Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer's Disease Prevention.

Matthew W Schelke,Aneela Rahman,Monica Mureb,Robert Krikorian,Robert Kachko,Bob Kaplan,Daniel J Palenchar,Lisa Mosconi,Peter Attia,Richard S Isaacson,Olivia Scheyer,Christine A Ganzer

doi:10.3389/fnagi.2018.00096

Abstract

Alzheimer’s disease (AD) is a neurodegenerative dementia that affects nearly 50 million people worldwide and is a major source of morbidity, mortality, and healthcare expenditure. While there have been many attempts to develop disease-modifying therapies for late-onset AD, none have so far shown efficacy in humans. However, the long latency between the initial neuronal changes and onset of symptoms, the ability to identify patients at risk based on family history and genetic markers, and the emergence of AD biomarkers for preclinical disease suggests that early risk-reducing interventions may be able to decrease the incidence of, delay or prevent AD. In this review, we discuss six mechanisms—dysregulation of glucose metabolism, inflammation, oxidative stress, trophic factor release, amyloid burden, and calcium toxicity—involved in AD pathogenesis that offer promising targets for risk-reducing interventions. In addition, we offer a blueprint for a multi-modality AD risk reduction program that can be clinically implemented with the current state of knowledge. Focused risk reduction aimed at particular pathological factors may transform AD to a preventable disorder in select cases.

Highlights

Alzheimer’s disease (AD) is a major source of morbidity and mortality worldwide, affecting one in eight individuals and costing over $400 billion annually (Wimo et al, 2013)
While some groups are studying gene delivery of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) as a possible therapeutic target for AD (Tuszynski and Nagahara, 2016), it is possible that increasing expression of these factors before patients are symptomatic may reduce risk or delay the clinical onset of AD
A successful dietary intervention doesn’t necessarily improve serum lipids and blood pressure; rather it corrects them to levels we would find in a healthy individual at low risk for CHD and AD

Summary

INTRODUCTION

Alzheimer’s disease (AD) is a major source of morbidity and mortality worldwide, affecting one in eight individuals and costing over $400 billion annually (Wimo et al, 2013). Systemic Interventions for Alzheimer’s Risk Reduction: Improving Glucose Metabolism and Insulin Sensitivity, Modulating Inflammation, and Reducing Oxidative Stress. As exercise prevents declines in hippocampal function in humans (Intlekofer and Cotman, 2013) and decreases amyloid burden in rodents (Adlard et al, 2005), an active exercise regimen may reduce the risk of AD through reduction in cerebral oxidative stress. While some groups are studying gene delivery of NGF and BDNF as a possible therapeutic target for AD (Tuszynski and Nagahara, 2016), it is possible that increasing expression of these factors before patients are symptomatic may reduce risk or delay the clinical onset of AD Both exercise and reduction of hypercortisolemia may promote neural plasticity through increased production of neurotrophic factors. It is too soon to tell if dysregulation of calcium signaling underlies the profound cognitive impairments seen with sleep deprivation

A MULTIFACTORIAL PROGRAM TO REDUCE AD RISK

Findings

CONCLUSION