Alzheimer’s Disease and Women – Disturbing Gender Bias and Neglect

Dr Frank Sabatino DC, PhD

There has been a long disappointing history of gender bias and disrespect for women in science, medicine, and the creative arts. From artists like Colette and Camille Claudel to the African American mathematicians that gave the US space program its initial jump start, the creativity of women has often been appropriated and obscured by men, who have profited from their work, even though a woman, Marie Curie, was one of only four people in history that received two Nobel prizes in science. The incredible X-ray diffraction studies of the DNA molecule by the English chemist, Dr Rosalind Franklin, were crucial to understanding the molecular structure of DNA, when they were appropriated by James Watson and Francis Crick. And while Watson and Crick eventually basked in the fame and Nobel limelight for their discovery of DNA, she became a relatively invisible and unknown footnote in the history of science.

This gender bias has been particularly apparent in the history of medical treatment and health care. For years, the excessive number of hysterectomies performed in the US has been an appalling attack on women especially when more supportive nutrition / conservative health care options could potentially have resolved a variety of female problems in a more life affirming manner. Trust me, if castrations were done with the ease and nonchalance of hysterectomies, there would be an army of male, Paul Revere-like whistle blowers galloping through the streets of our country, with guns drawn, clutching their genitals and screaming, “The surgeons are coming”. Without a doubt, there would be a constitutional amendment ensuring the divine right of men to bear testicles. Unfortunately, when the founding fathers declared that all men are created equal, what they meant was all white men and certainly not women and people of color. So women continue to fight a long battle for equal rights and fair treatment in the workplace, in boardrooms, and in the medical arena.

The history of routine hormone replacement therapy (HRT) is another glaring example of female abuse, negative bias, and neglect. When conjugated estrogens derived from horse urine (Premarin) was put on the market in the early 1940’s, it cornered the market on HRT, and became the most prescribed drug in America. Unfortunately, women were so undervalued and neglected that there were no rigorous controlled studies to address potential risks of this treatment. And what was overlooked, and certainly not shocking, was that reproductive steroid hormones derived from horses are not metabolized efficiently by the liver of human females. As a result, these estrogens linger longer in circulation increasing the risk of stroke and cancers of the breast, ovaries, and uterus. And this potential risk and abuse went on for 50 years before the rigorous double-blind Women’s Health Initiative Study was finally done between 1993-1998, and clearly showing that HRT did in fact increase the risk of stroke and cancer of women’s reproductive organs. A shameful 50 years of risk and abuse in which ‘modern’ medicine obliviously overlooked the specific health care needs of women.

Currently we are seeing gender discrepancy in one of the most frightening and devastating conditions of modern times, Alzheimer’s Disease, associated with severe memory loss and cognitive decline. Alzheimer’s Disease is the most common form of dementia affecting people over the age of 65, while approximately 200,000 Americans under age 60 live with early onset Alzheimer’s, either in an asymptomatic preclinical phase or with minor cognitive deficits. Alzheimer’s Disease affects almost 6 million people, is the sixth leading cause of death in the US, and in 2019 cost the nation close to 300 billion dollars. From 2000-2017, deaths from Alzheimer’s Disease increased by 145%, while death from heart disease increased by only 9%; Alzheimer’s Disease kills more people than breast and prostate cancer combined (1). But the fact that really got my attention and intrigues me is that 2 out of every 3 people with Alzheimer’s Disease are women. And since the pathological and early cognitive changes of Alzheimer’s Disease often occur before the age of 60, the fact that women live about 5 years longer does not account for the increased incidence in women (2). Therefore, it begs the question, why is Alzheimer’s Disease more prevalent in women?

Causes and effects

To address that question, it is essential to understand the significant neurological, vascular, and metabolic changes associated with Alzheimer’s Disease. As we discuss the debilitating pathology of Alzheimer’s Disease, please keep in mind that there are a constellation of risk factors and lifestyle choices, including a high saturated fat animal-based diet, obesity, smoking, alcohol consumption, high blood pressure, chronic stress, and sleep deprivation can affect the progression of this disease and the underlying pathological changes. The brain of people with Alzheimer’s Disease typically show the two changes that eventually cause deterioration and death of neurons.

• Senile-plaques formed from amyloid peptide produced by damaged brain cells.
• Neurofibrillary tangles formed by chemically modified protein (tau protein) within the internal architecture of brain cells (3).

