Introduction

The following protocol outlines evidence-based strategies for delaying or preventing cognitive decline.

Protocol

The protocol is organized by category and estimated impact, with recommendations marked by emojis. It draws primarily from statements made by Dr. Richard Isaacson (preventative neurologist) and Dr. Peter Attia (physician studying healthspan and lifespan), with support from peer-reviewed research.

TLDR

Exercise

• 💪 Even a little bit helps
• 💪 More is better
• 💪 Mix zone 2, HIIT/VO2 max, strength training

Biomarkers

• 🩸 Blood pressure: 120/70
• 🩸 LDL cholesterol: below 50 (positive effects start below 70)
• 🩸 Fasting glucose: below 95
• 🩸 Homocysteine: below 9 µmol/L
• 🩸 Vitamin D: 50 ng/mL
• 🩸 Omega-3 Index: 8-12%

Sleep

• 💤 7.5-8.5 hours of undisturbed sleep
• 💤 Adequate deep and REM sleep (1.5 hours each)

Smoking

• 🔴 Do not smoke

Alcohol

• 🔴 Limit alcohol (especially if you are an ApoE4 carrier)

Nutrition

• Principles
  • 🧩 Minimize fasting glucose
  • 🧩 Minimize glucose spikes
  • 🧩 Maintain energy balance (calories consumed = calories expended)
  • 🧩 Personalize (based on your biomarkers)
  • 🧩 Avoid harm first (bad nutrition may hurt more than good nutrition helps)
• Food
  • 🔴 Limit added sugar: <10-20g per day
  • 🔴 Avoid highly refined carbohydrates
  • 🔴 Avoid ultra-processed foods (especially those with trans fats)
  • 🟢 Eat dark leafy green vegetables: 6 or more servings per week
  • 🟢 Eat fatty fish: 2 servings per week
  • 🟢 Consume extra virgin olive oil: 2-3 tablespoons per day
  • 🟢 Eat blueberries and strawberries: ~0.5 cups 2-3x per week
  • 🟢 Eat plant-based fats (e.g. avocado, seeds, hazelnuts, almonds): 2 tablespoons per day

Vitamins and Supplements

• 💊 B12, B9/Folate, B6 Vitamins (when homocysteine elevated)
• 💊 Vitamin D (if deficient)
• 💊 Omega-3 Fatty Acids (if deficient)
• 💊 Theracurmin/Curcumin (consult physician; contraindications exist)
• 💊 Cocoa Flavanols
• 💊 Magnesium L-Threonate

Oral Health

• 🦷 Brush twice daily for two minutes with an electric toothbrush
• 🦷 Floss daily
• 🦷 Monitor gum health and visit the dentist regularly for thorough check-ups

Other Interventions

• 👂 Get hearing tested regularly and correct any hearing loss promptly with hearing aids
• 🧠 Engage in complex, varied activities that challenge both brain and body (e.g. learning a new language, playing a musical instrument, or dancing)
• 🧘 Manage/treat chronic stress, anxiety, and depression

Exercise

Dr. Peter Attia and Dr. Richard Isaacson consider exercise the most effective way to protect against cognitive decline.[1][2][3]

💪 Even a little bit helps: walking 3-5k steps per day is associated with slower cognitive decline[4]; according to Dr. Peter Attia going from zero exercise to 90 minutes per week of physical activity is associated with a 14% reduction in all-cause mortality[5] and going from zero to 180 minutes of optimal exercise is associated with an almost 50% reduction[6]
💪 More is better: in general, higher levels of regular exercise are associated with better cognitive outcomes[7]; a large study suggests that grip strength (excellent proxy for overall strength) was strongly and inversely associated with incidence of dementia and there there is no upper limit to relationship (greater someone’s grip strength, the lower their risk of dementia)[2][8]; a large study suggests that cardiorespiratory fitness is inversely associated with long-term mortality with no observed upper limit of benefit[9]
💪 Mix zone 2, HIIT/VO2 max, strength training: a meta analysis performed by Dr. Peter Attia suggests that the most effective types of exercise for delaying/preventing cognitive decline are aerobic, resistance, and mind-body or “multi-component” exercises[6]

See Appendix > Exercise Details for additional information.

Sources:
[1] How to Save Your Brain From Cognitive Decline - Dr Peter Attia (5/17/2023)
[2] Outlive (Chapter 9: Chasing Memory) (4/4/2022)
[3] Ask a Brain Doctor Live Q&A with Richard Isaacson, MD + Max Lugavere (50:30; 9/10/2025)
[4] Physical activity as a modifiable risk factor in preclinical Alzheimer’s disease (11/3/2025)
[5] Outlive (Chapter 11: Exercise) (4/4/2022)
[6] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[7] How to Slow Cognitive Decline | Dr. Peter Attia & Dr. Andrew Huberman (5/17/2023)
[8] Handgrip strength and all-cause dementia incidence and mortality: findings from the UK Biobank prospective cohort study (June 2022)
[9] Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing (10/19/2018)

Biomarkers

The below vascular and nutritional markers can be measured using common blood tests.

