Women's Health and Cognitive Decline – Summing-Up What You Need to Know

October 16, 2023

Numerous factors shape the unique aging process of women's brains relative to men's.  When looking at Alzheimer's risk factors in-general, elements like insufficient physical activity, poor diet, smoking habits, diabetes, or a genetic predisposition may take the spotlight.  While all of these elements can affect susceptibility to Alzheimer's, the two primary predictors remain biological sex and the aging process.  Intriguingly, women, who generally outlive men, have long been recognized as having a greater likelihood of developing Alzheimer's.  In fact, a substantial majority, approximately two-thirds, of Alzheimer's patients are women.1 

We've connected with esteemed experts in women's brain health to compile their invaluable advice for preserving cognitive wellness throughout the aging process.   Whether facing the complexities of menopause, hormonal shifts, or seeking simple everyday enhancements, these experts generously share their insights to empower women worldwide on their journey to prioritize and better their brain health.  Find their insights throughout this article.  Now, let's dive into some of the most critical factors that women should be aware of when it comes to safeguarding their cognitive health. 

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Estrogen and it’s Role in Women’s Brain Health 

“Not only are women at a 2-fold higher risk of dementia than men, but also the disease seems to progress differently in women compared to men.  We now understand that Alzheimer’s disease starts years before the first obvious symptom of memory loss--in midlife—which coincides with the complex hormonal changes of perimenopause.  Brain imaging studies have found that during this period, women have higher amyloid accumulation, impaired glucose metabolism and accelerated brain shrinkage.  We now have multiple lines of evidence to support the neuroprotective role of estrogen and believe the abrupt drop in reproductive hormones, particularly 17B-estradiol, that occurs during perimenopause may, at least in part, account for these findings and explain why women are disproportionately impacted by Alzheimer’s.  Our understanding of the factors driving women’s differential susceptibility to disease like Alzheimer’s is still evolving and I have no doubt that this will have implications in terms of how we treat and prevent disease on an individual level.” - Dr. Kellyann Niotis, Expert in Preventative Neurology and Brain Health at Early Medical 

Estrogen isn't just crucial for reproductive functions; it also acts as a vital player in brain health.  This hormone crosses the blood-brain barrier, binding to specific receptors on brain neurons.  This connection triggers the production of protective substances against oxidative stress and enhances neuron connectivity.  Moreover, estrogen regulates glucose utilization in the brain, its primary energy source.  When estrogen levels drop, as in menopause, the brain faces an energy crisis, leading to symptoms like hot flashes and memory issues, referred to as "the whatchamacallit syndrome" by experts like Dr. Roberta Brinton.  Research highlights that more years of estrogen exposure correlates with a reduced risk of Alzheimer's, making the decrease of estrogen during menopause a critical piece for women's brain health.2 

As approximately 1.3 million women in the United States begin their menopausal journey each year, they enter a potentially higher risk phase of their lives.3  When researchers meticulously matched middle-aged women and men in all other risk factors, a distinct pattern emerged, foretelling the early stages of Alzheimer's development for women, often long before any symptoms manifest.  Strikingly, the women experiencing menopause exhibited the most pronounced abnormalities in certain biomarkers (or biological signals often in the blood or imaged), including impaired glucose metabolism, reduced brain volume, and increased plaques and tangles (in the brain) associated with Alzheimer's.4  This intriguing revelation suggests that the menopausal phase may serve as a crucial "window of opportunity" for these detrimental brain changes to take hold. 

What If I Got a Hysterectomy? 

A hysterectomy is a medical procedure that involves the removal of a woman's uterus, and in some cases, other reproductive organs like the ovaries or fallopian tubes.  One of the most notable consequences of a hysterectomy is the abrupt drop in estrogen levels.  For many women who undergo a hysterectomy, especially if the ovaries are also removed (a procedure known as oophorectomy), menopause can occur earlier than expected (also called “surgical menopause”).  Recent research has shed light on the potential impact of a hysterectomy on brain health, especially if hormone replacement therapy (HRT) is not administered afterward.  Studies indicate that women who had a hysterectomy without subsequent accompanying HRT may exhibit certain biomarker abnormalities linked to Alzheimer's disease.5  

Considering HRT as a Woman 

Hormone Replacement Therapy (HRT) is a treatment involving the use of medications containing hormones, often estrogen and progesterone, to supplement the body's natural hormone levels.  It is primarily prescribed to alleviate the symptoms of menopause, such as hot flashes, night sweats, and mood swings, by replenishing these diminishing hormone levels.  The decision to begin HRT should be a well-informed one, considering both its potential benefits and risks, especially in relation to cognitive health.  While HRT may offer immediate relief from menopausal symptoms, its impact on cognitive health varies.  Research suggests that starting HRT immediately after entering menopause might be beneficial in mitigating the adverse effects of low estrogen on the brain.6  However, if there has been a considerable gap since menopause, HRT may not be as effective and could even pose risks.  Given this complexity, it is crucial to consult with your healthcare provider to assess your individual circumstances and determine if HRT is suitable for you. 

