Stephanie Yang, ND

Discover how a 53-year-old woman with a strong family history of Alzheimer’s took a proactive, root-cause approach to protect her cognitive future through lifestyle, neuroprotective therapies, and metabolic support.

Abstract and Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative condition and the sixth leading cause of death in the United States.¹ Although it typically begins after age 65, research shows that changes in the brain, such as inflammation, oxidative stress, mitochondrial dysfunction, and protein buildup, can begin silently 10–20 years before any memory symptoms appear.

A key driver is a brain-specific form of insulin resistance—often called “Type 3 Diabetes”—that interferes with how brain cells use glucose, their main fuel. When neurons can’t generate enough energy, they become vulnerable to damage. This breakdown contributes to the buildup of beta-amyloid plaques and tau tangles—sticky proteins that disrupt communication, waste clearance, and repair, weakening memory networks.^8,9

Amyloid plaques often accumulate silently for years before symptoms arise, while tau-related neurofibrillary tangles—twisted fibers inside brain cells that impair function—appear later and more closely track cognitive decline. According to the biomarker cascade model⁴, a reduced Aβ42/40 ratio is one of the earliest measurable signs of Alzheimer’s disease, emerging long before tau elevation or memory loss.

Genetics like the ApoE ε4 gene can increase risk, but lifestyle factors such as nutrition, sleep, movement, and stress influence how genes are expressed—a concept known as epigenetics. This means even inherited risk can be shaped by daily choices, making early detection and prevention essential.

Advances in biomarker testing now allow us to identify these changes years before symptoms appear. Key tools include:

• Neurofilament Light Chain (NfL): Indicates damage to nerve fibers in the brain
• Apolipoprotein E (ApoE ε3/ε4): The strongest known genetic risk factor
• Low plasma Aβ42/40 ratio: Reflects early amyloid-beta accumulation
• pTau-217: Helps distinguish preclinical AD from other neurodegenerative diseases

This case highlights how a 49-year-old woman with a strong family history of Alzheimer’s took early action using a holistic and root-cause approach. With the help of advanced testing, targeted nutrition, supplements, and nervous system support, she built a personalized plan to delay or prevent cognitive decline.

Case Presentation

Patient Profile

• Name: Serena (pseudonym)
• Age: 53
• Gender: Female
• Occupation: Attorney
• Primary Concern: Family history of Alzheimer’s disease

1. Subjective Findings

Serena, a 53-year-old attorney, was concerned about subtle changes in her memory and mental clarity. She described occasional word-finding issues, misplacing everyday items, and needing to re-read materials to absorb them, especially in the evenings. She also noticed more frequent mental fatigue and difficulty staying focused during complex tasks at work.

In addition, she reported delayed sleep onset and nighttime anxiety, especially after mentally demanding days. She has a long-standing history of anxiety dating back to her 20s, although she’s never taken medication. She denied any history of mood disorders, trauma, tremor, or diagnosed neurological conditions.

Her maternal grandmother and uncle were both diagnosed with Alzheimer’s disease in their early 60s. Given her family history and high cognitive demands at work, Serena was highly motivated to explore early prevention strategies.

2. Objective Findings

Here’s a breakdown of Serena’s lab results to help you understand what’s going on inside her brain and body, and why we focused on the areas we did.

Cognitive & Genetic Markers

• MoCA Score (28/30): Her thinking and memory are still healthy. But because she notices small changes and has a family history of Alzheimer’s, we didn’t want to wait for bigger problems.
• ApoE Genotype (ε3/ε4): She carries one gene (ε4) linked to higher Alzheimer’s risk. This means her brain may be more sensitive to inflammation and stress, so prevention is key.

Alzheimer’s Biomarkers

• pTau-217 (0.61 pg/mL): This is a marker of brain cell damage (tau tangles). Her level is still in the normal range, which is good, but we know things can shift quickly if other risks aren’t addressed.
• Aβ42/40 Ratio (0.064): This ratio is slightly low, which may mean her brain is starting to hold on to sticky amyloid proteins. These are some of the earliest signs of Alzheimer’s-related changes.
• Neurofilament Light Chain (NfL, 8.3 pg/mL): A axonal injury marker reflecting early neurodegeneration. Thankfully, her level is within the normal range, indicating no active nerve damage and supporting a focus on prevention.