Vascular

Dr. Peter Attia considers lipid management (see LDL cholesterol below) and not having type 2 diabetes (see fasting glucose below) to be the second and third most effective way to protect against cognitive decline.[1] Vascular risk factors (high blood pressure, high cholesterol, type 2 diabetes) can fast-forward AD and dementia pathologies.[2]

🩸 Blood pressure: 120/70[2]
🩸 LDL cholesterol: below 50; positive effects start below 70[2]
🩸 Fasting glucose: below 95[2]

See Appendix > Biomarker Management Strategies for additional information.

Sources:
[1] How to Save Your Brain From Cognitive Decline - Dr Peter Attia (5/17/2023)
[2] Mastering Brain Health: Vascular Brain Health (11/26/2020)

Nutritional

🩸 Homocysteine: below 9 µmol/L[1]
🩸 Vitamin D: 40-60 ng/mL with 50 ng/mL potentially being ideal[1][2]
🩸 Omega-3 Index (a blood test of EPA+DHA as % of total fatty acids): 8-12%[3]

See Appendix > Biomarker Management Strategies for additional information.

Sources:
[1] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[2] Mastering Brain Health: Supplements and Vitamins (12/1/2020)
[3] AMA #83 – Bill Harris, Ph.D.: Omega-3 fatty acids (12/9/2019)

Sleep

Dr. Peter Attia considers adequate sleep to be the fourth most effective way to protect against cognitive decline.[1]

💤 7.5-8.5 hours of undisturbed sleep: Dr. Richard Isaacson recommends 7.5-8 hours of sleep per night[2]; Dr. Peter Attia recommends 7.5-8.5 hours per night[3]
💤 Adequate deep and REM sleep: Dr. Richard Isaacson recommends 1.5 hours of both deep/slow-wave and REM sleep[2]

Both can be measured reasonably accurately with a sleep tracking device, such as an Apple Watch. Self-reported sleep volume is often meaningfully higher than actual volume.[2]

Why:

• Studies suggest a 160% increase in dementia risk for people who get <5 hours of sleep vs people getting >7 hours[4]
• Studies suggest a 60% increase in dementia risk for people with disturbed sleep vs undisturbed sleep[4]
• Studies suggest adults in mid-life who consistently sleep fewer than 6 hours per night have a 50% increased likelihood in developing Alzheimer’s[5]

Other things to note:

• Successfully treating sleep disturbance may delay the age of onset into MCI by about 11 years and may improve cognitive function in patients already diagnosed with Alzheimer’s[3]
• Research points to the forties and sixties as the decades of life when deep sleep is especially important for the prevention of Alzheimer’s disease. People who have slept less during those decades seem to be at higher risk of developing dementia later on[3]

See Appendix > Sleep Improvement Strategies for additional information.

Sources:
[1] How to Save Your Brain From Cognitive Decline - Dr Peter Attia (5/17/2023)
[2] Strategies for Better Sleep (12/24/2020)
[3] Outlive (Chapter 16: The Awakening) (4/4/2022)
[4] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[5] #106 - Can A Sleeping Pill Help Fight Alzheimer’s? (9/1/2025)

Smoking

🔴 Do not smoke

Why:

• Smoking is associated with increased risk of cognitive decline[1][2][3]

Sources:
[1] Smoking as a Risk Factor for Dementia and Cognitive Decline: A Meta-Analysis of Prospective Studies (6/14/2007)
[2] Impact of Smoking on Cognitive Decline in Early Old Age (June 2012)
[3] Association of Changes in Smoking Intensity With Risk of Dementia in Korea (1/19/2023)

Alcohol

🔴 Limit alcohol

Why:

• Chronic drinking has strong associations with dementia[1][2][3]
• Small study showed patients at higher risk for AD (ApoE4 carriers) who never drank were 2.3x and 3.6x less likely to develop dementia relative to high-risk patients that drank infrequently and frequently[4]
• Dr. Peter Attia states that the role of alcohol in AD is controversial, but recommends patients not drink[5]; if abstinence is not possible, Dr. Attia recommends a maximum of 7-8 drinks per week with no more than 2 drinks in a given day[4]
• Dr. Richard Isaacson recommends patients with one or two copies of ApoE4 not drink; if abstinence is not possible, Dr. Isaacson recommends 1-2 drinks per week max[6]

Sources:
[1] Contribution of alcohol use disorders to the burden of dementia in France 2008–13: a nationwide retrospective cohort study (March 2018)
[2] Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study (August 2018)
[3] Alcohol and Dementia – What is the Link? A Systematic Review (1/9/2020)
[4] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[5] Outlive (Chapter 9: Chasing Memory) (4/4/2022)
[6] Ask a Brain Doctor Live Q&A with Richard Isaacson, MD + Max Lugavere (26:00; 9/10/2025)

Nutrition

Finding an optimal nutrition program requires blood tests and the use of a CGM (continuous glucose monitor).

