Any discussion of aging naturally brings us to one of the biggest paradoxes in modern science. We have essentially doubled life expectancy since 1900, when the mean duration of life was only 48 years, but we don’t know how to preserve brain function in our oldest patients, even if they are in optimal physical health.
By the ages of 90 – 100, almost everyone has significant problems when thinking and remembering how to complete even the simplest routines of daily life. Melissa Gonzales McNeal, MS, and her colleagues at the Oregon Health Sciences University found in a study of 100 healthy adults older than 85 that by the time we reach a mean age of 97, 65 percent of us will have what science calls cognitive impairment (a general term for forgetfulness and the inability to concentrate, solve problems, and deal with the ordinary challenges of self-care). By age 100, almost half of us (49 percent) will have Alzheimer’s disease, one of the severest forms of cognitive impairment.
Although women retain more brain function later in life, once it goes, it really goes. Women have a higher risk for Alzheimer’s than men, age for age, and may be more susceptible than men to dementia. (It’s also worth noting that Alzheimer’s doesn’t just affect women in greater numbers because we are more likely to get it. We’re also more likely to end up taking care of someone who has it, like a spouse, a parent, or a sibling).
Why do Women seem to be more prone to dementia? Researchers have proposed the following:
- Loss of Brain Mass: Women may lose less brain mass than men do, but they also start out with less. Since women begin with fewer neurons than men, the loss of even one neuron may be relatively more important than for a man. The greater interconnection of neurons within the female cortex may also explain why women are more susceptible to the dementia of aging. Like one bulb going on a string of Christmas lights, the loss of one neuron has a widespread effect on others. Men’s more centralized processing may contain the damage.
- Longer Lifespan: Part of the problem may also be that women live longer. Men are more vulnerable to disease and early death than women are, with the result that by age 85, women outnumber men 2 to 1, although we started out life in approximately equal numbers. (When young women tell me that there are no men out there, I tell them that they’re sitting pretty compared to their widowed grandmothers). It’s possible that the men who have managed to survive to “old-old” age (a new phrase coined at the NIH) are more fit and sound than the rest of their sex. In any case, by the time we’re over age 85, women are more likely to have problems with thinking compared to men – the few who are left to keep us company.
Hope for Interventions
We don’t know why dementia strikes. So much threatens our brain cells: accumulation of damaged (oxidized) molecules (scientists call this the “oxidative stress of aging”), inadequate energy supplies, mistakes in the production of new proteins because of gene mutation, insufficient blood supply, and those are just a few of the most obvious challenges.
There’s hope though. The more we learn about at the brain and aging, the more apparent it becomes that the brain has a remarkable ability to preserve neurons in many areas and to compensate for the loss of neurons by increasing the connectivity between remaining neurons.
We seem to be very resourceful creatures. As the frontal lobes of our brains shrink, we seem to recruit other areas of the brain to help us carry out the higher functions they once controlled. A study done on a group of people in their 20s and 30s showed that they used their frontal lobes for tasks that required memory and the organization of information. Older people use a different part of the brain usually involved in registering and processing visual information. Young and old did equally well in learning and remembering a list of words that they had to organize into categories and recall accurately.
Additionally, neuroscientists are concentrating on interventions that can combat changes in our brains that may give away to dementia. For instance, we know that the brain contain stores of some stem cells that can – under the right circumstances – divide and differentiate into functioning neurons. One of these warehouses is located in the hippo campus, the part of the brain that we use for spatial learning and short-term memory. Aging subjects often show shrinkage in this part of the brain and will often have problems in recalling pictures of common objects or in navigating a maze seen the previous day. (As you may remember, chronic stress is deadly for the hippo campus and for memory; prolonged exposure to high levels of the stress hormone cortisol destroys cells in this part of the brain). So, facilitating the right circumstances for those cells to turn into working neurons may mean that we can regain some memory and spatial function.
