Brain Starvation and Why It Is Important

Alzheimer’s disease (AD) currently afflicts more than 5 million Americans and healthcare costs for those who will be affected in 2050 are predicted to surpass one trillion dollars! It is a disease that takes away uniquely human traits and for which there is no cure. In addition, there appears to be little that we can do to delay or prevent its occurrence. However, a recent article published in Archives of Neurology may soon change that. Reductions in cerebral glucose metabolic rate (CMRglu) in the parieto-occipital, frontal and cingulate cortices are associated with increased AD risk and can be identified years before onset of dementia.

In this study, researchers investigated cerebral glucose metabolism in the brains of subjects with normal cognitive function who were recently diagnosed with type 2 diabetes or prediabetes. Their mean age was 74 years. Each participant underwent biochemical testing to measure their degree of resistance to the action of the hormone insulin (using the homeostasis model of insulin resistance HOMA-IR).

Results revealed that greater resistance to the action of insulin was associated with an AD-like pattern of reduced cerebral glucose metabolism. The relationship between CMRglu and insulin resistance was independent of age, 2 hour glucose level following oral glucose tolerance testing and apolipoprotein E ?4 allele carriage.
The conclusion of the researchers was that even mild abnormalities in insulin metabolism may be a marker of AD risk that is associated with reduced regional brain glucose metabolism that closely resembles that seen in AD even at the earliest stages of the disease.

These findings of diminished glucose use in the brain have been referred to as brain starvation by other neuroscience researchers currently investigating AD because similar findings can be produced when glucose uptake or metabolism is blocked. These brain regions experience localized decreases in energy generation, which has been hypothesized to play a key role in the etiology of AD.

Other neuroscientists have identified abnormalities in the insulin-signaling pathways in the brain that affect brain glucose metabolism, energy generation and neuronal functions including memory and learning. In the presence of peripheral insulin resistance, related abnormalities in cerebral insulin signaling have been identified. The location of brain insulin receptors (the molecular mediators of the insulin signal) reflect the distribution of CMRglu abnormalities seen in these studies.

The significance of these findings is linked to the ability to reverse peripheral insulin resistance by making appropriate dietary and lifestyle choices such as eating fewer calories, choosing more brain-healthy fats, fewer manufactured sugars and refined carbohydrates and avoiding products that contain trans-fats (such as partially hydrogenated vegetable oils). The hope is that by improving insulin metabolism the burden of AD can be diminished. It has been estimated that if he diagnosis can be delayed by seven years that AD could be eradicated.


Baker LD, Cross DJ, Minoshima S, Belongia D, Watson GS, & Craft S (2011). Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Archives of neurology, 68 (1), 51-7 PMID: 20837822

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  • matthardy

    Thanks for the post Doctor, it is quite interesting to read about the brain.

  • Pingback: A jumble of interesting articles I’ve read lately on da internet – April 1, 2011()

  • Really interesting post. So would these levels be indicative for both early-onset and more advanced stages of AD? AD research is really starting to take off with so many of the baby boomers starting to develop neurological illnesses.

  • sara

    It’d be interesting to see how those subjects develop/do not develop MCI or AD moving forward.

  • Frank Tsu

    Could you clarify if i am understanding what is being said in these two articles. The brain
    starvation article is denoting a reduction in CMRglu is used as a marker for Alzheimer’s disease. This article is
    is indicating that insulin resistance is associated with plaques as the markers for Alzheimer’s when traced via glusoce monitoring ?

Larry McCleary, MD

Larry McCleary, MD, is the former acting Chief of Pediatric Neurosurgery at Denver Children’s Hospital. He is trained and has practiced as a pediatric neurosurgeon and has completed post-graduate training in theoretical physics. His scientific publications span the fields of metabolic medicine, tumor immunology, biotechnology and neurological disease. He has lectured to audiences around the world. He is the author of Feed Your Brain Lose Your Belly (Greenleaf Book Group, 4/1/11).

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