Principles

🧩 Minimize fasting glucose: nutrition program should minimize fasting glucose levels to reduce risk of type 2 diabetes[1], which develops when the body can no longer control blood sugar effectively and leads to chronically high glucose (measurable with fasting glucose test); patients with type 2 diabetes may have a 58% increase in risk for dementia[2]; patients with both type 2 diabetes and ApoE4 may have a ~5.5x increase in risk of developing AD[1]
🧩 Minimize glucose spikes: nutrition program should minimize glucose spikes (temporarily high glucose levels), as measured by a CGM; repeated glucose spikes are associated with inflammation that accelerates amyloid production and deposition[3] and are linked with cognitive decline[4][5]; Dr. Peter Attia tries to avoid spikes above 130mg/dL[6]; Dr. Attia tries to keep average glucose at or below 100mg/dL with a standard deviation of less than 15mg/DL[7]; ApoE4 carriers are particularly prone to glucose spikes[7]
🧩 Maintain energy balance: nutrition program should achieve an energy balance (calories consumed = calories expended)[1]; higher caloric intake is associated with increased AD risk[8]
🧩 Personalize: Dr. Richard Isaacson personalizes nutrition programs based on cholesterol, Omega-3 fatty acids, monounsaturated fats, trans fats, vitamin D, B12, metabolic biomarkers (e.g. glycosylated hemoglobin (HbA1c), fasting glucose, and fasting insulin), and homocysteine levels found in blood as well as body mass index[3][9; 22:00][10]
🧩 Avoid harm first: Dr. Peter Attia believes bad nutrition can hurt us more than good nutrition can help[7]

Food

There have been no long-term human studies conducted to determine effective nutrition patterns for preventing cognitive decline. The below food and dose recommendations are largely based on observational data and clinical experience rather than rigorous clinical trials.

🔴 Limit added sugar: Dr. Richard Isaacson guides patients to <10-20g of added sugar per day[3]; higher sugar intake is associated with worse cognitive outcomes[11]; study found that AD incidence was twice as high in Africans living in the United States compared to those in Nigeria (despite high ApoE4 prevalence), where sugar consumption is one-quarter that of Americans[12]
🔴 Avoid highly refined carbohydrates: Dr. Peter Attia recommends patients cut out highly-refined carbohydrates[13]; rule of thumb: if it’s made from white flour or added sugar, it’s a highly-refined carbohydrate
🔴 Avoid ultra-processed foods (especially those with trans fats): Dr. Richard Isaacson recommends avoiding ultra-processed foods[9; 26:50][3]; rule of thumb: an ultra-processed food is a food you couldn’t make in your kitchen, if you tried[9]; trans fats are among the most brain unhealthy foods that we know of[3]; rule of thumb: if the ingredient list includes “partially hydrogenated oils”, the product contains trans fats

🟢 Eat dark leafy green vegetables: Dr. Richard Isaacson believes these vegetables are the most important part of a brain-healthy diet [9; 25:10] and they delay cognitive decline[3]; 6 or more servings per week[10]; examples of DLGVs include: kale, spinach, collard greens, swiss chard, etc
🟢 Eat fatty fish (polyunsaturated fats): Dr. Richard Isaacson believes fatty fish, particularly for ApoE4 carriers, eaten a couple of times per week is equally as or more important (vs dark leafy vegetables) [9; 25:20]; examples of fatty fish include: wild-caught salmon, sardines, mackerel, lake trout, herring, albacore tuna, etc
🟢 Consume extra virgin olive oil (monounsaturated fats): Dr. Richard Isaacson believes EVOO is one of the most powerful things people can do to optimize brain health[9; 12:00][3]; 2-3 tablespoons per day[14]
🟢 Eat blueberries and strawberries: study suggests consuming >0.5 cup of blueberries or strawberries 2-3x per week can delay cognitive decline by >2.5 years[15]
🟢 Eat plant-based fats (e.g. avocado, seeds, hazelnuts, almonds): Dr. Richard Isaacson believes that nuts are great for brain health[3]; 2 tablespoons of nuts per day[14] and/or 5 or more servings of plant-based fats per week[10]

The most common patterns associated with brain health are Ketogenic, Mediterranean, and MIND (alpha-sorted). See Appendix > Nutrition Patterns for information.

Sources:
[1] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[2] Impact of diabetes on the association between serum urate levels and incident dementia: a cohort study in the UK biobank (December 2024)
[3] Mastering Brain Health: Diet and Nutrition 1 (11/26/2020)
[4] Insulin metabolism and the risk of Alzheimer disease: the Rotterdam Study (11/30/2010)
[5] Hyperinsulinemia and cognitive decline in a middle-aged cohort (December 2006)
[6] AMA #24: Deep dive into blood glucose: why it matters, important metrics to track, and superior insights from a CGM (6/14/2021)
[7] Outlive (Chapter 15: Putting Nutritional Biochemistry into Practice) (4/4/2022)
[8] Caloric Intake and the Risk of Alzheimer Disease (August 2002)
[9] Ask a Brain Doctor Live Q&A with Richard Isaacson, MD + Max Lugavere (9/10/2025)
[10] Brain Health & Dementia Risk Reduction (5/31/2019)
[11] Associations of sugar intake, high-sugar dietary pattern, and the risk of dementia: a prospective cohort study of 210,832 participants (7/18/2024)
[12] Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers (3/5/2021)
[13] Outlive (Chapter 9: Chasing Memory) (4/4/2022)
[14] Retain Health (company that Dr. Richard Isaacson founded and is clinical advisor to): nutrition routines
[15] Dietary intakes of berries and flavonoids in relation to cognitive decline (July 2012)

Vitamins and Supplements

The most optimal way to achieve recommended levels is by eating whole foods. Supplementation is only advised when dietary intake is insufficient.

Among the vitamin/supplement brands, Momentous, Thorne, Pure Encapsulations, Nordic Naturals, Jarrow Formulas, and Carlson seem to be widely regarded as having some of the highest quality and sourcing standards.