In addition to these neurological changes, it is now widely recognized that Alzheimer’s Disease is also a vascular disease associated with high cholesterol, and an increase in atherosclerotic plaques that reduce blood supply to the brain. Both PET scans and electron microscopic analysis have shown that high cholesterol also promotes the formation of amyloid plaques and neurodegenerative brain changes (4).

There are also data to suggest that LDL cholesterol, the risky ‘bad” form of cholesterol, can damage the vascular barrier that separates blood circulation from the brain (the blood brain barrier) allowing cholesterol to access and accumulate in the brain and foster the devastating changes of Alzheimer’s Disease. Cholesterol in the brain can also be oxidized into a dangerous reactive free radical form promoting oxidative stress and brain damage. This makes it so imperative to eliminate all meat and dairy foods providing saturated fat and cholesterol, and eat a broad base of plant foods containing the greatest concentration of antioxidants that reduce oxidative stress. 

Consistent with this vascular component, there are data that support the association of increased homocysteine with the cognitive pathology of Alzheimer’s Disease (5-8). Meat, eggs, and dairy products have high levels of the amino acid methionine that is metabolized to the vascular toxin homocysteine. B vitamins / folic acid can transform and reduce blood levels of homocysteine and decrease potential vascular damage and plaque formation in the heart and brain. Unfortunately, the typical meat-based diet has a dearth of veggies, and therefore lacks the B vitamins to modify its high homocysteine content. A plant-based diet loaded with plant proteins, including greens, legumes, and grains has much lower levels of methionine and a high B vitamin content, which is ideal for reducing the vascular damage and plaque formation associated with Alzheimer’s Disease. For these reasons, in addition to the routine monitoring of your cholesterol profile, I also recommend measuring blood levels of homocysteine for people over the age of 50. 

Metabolically, oxidative stress and insulin resistance also play a major role in promoting the underlying pathology of Alzheimer’s Disease. Eating a meat and dairy based diet high in saturated fat overloads liver and muscle cells with fat and interferes with insulins ability to promote the entry of sugar into these cells. As cells resist the normal healthy action of insulin, sugar cannot enter these cells, and abnormally increases in the blood ultimately being converted into fat and weight gain. The elevated blood sugar and decreased glucose metabolism, along with insulin resistance, provokes the body to over produce insulin. Excessive insulin in the blood along with decreased glucose metabolism is found in the early asymptomatic preclinical phase of Alzheimer’s Disease and promotes the beginning of amyloid plaques long before the actual outcome of cognitive changes and dementia. Keep in mind that Alzheimer’s Disease is usually diagnosed in the mild to moderate dementia phase. However, with new imaging technologies, including PET scans and MRI’s, early deposits of amyloid, and amyloid plaque formation, can now be seen in the pre-clinical phase before there are any noticeable cognitive symptoms.

Redressing the balance

In relation to women, brain imaging studies have demonstrated a link between estrogen decline and an increased risk of Alzheimer’s Disease in women. Typically women  entering the perimenopausal period, between the ages of 40-60 (when estrogen levels begin to change / decline prior to true menopause) have demonstrated a decline in brain energy and an increase in Alzheimer’s plaques (9). Consistent with these data, women who have hysterectomies, especially earlier in life, demonstrate a higher incidence of Alzheimer’s Disease. So, even though Alzheimer’s Disease is triggered by a decline in estrogen, there is very little research and almost no public recognition of this connection.

While menopause is typically associated with aging and decline of reproductive function, it is the reduction of brain estrogens that are linked with the disturbing neurological symptoms of menopause including hot flashes, disturbed sleep, depression, and memory decline. And while the loss of the neuroprotective effect of estrogen is not the cause of Alzheimer’s Disease, it certainly is a trigger that warrants more attention. It is important to realize that just taking additional estrogen is not the solution because of the stroke and cancer risk associated with estrogen, both in animal derived or bioidentical form, and also because there are no short or long term controlled studies showing that HRT actually eliminates the early or progressive pathological changes of Alzheimer’s Disease. Much more work needs to be done, and is actually finally being done, to unravel the intricacies of the female connection to Alzheimer’s Disease.

There is no effective medical treatment for end stage Alzheimer’s Disease. Yet there are numerous anecdotal reports surfacing every day about people in advanced states of cognitive decline reversing their dementia with a combination of supportive lifestyle factors. These reports typically espouse a whole food plant-based diet containing dark berries, walnuts, and a panorama of deep greens, cruciferous and starchy vegetables as instrumental in their recovery. While these stories are promising and should not be overlooked, they certainly do not provide the evidence base of more rigorous controlled clinical trials. At least not yet. However, they do hint at a remarkable plasticity and recovery of the brain even in advanced stages of degeneration.

