According to the PAQUID study, approximately one million French people over the age of 65 suffer from Alzheimer’s disease; 17% of people over 75 are affected. And we expect 1,800,000 cases by 2050, or nearly one in ten people over the age of 65.
Still according to PAQUID, in the mild or early stages, only one in three cases is known to the patient or his doctor.
However, there is currently no effective treatment for Alzheimer’s disease, nor for neurodegenerative diseases such as fronto-temporal dementia and amyotrophic lateral sclerosis. Secretase inhibitors have failed to improve patients in clinical trials and may even hasten disease progression. Monoclonal antibodies are under study: aducanumab has been approved by the US Food and Drug Administration, but not by the European Medicines Agency, due to insufficient evidence of effectiveness. Another drug, lecanemab is being evaluated, an application for accelerated authorization was made in March 2023. But these treatments seem to reduce brain volumea disturbing effect that questions specialists.
The role of lifestyle
It is in this context that a few years ago emerged a personalized approach stemming from precision medicine, of which the American neurologist Dale Bredesen is the pioneer. Dale Bredesen has written several books about it, including The first survivors of Alzheimer’s, a collection of cases of early-stage patients who have recovered their memory thanks to its ReCODE protocol, which mainly involves lifestyle changes. If this therapeutic approach is confirmed, it
The ReCODE protocol involves identifying in patients, if possible in the early stages of the disease or cognitive impairment, the factors thought to contribute to Alzheimer’s and then treating them, most often through dietary and lifestyle changes. life.
Several factors have been identified in epidemiological, pathological, toxicological, genetic and biochemical studies: insulin resistance, neuroinflammation, nutrient and hormone deficiencies, exposure to toxins, chronic stress, etc.
The ReCODE protocol has already been applied to several hundred patients, and these cases reported in the scientific literature, but we now have intervention studies.
The most recent is a proof of concept trial, conducted by researchers including Dr. Bredesen on 25 American patients with Alzheimer’s disease or mild cognitive impairment and aged 50 to 76 years.
Standard physical and neurological examinations were performed on each patient. Genetic testing has also been done to identify genomic variants that may contribute to cognitive decline, including the APOE genotype.
Biochemical tests were performed to identify markers of insulin resistance (HOMA-IR), protein glycation (hemoglobin A1c), vascular diseases (advanced lipid panel, C-reactive protein, homocysteine), systemic inflammation (protein C -reactive, fibrinogen, homocysteine), chronic infection (herpes simplex type 1, herpes simplex type 2, Epstein-Barr virus, Borrelia, Babesia, Bartonella, Treponema pallidum, human immunodeficiency virus and hepatitis C), gastrointestinal health (stool analysis for gut pathogens, digestion, absorption, gut immune markers and microbiome analysis), hormonal dysregulation (serum estradiol, progesterone, pregnenolone, DHEA sulfate, free and total testosterone, sex hormone binding globulin, prostate specific antigen, thyroid hormones (free T3, free T4, reverse T3 and TSH), nutritional status (B vitamins, vitamin D, vitamin E, magnesium, zinc, copper, CoQ10, lipoic acid, omega-6/omega -3 ratio, omega-3 index), exposure to toxins or toxic substances (metals, organic toxic substances and biotoxins (urinary mycotoxins), autoimmune markers (eg. eg, thyroid peroxidase, thyroglobulin, antinuclear antigen), immunoglobulins, CD57, nocturnal hypoxemia (oximetry to identify sleep apnea and upper airway resistance syndrome), and other biochemical parameters associated with cognitive decline.
Magnetic resonance imaging (MRI) of the brain with volumetry was performed for each patient, at initial assessment and again at the end of the 9-month treatment protocol.
Patients were treated for nine months with a personalized precision medicine protocol that targeted factors identified in each patient that may contribute to their disease or disorder, and cognition was measured at study entry, then 3, 6, and 9 months later.
The diet followed by the patients was a plant-rich, high-fiber, mildly ketogenic diet, high in leafy greens and other non-starchy vegetables, high in unsaturated fats, with a low glycemic load, and 12 to 16 hours of fasting. each night, between the evening meal and the first meal of the following day.
Organic produce, low-mercury wild-caught fish (salmon, mackerel, anchovies, sardines, and herring), and moderate consumption of grass-fed eggs and meats were encouraged, along with avoidance of ultra-processed foods, simple carbohydrates, foods containing gluten, and dairy products. Blood ketone levels were monitored with ketone meters with the goal being between 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 (for aerobic exercise) and at least twice per week (for strength training). Interval training (HIIT) was recommended at least twice a week.