ApoE4 Gene's Impact on Women's Brain Health 

The ApoE4 gene plays a significant role in Alzheimer's risk, especially for women.  There are three variants (or alleles) of the ApoE gene: ApoE2, ApoE3, and ApoE4, with individuals inheriting any combination of two of these alleles.  The ApoE4 allele is considered a risk gene for late-onset Alzheimer's. Having one ApoE4 copy increases the risk by three to five times, and two copies may elevate it by 15 times.7 

Female ApoE4 carriers also encounter unique challenges related to glucose metabolism and energy production.  They struggle to access ketones, an alternate energy source produced during fasting by the liver.  While the brain can usually switch between glucose and ketones as its fuel source, perimenopausal women with ApoE4 face impairments in both pathways, increasing the likelihood of brain fog and potentially Alzheimer's in the future.  To understand these genetic factors more in depth, please visit our previous article here.  

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Factors You Can Navigate for Brain Health 

“Women often take care of everyone but themselves.  When it comes to Alzheimer's prevention, this needs to change! It starts by embracing a brain-healthy way of eating.  This spills over into hitting target levels for exercise, reducing stress, and getting enough sleep.  Women may be especially vulnerable to getting Alzheimer's, but they are also uniquely equipped to be the change-makers who turn this epidemic around.” - Dr. Annie Fenn, Founder of Brain Health Kitchen and NeuroReserve Medical Advisor  

Lifestyle

Physical Activity: Exercise is a game-changer for brain health.  A single workout immediately boosts mood and sharpens focus.  Increased exercise is neuroprotective, reducing long-term risk of neurodegenerative disease (like Alzheimer’s, Parkinson’s).  Thirty minutes of aerobic exercise 3-4 times per week can be enough to make a meaningful difference.8 

Sleep: Hormonal changes might make sleep more difficult to come by.  An analysis of studies looking at the relationship between sleep and Alzheimer’s found a significantly higher risk of Alzheimer’s in those that had sleep disturbances or sleep disorders.9  Prioritize high quality sleep by sticking to a regular sleep schedule and avoiding alcohol or caffeine before bed.  Also, if you or your spouse suspects it, get checked for sleep apnea or undergo a sleep study with your physician. 

Socialization: Interacting with people close to you stimulates different parts of the brain and supports attention and memory.  Perhaps most importantly, socialization provides a means by which to build relationships and life purpose.  In fact, studies have linked more social activity with less cognitive decline during old age.10  

Caregiving

It comes as no surprise that not only are 2/3 of Alzheimer’s patients  women, but 60% of caregivers are also women.  Being in a caregiving role for someone with Alzheimer's can be incredibly challenging.  Caregivers who find themselves in situations with limited social support or feelings of isolation may experience heightened stress and feelings of being overwhelmed.  Prolonged caregiving periods can lead to chronic stress and increased risk of mental health issues.11  There's an integral connection between mental health and brain health, as poor mental well-being can wreak havoc on cognitive function and increase the risk of Alzheimer's and dementia, indicating this as much as 9 years ahead of diagnosis.12  Given this, caregivers should prioritize their mental health by making time for stress reduction, self-care, and socialization. 

Diet 

The impact of diet on a woman’s cognitive health can be game-changing as well.  Studies have reported associations between diets high in saturated fats and refined carbohydrates and impaired cognitive function, emphasizing the importance of dietary choices.  The Mediterranean diet, known for its brain-boosting qualities, is particularly relevant for women's cognitive health.  Research suggests that healthy dietary patterns, such as the Mediterranean diet, can offer protection against dementia and mild cognitive impairment.  The 'whole diet approach,' focusing on diet as a whole rather than individual foods or nutrients, proves beneficial for brain health.13  For women navigating the challenges of menopause, exploring specific dietary areas to concentrate on can be a valuable step toward maintaining cognitive well-being. Learn more specific recommendations by downloading our free guide  “Top 6 Things Women in Midlife Should Be Doing for Cognitive Wellness.” 