Vitamins

💊 B Vitamins (B12, B9/Folate, B6)

Why:

• There is a clear relationship between homocysteine, which is regulated by B12, B9, and B6, and brain health[1]
• Studies in older adults with mild cognitive impairment suggest that high-dose B-vitamin supplementation (folic acid, B12, B6) may slow brain atrophy (particularly in individuals with higher baseline omega-3 fatty acid levels)[2][3][4]
• Study showed that folic acid supplementation in older adults may improve memory and processing-speed performance compared with placebo[5]
• A 2-year lifestyle and nutritional program, which included improving folate and B12 status, was associated with slower cognitive decline in older adults at risk for dementia[6]

Caveats:

• Analysis suggests there is no evidence that B vitamin supplementation improves cognition in younger, cognitively healthy adults[7]
• It’s not clear homocysteine is causal so “improving it” may not do anything[1]

How to use:

• Most important B vitamins are: vitamin B12, B9/folate, and B6[5][8]
• Dr. Richard Isaacson recommends patients in his practice take B vitamins if their B-12 levels are low or their homocysteine levels are high[9]
• Dr. Peter Attia targets homocysteine levels below 9 in his practice[1]
• Many well-known trials use a ~1:1:40 ratio (B12:B9:B6)[2][10][11]:
  • Vitamin B12: 400–500 µg/day
  • Folic acid: 400–800 µg/day
  • Vitamin B6: 20–25 mg/day

Sources:
[1] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[2] Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial (9/8/2010)
[3] Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment (5/20/2013)
[4] Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial (4/15/2015)
[5] Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial (1/20/2007)
[6] A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial (6/6/2015)
[7] Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression (3/12/2021)
[8] Dr Peter Attia - Top 5 Supplements To Help You Feel Your Best (4/17/2024)
[9] Mastering Brain Health: Supplements and Vitamins (12/1/2020)
[10] The SU.FOL.OM3 Study: a secondary prevention trial testing the impact of supplementation with folate and B-vitamins and/or Omega-3 PUFA on fatal and non fatal cardiovascular events, design, methods and participants characteristics (6/10/2008)
[11] Rationale, design and baseline characteristics of a large, simple, randomized trial of combined folic acid and vitamins B6 and B12 in high-risk patients: The Heart Outcomes Prevention Evaluation (HOPE)-2 trial (January 2006)

💊 Vitamin D

Why:

• Risk of dementia and AD is higher with low levels of Vitamin D[1][2][3]
• Vitamin D levels are correlated with health and cognitive outcomes (higher levels, better outcomes)[4]

Caveat: Strength of association with vitamin D and AD might be because fit people are outside exercising (increasing their vitamin D levels) and, because of that exercise, are at a lower risk[4]

How to use:

• Dr. Peter Attia targets 40-60 ng/mL for his patients[4]
• Dr. Richard Isaacson believes levels below 30 ng/mL are problematic and that the optimal level is approximately 50 ng/mL[5]
• Consume with fat to help maximize absorption[5]

Sources:
[1] Vitamin D and the risk of dementia and Alzheimer disease (9/2/2014)
[2] Association of vitamin D with risk of dementia: a dose-response meta-analysis of observational studies (9/9/2025)
[3] Association of Vitamin D Levels with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Studies (2024)
[4] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[5] Mastering Brain Health: Supplements and Vitamins (12/1/2020)

Supplements

💊 Omega-3 Fatty Acids (DHA and EPA)

Why:

• “Most brain healthy supplement” - Dr. Richard Isaacson[1]
• Some evidence that supplementation with Omega-3s may help maintain brain health[2]
• Both Dr. Isaacson and Dr. Peter Attia believe ApoE4 carriers benefit from higher levels of Omega-3s[1][3]
• Studies show mice with a diet rich in DHA have 40% reduction in plaque buildup[4]; human data is less clear, but studies are flawed[3]
• EPA/DHA supplementation seems to reduce inflammation[3][5]

How to use:

• Dose:
  • Dr. Isaacson recommends at least 900-1,000mg of DHA and 500-600mg of EPA to his patients (numbers are adjusted up based on blood markers; there are Omega-3 Fatty Acid tests available)[1]
  • Dr. Attia takes 3 2,000mg Carlson pills per day[6]
• Higher doses of EPA and DHA (5-10 grams) may increase risk of atrial fibrillation (ideal range for Omega-3 levels in blood is 10-12%)[5]

Sources:
[1] Mastering Brain Health: Supplements and Vitamins (12/1/2020)
[2] Outlive (Chapter 9: Chasing Memory) (4/4/2022)
[3] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[4] A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model (3/23/2005)
[5] AMA #59: Inflammation: its impact on aging and disease risk, and how to identify, prevent, and reduce it (5/13/2024)
[6] Dr Peter Attia - Top 5 Supplements To Help You Feel Your Best (4/17/2024)

💊 Theracurmin/Curcumin

Why:

• Dr. Peter Attia recommends this to his patients with higher risk for neurodegenerative disease[1]
• Study showed that it may delay amyloid accumulation in the brain of people at risk for AD[2]
• Small study showed AD patients that took it were stable whereas patients who didn’t take it continued their decline[3]
• Has potent anti-inflammatory effect[1][4]

How to use: 30-90 milligrams per day (theracurmin; theracurmin is a better absorbed form of curcumin)[1][5]

Sources:
[1] AMA #59: Inflammation: its impact on aging and disease risk, and how to identify, prevent, and reduce it (5/13/2024)
[2] Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial (March 2018)
[3] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[4] Effect of curcumin on C-reactive protein as a biomarker of systemic inflammation: An updated meta-analysis of randomized controlled trials (1/17/2021)
[5] Mastering Brain Health: Supplements and Vitamins (12/1/2020)

💊 Cocoa Flavanols

Why:

• Study showed that having 1-2 servings per day for several months may improve memory/executive function, insulin sensitivity, and blood pressure control[1][2]
• Dr. Richard Isaacson seems to recommend this to his patients[3]
• Dr. Peter Attia recommends this to his high AD-risk patients[4]

How to use: 1-2 servings per day; Dr. Isaacson recommends CocoaVia brand to his patients (recommended because it has been studied in multiple randomized control trials)[3]

Sources:
[1] Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cognition, and Aging (CoCoA) Study–a randomized controlled trial (March 2015)
[2] Benefits in cognitive function, blood pressure, and insulin resistance through cocoa flavanol consumption in elderly subjects with mild cognitive impairment: the Cocoa, Cognition, and Aging (CoCoA) study (September 2012)
[3] Mastering Brain Health: Diet and Nutrition 1 (11/26/2020)
[4] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)

💊 Magnesium L-Threonate

Why:

• Dr. Peter Attia uses this in his practice with high AD-risk patients[1]
• MgT may improve cognitive function in healthy adults[2]
• MgT may improve cognitive function in patients with AD and dementia[3]
• MgT may improve sleep quality (especially deep/REM sleep stages), mood, energy, alertness, and daily activity and productivity[4]

How to use: 2-3 capsules (2 grams each) before sleep[5]

Sources:
[1] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[2] A Magtein®, Magnesium L-Threonate, -Based Formula Improves Brain Cognitive Functions in Healthy Chinese Adults (12/8/2022)
[3] Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial (2016)
[4] Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial (8/17/2024)
[5] AMA #54: Magnesium: risks of deficiency, how to correct it, supplement options, potential cognitive and sleep benefits, and more (12/11/2023)

💊 Creatine Monohydrate

Why:

• Creatine monohydrate may confer beneficial effects on cognitive function in adults, particularly in the domains of memory, attention time, and information processing speed[1]
• Study suggests patients with AD who take 20mg of creatine monohydrate daily may see cognitive performance improvement on several neuropsychological tests (global, fluid cognition, working memory, reading recognition)[2]

Caveats:

• Dr. Richard Isaacson believes that the protective effects of creatine monohydrate on brain health are currently unproven[3]

How to use: 5 grams daily (doesn’t matter time of day)[3][4]

Sources:
[1] The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis (7/12/2024)
[2] Creatine monohydrate pilot in Alzheimer’s: Feasibility, brain creatine, and cognition (April 2025)
[3] Ask a Brain Doctor Live Q&A with Richard Isaacson, MD + Max Lugavere (33:30; 9/10/2025)
[4] Dr Peter Attia - Top 5 Supplements To Help You Feel Your Best (4/17/2024)

Oral Health

🦷 Brush twice daily for two minutes with an electric toothbrush[1]
🦷 Floss daily[1]
🦷 Monitor gum health and visit the dentist regularly for thorough check-ups[2]

Why:

• A large epidemiologic analysis found that periodontitis (gum disease) was associated with approximately a 1.7x increased risk of developing AD[3] and may factor into other neurodegenerative diseases[1]
  • Potential mechanism: periodontal disease drives chronic systemic inflammation; key gum-disease bacteria (e.g. P. gingivalis) increase inflammatory markers such as IL-6, and their toxins have been found in the brain, where they may promote neuroinflammation and accelerate AD[4][5]

Caveats:

• While there’s a strong correlation between poor oral health and major health issues, the causal relationship isn’t proven[2]

Sources:
[1] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[2] AMA #59: Inflammation: its impact on aging and disease risk, and how to identify, prevent, and reduce it (5/13/2024)
[3] Periodontal Disease and Alzheimer’s: Insights from a Systematic Literature Network Analysis (4/19/2022)
[4] Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors (1/23/2019)
[5] Systemic inflammation and disease progression in Alzheimer disease (9/8/2009)

Other Interventions

Hearing

👂 Get hearing tested regularly and correct any hearing loss promptly with hearing aids[1]

Why:

• Hearing loss is associated with approximately a 90% increase in the risk of dementia and is viewed by the
• The Baltimore Longitudinal Study of Aging found a dose-response relationship between hearing loss severity and dementia risk: mild hearing loss (25-40 dB threshold) increased risk 89%, moderate hearing loss (41-70 dB threshold) increased risk 200%, severe hearing loss (>70 dB threshold)increase risk nearly 400%[2]
• 2020 Lancet Commission on dementia views hearing loss as one of the most critical modifiable variables in the prevention of neurodegenerative disease[3]

Caveats:

• We do not yet have causal data that hearing loss impacts dementia (because the experiments have not been done)[1]

Sources:
[1] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[2] Hearing loss and incident dementia (February 2011)
[3] Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (7/30/2020)

Cognitive Engagement

🧠 Engage in complex, varied activities that challenge both brain and body: Learning a new language, playing a musical instrument, or dancing can protect against cognitive decline[1][2][3]

