#138 - Lauren Miller Rogen and Richard Isaacson, M.D.: Alzheimer's disease prevention—patient and doctor perspectives
Peter Atiyah hosts Lauren Miller Rogen (actress, director, HFC co-founder) and Dr. Richard Isaacson (Director, Alzheimer's Prevention Clinic at Weill Cornell). They discuss Lauren's family history of Alzheimer's, her preventative protocol guided by Dr. Isaacson, and the science of personalized Alzheimer's prevention, emphasizing lifestyle's role in modifying genetic risk.
Deep Dive Analysis
15 Topic Outline
Lauren's Lifelong Experience with Familial Alzheimer's Disease
Understanding Early Onset and Genetic Predisposition to Alzheimer's
Lauren's Mother's Disease Progression and Family Impact
Diverse Manifestations and Stages of Alzheimer's Disease
Richard's Detective Work on Lauren's Family History
The Role of Exercise and Gender Differences in Alzheimer's Risk
Importance of APOE Status and Head Trauma Considerations
Personalizing Alzheimer's Care with Genetic Testing
Lauren's Personal Protocol for Alzheimer's Prevention
Unique Treatment Considerations for ApoE4 Carriers
Discussion on CBD and THC for Disease Prevention
Cognitive Testing Procedures and Lauren's Results
Relevance of Sense of Smell and Hearing in Alzheimer's Risk
Emotional Benefits of Proactive Health Management
Hilarity for Charity (HFC) Mission and Impact
7 Key Concepts
Alzheimer's Disease Progression
Alzheimer's disease begins decades before the first symptoms of memory loss appear, often in a preclinical phase without clinically apparent symptoms. The pathology spreads through different brain regions, leading to varied symptoms depending on the affected area.
Early Onset Alzheimer's
This is a rare form of Alzheimer's disease, typically occurring in individuals in their 40s or 50s, often due to specific genetic mutations like presenilin one, presenilin two, or amyloid precursor protein gene mutation. However, most earlier onset cases are due to a combination of polygenic risk and lifestyle factors.
Polygenic Risk
This concept describes how multiple genes, rather than a single one, interact to influence a person's risk for Alzheimer's disease. Some genes increase risk, while others may decrease it, creating a complex interplay that determines individual susceptibility.
Epigenetics
Epigenetics refers to the interplay between a person's genetics and environmental factors, lifestyle, behavior, or exposures (e.g., viruses, trauma) that can trigger genes to function in specific ways, thereby influencing disease risk.
APOE4 Variant
The APOE4 variant is the most common genetic risk factor for Alzheimer's disease; inheriting one or two copies of this allele increases risk. It is also a cardiovascular risk gene, increasing vascular risk and the likelihood of amyloid protein accumulation in the brain.
Perimenopause as a Brain Condition
The perimenopause transition involves bioenergetic shifts in the brain and a precipitous drop in neuroprotective estrogen, which can predispose susceptible women (e.g., those with APOE4) to accelerated Alzheimer's pathology. Symptoms like hot flashes and brain fog are manifestations of these brain changes.
ABCs of Alzheimer's Prevention
This is a structured approach to Alzheimer's prevention involving regular follow-up and tracking. 'A' stands for Anthropometrics (body composition), 'B' for Blood-based biomarkers (cholesterol, inflammation, metabolism, nutrition, genetics), and 'C' for Cognitive function.
7 Questions Answered
Alzheimer's disease progresses through three stages: the preclinical phase (disease in the brain without symptoms), mild cognitive impairment (noticeable memory glitches but the person can still care for themselves), and dementia (symptoms worsen, and the person can no longer care for themselves).
The APOE4 variant increases the risk of Alzheimer's disease by elevating vascular risk and accelerating the accumulation of amyloid protein in the brain. It is considered a significant cardiovascular risk gene as well.
Beyond living longer, women, especially those with APOE4, are significantly impacted by bioenergetic shifts and the precipitous drop of neuroprotective estrogen during the perimenopause transition, which can accelerate Alzheimer's pathology.
