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#18 – Richard Isaacson, M.D.: Alzheimer’s prevention — Whalespan

Content›Video›#18 – Richard Isaacson, M.D.…

#18 – Richard Isaacson, M.D.: Alzheimer’s prevention

Peter Attia2h 25m · 2020-01-01

Support Rate

66%

180 of 271 claims supported

Support rate

180 of 271 claims supported

180 supported91 partial / not

Claims from this content

173

◐Partially SupportedStatin use may impair cholesterol synthesis in the brain, potentially impacting cognition.✓Well SupportedPeter Attia shares updates on activities, papers, and longevity science via a weekly email newsletter.◐Partially SupportedThe ApoE4 isoform is associated with a 2-3 fold increased risk of Alzheimer's disease for the 3-4 genotype and an 8-10 fold increased risk for the 4-4 genotype.✓Well SupportedAlzheimer's disease has a pre-clinical, pre-symptomatic phase.✓Well SupportedAlzheimer's disease is referred to as 'type 3 diabetes' due to similarities with brain diabetes.

More from Peter Attia

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Peter Attia on Rapamycin (with Matt Kaeberlein)

Attia walks back the clinic protocol: too aggressive for healthy adults

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A. Volkovreader

4h

Bookmarking — the dossier-vs-overview split is the right call. Most of the time I want overview; sometimes I want receipts.

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Would love a "what would change this verdict" RSS feed. Sign me up if it exists.

✓Well Supported

Amyloid PET scans have about 97% accuracy in diagnosing Alzheimer's disease in living people compared to post-mortem analysis.

◐Partially SupportedNo statin trial has had dementia as a primary outcome, but in trials where dementia was a secondary outcome, there was either no change or a reduction in dementia risk.

✓Well SupportedCardiovascular disease is the most preventable of the major disease categories (atherosclerosis, cancer, neurodegenerative disease) due to better understanding of its pathology and more effective prevention tools.

✓Well SupportedThe menopause transition acts as a brain aging accelerator, leading to mitochondrial decline or waste product accumulation manifested as amyloid and tau.

◐Partially SupportedThe prevalence of APOE genotypes is approximately 50-55% for E3/E3, 25% for E3/E4, 5-10% for E2/E4, and E2/E2 is the rarest.

◐Partially SupportedThe APOE4 allele increases Alzheimer's disease risk, while APOE2 appears to decrease it.

✓Well SupportedBlueberries, specifically anthocyanins, may provide antioxidant benefits and are being studied for Alzheimer's disease.

✓Well SupportedThe APOE gene has three types (2, 3, and 4), and individuals have two copies, leading to six possible combinations.

✓Well SupportedLifestyle interventions are effective for Alzheimer's disease prevention in individuals with the ApoE3/4 genotype.

✓Well SupportedMetformin use in people with type 2 diabetes is associated with significantly less breast cancer, regardless of diabetes status, obesity, or hyperinsulinemia.

✓Well SupportedCognitive benefits of reducing homocysteine with B vitamins are most pronounced in individuals with the highest tertile of omega-3 status (specifically DHA).

✓Well SupportedIndividuals with ApoE e4e4 or e3e4 genotypes have an increased risk and should take preventative measures seriously.

✓Well SupportedAutosomal dominant mutations in PSEN1, PSEN2, or APP genes can cause early-onset Alzheimer's disease.

✓Well SupportedCognitively engaged individuals with Alzheimer's disease and strong cognitive reserve may experience a slower rate of decline.

✓Well SupportedThe APOE E3/E3 genotype is the most common genotype and is considered the baseline regarding Alzheimer's risk.

✓Well SupportedThe ApoE2/2 genotype, which is rare, is associated with approximately a 20% risk reduction for Alzheimer's disease.

✓Well SupportedFunding for Alzheimer's research should be balanced between treatment and prevention, with a potential split favoring prevention.

◐Partially SupportedProgressive short-term memory loss and other changes are likely Alzheimer's disease until reversible causes like thyroid issues or B12 deficiency are ruled out.

◐Partially SupportedClinical diagnosis of Alzheimer's disease is not always accurate, necessitating the use of biomarkers.

✓Well SupportedSeeing biomarkers improve provides positive reinforcement for patients actively engaged in their health.

◐Partially SupportedIndividuals with ApoE3/3 genotype and a family history of Alzheimer's may have other unidentified genetic risk factors.

✓Well SupportedPatients with type 2 diabetes have a higher risk of Alzheimer's disease.

◐Partially SupportedAlzheimer's risk can be stratified by APOE genotype to implement different preventative strategies.