Sleep hygiene was given special attention to ensure 7-8 hours of quality sleep per night, and all patients without known sleep apnea were tested over multiple nights using devices home. People diagnosed with sleep apnea or upper airway resistance syndrome were advised to obtain either a continuous positive airway pressure machine or a dental splint device.
Stress management included training in biofeedback and cardiac coherence-type heart rate variability.
Brain training was performed using BrainHQ, for a minimum of 15 minutes per day. Participants trained on 29 cognitive exercises that target the speed and accuracy of information processing.
For patients with suboptimal hormone status, bioidentical hormone replacement and appropriate supplements were provided to optimize sex hormone levels, neurosteroids (DHEA, pregnenolone, and vitamin D) and thyroid medications were prescribed in the case of suboptimal thyroid function. For those with insufficient nutrient status (eg vitamin D, omega-3, B vitamins, CoQ10 or minerals), the appropriate nutrients were provided.
For those with gastrointestinal hyperpermeability, infections, inflammation, or impaired absorption and digestion, bowel healing with dietary restriction, nutrient and digestive enzyme support if indicated, as well as treatment for any dysbiosis identified, were undertaken. Gastrointestinal hyperpermeability was assessed by testing the antibody response to the following permeability-related antigens: actomyosin (IgA), occludin/zonulin (IgA, IgG, IgM), and lipopolysaccharide (IgA, IgG, and IgM).
For those with signs of systemic inflammation, pro-resolving mediators and herbal anti-inflammatory supplements were provided; low dose naltrexone was prescribed (if there was evidence of autoimmunity). Omega-3 fatty acids have been included via diet and supplements.
Infectious agents associated with cognitive decline or systemic inflammation have been identified and treated. For people with signs of Herpes simplex infection or a history of outbreaks, valacyclovir was prescribed for 2-6 months. For those showing signs of tick-borne infections such as Borrelia, Babesia or Bartonella, treatment was prescribed, along with immune support.
For those with toxicity associated with metals (eg, mercury or lead), organic pollutants (eg, benzene, phthalates, or organophosphate insecticides), or biotoxins (eg, trichothecenes, ochratoxin A or gliotoxin), targeted detoxification was undertaken with sequestering agents and dietary restriction of seafood if indicated.
A significant reduction in inflammation was observed (lower serum high-sensitivity C-reactive protein). The level of glycation decreased (decrease in hemoglobin A1c), insulin resistance decreased insignificantly (HOMA-IR), the lipid profile was improved (decrease in the ratio of triglycerides to high density lipoproteins ) and serum vitamin D increased.
All 25 participants experienced overall subjective improvement (as judged by their study partners) over the treatment period.
CNS Vital Signs is a computerized neuropsychological assessment used to assess performance and cognitive changes. The comparison of the results between the start of the study and the end of the study shows a significant improvement in the Neurocognitive Index. This improvement mainly concerns psychomotor speed, executive functioning, motor speed, verbal memory, simple attention, cognitive flexibility and reaction time.
Other tests like the MoCA and BrainHQ recorded an improvement in cognitive abilities.
Patient gray matter volumes increased an average of 0.3% on an annualized basis. By comparison, longitudinal gray matter volumes generally decline on average by 0.83 to 0.92% per year for people without cognitive decline and by 2.20 to 2.37% for people with dementia. Alzheimer’s.
The hippocampal volumes of the patients in the trial decreased at an annualized rate of 1.29%. By comparison, hippocampal volumes decrease in patients with MCI or Alzheimer’s disease at an annualized rate of 3.5-4.66%, and in cognitively stable controls at an average rate of 1.41 to 1.73%.
Further analysis of MRI results detected no loss of brain volume or cortical thinning was detected in the participants.
Although the study, like most trials of its type, is not without its weaknesses, its results taken together suggest that a precision medicine approach using the ReCODE protocol may be an effective strategy in the early stages of Alzheimer’s disease and in patients with cognitive decline.
It should be added that no serious adverse event was recorded. On the contrary, most patients have improved in their general health, and unpublished observations show that some patients will no longer require antihypertensive drugs, antidiabetic drugs or lipid-lowering agents, because the protocol they followed addresses these factors that can contribute to cognitive decline.
Finally, this study confirms and extends anecdotal reports that it is possible to reverse cognitive decline and early onset dementia with a personalized precision medicine protocol. A larger clinical trial is underway.
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