Why:

• Dr. Peter Attia believes that the more neural networks and pathways built over a lifetime via education, experience, or developing complex skills, the more resistant to cognitive decline one will tend to be[3]
• Systematic review and meta-analysis as well as a large prospective cohort study found that cognitively stimulating leisure activities are associated with a reduced risk of dementia and cognitive impairment later in life[4][5]; studies have found a strong association between playing musical instruments and lower risk of dementia[6][7]; studies have found that lifelong bilingualism is associated with delayed onset of dementia[8][9]
• Study suggests that mentally demanding occupations are associated with lower rates of cognitive impairment and dementia compared to less demanding, repetitive roles[10]
• A 2-year randomized controlled trial with 1,200+ at-risk older adults showed that interventions around nutrition, physical activity, and cognitive training helped maintain cognitive function and prevent cognitive decline[11]

Caveats:

• Brain games (e.g. crossword puzzles, Sudoku, etc.) by themselves don’t appear to transfer to other cognitive abilities or protect against cognitive decline[1]; the key is variety and complexity, not repetitive games[3]
• Healthy user bias makes data on cognitive engagement and prevention conflicted – people who are more cognitively engaged may have other lifestyle factors contributing to lower dementia risk[3]

How to use:

• Engage in complex activities that challenge both brain and body, such as dancing, learning a new language, or playing a musical instrument[2][12]
• Dr. Peter Attia recommends staying intellectually engaged throughout life: “We should think about retiring as a time when we don’t work for money anymore. But I really think it’s probably important that people are working throughout their entire lives, meaning they’re working on something that is keeping their brain challenged.”[2]
• Dr. Richard Isaacson prescribes brain training exercises (through alzu.org) for 30 minutes twice a week[12]

Sources:
[1] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[2] AMA #60: Preventing cognitive decline, nutrition myths, lowering blood glucose, apoB, and blood pressure, and more (6/17/2024)
[3] Outlive (Chapter 9: Chasing Memory) (4/4/2022)
[4] Cognitive leisure activities and future risk of cognitive impairment and dementia: systematic review and meta-analysis (8/9/2016)
[5] Leisure activities and the risk of dementia in the elderly (6/19/2003)
[6] Playing a musical instrument and the risk of dementia among older adults: a systematic review and meta-analysis of prospective cohort studies (10/27/2022)
[7] Playing a Musical Instrument as a Protective Factor against Dementia and Cognitive Impairment: A Population-Based Twin Study (12/2/2014)
[8] Bilingualism for Dementia: Neurological Mechanisms Associated With Functional and Structural Changes in the Brain (11/14/2019)
[9] Protective effect of bilingualism on aging, MCI, and dementia: A community‐based study (2/20/2024)
[10] Trajectories of Occupational Cognitive Demands and Risk of Mild Cognitive Impairment and Dementia in Later Life (4/17/2024)
[11] A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial (6/6/2015)
[12] Cognitive Engagement, Educational Attainment, Brain Training (12/2/2020)

Stress, Anxiety, and Depression

🧘 Manage/treat chronic stress, anxiety, and depression

Why:

• Chronic or prolonged stress exposure is associated with an increased risk of later cognitive impairment and dementia[1][2][3]
• Repetitive negative thinking patterns (characterized by worry and rumination) have been prospectively linked to cognitive decline, increased risk of progression toward dementia[2][4][5]
• Depression (especially when recurrent, severe, or emerging in later life) is consistently associated with higher risk of developing dementia and with faster cognitive decline[6][7][8]; Dr. Richard Isaacson considers depression to be an independent risk factor for AD[9]

Note: Mindfulness-Based Stress Reduction (MBSR) has consistently been found to reduce symptoms of stress, anxiety, and depression[9][10][11]

Sources:
[1] Stress, depression, and risk of dementia – a cohort study in the total population between 18 and 65 years old in Region Stockholm (10/2/2023)
[2] Association of Stress with Risk of Dementia and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis (2021)
[3] The Influence of Chronic Stress on Dementia-Related Diagnostic Change in Older Adults (7/1/2013)
[4] Repetitive negative thinking is associated with subjective cognitive decline in older adults: a cross-sectional study (10/9/2020)
[5] Repetitive negative thinking is associated with cognitive function decline in older adults: a cross-sectional study (6/2/2025)
[6] Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis (May 2006)
[7] Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies (May 2013)
[8] Depression as a Risk Factor for Dementia: A Meta-Analysis (2024)
[9] Stress Management (12/2/2020)
[10] Mindfulness-based stress reduction for healthy individuals: A meta-analysis (June 2015)
[11] The effect of mindfulness-based therapy on anxiety and depression: A meta-analytic review (April 2010)

Appendix

Exercise Details

There have been no long-term randomized controlled human trials that definitively establish a specific exercise program for preventing cognitive decline. Most large-scale exercise studies focus on reductions in all-cause mortality. However, this evidence is still indirectly and mechanistically relevant to dementia risk, because the strongest drivers of mortality reduction (improved cardiovascular fitness, metabolic health, and vascular function) are also key determinants of brain health and dementia risk.

