Protecting from Alzheimer in the Female Brain

January 10, 2019
Timothy R. Jennings, MD

The fact that nearly 7 of every 10 Alzheimer diagnoses are made in women is not just associated with longer age expectancy.

Timothy R. Jennings, MD

Alzheimer Disease (AD), the Grim Reaper of the modern world, is a devastating illness that respects no social class, race, or nationality. Yet 65% of people with AD are female, and this higher occurrence is not simply due to the fact women live longer than men.

In some of my previous works detail that many risk factors that affect both men and women, along with preventative measures for all. In this article, I will focus on the potential factors that may contribute to this gender difference.

AD occurs when the brain’s normal maintenance system is impaired. Throughout our lives the brain is in a continual state of change, making new connections, pruning unused pathways—all in response to our choices and life experiences.

When neurons die or are pruned back, waste products are left behind that need to be removed. The brain has an elegant system to remove these various remnants. Trace chemicals like copper and zinc that are left behind when a neuron dies are cleaned up by a protein called beta amyloid (BA). If BA is not removed from the brain, it becomes toxic, causing more cellular damage and a reinforcing, destructive loop occurs: neuronal loss, BA scavenges trace chemicals, removal system impaired, BA builds up causing more cell death, and more trace chemicals with new BA that is not removed.

In patients with AD, the brain’s cleanup system becomes impaired, leading to this reinforcing negative loop. And what causes the cleanup system to become impaired? Chronic inflammation which causes insulin resistance in the brain. Insulin in the brain is the key that turns on the systems to remove BA from the brain. When the insulin receptors in the brain no longer respond normally to insulin, then BA builds up contributing to a cascade of neuronal death in AD.

Understanding this process gives insight into potential factors that may explain why women have a higher rate of AD than men—because women are at higher risk for chronic inflammatory stress than men.

One in 3 women are sexually assaulted before the age of 20. One in 5 women in the US has been raped in their lifetime, whereas only one in 71 men are raped in their lifetime, according to the US Centers for Disease Control and Prevention. Such trauma alters brain development, upregulates stress pathways and increases inflammatory factors throughout one’s life. Chronic inflammation, secondary to trauma, results in marked increases in mood disorders, obesity, insulin resistance (diabetes type II), and hypercholesterolemia, all of which increase the risk of dementia.

The first factor contributing to higher rates of AD in women is chronic mental stress. The second factor is childbearing.

A recent study documented that women who gave birth to more than five children have a 70% higher rate of AD than women with 1-4 children, while women who had either a miscarriage or an abortion in the first trimester had lower rates of AD.

Multiple factors are likely involved in increasing the risk of AD for women with more than five children. When a woman gives birth, a small number of fetal progenitor cells enter her body and for the rest of the mother’s life these cells produce various mature cells, which have her child’s unique immune markers. The more children a woman has, the greater her risk of immune system activation with increased risk of inflammation.

Another risk factor due to multiple child births is the potential depletion of maternal resources (micronutrients and omega-3 fatty acids) with each pregnancy—more pregnancies greater risk of depletion. Studies in older women document that those women with lower levels of omega 3 fatty acids have less brain volume and higher rates of AD than women with higher levels of these essential fats. Finally, the authors of the study believed that hormone changes during pregnancy were also involved, with the estrogen levels during the first trimester conveying a protective effect resulting in lower rates of AD in those who had an incomplete pregnancy.

The involvement of estrogen as a protective factor is supported by other research in post-menopausal women which found that estrogen replacement therapy reduced AD risk by 40-50% in women who initiated treatment within 5 years of menopause and continued treatment for 10 years or more. No benefit was seen in women who initiated hormone replacement more than 5 years after menopause.

AD is a devastating illness with increased inflammation contributing to insulin resistance in the brain. The good news is that there are a host of lifestyle factors we can employ that will reduce inflammation, re-sensitize our insulin receptors, enhance the clearance of BA from the brain and thereby reduce our risk of AD.

Timothy R. Jennings, MD, has been in private practice as a Christian psychiatrist and certified master psychopharmacologist since 1997. Board certified in psychiatry by the American Board of Psychiatry and Neurology, Jennings has spent more than 2 decades researching the interface between biblical principles and modern brain science. He is also a lecturer and international speaker, and the author of The Aging Brain: Proven Steps to Prevent Dementia and Sharpen Your Mind, The God-Shaped Brain, and The God-Shaped Heart. He is in private practice in Chattanooga, Tennessee. The piece reflects his views, not necessarily those of the publication.

Healthcare professionals and researchers interested in responding to this piece or contributing to MD Magazine® can reach the editorial staff here.


x