Metabolic & Inflammatory Markers

• Omega-3/6 Ratio (0.19): A low omega-3 to omega-6 ratio can worsen neuroinflammation and contribute to amyloid buildup. Optimizing omega-3 levels helps protect brain tissue and modulate inflammation.
• Glucose, Insulin, A1c: Her blood sugar isn’t dangerously high, but it’s high enough to show early signs of insulin resistance—what we call “Type 3 diabetes” when it affects the brain. This can starve brain cells of fuel and raise inflammation.
• ESR (26 mm/hr) and CRP (3.9 mg/L): These inflammation markers are both elevated. Chronic inflammation is like a slow fire in the brain—it’s one of the key triggers for memory problems later in life.

Nutritional & Methylation Markers

• Vitamin D (23 ng/mL): Her levels are too low. Vitamin D is more than a bone vitamin—it helps the brain clear out toxins and regulates the immune system.
• MTHFR Gene + MMA (B12): Her MTHFR gene is negative, and her B12 markers (including MMA) are within normal range, indicating efficient methylation and no functional deficiency.

3. Assessment

• Genetic Risk for Alzheimer’s Disease (Z82.3)
• Early Amyloid Deposition (R41.3 + Z13.850)
• Type 3 Diabetes Physiology / Insulin Resistance (E88.81)
• Neuroinflammation (R53.83 + R79.82)
• Vitamin D Deficiency (E55.9)

4. Plan

Weeks 0–4: Foundations

In addition to naturopathic and lifestyle interventions, Serena was referred to neurology for supportive co-management. This allowed us to pursue prevention using evidence-based, natural strategies while keeping her connected to conventional care if future needs arise.

Each intervention was selected based on Serena’s unique biomarker profile and personalized root-cause assessment. Below is a summary of the foundational strategies:

• MIND Diet: This diet combines the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) to deliver neuroprotective nutrients like polyphenols, omega-3s, and folate. It is designed to lower inflammation, oxidative stress, and insulin resistance. Moderate adherence is associated with a 35% lower risk of Alzheimer’s.²
• Exercise: Combination of aerobic activity (30 minutes, 3x/week) and strength training (2x/week). Research shows that aerobic activity helps reduce amyloid plaque buildup, while resistance training supports insulin sensitivity and protects against brain atrophy.^11,12
• Lifestyle: 60 minutes of daily stress management through meditation, breathwork, or yoga reduces cortisol, protects the hippocampus (an area in the brain associated with memory), and supports restorative sleep.

Supplements & Botanicals:

• Vitamin D3 (5,000 IU/day): Supports neuroimmune health, reduces inflammation, and improves glymphatic waste clearance.
• Omega-3s (2,000 mg EPA + DHA/day): Supports brain cell membrane health, reduces neuroinflammation, and may lower amyloid burden.
• Mitochondrial Support Formula (containing Acetyl-L-carnitine 1.5 g, CoQ10 100 mg, and Alpha-Lipoic Acid 900 mg): Enhances mitochondrial energy production and reduces oxidative stress.
• Berberine (1,500 mg/day): Improves insulin sensitivity and metabolic function.

Nootropics: 

• Lion’s Mane (1,000 mg/day): Stimulates nerve growth factor, improves neuroplasticity, and supports memory in early cognitive decline.¹³
• Bacopa monnieri (350 mg/day): Enhances memory, focus, and stress resilience; protects neurons from beta-amyloid toxicity.¹⁴
• Curcumin (1,000 mg/day with black pepper): Crosses the blood-brain barrier to reduce inflammation and amyloid accumulation; improves working memory and mood.¹⁰

Outcomes: By 12 weeks, Serena reported:

• Improved focus and mental energy
• Reduced brain fog after meals
• More restorative sleep
• Lab follow-up: Vitamin D improved to 48 ng/mL, A1c stabilized at 5.5%, CRP decreased to 1.8 mg/L

Serena felt empowered by her progress and committed to long-term monitoring and support.

Discussion and Conclusion

This case illustrates how proactive, personalized care can shift the trajectory of cognitive health in individuals with elevated Alzheimer’s risk, before symptoms begin. By integrating advanced biomarker testing with functional assessments, we identified subtle signs of neuroinflammation, early amyloid deposition, and metabolic dysfunction consistent with the early Alzheimer’s continuum.

Her low Aβ42/40 ratio, elevated inflammatory markers, and insulin resistance suggested a silent but active process of neurodegeneration, even in the absence of tau elevation or memory loss. This reflects the “amyloid-first” progression outlined in the biomarker cascade model⁴, reinforcing the importance of early intervention.