✓Well SupportedMetabolic health is a critical factor in Alzheimer's disease and links all chronic diseases.

✓Well SupportedSpecific B complex vitamins can address high homocysteine levels, an independent risk factor.

✓Well SupportedFinding the right statin involves trying different options to balance efficacy and side effects.

✓Well SupportedLDL cholesterol levels below 100 are desirable, with levels below 70 being preferred.

?Limited ResearchConflicting alcohol consumption guidelines exist, with older studies suggesting protective effects of moderate intake and newer studies indicating zero alcohol is better.

◐Partially SupportedUsers can download their data from 23andMe and upload it to services like Prometheus for genetic analysis.

◐Partially SupportedOnly about 100 out of 20,000 human genes are deterministic, meaning they guarantee a specific disease if mutated.

◐Partially SupportedFor children of parents with APOE 3-4 genotype, there is a 25% chance of being 4-4, a 50% chance of being 3-4, and a 25% chance of being 3-3.

✓Well SupportedEngaging in 2-3 half-hour strength training sessions per week is recommended.

◐Partially SupportedHigh-intensity interval training (HIIT) is necessary for significant weight loss, whereas 20 minutes of elliptical training three times a week is insufficient.

✓Well SupportedWhen initiating HRT in perimenopausal women, lower doses can be used compared to full menopause.

✓Well SupportedSupplementing with 5-methyltetrahydrofolate and methylcobalamin (Vitamin B12) can lower homocysteine levels in individuals with MTHFR gene polymorphisms.

◐Partially SupportedMixing different types of exercise is important for overall health.

◐Partially SupportedTracking genetic influence, such as APOE status and Lp(a), in families with Alzheimer's disease or cardiovascular disease can help understand disease origins and genetic contribution.

◐Partially SupportedThe Alzheimer's Prevention Manifesto is available as a free online CME course for physicians via ailsyou.org.

◐Partially SupportedDelaying the onset of Alzheimer's disease by two to ten years can lead to individuals dying from other causes or gaining time for future treatments.

◐Partially SupportedEpigenetics, influenced by genetics and environment/lifestyle, is a key factor in how genes influence Alzheimer's risk.

◐Partially SupportedRisk factors for Alzheimer's disease can change at different points in the life course.

◐Partially SupportedAlzheimer's disease biomarkers can be detected 20-30 years before clinical onset, and APOE4 variants may be associated with smaller brains at birth.

◐Partially SupportedAerobic exercise, with a minimum of 150-180 minutes per week, often recommended as two-thirds cardio and one-third strength training, is supported by the majority of evidence.

◐Partially SupportedTesting for TOMM40 gene variants relevant to Alzheimer's is not commercially available.

◐Partially SupportedAttentional deficits, rather than memory impairment, may cause difficulty remembering, and treating depression can improve attention and memory.

◐Partially SupportedAn N-of-one approach leads to the most success in health and longevity.

◐Partially SupportedAlzheimer's prevention management includes anthropometrics, blood biomarkers, and cognitive function, assessed every six months.

◐Partially SupportedThe APOE4 gene may require fewer participants to detect a cognitive benefit from HRT.

◐Partially SupportedThe presence of the TNF-alpha gene in combination with an APOE e4 allele can increase Alzheimer's risk six-fold, potentially leading to early onset disease.

◐Partially SupportedExercise is the most effective intervention for reducing or slowing the accumulation of amyloid in the brain.

◐Partially SupportedEngaging in musical activities from early to mid-life can build cognitive reserve and increase resilience to Alzheimer's.

✓Well SupportedSedentary lifestyles and metabolic conditions negatively impact the hippocampus, leading to its shrinkage.

✓Well SupportedAlzheimer's disease is fundamentally a mitochondrial-based disease, with amyloid accumulation being an upstream effect of mitochondrial dysfunction.

◐Partially SupportedLoss of a collaborative partner can lead to sharper cognitive decline in individuals with Alzheimer's.

◐Partially SupportedFour out of ten cases of Alzheimer's disease may be preventable if all recommended lifestyle and medical interventions are implemented.

◐Partially SupportedIn women over 65, female gender, APOE4 genotype, and age significantly increase the likelihood of amyloid deposition.

◐Partially SupportedWomen, on average, have lower mortality rates than men across most major causes of death, with the exception of Alzheimer's disease.

◐Partially SupportedLowering systolic blood pressure to 120 mmHg compared to 140 mmHg significantly improves cardiovascular outcomes and reduces the risk of cognitive decline.

