Higher brain glucose levels may mean more severe Alzheimer’s

About Liz Seegert

Liz Seegert (@lseegert), is AHCJ’s topic editor on aging. Her work has appeared in NextAvenue.com, Journal of Active Aging, Cancer Today, Kaiser Health News, the Connecticut Health I-Team and other outlets. She is a senior fellow at the Center for Health Policy and Media Engagement at George Washington University and co-produces the HealthCetera podcast.

Image courtesy of the National Institute on Aging/National Institutes of HealthBeta-amyloid plaques and tau in the brain

For the first time, scientists have found a connection between abnormalities in how the brain breaks down glucose and the severity of the signature amyloid plaques and tangles in the brain, as well as the onset of eventual outward symptoms of Alzheimer’s disease.

Researchers from the National Institute on Aging (NIA) found distinct abnormalities in glycolysis, the main process by which the brain breaks down glucose, with evidence linking the severity of the abnormalities to the severity of Alzheimer’s disease.

Lower rates of glycolysis and higher brain glucose levels correlated to more severe plaques and tangles found in the brains of people with the disease. More severe reductions in brain glycolysis were also related to common symptoms of Alzheimer’s disease during life, such as problems with memory.

Researchers have thought about the possible links between how the brain processes glucose and Alzheimer’s for some time, according to NIA Director Richard J. Hodes, M.D. This type of research can help scientists think about new ways to investigate these connections as they search for better and more effective ways to treat or prevent this disease.

Brain tissue samples at autopsy from participants in the Baltimore Longitudinal Study of Aging  (BLSA), were analyzed. The BLSA is one of the world’s longest-running scientific studies of human aging, tracking neurological, physical and psychological data on participants over several decades. Researchers measured glucose levels in different brain regions, some vulnerable to Alzheimer’s disease, such as the frontal and temporal cortex, and some that are resistant, like the cerebellum.

Three groups of BLSA participants were assessed: those with Alzheimer’s symptoms during life and with confirmed Alzheimer’s disease pathology (beta-amyloid protein plaques and neurofibrillary tangles) in the brain at death; healthy controls; and individuals without symptoms during life but with significant levels of Alzheimer’s pathology found in the brain post-mortem.

Similarities between diabetes and Alzheimer’s have been difficult to evaluate, since insulin is not needed for glucose to enter the brain or to get into neurons, according to principal investigator Madhav Thambisetty, M.D., Ph.D., chief of the Unit of Clinical and Translational Neuroscience in the NIA’s Laboratory of Behavioral Neuroscience. However, the team was able to determine that enzymes controlling the brains use of glucose were lower in Alzheimer’s cases compared to normal brain tissue samples. Additionally, lower enzyme activity was associated with more severe Alzheimer’s disease in the brain and the development of symptoms.

Thambisetty cautioned that it is not yet completely clear whether abnormalities in brain glucose metabolism are definitively linked to the severity of Alzheimer’s disease symptoms or the speed of disease progression. It’s also important to remember that correlation does not equal causation. However, this study further supports the theory that glucose impacts development and severity of Alzheimer’s. The study appears in the Nov. 6, 2017, issue of Alzheimer’s & Dementia: the Journal of the Alzheimer’s Association

According to the Alzheimer’s Association, more than 5 million people in the U.S. are living with Alzheimer’s disease and other dementias, costing an estimated $259 billion. By 2050, there could be as many as 16 million people in the U.S. with the disease, at a cost of $1.1 trillion. More than 15 million caregivers provide an estimated 18.2 billion unpaid care hours for those with the disease in 2016.

November is  National Alzheimer’s Disease Awareness Month and National Family Caregiver’s Month.

  • The Arch Respite Network provides links to local and state respite resources for caregivers as well as training for professionals.
  • The Caregiver Action Network offers a family caregiver toolbox, including tips, videos, checklists, and nutrition counseling. Be aware that some of these sections are sponsored by commercial entities.
  • The Alzheimer’s Foundation of America has an excellent summary of common signs, symptoms and stages of the disease.
  • The Alzheimer’s Association offers a multi-lingual interactive brain tour, explaining how the brain works and how the disease affects it.