The “how much is enough?” suggestions below are from Dr. Peter Attia’s “recommend” protocol as well as his “I only have 3 hours per week for exercise” protocol. The idea behind the “3 hours paper week” protocol is that, according to Dr. Attia, the clinical research suggests that going from a hundred percent inactivity to just three well thought out hours a week of exercise can result in an almost a 50% reduction in mortality.[1]

Aerobic Efficiency (Zone 2) Training

What is it? Cardio where the effort is low enough that you can still maintain a conversation, but fast enough that the conversation might be a little strained. At the top of zone 2, you should be able to talk, but should not be particularly interested in holding a conversation. If you can’t speak in complete sentences, you’re likely into zone 3. If you can comfortably converse, you’re likely in zone 1[2]

Why:

• Zone 2 training stimulates the creation of many new and more efficient mitochondria and eliminates mitochondria that has become dysfunctional. Healthy mitochondria are important for maintaining the health of our brain and for controlling potential bad actors like oxidative stress and inflammation[3][4]
• Zone 2 training also improves VO2 max[3] (see next section)

How much is enough? According to Dr. Peter Attia, 3 hours per week is the minimum required for most people to derive a benefit and make improvements[2]; if you only have 3 hours per week to dedicate to exercise, Dr. Attia recommends spending 1 hour on zone 2 training[1]

Maximum Aerobic Output (VO2 Max or High-Intensity Interval) Training

What is it? V02 max (the maximum rate at which a person can utilize oxygen; the more oxygen your body is able to use, the higher your VO2) efforts are hard, minutes-long efforts. Intervals range from 3-8 minutes and can be done on a stationary bike, rowing machine, treadmill/track, etc. The formula is to go for 4 minutes at the maximum pace you can sustain for this amount of time then ride or jog for 4 minutes at an easy pace to recover (let heart rate come back down to below 100). Repeat this 4-6 times to complete a session[2]

Why:

• A large study suggests that cardiorespiratory fitness is inversely associated with long-term mortality with no observed upper limit of benefit[5]

How much is enough? According to Dr. Peter Attia, 1-2 sessions per week[2]; if you only have 3 hours per week to dedicate to exercise, Dr. Attia recommends 1 hour of something high intensity with coordinated movement (e.g. shadowboxing, active dance class, etc.)[1]

Strength Training

What is it? Dr. Peter Attia structures strength training on[2]:

• Grip strength (how hard you can grip with your hands); lifts include: dead hang, farmer’s carry, etc
• Concentric and eccentric loading (i.e. loading muscles when they are shortening and when they are lengthening) and pulling motions; lifts/activities include: pullups, pulldowns, deadlifts, rows, etc
• Hip-hinging movements (bend at the hips – not the spine – to harness body’s largest muscles, the gluteus maximus and the hamstrings); lifts include: deadlifts, squats, step-ups, hip-thrusters, and single-leg variants of exercises that strengthen the legs, glutes, and lower back

Why:

• A large study suggests that grip strength (excellent proxy for overall strength) was strongly and inversely associated with incidence of dementia and there there is no upper limit to relationship (greater someone’s grip strength, the lower their risk of dementia)[6][7]

How much is enough? Dr. Peter Attia lifts heavy weights four times per week[2]; if you only have 3 hours per week to dedicate to exercise, Dr. Attia recommends 1 hour of strength training[1]

Sources:
[1] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[2] Outlive (Chapter 11: Exercise) (4/4/2022)
[3] Outlive (Chapter 12: Training 101) (4/4/2022)
[4] Adaptations to Endurance and Strength Training (June 2018)
[5] Handgrip strength and all-cause dementia incidence and mortality: findings from the UK Biobank prospective cohort study (June 2022)
[6] Outlive (Chapter 9: Chasing Memory (4/4/2022)
[7] Handgrip strength and all-cause dementia incidence and mortality: findings from the UK Biobank prospective cohort study (June 2022)

Biomarker Management Strategies

Blood pressure:

• Primary: weight loss (if overweight), dietary sodium reduction (especially processed and restaurant foods), DASH-style or Mediterranean diet (high in fruits, vegetables, potassium, magnesium), regular aerobic exercise, antihypertensive medications (when indicated; ACE inhibitors, ARBs, thiazides, calcium-channel blockers)
• Secondary: potassium intake optimization (primarily from whole foods; supplements only when appropriate), reducing alcohol intake, reducing stress (chronic sympathetic activation raises BP), treating sleep apnea (if present), improved sleep duration and quality, reducing NSAID use (where possible)

LDL cholesterol:

• Primary: dietary saturated fat reduction (replace with unsaturated fats: olive oil, nuts, seeds, fatty fish), weight loss (if overweight), Statins (when indicated; strongest LDL-lowering and outcome data), increased soluble fiber (e.g. oats, psyllium, legumes), reduced dietary cholesterol (modest effect, but additive in “hyper-responders” such as individuals with ApoE4, insulin resistance, low-fiber or high-saturated fat diet, etc)
• Secondary: Ezetimibe (if statins insufficient or not tolerated), PCSK9 inhibitors (for very high-risk cases or if statins insufficient), plant sterols/stanols (clinically meaningful doses usually come from fortified foods and supplements), replacing refined carbs with whole foods (indirect LDL benefit), consistent aerobic exercise (modest LDL effect; stronger for triglycerides and HDL)

Fasting glucose:

• Primary: weight loss (if overweight), dietary carbohydrate reduction (especially refined carbs such as sugary drinks, pastries, etc), regular aerobic + resistance exercise, improved sleep duration and quality, Metformin (when indicated)
• Secondary: time restricted eating, increased fiber intake, reduced alcohol intake