◐Partially SupportedThe term 'prevention' in Alzheimer's research is debated, with 'risk reduction' being a more accurate alternative in some contexts.

◐Partially SupportedThe prevalence of Alzheimer's disease has increased due to people living longer, improved diagnostic tools, and potentially increasing true incidence.

◐Partially SupportedAlzheimer's disease can be categorized into pre-clinical, mild cognitive impairment, and dementia phases.

◐Partially SupportedCognitive assessments aim to identify specific deficient cognitive domains such as memory, processing speed, attention, and executive function.

◐Partially SupportedComprehensive genetic analysis for Alzheimer's risk is primarily performed for patients with APOE4 genotype or family history.

◐Partially SupportedLewy body dementia can present with Parkinson's-like symptoms including slowed movements, paranoia, hallucinations, and acting out dreams.

◐Partially SupportedWomen are in the express lane for Alzheimer's disease, potentially due to factors related to life course, number of children, and increased stress.

◐Partially SupportedAilsyou.org provides information on controllable and uncontrollable factors related to Alzheimer's disease.

◐Partially SupportedMitochondrial dysfunction can be caused by bioenergetic shifts during perimenopause.

◐Partially SupportedGenes and genetic variations besides apoe predispose individuals to alzheimer's disease.

◐Partially SupportedThe MTHFR gene plays a role in Alzheimer's risk via homocysteine metabolism.

◐Partially SupportedThe Alzheimer's Association offers 10 tips for brain health.

◐Partially SupportedTau protein scans will soon be available for diagnosing Alzheimer's disease.

◐Partially SupportedA face-name associative memory test can predict amyloid in the brain.

◐Partially SupportedHaving a brain means a person is at risk for Alzheimer's disease.

◐Partially SupportedLifestyle interventions can have a bigger impact on Alzheimer's prevention than pharmacological treatments.

◐Partially SupportedStress reduction through meditation, deep breaths, and adequate sleep is crucial for health and aging.

◐Partially SupportedKey personal health numbers to know include blood pressure, pulse, body fat percentage, weight, cholesterol, and blood sugar.

◐Partially SupportedMany primary prevention studies miss the mark because they do not account for the time course of the disease.

◐Partially SupportedPeter Attia conducted an experiment to assess cognitive performance deterioration after alcohol consumption using a learnable cognitive test.

◐Partially SupportedEven with a deterministic gene for early-onset Alzheimer's, developing the disease is not guaranteed.

◐Partially SupportedIndividuals with a family history of Alzheimer's disease or subtle early signs of cognitive impairment are eligible for a prevention clinic, provided they have normal cognitive function.

◐Partially SupportedAlzheimer's disease can develop through multiple pathways, including microvascular disease, diabetes, and mitochondrial dysfunction.

◐Partially SupportedFor non-smoking individuals over 40, the probability of dying from cerebrovascular disease, cardiovascular disease, cancer, or Alzheimer's exceeds 75%.

◐Partially SupportedThe menopausal transition is a critical window for intervention in women's brain health.

◐Partially SupportedAmyloid in the brain is indicative of Alzheimer's disease but can also be seen in Lewy body dementia.

◐Partially SupportedAlzheimer's disease is an indirect cause of death, often leading to complications like urinary tract infections, sepsis, or aspiration pneumonia.

◐Partially SupportedAn estimated 47 million Americans have preclinical Alzheimer's disease.

◐Partially SupportedThe male menopause transition, or andropause, is being studied for its impact on brain health.

◐Partially SupportedApproximately 5 million Americans have dementia due to Alzheimer's disease.

◐Partially SupportedCombining exercise, blueberries, low-carbohydrate diets, and precision medicine can lead to tangible improvements in health.

◐Partially SupportedThe link between Alzheimer's and the APOE gene (APOE4) might be an artifact of Genome-Wide Association Studies (GWAS) that have not tested interventions.

◐Partially SupportedHigh-sensitivity C-reactive protein is the most informative inflammation marker, and myeloperoxidase is a risk factor for vascular cognitive impairment.

◐Partially SupportedBiomarkers for Alzheimer's prevention include cholesterol analysis, inflammation markers, and nutritional biomarkers.

◐Partially SupportedA study showed a 19% risk reduction of mild cognitive impairment (MCI) after four years of treatment, with effects observed three years after the study stopped.

◐Partially SupportedFunding research for Alzheimer's prevention, particularly the type conducted by practitioners like Richard Isaacson, is crucial and severely underfunded.

