By Joseph E. Scherger, MD, MPH

Vice President, Primary Care, Eisenhower Medical Center; Clinical Professor, Keck School of Medicine, University of Southern California, Los Angeles

Dr. Scherger reports no financial relationships relevant to this field of study.

SYNOPSIS: Insulin resistance is associated with cognitive decline and Alzheimer’s disease. Patients who are positive for the apolipoprotein E4 gene are at increased risk for Alzheimer’s disease. This risk may be reversed by treating insulin resistance.

SOURCE: Johnson LA, Torres ER, Impey S, et al. Apolipoprotein E4 and insulin resistance interact to impair cognition and alter the epigenome and metabolome. Sci Rep 2017;7:43701.

The incidence of cognitive decline and Alzheimer’s disease is increasing parallel with the increase in insulin resistance and type 2 diabetes.1 Researchers are establishing a causative association between these conditions.2 Treating insulin resistance and normalizing blood sugar may reverse cognitive decline and early Alzheimer’s disease.3

Patients who test positive for the apolipoprotein E4 (ApoE4) gene demonstrate an increased incidence of Alzheimer’s disease.4 Johnson et al studied mice and the biological connection of the ApoE4 gene and insulin resistance. The presence of insulin resistance produces cognitive changes in ApoE4-positive mice, which is reversible if insulin resistance is resolved through dietary change.


2017 was a breakthrough year for understanding and treating cognitive decline and Alzheimer’s disease. Previously, this condition was thought to be irreversible. Three credible books, published between August and November 2017, were about research on nutrition and other lifestyle measures to reverse cognitive decline in separate clinical trials.2,5-6

Dale Bredesen, MD, is a visiting professor of neurology at UCLA and founding president of the Buck Institute for Research on Aging. His protocol for preventing and reversing cognitive decline is called ReCODE (reverse cognitive decline). ReCODE calls for at least 12 hours of daily fasting to achieve nutritional ketosis and a healthy Mediterranean diet of nuts, seeds, and vegetables, including avocado, olive oil, and wild caught fish. The book covers foods in detail, along with the supplements Bredesen recommends.2 Other parts of the protocol are exercise, sleep, and stress reduction. Bredesen’s research regarding reversing Alzheimer’s disease has been published since “patient zero” in 2014.7

Dale Sherzai, MD, and Ayesha Sherzai, MD, are neurologists at Loma Linda University. Co-directors of the Brain Health and Alzheimer’s Prevention Program at Loma Linda University Medical Center, they developed the NEURO (Nutrition, Exercise, stress reduction [Unwind], Restorative sleep, and Optimize brain function) protocol, which is similar to ReCODE. Patients also engage in multiple cognitive exercises.5 NEURO differs from ReCODE in that NEURO is a whole food, plant-based diet (vegan or vegetarian). The creators of ReCODE and NEURO made similar discoveries, which means patients could use ReCODE, NEURO, or possibly a combination of each.

Daniel Amen, MD, is a psychiatrist who operates six clinics that treat various brain diseases. He has written many articles and books and uses imaging and comprehensive testing to design treatment protocols. His latest book, Memory Rescue: Supercharge Your Brain, Reverse Memory Loss, and Remember What Matters Most, is about an approach that includes nutrition, some supplements, and lifestyle adjustments.6

Reversing cognitive decline is a game changer for medicine. No longer do clinicians simply help patients and families cope with a progressive disease that is irreversible. Intensive low-carbohydrate and anti-inflammatory nutrition and lifestyle change are skill sets that have become vitally important to good primary care practice.


  1. James BD, Leurgans SE, Hebert LE, et al. Contribution of Alzheimer’s disease to mortality in the United States. Neurology 2014;82:1045-1050.
  2. Bredesen DE. The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline. New York: Avery (Penguin House); 2017.
  3. Bredesen DE, Amos EC, Canick J, et al. Reversal of cognitive decline in Alzheimer’s disease. Aging 2016;8:1-9.
  4. National Institute on Aging. Alzheimer’s Disease Genetics Fact Sheet. Available at: Accessed Dec. 27, 2017.
  5. Sherzai D, Sherzai A. The Alzheimer’s Solution: A Breakthrough Program to Prevent and Reverse the Symptoms of Cognitive Decline at Every Age. New York: HarperOne; 2017.
  6. Amen DG. Memory Rescue: Supercharge Your Brain, Reverse Memory Loss, and Remember What Matters Most. Carol Stream, IL: Tyndale House Publishers; 2017.
  7. Bredesen DE. Reversal of cognitive decline: A novel therapeutic program. Aging 2014;6:707-717.