1 thought on “Higher brain glucose levels may mean more severe Alzheimer’s

  1. Edward Blonz

    Some background information if considering covering this research paper:

    This paper reports on brain glucose dysregulation with Alzheimer’s disease (AD), but the results reported are at odds with other studies. (The paper reports that high brain glucose is associated with AD, while the general trend from the literature is the opposite.) It is important to understand that glucose is the main source of metabolizable energy, i.e., fuel, used by the brain. In the scientific literature we find studies reporting that as we age, there are progressively lower levels of glucose in the central nervous system (CNS), where the brain resides. Lower levels of glucose in the CNS have been associated with the pathogenesis of Alzheimer’s disease (AD) and the development of amyloid-beta plaque and tau tangles, but why and how this happens has remained elusive (there are new theories, but that is a different story).

    Keep in mind that when we refer to brain glucose we are referring to the level glucose in the CNS, not the level in the bloodstream, where it can be elevated – especially in those with conditions such as diabetes. Glucose gains entry to the CNS, but only after being escorted by a special protein through body’s protective blood-brain barrier (BBB), this being the border that controls access of substances to the CNS. The level of glucose in our blood does not necessarily correlated the level of available glucose in the brain. The paper reports abnormalities in glycolysis (the pathway by which glucose is metabolized and its energy released), which makes sense when the living brain has an insufficient amount of glucose to provide for its energy needs.

    But, again, papers have associated lower level of glucose in the CNS with an increased risk of AD, yet this paper has as one of its highlights, a report of higher levels of glucose in the CNS correlating with AD. You will want to get the author’s explanation for this.

    Of particular relevance in this paper, is its reliance on data from post-mortem tissues; there are unique considerations with this type of data. After death there is a disruption/breakdown of cells and tissues, including those of the blood-brain barrier. Much, of course, will depends on what was going in prior to death and how the tissue was stored, treated and analyzed during the immediate pre & post-mortem period. You can get additional information from a pathologist to “flesh” out these considerations. But in particular, as regard the findings of this paper, the age-related progressively impaired ability of glucose to cross the blood-brain barrier will get physically relieved after death when the BBB ceases its functionality. Think of it like borders collapsing and the border guards no longer at their posts. At that point it becomes a matter of physics with substances at higher concentration free to flow into areas of lower concentration.

    There is no consideration of post-mortem effects in the NIH press release that states: “Finally, the team checked blood glucose levels in study participants years before they died, finding that greater increases in blood glucose levels correlated with greater brain glucose levels at death.” (To be more precise it should say “in brain tissue, post-mortem.”)
    Another point of consideration: There are genetic traits associated with the risk of AD. This paper reports no difference with individuals having the APOe4 genetic trait. This is the most common genetic trait associated with a higher risk of AD, and one where symptoms of AD are more likely to be exhibited at an earlier age. (Understand we are only dealing with statistical risks here, not absolute determinants. People who don’t have this genetic trait can develop AD, and those having it may never develop AD.) Of interest with this paper is that it ties in to the whole glucose thing because models of AD studying this genetic trait have reported the trait is associated with a decreased ability for glucose to cross the BBB. Thus the higher risk of AD with this genetic trait, and the reason it is more likely to show up earlier in life, can be explained by the individual possessing having a decreased baseline ability for glucose to cross their BBB. But in this paper they report no difference, which is a bit of a red-flag in and of itself. This could have been due to their sample size, variabilities in the quality of the tissues examined, or the fact that post-mortem tissues are not appropriate samples on which to base these conclusions.

    You will develop your own questions but here some that I have considered (in addition to the above):

    How do the authors’ interpretations of the data with regard to the level of glucose in the brain, and its relationship to AD, compare with other evidence in the scientific literature?

    How do the authors account for their reported finding of no difference with those having, the APOe4 genetic trait?

    What are the limitations to the use of post-mortem brain tissues analyses to assess levels of substances and base conclusions regarding processes in living cells? What about tissues that would normally be be isolated from the general circulation by the blood-brain barrier?

    As a scientist, I value new research data, but there always needs to be cautious in what can be concluded. Final note: I have references for all my statements provided above.

    Edward R. Blonz, PhD
    Assistant Clinical Professor
    University of California, San Francisco

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