The brain needs around 20% of the body’s energy. If the brain is supplied with less energy than it needs, cognition will suffer. Under conditions where the supply of fuel is too low, the cells in the brain will prioritize their limited resources toward the essential functions they need to stay alive. This means there may not be enough energy left over for the brain cells to engage in energy-intensive non-essential activities, such as the electrical activity that underlies learning and memory. This is similar to a monetary budget, where spending on luxury items is restricted when money is tight. This strategy can work in the short term, but over the long term, it can become unsustainable. The longer the energy shortage goes on, the brain cells start failing to keep up with all of their essential functions; the cell equivalent of being forced to choose between heat and food due to lack of money.
When total body energy resources are low, the energy supply to the brain is prioritized, so under most physiological conditions, normal brain function can be maintained. What are the conditions, then, that would lead to an energy shortage in the brain? Aside from traumatic events, such as a brain injury or stroke, the two most common conditions associated with reductions in brain energy levels are aging and diabetes [1]. Under these conditions, there is enough total energy in the body to meet demand, but there is a supply chain problem. The fuel is stuck in the blood and not able to go to the parts where it is most needed, namely, the brain.
Type 2 diabetes is characterized by elevated blood sugar levels stemming from resistance to insulin. Insulin is important for directing sugar, called glucose, out of the blood and into the cells that need it for energy. This process involves special proteins on cells called glucose transporters that are responsible for moving the glucose into the cell. In people with diabetes, the level of these transporters is decreased, which reduces the capacity of the cells to take up the glucose [2]. This means that even though the total amount of glucose available in the blood is more than sufficient to meet the energy demand of the cells, the cells can’t access it. Since glucose is the primary fuel source used by the brain, the cells in the brain are preferentially impacted by the inability to take up glucose.
During the later stages of the adult lifespan, the ability of brain cells to take up glucose is reduced, which prevents them from operating at their peak level, and can result in a slowing of certain cognitive tasks that require a lot of energy [2]. In animal models, restoring the ability of the aged brain cells to take up glucose can protect against these impairments [3]. Special brain imaging techniques have been used to show that the reduction in glucose makes brain cells less active [4]. Declines in brain activity are seen with age, but certain areas of the brain are affected more than others. The most heavily impacted brain regions are those involved in executive functions, such as planning, processing speed, and attention [1; 4]. Consequently, these are the types of cognitive tasks that tend to decline most with aging.
A large study in the UK with over 20,000 participants found that the changes to the brain, in terms of structural changes and cognition, that are seen in people with type 2 diabetes are the same ones seen in the elderly [1]. This suggests that type 2 diabetes can be considered a form of accelerated brain aging. For example, the rate of brain cell loss was 26% faster in diabetics compared to their age-matched non-diabetic counterparts. Since age is the number one risk factor for dementia, the accelerated brain aging in diabetics may be a mechanistic link for why diabetes is also one of the top risk factors for dementia.
As mentioned, the longer the brain cells experience an energy shortage, the more likely it is that the cells fail to perform essential functions and, thus, start dying. Since type 2 diabetes is most commonly diagnosed during middle age, brain cells may be under low energy stress for several decades, which makes it critical for the diabetes to be managed as early as possible. Diabetes medications may help restore energy levels.
While getting older is unavoidable, the age-related declines in glucose uptake can be mitigated. Lifestyle interventions known to be associated with healthy brain aging, such as exercise and a Mediterranean diet, rich in polyphenols, may increase brain energy levels by promoting glucose uptake into brain cells [5].
Betsy Mills, PhD, is a member of the ADDF's Aging and Alzheimer's Prevention program. She critically evaluates the scientific evidence regarding prospective therapies to promote brain health and/or prevent Alzheimer's disease, and contributes to CognitiveVitality.org. Dr. Mills came to the ADDF from the University of Michigan, where she served as the grant writing manager for a clinical laboratory specializing in neuroautoimmune diseases. She also completed a Postdoctoral fellowship at the University of Michigan, where she worked to uncover genes that could promote retina regeneration. She earned her doctorate in neuroscience at Johns Hopkins University School of Medicine, where she studied the role of glial cells in the optic nerve, and their contribution to neurodegeneration in glaucoma. She obtained her bachelor's degree in biology from the College of the Holy Cross. Dr. Mills has a strong passion for community outreach, and has served as program presenter with the Michigan Great Lakes Chapter of the Alzheimer's Association to promote dementia awareness.
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