Homocysteine:

• Adequate vitamin B (B12, folate, B6) status (see Vitamins and Supplements > Vitamins section), treat underlying causes, address medications that raise homocysteine

Vitamin D:

• Sunlight exposure (regular, non-burning UVB exposure when seasonally and geographically feasible), vitamin D3 (cholecalciferol) supplementation (most reliable way to raise and maintain blood levels; see Vitamins and Supplements > Vitamins section), weight management (vitamin D is sequestered in adipose tissue; obesity lowers bioavailability), adequate dietary fat intake (vitamin D is fat-soluble; improves absorption)

Omega-3 Index:

• Regular consumption of fatty fish (e.g. salmon, sardines, mackerel, anchovies; typically 2–3 servings/week or more as needed), omega-3 supplementation (EPA+DHA) when dietary intake is insufficient to reach target blood levels (see Vitamins and Supplements > Supplements section)

Sleep Improvement Strategies

• Completely dark and cool room[1][3]
• Limit blue light (in bulbs and electronic devices), which tells our brain it is daytime, 2 hours before bedtime[3]
• Avoid anything anxiety-producing or stimulating (e.g. work emails) >1 hour before bedtime[1][3]
• Passive activities better than active (e.g. read a book, watch TV)[3]
• Keep bedroom cool (65F seems optimal)[3]
• Temperature-controlled mattress[1]; may increase time spent in deep sleep and total time asleep[2]
• Don’t drink alcohol (it’s very difficult to have a good night’s sleep if you have alcohol in the proximity of bedtime)[1][3]
• Don’t drink coffee after noon (half-life of coffee is up to 6 hours)[3]
• Sustained endurance exercise (zone 2) done in morning/afternoon (>3 hours before bedtime) can create sleep pressure[3]
• +30 minute dose of strong daylight during the daytime[3]
• Manage stress[3]
• Don’t eat anything <3 hours before bedtime[3]
• Eat healthily[3]
• Spend time in a sauna (dry sauna; 198F; 15 minutes) or hot tub before bed[1][7]
• Give yourself enough time to sleep (ideally going to bed 9 hours before you need to wake up)[3]
• Fix wakeup time and don’t deviate from it (even on weekends)[3]
• Pharmaceutical agents/medications[1]:
  • Pregabalin
  • Trazodone
• Supplements[1]:
  • Glycine
  • Ashwagandha
  • Magtein or magnesium L-threonate
  • Melatonin (Dr. Peter Attia does not recommend frequent use)

Sources:
[1] AMA #42: Optimizing sleep – bedtime routine, molecule regimen, sleep trackers, sauna, & more (12/5/2022)
[2] Sleeping for One Week on a Temperature-Controlled Mattress Cover Improves Sleep and Cardiovascular Recovery (4/3/2024; funded by Eight Sleep)
[3] Outlive (Chapter 16: The Awakening) (4/4/2022)

Nutrition Patterns

Ketogenic

The ketogenic diet relies on very low carbohydrate intake, high fat consumption, and moderate protein intake to shift metabolism toward fat-derived ketones as the primary energy source.

Why:

• Randomized controlled trials suggest that ketogenic therapies can general cognition and memory in subjects with MCI and early-stage Alzheimer’s disease[1]

Pattern Definition[2]

Sources:
[1] Outlive (Chapter 9: Chasing Memory) (4/4/2022)
[2] Ketogenic Diet 101

Mediterranean

The Mediterranean-style diet relies on more monounsaturated fats, fewer refined carbohydrates, and the regular consumption of fatty fish.

Why:

• A series of studies (PREDIMED) suggest the Mediterranean diet supplemented with extra-virgin olive oil (EVOO) or nuts may be associated with better cognitive performance (relative to a low-fat control diet)[1] as well as slower cognitive decline and lower risk of mild cognitive impairment (MCI), particularly in the EVOO group[2]
• Mediterranean diet and lifestyle are associated with cognitive longevity. For example, Southern Italians who carry ApoE4 and live in Italy exhibit a normal rate of living to be in the oldest 1% of the population. However, Southern Italians who carry ApoE4, but who live in the United States exhibit a highly reduced chance of living into late old age[3]
• Mediterranean style diet when followed by people with two copies of ApoE4 may lower risk of dementia by 35% [4; 4:00]

Pattern Definition[5]

Sources:
[1] Mediterranean Diet and Age-Related Cognitive Decline
A Randomized Clinical Trial (July 2015)
[2] Virgin olive oil supplementation and long-term cognition: the PREDIMED-NAVARRA randomized, trial (June 2013)
[3] Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers (3/5/2021)
[4] Ask a Brain Doctor Live Q&A with Richard Isaacson, MD + Max Lugavere (9/10/2025)
[5] Mediterranean Diet

MIND

The MIND diet emphasizes leafy green vegetables, berries, whole grains, nuts, olive oil, and regular fish consumption, while limiting red meat, butter, cheese, sweets, and fried foods.

Why:

• Study suggests that patients with high adherence to MIND diet may have a relative dementia risk reduction of 50%[1]

Pattern Definition[2]

Sources:
[1] AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more (4/17/2023)
[2] The Mind Diet (11/16/2016)

Changes

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