Key strategies included optimizing vitamin D levels, reducing systemic inflammation, improving insulin sensitivity, and supporting mitochondrial and neuronal resilience through lifestyle, targeted supplementation, and stress management. 

Over 12 weeks, Serena Outcomes: By 12 weeks, Serena reported improvements in focus, mental clarity, sleep quality, and inflammatory markers—showing that risk reduction is measurable and meaningful.

While Serena had no overt symptoms, her labs revealed:

• ApoE ε3/ε4 genotype: Increased AD risk
• Low Aβ42/40 ratio: Early amyloid burden despite normal tau
• Elevated CRP and ESR: Systemic inflammation
• Insulin resistance: A key metabolic driver of neurodegeneration

This case demonstrates that brain health is modifiable even with a genetic predisposition. With the right tools, education, and guidance, individuals like Serena can build resilience, delay neurodegeneration, and take ownership of their cognitive future.

Stephanie Yang, ND is a licensed primary care naturopathic physician specializing in cognitive health for busy professionals. Having experienced brain fog firsthand, Dr. Yang understands the profound impact it has on both work and personal life. She helps individuals overcome cognitive symptoms by addressing root causes such as chronic stress, perimenopausal shifts, digestive inflammation, metabolic imbalances, and nutritional deficiencies. Using a holistic approach, Dr. Yang combines Eastern, Western, and Naturopathic medicine to create evidence-based and personalized solutions that restore focus, resilience, and well-being. Dr. Yang offers online consultations through her telemedicine practice and in-person consultations at Puget Sound Family Health in Tacoma, Washington.

References

1. Alzheimer’s Association. (2023). 2023 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 19(4), 1598–1695. https://doi.org/10.1002/alz.13055
2. Morris, M. C., et al. (2015). MIND diet slows cognitive decline. Alzheimer’s & Dementia, 11(9), 1007–1014. https://doi.org/10.1016/j.jalz.2015.04.011
3. Rockwood, K., et al. (2002). Prevalence and outcomes of vascular risk factors in dementia. CMAJ, 166(5), 507–512.
4. Jack, C. R., Jr., et al. (2010). Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. The Lancet Neurology, 9(1), 119–128. https://doi.org/10.1016/S1474-4422(09)70299-6
5. Liu, C. C., et al. (2013). Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy. Nature Reviews Neurology, 9(2), 106–118. https://doi.org/10.1038/nrneurol.2012.263
6. Janelidze, S., et al. (2016). Plasma β-amyloid in Alzheimer’s disease. Scientific Reports, 6, Article 26801. https://doi.org/10.1038/srep26801
7. Palmqvist, S., et al. (2020). Accuracy of plasma phospho-tau217 for Alzheimer diagnosis. JAMA, 324(8), 772–781. https://doi.org/10.1001/jama.2020.12134
8. de la Monte, S. M., & Wands, J. R. (2008). Alzheimer’s disease is type 3 diabetes. Journal of Diabetes Science and Technology, 2(6), 1101–1113. https://doi.org/10.1177/193229680800200619
9. Arnold, S. E., et al. (2018). Brain insulin resistance in Alzheimer’s disease. Nature Reviews Neurology, 14(3), 168–181. https://doi.org/10.1038/nrneurol.2017.185
10. Small, G. W., et al. (2018). Bioavailable curcumin improves memory. The American Journal of Geriatric Psychiatry, 26(3), 266–277. https://doi.org/10.1016/j.jagp.2017.10.010
11. Erickson, K. I., Voss, M. W., Prakash, R. S., Basak, C., Szabo, A., Chaddock, L., … & Kramer, A. F. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 3017–3022. https://doi.org/10.1073/pnas.1015950108
12. Cassilhas, R. C., Viana, V. A. R., Grassmann, V., Santos, R. T., Santos, R. F., Tufik, S., & Mello, M. T. (2007). The impact of resistance exercise on the cognitive function of the elderly. Medicine & Science in Sports & Exercise, 39(8), 1401–1407. https://doi.org/10.1249/mss.0b013e318060111f
13. Mori, K., Inatomi, S., Ouchi, K., Azumi, Y., & Tuchida, T. (2009). Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: A double-blind placebo-controlled clinical trial. Phytotherapy Research, 23(3), 367–372. https://doi.org/10.1002/ptr.2634
14. Calabrese, C., Gregory, W. L., Leo, M., Kraemer, D., Bone, K., & Oken, B. (2008). Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: A randomized, double-blind, placebo-controlled trial. Journal of Alternative and Complementary Medicine, 14(6), 707–713. https://doi.org/10.1089/acm.2008.0018