Precision Medicine Approach to Alzheimer’s Disease: Successful Proof-of-Concept Trial

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Alzheimer’s disease has become the third leading cause of death.

Studies have provided candidate mechanisms for the neurodegeneration associated with Alzheimer’s disease, such as neuroinflammation, insulin resistance, and reduction in trophic support.

One complicating feature is that their etiology remains controversial, with many competing theories, such as “type 3 diabetes”, viral infection, misfolded or prions proteins, none of which has led to effective treatment.

The approach utilized in a new innovative trial departs sharply from traditional treatment strategies for MCI and Alzheimer’s disease, which have largely been monotherapeutic, monophasic, non-personalized, 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.

In the field of oncology, a personalized, precision medicine approach, in which the presumptive molecular drivers of the disease process are targeted therapeutically, has improved outcomes in at least some studies.

However, this strategy has not been applied successfully to neurodegenerative diseases.

A recent BioRxiv article presents a proof-of-concept trial of precision medicine approach to Alzheimer’s disease.

Twenty-five patients with Alzheimer’s disease or mild cognitive impairment, ages 50-76, were recruited to three clinical sites and were evaluated for markers of inflammation, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure (metals, organic toxicants, and biotoxins), genetic predisposition to cognitive decline, and other biochemical parameters associated with cognitive decline. Brain magnetic resonance imaging with volumetrics was performed at baseline and study conclusion.

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

Diet was a plant-rich, high-fiber, mildly ketogenic diet, high in leafy greens and other nonstarchy vegetables(raw and cooked), high in unsaturated fats, with a fasting period of 12- 16 hours each night.

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.

For those patients with suboptimal hormonal status, bioidentical hormone replacement and appropriate supplements were provided to optimize sex hormone levels, neurosteroids, and thyroid medications as indicated for sub-optimal thyroid function.

Infectious agents associated with cognitive decline or systemic inflammation were identified and treated.

All outcome measures revealed improvement: statistically highly significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and AQ-C were documented. No serious adverse events were recorded.

On overall results support the notion that a precision medicine approach to the cognitive decline of Alzheimer’s disease and mild cognitive impairment may be an effective strategy, especially with continued optimization over time.

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