Background: Effective therapeutics for Alzheimer’s disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, which may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective strategy. Objective: To determine whether a precision medicine approach to Alzheimer’s disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial. Methods: 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, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure, 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, and cognition was assessed at t = 0, 3, 6, and 9 months. Results: All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer’s Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved. Conclusion: Based on the cognitive improvements observed in this study, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.

Adverse reactions to foods and adverse drug reactions are inherent in product defects, medication errors, and differences in individual drug exposure. Pharmacogenetics is the study of genetic causes of individual variations in drug response and pharmacogenomics more broadly involves genome-wide analysis of the genetic determinants of drug efficacy and toxicity. The similarity of nutritional genomics and pharmacogenomics stems from the innate goal to identify genetic variants associated with metabolism and disease. Thus, nutrigenomics can be thought of as encompassing gene-diet interactions involving diverse compounds that are present in even the simplest foods. The advances in the knowledge base of the complex interactions among genotype, diet, lifestyle, and environment is the cornerstone that continues to elicit changes in current medical practice to ultimately yield personalized nutrition recommendations for health and risk assessment. This information could be used to understand how foods and dietary supplements uniquely affect the health of individuals and, hence, wellness. The individual's gut microbiota is not only paramount but pivotal in embracing the multiple-functional relationships with complex metabolic mechanisms involved in maintaining cellular homeostasis. The genetic revolution has ushered in an exciting era, one in which many new opportunities are expected for nutrition professionals with expertise in nutritional genomics. The American College of Nutrition's conference focused on "Personalized Nutrition: Translating the Science of NutriGenomics Into Practice" was designed to help to provide the education needed for the professional engagement of providers in the personalized medicine era.

Considerable evidence is emerging that Autism Spectrum Disorder (ASD) is most often triggered by a range of different genetic variants that interact with environmental factors such as exposures to toxicants and changes to the food supply. Up to 80% of genetic variations that contribute to ASD found to date are neither extremely rare nor classified as pathogenic. Rather, they are less common single nucleotide polymorphisms (SNPs), found in 1–15% or more of the population, that by themselves are not disease-causing. These genomic variants contribute to ASD by interacting with each other, along with nutritional and environmental factors. Examples of pathways affected or triggered include those related to brain inflammation, mitochondrial dysfunction, neuronal connectivity, synapse formation, impaired detoxification, methylation, and neurotransmitter-related effects. This article presents information on four case study patients that are part of a larger ongoing pilot study. A genomic clinical decision support (CDS) tool that specifically focuses on variants and pathways that have been associated with neurodevelopmental disorders was used in this pilot study to help develop a targeted, personalized prevention and intervention strategy for each child. In addition to an individual’s genetic makeup, each patient’s personal history, diet, and environmental factors were considered. The CDS tool also looked at genomic SNPs associated with secondary comorbid ASD conditions including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections/pediatric acute-onset neuropsychiatric syndrome (PANDAS/PANS). The interpreted genomics tool helped the treating clinician identify and develop personalized, genomically targeted treatment plans. Utilization of this treatment approach was associated with significant improvements in socialization and verbal skills, academic milestones and intelligence quotient (IQ), and overall increased ability to function in these children, as measured by autism treatment evaluation checklist (ATEC) scores and parent interviews.

