Episode # 10
The Alzheimer's Solution Revolution
#10—Why Low Estrogen Levels in Women Are Linked to an Increased Risk for Alzheimer’s Disease
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EPISODE 5
Summary and Audio
In the U.S., two-thirds of diagnosed cases of dementia and Alzheimer’s disease are women.
And, a number of studies have shown that lower estrogen levels “before, during, and after menopause” is a risk for late-onset Alzheimer’s disease (LOAD).
However, the risk factors associated with declining estrogen levels and late-onset Alzheimer’s disease (LOAD) in women as they age is not widely known.
One key bridge that connects declining estrogen levels in postmenopausal women in the risk for LOAD is mitochondrial energy metabolism deficits.
Estrogen is a regulator of glucose metabolism in women and brain estrogen deficiency sets in motion a brain energy metabolism crisis in women—particularly after menopause.
A decline in estrogen levels in postmenopausal women is commensurate with a decline in cerebral glucose metabolism.
Thus, the inability to efficiently metabolize glucose in the aging brain (glucose hypometabolism) predicates the need for an alternate fuel to sustain the brain’s high demands for energy.
The demand for an alternate mitochondrial fuel in low estrogen states results in a compensatory shift to ketone metabolism that is enabled by the metabolism of fats derived from myelin—a nerve sheath substance that wraps around the axon extension of nerves.
That catabolism of myelin (grey matter demyelination) is a signature hallmark of grey matter atrophy and the loss of brain volume, which in turn is a pathological feature in the progression of Alzheimer’s disease in the aging brain.
Additionally, female ApoE4 carriers may be at higher risk for glucose hypometabolism and an earlier onset of myelin breakdown.
ApoE4-related mitochondrial dysfunction is also linked to the development of late-onset Alzheimer’s disease.
Since “mitochondrial DNA is maternally inherited and mitochondrial defects that contribute to the risk for brain metabolic deficits that include glucose hypometabolism and oxidative stress is seen in adult offspring of mothers with a history of Alzheimer’s.”, optimizing mitochondrial function in the aging brain is of critical importance—particularly in ApoE4 carriers.
Please listen in to episode # 10 for more on this vital association between estrogen deficiency and the increased risk for of late-onset Alzheimer’s disease in women.
Top Takeaways
• Women and Alzheimer’s Risk: Approximately two-thirds of Alzheimer’s patients diagnosed after the age of 65 are women, therefore, the early intervention strategies for prevention earlier in life are critical.
• Estrogen’s Critical Role: Estrogen isn’t just a hormone; it’s a regulator of brain glucose metabolism and mitochondrial energy production.
• Energy Crisis in the Brain: Loss of estrogen triggers brain glucose hypometabolism which increases the risk for cognitive decline.
• ApoE4 + Low Estrogen = High Risk: Women carrying the ApoE4 gene variant face a compounded risk for Alzheimer’s.
• Estrogen as a Defender: Beyond hormone balance, estrogen acts as an antioxidant and activates protective enzymes like glutathione peroxidase.
• Phytoestrogens as Allies: Plant-based estrogens such as genistein can partially mimic estrogen’s protective effects and reduce oxidative stress.
• Hormone Therapy: Proceed with Caution: While beneficial for some, estrogen therapy carries cancer-related risks—bioidentical and natural options may be safer.
• Your Mother’s Mitochondria Matter: Mitochondrial DNA is inherited from mothers, influencing energy metabolism and Alzheimer’s risk.
• Midlife is Your Window of Opportunity: Interventions such as ketogenic diets, medium chain triglyceride (MCT) oil, and lifestyle changes at midlife protects against the risk for cognitive decline in later life.
• Pregnenolone and DHEA: Hormone replacement therapy can support brain health but must be under the expert supervision of a clinician.
• A healthy lifestyle, and diet that is abundant in antioxidant-rich foods are essential for reducing the risk for Alzheimer’s disease in the aging process.
Epidsode 10
Timestamp Highlights
In this Episode
[00:53] Welcome and episode overview: Introduction to the topic: Why low estrogen levels increase the risk for Alzheimer’s disease in women.
[01:49] New study (May 2022) findings: lifestyle factors, amyloid burden differences in men vs. women, and their implications in the risk for Alzheimer’s disease.
[02:58] Metabolic and vascular health, and ApoE4 genetic variant—study found an increased beta-amyloid amyloid burden in women over men.
[04:30] Introduction by co-host Susan Brender—framing the discussion on woman’s risk for late-onset Alzheimer’s disease (LOAD) which was recorded a couple of years earlier (2020).
[05:49] Neuroenergetics explained: The importance of brain energy metabolism and mitochondrial health in the risk for LOAD.
[07:03] Alzheimer’s prevalence statistics (2020): Women vs. men and aging as a major risk factor for LOAD.
[09:20] Women’s estrogen levels decline in post-menopause which increases the risk for cardiometabolic disease and LOAD for aging women.
[11:34] Estrogen therapy controversies: Cancer risk and historical context of synthetic hormones.
[12:02] Safer alternatives: Natural estrogens vs. synthetic hormones and current research gaps.
[13:38] Estrogen’s role in glucose metabolism: Why it’s a missing link in brain health.
[14:25] ApoE4 carriers and energy metabolism deficits—the compounded risk it represents when combined with estrogen decline.
[15:54] Strategies for hormone balance in the aging process: Estrogen therapy, phytoestrogens, and Traditional Chinese Medicine.
[16:42] DHEA and pregnenolone: Brief reference to other hormone replacement therapies (HRT).
[17:50] HRT options—Phytoestrogens like genistein (soy isoflavone) provide powerful antioxidant and anti-inflammatory protective effects.
[18:58] Estrogen functions as an antioxidant and anti-inflammatory hormone: How it protects brain cells and reduces oxidative stress.
[20:00] Genetic antioxidant expression: Estrogen’s role in upregulating antioxidant enzymes like glutathione peroxidase.
[20:59] Maternal family history: Mitochondrial DNA inheritance and its impact on energy metabolism.
[22:38] Midlife interventions: tailored dietary therapies such a ketogenic and caloric restriction diets, MCT oil, and lifestyle strategies for brain health.
[24:20] Q&A: Estrogen phytoestrogen therapy and cancer risk—navigating the controversy.
[28:00] BrainDefend® program explained: Personalized prevention strategies for brain health and healthy aging.
[29:48] Ralph’s book: The Diabetic Brain in Alzheimer’s Disease and where to find it.
[31:30] Next episode preview: Hormone replacement therapy and more regarding “neurosteroids” (brain hormones).
Please listen in!
Ralph Sanchez, MTCM, CNS, D.Hom
BrainDefend®
www.facebook.com/TheAlzheimersSolution
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