◐Partially SupportedPlaying music recruits multiple brain regions, strengthening neural pathways and improving cognitive function, potentially enhancing resilience to Alzheimer's.

◐Partially SupportedLong-term educational attainment is the most effective early-life intervention to mitigate Alzheimer's risk.

◐Partially SupportedRichard Isaacson avoids onions, garlic, shallots, scallions, and all alliums.

◐Partially SupportedCurcumin use should be based on individual factors like inflammatory markers or genetic predisposition.

✕Not SupportedThe success rate for pharmacological treatments for Alzheimer's disease is 0.4%.

◐Partially SupportedIndividuals with amyloid in their brain should ensure they are taking the correct form of curcumin.

◐Partially SupportedCurcumin may improve cognitive function and increase CD50 levels.

✕Not SupportedTraditional exercise like 20 minutes of elliptical training three times a week is insufficient for significant weight loss and may only help with maintenance.

✕Not SupportedThe prevailing view in Alzheimer's research focusing solely on amyloid and tau is being challenged by those who consider metabolic and mitochondrial factors.

✕Not SupportedMost commercially available cognitive tests are scaled and validated for people with dementia, making them insensitive to early cognitive decline in individuals without dementia.

◐Partially SupportedIntervention timing around menopause is key for preventing Alzheimer's disease.

?Limited ResearchThe increased incidence and prevalence of Alzheimer's disease suggest a combination of environmental factors and increased awareness/diagnostic acumen.

◐Partially SupportedHaving an early onset Alzheimer's gene does not guarantee the individual will develop the disease, especially with potential interventions.

◐Partially SupportedCurcumin did not show efficacy in a randomized study for mild to moderate Alzheimer's, potentially due to poor absorption.

✕Not SupportedHigh-intensity exercise where one cannot talk and heart rate exceeds 150 bpm is more effective than low-intensity activity.

◐Partially SupportedThe dose of curcumin used in a small study was one pill per day, with a potential dose of 500-600mg.

?Limited ResearchThe evidence for hormone replacement therapy's application in perimenopausal women is not robust.

◐Partially SupportedIntervention studies may yield negative results if the time course of the disease and the intervention are not appropriately matched.

◐Partially SupportedApproximately two-thirds of Alzheimer's patients in the US have at least one copy of the APOE4 gene.

◐Partially SupportedMost cancers arise from somatic mutations, not inherited germline mutations, and are therefore not deterministic from birth.

◐Partially SupportedIt is no longer possible to upload 23andMe data to Prometheus for detailed genetic analysis due to FDA restrictions.

◐Partially SupportedExercise is the only intervention with Level 1 evidence for Alzheimer's disease risk reduction and treatment.

◐Partially SupportedDietary choices, such as avoiding ice cream, may impact breast cancer risk, particularly given the insulin sensitivity of most breast cancers.

◐Partially SupportedA fasting blood glucose cutoff of 97 is recommended for brain health and cognitive function.

◐Partially SupportedHigh-intensity interval training carries a risk of muscle injury if overdone.

◐Partially SupportedBelieving that higher education, mental engagement, social support, purpose, and learning musical instruments are beneficial for cognitive health carries no risk of increasing Alzheimer's risk.

◐Partially SupportedDismissing an intervention based on a study with no observed effect is only valid if the study was conducted correctly, including appropriate matching of the intervention's time course to the disease's progression.

◐Partially SupportedA precision medicine approach for Alzheimer's prevention incorporates cholesterol, inflammation, metabolism, nutrition, biomarkers, genetics, body fat, and cognitive function.

◐Partially SupportedIndividuals with Alzheimer's who maintain high cognitive engagement and strong backup neural pathways may experience a slower decline.

◐Partially SupportedAge-related cognitive change is distinct from Alzheimer's disease and does not cause pathological brain changes or affect daily living.

◐Partially SupportedMany commercially available cognitive tests require high skill to administer and are not suitable for practices without specialized expertise or high patient volume.

◐Partially SupportedBrain imaging like MRI is recommended to rule out tumors and assess vascular burden or atrophy, especially in the frontal, temporal lobes, and hippocampus.

◐Partially SupportedAlzheimer's disease is a life course disease where silent pathology may build up from early life.

◐Partially SupportedIndividuals can take steps to reduce their risk of Alzheimer's disease.

◐Partially SupportedAlzheimer's disease was traditionally diagnosed clinically based on progressive short-term memory loss and other cognitive changes that impair daily living.

◐Partially SupportedExercise personalization requires considering body fat and muscle mass.