Importance: Effective therapeutics for Alzheimer's disease and mild cognitive impairment are needed. Objective: To determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment, in which potential contributors to cognitive decline are identified and targeted therapeutically, is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial. Rationale: Previous clinical trials for Alzheimer's disease have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, that may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective therapeutic strategy. Hypothesis: Alzheimer's disease is a multi-factorial network dysfunction that results from a chronic or repeated insufficiency of support for a neuroplasticity network; thus factors that increase demand — such as infections or toxin exposure — or reduce support — such as reduced energetics or trophic support — may contribute to the neurodegenerative process. Rectifying this hypothesized network dysfunction represents a rational approach to the treatment of the cognitive decline associated with Alzheimer's disease and mild cognitive impairment. Design: Twenty-five patients with Alzheimer's disease or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, 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, and cognition was assessed at t = 0, 3, 6, and 9 months. Trial registration and IRB approval: The clinical trial was registered at clinicaltrials.gov (NCT03883633), 1 and approved by the Advarra IRB. Support for the trial: The trial was supported by a grant from the Four Winds Foundation via Evanthea, LLC, and we are grateful to Diana Merriam and Gayle Brown for their interest, discussions, and support. Main Outcome Measures: Trained external raters evaluated the study subjects with the Montreal Cognitive Assessment (MoCA), CNS Vital Signs (a computerized cognitive assessment battery), AQ-21 (a subjective scale completed by the significant other or study partner), and AQ-C change scale (a subjective scale of cognitive improvement or decline, completed by the significant other or study partner). Follow-up brain MRI with volumetrics was carried out at the completion of the trial. Results: 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. Conclusions and Relevance: Based on the cognitive improvements observed in this study of patients with Alzheimer's disease or mild cognitive impairment, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.

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Molecular biology combined with genomics can be a powerful tool for developing potential intervention strategies for improving outcomes in children with autism spectrum disorders (ASD). Monogenic etiologies rarely cause autism. Instead, ASD is more frequently due to many polygenic contributing factors interacting with each other, combined with the epigenetic effects of diet, lifestyle, and environment. One limitation of genomics has been identifying ways of responding to each identified gene variant to translate the information to something clinically useful. This paper will illustrate how understanding the function of a gene and the effects of a reported variant on a molecular level can be used to develop actionable and targeted potential interventions for a gene variant or combinations of variants. For illustrative purposes, this communication highlights a specific genomic variant, SHANK3. The steps involved in developing molecularly genomically targeted actionable interventions will be demonstrated. Cases will be shared to support the efficacy of this strategy and to show how clinicians utilized these targeted interventions to improve ASD-related symptoms significantly. The presented approach demonstrates the utility of genomics as a part of clinical decision-making.

In the face of the current pandemic, I believe that by using already published scientific studies, we can decrease the impact, negative health effects of COVID and dramatically decrease Coronavirus related hospitalization rates. I believe we can also change the perception and reality of coronavirus into a treatable illness, generally managed in an outpatient setting.

The landscape of therapeutics for mild cognitive impairment and dementia is quite limited. While many single-agent trials of pharmaceuticals have been conducted, these trials have repeatedly been unable to show improvement in cognition. It is hypothesized that because Alzheimer’s, like many other chronic illnesses, is not a monogenic illness, but is instead caused by the downstream effects of an individual’s genetic variants interacting with each other, the environment, and lifestyle, that improving outcomes will require a personalized, precision medicine approach. This approach requires identifying and then addressing contributing genomic and other factors specific to each individual in a simultaneous fashion. Until recently, the utility of genomics as part of clinical decision-making for Alzheimer’s and cognitive decline has been limited by the lack of availability of a genomic platform designed specifically to evaluate factors contributing to cognitive decline and how to respond to these factors The clinical decision support (CDS) platform used in the cases presented focuses on common variants that relate to topics including, but not limited to brain inflammation, amyloid processing, nutrient carriers, brain ischemia, oxidative stress, and detoxification pathways. Potential interventions based on the scientific literature were included in the CDS, but the final decision on what interventions to apply were chosen by each patient’s physician. Interventions included supplements with “generally regarded as safe (GRAS)” rating, along with targeted diet and lifestyle modifications. We hypothesize that a personalized genomically targeted approach can improve outcomes for individuals with mild cognitive impairment who are at high risk of Alzheimer’s. The cases presented in this report represent a subset of cases from three physicians’ offices and are meant to provide initial proof of concept data demonstrating the efficacy of this method and provide support for this hypothesis. These patients were at elevated risk for Alzheimer’s due to their apolipoprotein E ε4 status. While further prospective and controlled trials need to be done, initial case reports are encouraging and lend support to this hypothesis of the benefit of a genomically targeted personalized medicine approach to improve outcomes in individuals with cognitive decline who are at high risk for Alzheimer’s.