But the really great, hopeful news for all women and men is that because of the known risk factors, and the long latent period between the formation of the plaques and tangles of Alzheimer’s Disease, and the outcome of severe cognitive decline / memory loss, early and ongoing lifestyle prevention strategies may dramatically reduce the severity of Alzheimer’s Disease. While a number of small studies looking at short term, single lifestyle prevention factors have been disappointing, the large Finger study from Finland, which targeted a combination of several important lifestyle behaviors and vascular risk factors simultaneously, demonstrated great promise and hope (10). In this study, between 2012-2014, 1,260 people aged 60-77 participated in a multi-domain approach, including a diet combining whole plant foods with small amount of animal products, an activity program that included both aerobic (walking) and resistance weight training, cognitive intellectual activity / training, social activities, and monitoring and management of metabolic and vascular risk factors. This landmark clinical trial showed significant improvement in all cognitive functions, including executive function (ability to manage and regulate ourselves, and set and achieve goals), memory and psychomotor speed, clearly demonstrating that it is possible to prevent cognitive decline with a broad based, lifestyle approach.

Our attention needs to be fully focused on prevention, and these data provide a remarkable picture of hope. It has become apparent that a whole food, plant-based diet provides the most important foundation for the necessary lifestyle modifications. A plant-based approach has more than 50 times the antioxidant potential than any other eating plan on planet earth, and it is the most successful way to eliminate the oxidative stress associated with Alzheimer’s Disease. 

Completely eliminating the saturated fat and cholesterol found in meat and dairy products is the most effective way to reduce both amyloid and atherosclerotic plaques associated with Alzheimer’s Disease. And this plant-based, low fat approach is mandatory for healing the problem of insulin resistance, and compromised glucose metabolism, that promotes the cellular changes of Alzheimer’s Disease. Correcting these metabolic conditions and promoting an effective routine of consistent physical / intellectual activity, stress management, sleep, social interaction, while eliminating drugs, alcohol, and nicotine, is absolutely essential. This lifestyle approach is beneficial for all people at any stage of Alzheimer’s Disease progression, but it is especially important for women during the transition to perimenopause and menopause when the brain is most potentially vulnerable due to estrogen decline.

Never forget that Alzheimer’s Disease is not an inevitable outcome of aging and longevity. Never underestimate the power of your personal, constructive, lifestyle choices. And never underestimate the incredible power of a whole food exclusive plant diet for promoting your optimal health span in general and in preventing devastating conditions like Alzheimer’s Disease in particular. The choice is yours.

References

1. Alzheimer’s Association.

2. Dr Lisa Mosconi, Women’s Brain Initiative.

3. Walters, M, et al. Role of nutrition to promote healthy brain aging and reduce risk of Alzheimer’s disease. Curr Nutr Rep (2017) 6: 63-71.

4. Dr Michael Greger, Cholesterol and Alzheimer’s Disease-Nutrition Facts. 

5. Seshadri, S, et al. NEJM, Feb 14 (2002); 346:476-83.

6. Seshadri, S, et al. Framingham Offspring Study: Arch Neurol (2008) 65(5): 642-8.

7. Prins, ND. Rotterdam Scan Study. Neurol (2002); 59: 1375-80. 

8. Chung, YC, et al. J Throm Haemost (2016), 14: 1442-52.

9. Mosconi, L, et al. Increased Alzheimer’s risk during the menopause transition: A 3 year longitudinal brain study. PLos one (2018) Dec 12; 13(12): e0207885.

10. A multidomain 2-year randomized controlled trial to prevent cognitive impairment. Finnish Geriatric Intervention Study to Prevent Cognitive Impairment (Finger Study).

(See also our articles The Effect of Lifestyle on Cognitive Impairment and Chronic Knee Pain and Dementia)

Dr Frank Sabatino is a Chiropractic physician with a PhD in cell biology and neuroendocrinology from the Emory University School of Medicine.  While an assistant Professor at the Health Science Center of the University of Texas School of Medicine, he conducted extensive landmark research on calorie restriction, stress and aging, and has published a number of major scientific papers in some of the most well-respected peer reviewed journals in the fields of cell biology, endocrinology, and neuroscience. He has also written numerous articles for lay magazines and journals in the areas of clinical nutrition, healthy weight loss, women’s hormones, stress management, addiction, and healthy aging. Dr Sabatino is the recipient of the prestigious Brookdale Fellowship.