Decreased odor identification, or the inability to precisely identify certain smells, can be an early indicator or 'harbinger of badness' for neurodegenerative diseases like Alzheimer's, similar to its role in Parkinson's disease.
Exercise and physical activity, particularly high-intensity interval training, are considered the most impactful lifestyle interventions for Alzheimer's prevention. For APOE4 carriers, exercise is even more critically important as a sedentary lifestyle exacerbates Alzheimer's pathology in these individuals.
Genetic testing, especially for APOE status and other polygenic risk factors, helps doctors understand an individual's specific risk profile. This information allows for targeted, personalized lifestyle interventions and supplement recommendations to mitigate disease risk.
Knowing one's genetic risk, such as APOE4 status, can be empowering, leading to proactive lifestyle changes and adherence to prevention protocols. Studies suggest that while initial anxiety may occur, there are no long-term negative psychiatric or psychological outcomes, and it enables personalized care.
19 Actionable Insights
1. Embrace Early Prevention Mindset
Recognize that Alzheimer’s disease begins decades before symptoms appear, making early intervention critical. Don’t wait until later in life; take control of your brain health as early as possible, as science provides tools to modify risk.
2. Prioritize High-Intensity Exercise
Engage in regular physical activity, specifically high-intensity interval training (HIIT), cardiovascular exercise, and strength training. This is especially crucial for individuals with the APOE4 variant, as it can significantly improve cognitive function and counteract the effects of a sedentary lifestyle.
3. Optimize Omega-3 Intake
Consume fatty fish and consider supplementing with omega-3 fatty acids, particularly DHA and EPA, aiming for higher doses (e.g., 2000mg combined DHA/EPA) if you carry the APOE4 variant. This is vital for brain protection, as E4 carriers may require more to achieve optimal red blood cell levels (aim for 12-14+ index).
4. Address Hormonal Shifts in Women
Women, especially those with APOE4, should be aware of bioenergetic shifts during perimenopause, which can accelerate Alzheimer’s pathology. Consult an OBGYN to discuss potential interventions with specific types of hormone replacement therapy (e.g., natural estrogen, progesterone) to mitigate the negative impact of estrogen withdrawal.
5. Prioritize Quality Sleep
Improve sleep habits, as poor sleep can negatively impact brain health and accelerate neurodegenerative processes. Consider strategies like magnesium L-threonate, which may aid sleep and cognitive function.
6. Reduce Sugar and Refined Carbs
Limit consumption of sugar and high glycemic index foods, as excessive intake can contribute to metabolic dysfunction that impacts brain health. This is particularly important for individuals with a genetic predisposition to Alzheimer’s.
7. Manage Homocysteine Levels
Address elevated homocysteine levels, an independent risk factor for brain shrinkage and impaired memory, by supplementing with B-complex vitamins (B12, B6, folic acid). This intervention can help slow brain atrophy and improve memory function.
8. Optimize Vitamin D Levels
Ensure your vitamin D levels are optimal, aiming for a range of 40-50 ng/mL, or potentially 50-70 ng/mL for APOE4-4 carriers. Take vitamin D supplements with a fat-containing meal for better absorption and get 10-15 minutes of sun exposure between 11 AM and 1 PM.
9. Stay Cognitively Engaged
Continuously challenge your brain by learning new things and staying intellectually active. Cognitive engagement is critical for brain health, as the principle ‘if you don’t use it, you lose it’ applies to cognitive function.
10. Monitor Body Composition
For women, pay close attention to body fat percentage and visceral fat (enlarged waist circumference), as abdominal obesity increases dementia risk. For men, focus on maintaining muscle mass.
11. Screen and Correct Hearing Loss
Get early recognition and address any hearing impairment, as hearing loss is identified as a highly impactful modifiable risk factor for dementia. Correcting hearing loss may help maintain social engagement and cognitive function.
