By Ken Sharlin, M.D., M.P.H.
My grandmother, Frances, lived to be 95 years old. She remained a sharp-minded woman through most of her life, until the last couple of years before her death. Whether or not she had Alzheimer’s disease is a mystery. She did have significant memory loss. As a neurologist I would call her condition “dementia,” referring to the slow deterioration of mental function, but not a specific disease.
At present, it is estimated that 1 out of 3 adults age 85 years or older is affected by Alzheimer’s disease. Worldwide there are 46.8 million people with dementia, most of whom have Alzheimer’s, including 5.6 million Americans. The term “Late Onset Alzheimer’s Disease” has traditionally been defined by the age cut off 65 years and older. This represents most of those suffering from the condition, but it is also important because Late Onset Alzheimer’s Disease has a significant association with a gene variant called ApoE4.
Since each of our parents contributes one copy of the genes we inherit we can have up to two copies of ApoE4. Those with one copy have 3-4 times the risk of developing Alzheimer’s disease, and those with two copies have as much as 15 times the risk. Although there are three variants of the ApoE gene—ApoE2 (protective), ApoE3 (neutral risk), and ApoE4 (increased risk)—20 to 30% percent of the population has at least one copy of ApoE4. This should sound an alarm, because we now know that there are specific therapeutic targets that can reverse or prevent Alzheimer’s disease in ApoE4 carriers, if caught early.
Why Women Are At Higher Risk
Women, like my grandmother Frances, are at an especially high risk for Alzheimer’s disease. At any given age, this gender difference affects women at a rate nearly twice that of men, especially ApoE4 carriers. This is not the only gene variant placing women at higher risk than men. The Met66 variant of the gene for Brain Derived Neurotrophic Factor (BDNF) is associated with an increased risk of Alzheimer’s disease in women, but not in men. It is the job of BDNF to stimulate growth of new brain cells from stem cells in the brain.
Precision Medicine has as much to do with knowing what we can do to improve or maintain our health because of our unique genetic make-up as it does with the genes themselves. It is through our actions that we can turn on health-promoting genes, and turn off disease-promoting ones. In this sense, it is reasonable to ask what can women do to reduce their risk of Alzheimer’s disease? According to the work of Dr. Dale Bredesen, a neurologist and neuroscience researcher with The Buck Institute on Aging, and author of the forthcoming book The End of Alzheimer’s, there are as many as 36 unique actions that those at risk for Alzheimer’s can take to avert that risk.
Let’s look at a few examples. Women who have their ovaries removed surgically prior to menopause, a process called “oophorectomy,” experience an abrupt deficiency of estrogen, progesterone, testosterone and a disruption of the part of the brain that is responsible for the biological stress response. Studies have shown that estrogen has a protective effect on the brain. The Mayo Clinic Cohort Study of Oophorectomy and Aging showed an almost doubled risk of dementia in women who underwent removal of both ovaries before menopause.
However, women who started Hormone Replacement Therapy (HRT) after oophorectomy and continued HRT until at least the natural age of menopause did not experience and increased risk of Alzheimer’s disease. In the Cache County Study women who initiated HRT within 5 years of menopause had a 30% lower risk of Alzheimer’s disease compared to women who reported no use of HRT.
Ways Women Can Decrease Their Risk
Research has pointed toward career achievement and intellectual lifestyle (meaning a combination of education, occupation, and current cognitive activity) as having a higher reserve against disease. In a nutshell, subjects with higher education take longer to reach the dementia threshold. For women who have the opportunity and desire to further their education and careers there is a chance that they can offset some of the gender bias when it comes to Alzheimer’s disease.
Returning to the Met66 variant of the Brain-Derived Neurotrophic Factor gene the most potent stimulus of BDNF in the brain is exercise, and the most potent suppressor is stress. Early physical activity, especially, when the brain is developing, may be especially important. Physical activity in teenage years is associated with the greatest risk reduction in women. But even women who were not as active as teenagers, but who are physically active at age 30 and 50, have a reduced risk.
There is also need to have a regular practice of stress reduction. The severity of depressive symptoms is associated the risk for conversion to Alzheimer’s disease in women. We know that stress-reducing activities such as mindfulness meditation facilitates the release of Brain-Derived Neurotrophic Factor and should be seriously considered by any woman who wants to reduce their risk of Alzheimer’s disease.
Unhealthy Habits and Risk Factors
When it comes to unhealthy habits, cigarette smoking exacerbates the changes seen in the brains of those suffering with Alzheimer’s disease. Of course, no one should subject their bodies and brains to cigarette smoking for a variety of reasons. Women who do smoke need to know that the combination of smoking and heavy alcohol use may be especially detrimental because this combination predicts a significantly faster rate of decline compared to those smokers who are moderate alcohol users.
But breathing in harmful cigarette smoke is not the only concern when it comes to inhalants and the risk to women. Recently, University of Southern California scientists have reported on a tiny, dirty particle that comes from power plants and automobiles called PM2.5. Older women who live in places with fine particulate matter exceeding the EPA’s standard are 81% more at risk for cognitive decline and 92% more likely to develop dementia, including Alzheimer’s disease.
These particles get into our bodies directly through the nose and affect the brain. Cells in the brain treat these particles as invaders and react with inflammatory responses, which over the course of time appears to exacerbate and promote Alzheimer’s disease. Moreover, the adverse effects were even stronger in women who had the ApoE4 gene.
Since women in our society are the primary decision-makers when it comes to healthcare, it is a priority to make available the information they need to keep themselves and their families as healthy as possible. My grandmother had a long and fortunate life by anyone’s measure. Whether she would have been influenced by the current information I can only guess. But it’s fair to say she would have liked to know.