Patients were treated for nine months with a personalized, precision medicine protocol that addressed each patient’s identified potentially contributory factors, 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 (though in some cases yet to be proven causally) with Alzheimer’s-related cognitive decline: restore insulin sensitivity, improve hyperlipidemia, resolve inflammation if present (and remove the cause(s) of the inflammation), treat pathogens, optimize energetic support (oxygenation, cerebral blood flow, ketone availability, and mitochondrial function), optimize trophic support (hormones, nutrients, and trophic factors), treat autoimmunity if identified, and detoxify if toxins were identified.
The treatment team included a health coach, nutritionist, and a physical trainer, as well as the physician.
Diet was a plant-rich, high-fiber, mildly ketogenic diet, high in leafy greens and other non-starchy vegetables (raw and cooked), high in unsaturated fats, 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.
Exercise both aerobic and strength training, was encouraged for at least 45 minutes per day, at least six days per week, and facilitated by the personal trainers. High-intensity interval training (HIIT) was recommended a minimum of twice per week.
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 included biofeedback and heart-rate variability training with a HeartMath Inner Balance for IOS device, for a minimum of 10 minutes per day.
Brain training was carried out using BrainHQ, a HIPAA and SOC-2-compliant platform with empirical validation18, for a minimum of 15 minutes daily. Participants trained on 29 cognitive exercises that target the speed and accuracy of information processing.
Hormones and nutrients
For those patients with suboptimal hormonal status, bio-identical hormone replacement and appropriate supplements were provided to optimize sex hormone levels, neurosteroids, and thyroid medications as indicated for sub-optimal thyroid function. For those with suboptimal nutrients (e.g., vitamin D, omega-3, B vitamins, CoQ10, or minerals), the appropriate nutrients were provided.
Gastrointestinal health
For those with gastrointestinal hyperpermeability, infections, inflammation, or impaired absorption and digestion, gut healing with dietary restriction, gut-healing nutrients, and digestive enzyme support if indicated, along with treatment of any identified dysbiosis, was undertaken.
Inflammation
For those with evidence of systemic inflammation, pro-resolving mediators and anti-inflammatory herbal supplements were provided, low-dose naltrexone was prescribed (if there was evidence of autoimmunity), and omega-3 fats included via diet and supplements. Some patients utilized fasting-mimicking diets.
Infectious agents associated with cognitive decline or systemic inflammation were identified and treated. For those with evidence of Herpes simplex infection or a history of outbreaks, valacyclovir was prescribed for 2-6 months. Active Epstein-Barr Virus (EBV) was treated with herbal protocols. For those with evidence of tick-borne infections such as Borrelia, Babesia, or Bartonella, organism-sensitive treatment was prescribed with herbal anti-microbials and immune support.
Toxins and toxicants
For those with toxicity associated with metals (e.g., mercury or lead), organic pollutants (e.g., benzene, phthalates, or organophosphate insecticides), or biotoxins (e.g., trichothecenes, ochratoxin A, or gliotoxin), targeted detoxification was undertaken with binding agents (e.g., cholestyramine or bentonite clay), sauna, herbs, sulforaphane, and dietary restriction of seafood if indicated.
Treatment protocol from the preprint: