Precision Medicine Approach to Alzheimer's Disease

Twenty-five patients with dementia or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, were evaluated for markers of:

Inflammation: C-reactive protein, fibrinogen, homocysteine
Chronic infection: Herpes family viruses (Herpes simplex type 1, Herpes simplex type 2, Epstein-Barr virus, and Human herpesvirus 6), Borrelia, Babesia, Bartonella, Treponema pallidum, Human immunodeficiency virus, and Hepatitis C virus.
Dysbiosis: stool analysis of gut pathogens, digestion, absorption, gut immune markers, and microbiome analysis
Insulin resistance: HOMA- IR, protein glycation (hemoglobin A1c).
Protein glycation: hemoglobin A1c.
Vascular disease: advanced lipid panel, C-reactive protein, homocysteine
Nocturnal hypoxemia.
Hormone insufficiency or dysregulation: serum estradiol, progesterone, pregnenolone, DHEA sulfate, testos- terone (free and total), sex-hormone binding globulin, prostate-specific antigen (in males), free T3, free T4, reverse T3, and TSH.
Nutrient deficiency: B vitamins, vitamin D, vitamin E, magnesium, zinc, copper, CoQ10, lipoic acid, omega-6:omega-3 ratio, omega-3 index
Toxin or toxicant exposure: urinary mycotoxins
Other biochemical parameters associated with cognitive decline.

Brain magnetic resonance imaging with volumetrics was also performed at baseline and study conclusion. Patients were treated for nine months with a personalized, precision medicine protocol, and cognition was assessed at 0, 3, 6, and 9 months.

What Was The Treatment?

Patients were treated for nine months with a per- sonalized, precision medicine protocol that addressed each patient’s identified potentially contributory fac- tors, and cognition was assessed at t = 0, 3, 6, and 9 months. The goal was to identify and address the factors associated theoretically and epidemiologically with Alzheimer’s disease-related cognitive decline:

Restore insulin sensitivity.
Improve hyperlipidemia.
Resolve inflammation if present (and remove the cause(s) of the inflammation).
Treat pathogens.
Optimise energetic support (oxygenation, cerebral blood flow, ketone availability, and mitochondrial function).
Optimise trophic support (hormones, nutrients, and trophic factors).
Treat autoimmunity if identified.
Detoxify if toxins were identified.

Patients were treated for nine months with a personalised, precision medicine protocol that addressed each patient’s identified potentially contributory factors.

The treatment team included a health coach, nutri- tionist, and a physical trainer, as well as the physician.

Nutrition & Alzheimer’s

Diet was a plant-rich, high-fiber (soluble and insol- uble), mildly ketogenic diet, high in leafy greens and other non-starchy vegetables (raw and cooked), high in unsaturated fats, low in glycemic load, with a fasting period of 12–16 hours each night. Organic produce, wild-caught low-mercury fish (salmon, mackerel, anchovies, sardines, and herring), and modest consumption of pastured eggs and meats were encouraged, as well as avoidance of processed food, simple carbohydrates, gluten-containing foods, and dairy. Blood ketone levels were monitored with fingerstick ketone meters, with a goal of 1.0–4.0 mM beta-hydroxybutyrate.

Nutritional Status Helps Prevent Alzheimer’s Disease

There has been evidence linking the consumption of essential nutrients to preventing the disease conditions that result in cognitive decline.

Different factors, including nutrition, influence brain development. Various sources suggest a connection between improved nutrition and optimal brain function. Nutrients provide building blocks that play a significant role in cell proliferation, neurotransmitter, and hormone metabolism, and are essential constituents of enzyme systems in the brain.

What Nutrients Are Best For Alzheimer’s?

Bitamin B2 (riboflavin)
Vitamin B12
Vitamin C
Vitamin E
Essential fatty acid (omega-3 fatty acid)
Flavonoids

These all play a vital role in ensuring healthy aging, enhancing memory, and strengthening neuroprotection (1).