◐Partially SupportedClinical decisions should be made by triangulating information from multiple sources rather than relying on a single biomarker.

◐Partially SupportedAn individual's Alzheimer's disease trajectory can be influenced by hereditary and acquired risk factors.

◐Partially SupportedSudden onset Alzheimer's disease can lead to rapid health deterioration and death within months.

◐Partially SupportedGenome-wide association studies can be misleading if they do not account for the introduction of potential treatments for a disease.

✕Not SupportedMeasuring serum levels of fatty acids based on food frequency questionnaires is problematic.

◐Partially SupportedComprehensive genetic analysis for Alzheimer's risk assessment, including SNPs, is time-consuming, requiring significant physician and staff time.

◐Partially SupportedThera-curcumin has shown potential in reducing amyloid in PET scans in individuals with mild to moderate Alzheimer's disease.

◐Partially SupportedJ Rose offers a combined lozenge of methylfolate and methyl B12 that is verified and effective.

◐Partially SupportedNeurologic diagnoses are typically made based on history (80-90%), but biomarkers like amyloid scans and spinal fluid tests are available for Alzheimer's.

◐Partially SupportedA patient's mother having Alzheimer's at age 57 with APOE 3/4 genotype provides more reassurance than if she was 3/3, suggesting lower genetic risk in the latter case.

◐Partially SupportedDetailed lipid profiling is more informative than basic cholesterol measurements for assessing cardiovascular risk.

◐Partially SupportedAchieving success in weight loss and health improvement requires a non-one-size-fits-all approach based on individual biology and genetics.

◐Partially SupportedSeeing biomarkers improve provides positive reinforcement for patients struggling with weight loss and health changes.

◐Partially SupportedLower carbohydrate intake, green leafy vegetables, and fasting are recommended for nutrition.

◐Partially SupportedAdequate sleep is essential for fat loss, health, and preventing accelerated aging.

◐Partially SupportedWomen with vascular risk factors may respond preferentially to hormone replacement therapy.

◐Partially SupportedA fasting blood sugar cutoff of 95 is appropriate for brain health, memory, and cognitive function.

◐Partially SupportedUsing a biosensor like the Oura ring can provide comprehensive data on physiology, sleep patterns, exercise output, and heart rate metrics.

◐Partially SupportedCognitive function should be used to personalize care from a biological perspective.

◐Partially SupportedAilsyou.org provides free information on brain health.

◐Partially SupportedFor some individuals, alcohol's benefits like unwinding may offset downsides if liver function and coagulation factors are normal and no other adverse effects are present.

◐Partially SupportedEmerging observations suggest associations between metabolism and memory/learning that may be obscured by traditional statistical methods.

◐Partially SupportedProcessing speed may be associated with metabolism problems and high visceral body fat.

◐Partially SupportedMuscle mass is likely more protective of brain health than body fat in men.

◐Partially SupportedIt takes approximately 2.5 years to recycle brain DHA levels, meaning short-term studies may not show effects.

◐Partially SupportedA personalized recommendation for alcohol intake is four drinks per week for women and seven to ten drinks per week for men.

◐Partially SupportedAlcohol is a hepatic toxin, and any amount can be chronically toxic to the liver.

◐Partially SupportedPrecision medicine targeting individuals who need an intervention can yield different results than studies lumping all individuals.

◐Partially SupportedVascular risk factor modification, including cholesterol, diabetes, and blood pressure control, is a high priority for healthspan, second only to exercise.

◐Partially SupportedStatins can be beneficial for vascular and inflammatory health but may negatively impact cholesterol biosynthesis in susceptible individuals.

◐Partially SupportedRichard Isaacson suggests Omega-3 fatty acids instead of prescribing statins or directly treating cholesterol.

?Limited ResearchIntermittent fasting of 16 hours is potentially better than 12 hours, but current data has wide error bars and small sample sizes, making definitive conclusions difficult.

◐Partially SupportedAlzheimer's disease is likely to affect most individuals, either directly or indirectly through loved ones.

◐Partially SupportedAPOE3/3 genotype is generally good for Alzheimer's risk, but other genetic factors (SNPs) are needed for a complete individual risk assessment.

◐Partially SupportedLearning about brain health and making incremental changes throughout life is beneficial.

◐Partially SupportedNewer cognitive tests often lack robust validation in diverse populations.

◐Partially SupportedExecutive function is associated with lipid profiles, vitamin D, and homocysteine levels.

◐Partially SupportedThe distinction in recommended alcohol intake between men and women is likely related to body mass and muscle mass.