There are also growth factors (chemicals that actually promote the formation of new cells) that promote neuronal survival in the brain and may increase the connections between nerve cells, for example. Other researchers are exploring the role of a class of substances called chaperone proteins (I thought that was a charming name), which ensure the proper configuration of the large protein molecules produced in the brain and oversee the destruction of damage proteins. And perhaps unexpectedly, caloric restriction can also prompt the formation of new brain cells.
Medications are another option. For example, a medicine that improves the activity of a particular chemical called protein kinase A in rats improved the animal’s memories. But stimulating the very same chemical in the frontal cortex actually impairs certain kinds of thinking, so the problem is complicated.
Doctors are exploring the use of medications that suppress cell death, including cholesterol-lowering statins, which have a direct action on neurons. One day, we may have vaccines that prevent degenerative brain conditions like Alzheimer’s; these are already being developed.
But these are all in the future. As Paula Bickford, PhD, at the University of South Florida Center for Aging and Brain Repair in Tampa warned in a recent interview, so far, no drug has been developed that really improves memory in humans.
Marianne J. Legato, MD, Ph. D. (hon. c.), FACP is an internationally renowned academic, physician, author, lecturer, and pioneer in the field of gender-specific medicine. She is a Professor Emerita of Clinical Medicine at Columbia University College of Physicians & Surgeons and an Adjunct Professor of Medicine at Johns Hopkins Medical School. Dr. Legato is also the Director of the Foundation for Gender-Specific Medicine, which she founded in 2006 as a continuation of her work with The Partnership for Gender-Specific Medicine at Columbia University. She received an honorary PhD from the University of Panama in 2015 for her work on the differences between men and women.
At its core, gender-specific medicine is the science of how normal human biology differs between men and women and how the diagnosis and treatment of disease differs as a function of gender. Dr. Legato’s discoveries and those of her colleagues have led to a personalization of medicine that assists doctors worldwide in understanding the difference in normal function of men and women and in their sex-specific experiences of the same diseases.
She began her work in gender-specific medicine by authoring the first book on women and heart disease, The Female Heart: The Truth About Women and Coronary Artery Disease, which won the Blakeslee Award of the American Heart Association in 1992. Because of this research, the cardiovascular community began to include women in clinical trials affirming the fact that the risk factors, symptoms, and treatment of the same disease can be significantly different between the sexes. Convinced that the sex-specific differences in coronary artery disease were not unique, Dr. Legato began a wide-ranging survey of all medical specialties and in 2004, published the first textbook on gender-specific medicine, The Principles of Gender-Specific Medicine. The second edition appeared in 2010 and the third edition, dedicated to explaining how gender impacts biomedical investigation in the genomic era, won the PROSE Award in Clinical Medicine from the Association of American Publishers in 2018. A fourth edition is forthcoming.
She also founded the first scientific journals publishing new studies in the field, The Journal of Gender-Specific Medicine, and a newer version, Gender Medicine, both listed in the Index Medicus of the National Library of Medicine. She has founded a third peer-reviewed, open access journal, Gender and the Genome, which focuses on the impact of biological sex on technology and its effects on human life.
Dr. Legato is the author of multiple works, including: What Women Need to Know (Simon & Schuster, 1997), Eve’s Rib (Harmony Books, 2002), Why Men Never Remember and Women Never Forget (Rodale, 2005), Why Men Die First (Palgrave, 2008), The International Society for Gender Medicine: History and Highlights (Academic Press, 2017), and most recently, The Plasticity of Sex (Academic Press, 2020). Her books have been translated into 28 languages to date.
As an internationally respected authority on gender medicine, Dr. Legato has chaired symposia and made keynote addresses to world congresses in gender-specific medicine in Berlin, Israel, Italy, Japan, Panama, South Korea, Stockholm, and Vienna. In collaboration with the Menarini Foundation, she is co-chairing a symposium on epigenetics, Sex, Gender and Epigenetics: From Molecule to Bedside, to be held in Spring 2021 in Italy. She maintains one of the only gender-specific private practice in New York City, and she has earned recognition as one of the “Top Doctors in New York.”