There are others that have also been shown to be helpful. Check out my other blogs on Alzheimer’s for a summary of the research here.

Vitamin B1: Fortified cereals, lean meats, dried beans, peas, and soy foods
Vitamin B2: Turkey, nuts, yogurt, eggs, milk, fortified cereals, and green leafy vegetables
Vitamin B12: Beef, poultry, fish, milk, eggs, cheese, salmon, sardines, and cereals

Fats And Brain Health

A child’s full genetic potential for physical growth and mental development may be compromised due to dietary deficiencies

DHA, which is a type of omega-3 fat, plays an essential role in cognitive function. A decreased level of DHA in the blood results in cognitive decline in the elderly. Several studies have been conducted to correlate the effect of dietary DHA and cognitive function. In a study conducted, DHA increased cognitive function in a randomized controlled trial (RCT) that involved mentally healthy people older than 55. Daily DHA supplements for 24 weeks resulted in significantly lower paired associative learning errors than the placebo case.

When there is an imbalance in omega-3 and omega-6 PUFA, neurodevelopmental disorders occur by altering microglial activation that results in abnormal neuronal activity. We typically need more omega 3 fats in our diet.

Omega-3 fatty acid: Chia seeds, sardines, mackerel, anchovies, walnuts, salmon, and flax seeds
Omega-6 fatty acid: Corn oil, soybean oil, walnuts, cashew nuts, almonds, sunflower seeds, and mayonnaise

Nutrition And Vascular Dementia

Vascular dementia has been linked to various nutritional components, including lipids, folate, antioxidants, homocysteine, fish consumption, and vitamin B12. Vitamin E and C, fatty fish consumption was found to prevent vascular dementia. While elevated homocysteine, fried fish, and lower levels of vitamin B12 and folate caused an increased risk of vascular dementia

Exercise & Alzheimer’s

Exercise, both aerobic and strength training, was encouraged for at least 45 minutes per day, at least six days per week (for aerobic exercise) and at least twice per week (for strength training), and facilitated by the personal trainers. High-intensity interval training (HIIT) was recommended a minimum of twice per week.

Sleep & Alzheimer’s

Sleep hygiene was supported to ensure 7-8 hours of quality sleep per night, and all patients without known sleep apnea were tested over several nights using home sleep study devices. In those diagnosed with sleep apnea or upper airway resistance syndrome (UARS), referral for treatment with a continuous positive airway pressure apparatus (CPAP) or a dental splint device (for those identified with UARS) was provided.

Stress Management & Alzheimer’s

Stress management included biofeedback and heart-rate variability training with a HeartMath Inner Balance for IOS device, for a minimum of 10 minutes per day, chosen because of the ease of patient use and thus high compliance.

What Were The Results OF This Trial

All outcome measures revealed improvement: statistically significant improvement in:

MoCA scores.
CNS Vital Signs.
Neurocognitive Index.
Alzheimer’s Questionnaire Change score.

No serious adverse events were recorded. MRI volumetrics also improved.

Conclusion

The overall results support the notion that a precision medicine approach to the cognitive decline of Alzheimer’s disease and MCI may be an effective strategy, especially with con- tinued optimization over time. Furthermore, because of the contribution of numerous systemic factors, a precision medicine approach to cognitive decline is necessarily a systems medicine approach.

This precision medicine approach to Alzheimer’s approach, departs sharply from traditional treatment strategies for MCI and Alzheimer’s disease, which have largely been monotherapeutic, monophasic, non-personalised, and blind, i.e., cause-independent, thus not targeted to the underlying drivers of the disease in each person, but rather to common downstream consequences and/or secondary drivers, such as amyloidosis.

This is likely at least in part because Alzheimer’s disease remains a disease of unknown, and controversial, etiology, with many competing theories, none of which has led to effective treatment.

References:

Precision Medicine Approach to Alzheimer’s Disease: Successful Pilot Project (click here)

Precision Medicine Approach to Alzheimer’s Disease