Research Blog
A 9-month “precision medicine” “proof-of-concept” trial demonstrated significant improvements in metabolic and cognitive parameters in 25 patients with dementia or mild cognitive impairment. Exclusions from the study included subjects with major medical or psychiatric diseases as well as those on anticoagulants and statins.
The evaluations and interventions in the study mirror the functional naturopathic approach, i.e., early identification of metabolic dysfunction coupled with targeted nutrition and lifestyle interventions.
Pilot Protocol
Twenty-five patients with dementia or mild cognitive impairment with Montreal Cognitive Assessment (MoCA) scores of 19 or higher were evaluated.
The study assessed markers of
Systemic inflammation
hs-CRP, fibrinogen, homocysteine
Chronic infection
Titers for Herpes simplex 1 and 2, human herpesvirus 6, Epstein Barr virus, Borrelia, Babesia, Bartonella, Treponema pallidum, Human immunodeficiency virus, and Hepatitis C virus
Gastrointestinal health, dysbiosis
Stool analysis of gut pathogens, digestion, absorption, gut immune markers, and microbiome analysis
Insulin resistance
Protein glycation
Vascular disease
Advanced lipid panel, hs-CRP, homocysteine
Autoimmune markers
Thyroid peroxidase, thyroglobulin, anti-nuclear antigen
Immunoglobulins, CD57
Nocturnal hypoxemia
Oximetry to identify sleep apnea and upper airway resistance syndrome
Hormone insufficiency or dysregulation
Serum estradiol, progesterone, pregnenolone, DHEA sulfate, testosterone (free and total), sex-hormone binding globulin,(SHBG), prostate-specific antigen PSA (in males), free T3, free T4, reverse T3, and TSH
Nutrient status
CoQ10, lipoic acid
omega-6:omega-3 ratio, Omega-3 Index
Toxin or toxicant exposure
Metals, organic toxicants, and biotoxins (urinary mycotoxins)
Brain magnetic resonance imaging with volumetrics
Patients were treated for nine months with a personalized, precision medicine protocol. Cognition was assessed at t = 0, 3, 6, and 9 months.Diet
- Plant-rich, high-fiber (soluble and insoluble)
- Mildly ketogenic diet
- High in leafy greens and other non-starchy vegetables (raw and cooked)
- High in unsaturated fats
- Low in glycemic load
- Fasting period of 12–16 hours each night.
- Organic produce, wild-caught low-mercury fish (salmon, mackerel, anchovies, sardines, and herring)
- Modest consumption of pastured eggs and meats was 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 1.0–4.0mM beta-hydroxybutyrate
Genetics
- 4 were homozygous for APOE4
- 8 were heterozygous for APOE4
- 11 were homozygous for APOE3
- 2 were heterozygous for APOE2 and APOE3
Exercise
- Both aerobic and strength training was encouraged for at least 45 minutes, at least six days per week
- High-intensity interval training (HIIT) was recommended at least twice per week
Sleep
- Sleep hygiene was supported to ensure 7-8 hours of quality sleep nightly
- CPAP or dental splint provided for sleep apnea
Stress management
- Biofeedback and heart-rate variability training
Brain training
- 29 cognitive exercises
Targeted intervention as indicated:
- Bioidentical hormone replacement
- DHEA, pregnenolone, vitamin D
- Thyroid medication
- Nutrition intervention for
- Nutrient replenishment
- Gastrointestinal support for GI hyperpermeability, infection, inflammation, and impaired digestion and absorption
- Systemic inflammation
- Pro-resolving mediators
- Anti-inflammatory supplements, i.e., liposomal glutathione, fish oil, resveratrol, vitamin C, vitamin D, Boswellia, quercetin
- Autoimmunity
- Low-dose naltrexone
- Infections
- Pharmaceutical intervention (valacyclovir)
- Antimicrobial herbal protocols
- Toxicity
- Detoxification support with binding agents, sauna, herbs, sulforaphane, restriction of seafood
Results:
All outcome measures revealed improvement, with statistically significant improvement in:
- MoCA scores
- CNS Vital Signs
- Neurocognitive Index
- Alzheimer’s Questionnaire Change scores
- Inflammation
- Decreased hs-CRP, homocysteine
- Glycation
- Decreased HbA1C
- Lipid profile
- Decreased triglyceride/HDL ratio
- Vitamin D
- Increased
Non-significant improvement in insulin sensitivity
- Decrease in HOMA-IR
Serum biochemical tests prior to, and following, treatment for 9 months
Test Pre-treatment Post-treatment Significance
Hs-CRP 2.29±2.7 mg/L 0.89±0.98 mg/L p < 0.05
Hemoglobin A1c 5.39±0.36 % 5.18±0.31 % p < 0.05
HOMA-IR 1.58±1.32 1.23±0.63 NS
TG:HDL ratio 1.37±0.86 0.98±0.44 p < 0.05
Homocysteine 10.53±2.25mM 8.04±1.76mM p < 0.01
Vitamin D (25-OH) 41.8±14.2 ng/mL 51.5±10.5 mg/mL p < 0.01
Significance was calculated using a paired t-test, two-tailed. Hs-CRP, high-sensitivity C-reactive protein. HOMA-IR, homeostasis model assessment-estimated insulin resistance, calculated based on fasting insulin and fasting glucose (fasting insulin in mIU/L times fasting glucose in mg/dL, divided by 405.45). TG:HDL ratio, serum triglyceride-to-high-density-lipoprotein ratio. Vitamin D was measured as 25-hydroxycholecalciferol. Post-treatment tests were taken at the conclusion of the 9-month protocol for each patient, as described in the text. NS, not significant
Optimal Takeaway
Modern medicine is circling back to assessing the body as a whole instead of a network of unrelated organs and systems and applying a more natural, holistic approach to achieving optimal health, including brain health.
The Optimal DX approach and ODX functional blood chemistry analysis are ideal tools for identifying early trends in metabolic dysfunction and redirecting one’s journey back to optimal health.
Reference
Toups, Kat et al. “Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project.” Journal of Alzheimer's disease : JAD vol. 88,4 (2022): 1411-1421. doi:10.3233/JAD-215707 This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/35811518/
NOTE:
The current protocol is similar to the Bredesen Protocol developed by neurologist Dr. Dale Bredesen. You can read more about the Bredesen Protocol here:
- Apollo Health https://www.apollohealthco.com/bredesen-protocol/
- Dale Bredesen, MD https://healthylifedoctors.com/bredesen-recode
- Bredesen, Dale E. “Reversal of cognitive decline: a novel therapeutic program.” Aging vol. 6,9 (2014): 707-17. doi:10.18632/aging.100690 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25324467/
- Bredesen, Dale E et al. “Reversal of cognitive decline in Alzheimer's disease.” Aging vol. 8,6 (2016): 1250-8. doi:10.18632/aging.100981 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27294343/
- Bredesen, D. E., et al. "Reversal of cognitive decline: 100 patients." J Alzheimers Dis Parkinsonism 8.450 (2018): 2161-0460. https://www.researchgate.net/profile/Kenneth-Sharlin/publication/329063941_Reversal_of_Cognitive_Decline_100_Patients/links/5d965c00458515c1d391b494/Reversal-of-Cognitive-Decline-100-Patients.pdf
- Gustafson, Craig. “Dale E. Bredesen, MD: Reversing Cognitive Decline.” Integrative medicine (Encinitas, Calif.) vol. 14,5 (2015): 26-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712873/pdf/26-29.pdf