12. Reconsider Alcohol Intake (E4)
While light to moderate alcohol consumption (4-7 drinks/week) might be beneficial for non-APOE4 carriers, individuals with the APOE4 variant may benefit more from decreasing alcohol intake or abstaining altogether.
13. Avoid Tobacco Use
Refrain from tobacco use, as it exacerbates Alzheimer’s risk, especially for individuals with the APOE4 variant.
14. Be Cautious with Head Trauma
Individuals with the APOE4 gene may be more susceptible to the negative effects of head trauma. Reconsider participation in contact sports, particularly for children with this genetic predisposition.
15. Consider Curcumin Supplementation
For those at higher risk, especially with inflammatory markers like TNF alpha, consider a nanoparticle version of curcumin (e.g., Theracurmin) due to its potential anti-inflammatory effects and ability to cross the blood-brain barrier, as suggested by some studies.
16. Utilize Regular Health Tracking
Engage in regular follow-up with healthcare professionals, including body composition measurements (anthropometrics), blood-based biomarkers (cholesterol, inflammation, metabolism, nutrition), and cognitive function assessments. This iterative process allows for personalized care refinement.
17. Use Odor Identification Test
Be aware that a decreased ability to identify odors can be an early harbinger of neurodegenerative diseases like Alzheimer’s. While not perfect, it can be a useful objective indicator for monitoring brain health.
18. Approach THC/CBD Individually
If considering CBD or THC for sleep or stress reduction, treat it as an individualized ’n of 1’ study. Monitor objective metrics (e.g., sleep trackers, cognitive function) to assess its specific impact on your health, and consider edibles over inhaled forms.
19. Support Alzheimer’s Caregivers
Recognize the immense strain on primary caregivers for Alzheimer’s patients. Support organizations like Hilarity for Charity (HFC) that provide respite care, personalized support groups, and caregiver training to alleviate this burden.
6 Key Quotes
Alzheimer's disease starts in the brain decades before the first symptom of memory loss begins.
Richard Isaacson
Genes are not our destiny. We can absolutely win the tug of war against our genes.
Richard Isaacson
I don't want to live in the dark and not use the few tools that I've been given at this point. That seems way worse to me.
Lauren Miller Rogen
If you don't use it, you lose it. Staying cognitively engaged is like critical.
Richard Isaacson
I think there is so much control that can be had that we did not have even just a few years ago.
Lauren Miller Rogen
Four out of 10 cases of Alzheimer's may be preventable if that person does everything right.
Richard Isaacson
1 Protocols
Lauren Miller Rogen's Alzheimer's Prevention Protocol
Richard Isaacson and Lauren Miller Rogen- Attend regular follow-up appointments every six months.
- Repeat body composition measures (anthropometrics), blood-based biomarkers (cholesterol, inflammation, metabolism, nutrition, genetics), and cognitive function tests.
- Refine and fine-tune interventions based on repeat test results, memory function, and cholesterol levels.
- Prioritize high-intensity interval training (HIIT) for exercise.
- Consume fatty fish and take omega-3 fatty acid capsules (approximately 2000 mg of DHA and EPA combined) to achieve a red blood cell omega-3 index of at least 12-14.
- Take a very purified form of cocoflavanols.
- Take a specific nanoparticle version of curcumin for anti-inflammatory effects.
- Take specific B-complex vitamins (B12, B6, folic acid) to address homocysteine levels.
- Optimize vitamin D levels to 40-50 ng/mL (or 50-70 ng/mL for APOE4-4 carriers), taking supplements with a meal containing fat and getting 10-15 minutes of sun exposure between 11 AM and 1 PM.
- Consider magnesium L-threonate for brain health and sleep.
- Be cautious with high saturated fat and high glycemic index diets.
- Limit alcohol intake, possibly abstaining, especially for APOE4 carriers.
- Prioritize cognitive engagement and continuous learning.
- Address hearing loss early with an audiologist if necessary.