly, its spread.

Follow me on Twitter @NeelamDesai_MD