“Women make up 2/3 of Alzheimer’s patients as compared to men.  Because of this, I feel strongly that women should know their ApoE status.  This is because ApoE4 carriers are more sensitive to higher cholesterol levels than non-carriers and have to be more diligent about adhering to a low saturated fat diet and keeping their cholesterol levels below a certain level.  In addition, it appears that all ApoE4 carriers may respond better to higher doses of omega-3 fats specifically DHA from both fish as well as supplemental form.” - Dr. Heather Moday, Founder of the Moday Center, Medical Professional in Conventional and Functional/Integrative Medicine

For menopausal women with the ApoE4 gene, focusing on specific nutrients can potentially lower dementia risk.  Omega-3 fatty acids, especially DHA found in cold water fish like salmon, are vital for brain health and inflammation control.  ApoE4 carriers may need more DHA due to their unique brain metabolism. Additionally, consider supplementing with phosphatidylcholine-DHA (PC-DHA) for improved access to the brain by these omega-3’s.  Antioxidants like quercetin in onions and capers, and resveratrol in red grapes, could reduce the activity of MMP-9, a protein where higher levels are implicated with increased inflammation in combination with ApoE4 and declining estrogen.  These strategies may also counteract disrupted brain sugar metabolism in ApoE4 carriers during menopause, supporting cognitive health.  To learn more about nutrition and lifestyle to defy genetics and Alzheimer’s disease, read this article. 

For aging women who may find themselves juggling increasingly demanding responsibilities, finding the time and resources to fully manage every aspect of their cognitive health can be challenging.  In such cases, nutritional supplements may provide a practical tool.  Our supplement, RELEVATE, is designed to bridge the nutritional gaps that are often missing in the average American diet.  It contains a carefully curated blend of 17 brain-fueling nutrients from the Mediterranean diet, to strengthen an aging brain.  When time and circumstances make it difficult to maintain an ideal diet, RELEVATE steps in to help safeguard your brain health.  Learn more about RELEVATE by visiting here.  

References

  1. What is Alzheimer’s Disease? Symptoms & Causes | alz.org. (n.d.). Retrieved October 8, 2023, from https://www.alz.org/alzheimers-dementia/what-is-alzheimers/women-and-alzheimer-s
  2. Rahman, A., Jackson, H., Hristov, H., Isaacson, R.S., Saif, N., Shetty, T., Etingin, O., Henchcliffe, C., Brinton, R.D., and Mosconi, L. Sex and Gender Driven Modifiers of Alzheimer’s: The Role for Estrogenic Control Across Age, Race, Medical, and Lifestyle Risks. Front. Aging Neurosci., 2019, 11, 1–22.
  3. Peacock, K., & Ketvertis, K. M. (2022). Menopause. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK507826/
  4. Mosconi, L., Berti, V., Dyke, J., et al., Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition. Sci. Rep., 2021, 11, 1–16.
  5. Rocca, Walter A et al. “Hysterectomy, oophorectomy, estrogen, and the risk of dementia.” Neuro-degenerative diseases vol. 10,1-4 (2012): 175-8. doi:10.1159/000334764
  6. Mills, Zoe B et al. “Is Hormone Replacement Therapy a Risk Factor or a Therapeutic Option for Alzheimer's Disease?.” International journal of molecular sciences vol. 24,4 3205. 6 Feb. 2023, doi:10.3390/ijms24043205
  7. Alzheimer’s: Is it in your genes? - Mayo Clinic. (n.d.). Retrieved September 11, 2023, from https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-genes/art-20046552
  8. Basso, J. C. et al. Examining the Effect of Increased Aerobic Exercise in Moderately Fit Adults on Psychological State and Cognitive Function. Front. Hum. Neurosci. 16, (2022).
  9. Bubu, O. M., Brannick, M., Mortimer, J., et al., Sleep, Cognitive impairment, and Alzheimer’s disease: A Systematic Review and Meta-Analysis. Sleep, 2017, 40, 1–18.
  10. James, B. D., Wilson, R. S., Barnes, L. L., and Bennett, D. A., Late-Life Social Activity and Cognitive Decline in Old Age. J Int Neuropsychol Soc., 2011, 711–716.
  11. Caputo, Jennifer et al. “The Long-Term Effects of Caregiving on Women's Health and Mortality.” Journal of marriage and the family vol. 78,5 (2016): 1382-1398. doi:10.1111/jomf.12332
  12. Nedelec, T. et al. (2021). Identifying health conditions associated with Alzheimer's disease up to 15 years before diagnosis: an agnostic study of French and British health records. doi: https://doi.org/10.1016/S2589-7500(21)00275-2
  13. Puri, Seema et al. “Nutrition and cognitive health: A life course approach.” Frontiers in public health vol. 11 1023907. 27 Mar. 2023, doi:10.3389/fpubh.2023.1023907
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