As seen in Psychology Today.

In the popular imagination, Alzheimer’s disease [AD] is primarily a disorder that affects short-term memory, but it is a far more serious condition than many acknowledge. AD is a neurodegenerative disorder characterized by progressive cognitive and functional deficits that can also impact behavior and personality. In the early stages of the disease, behavioral changes may include irritability, apathy, and anxiety. In later stages, those who suffer from AD may become increasingly aggressive, restless, anxious, and even suffer from delusions.

Alzheimer’s is not only a progressively debilitating disease but is unfortunately becoming more common.  A 2019 report released by the Alzheimer’s Association notes that an estimated 5.8 million Americans are living with AD-related dementia in 2019, and that the disease affects one in ten individuals over the age of 65. This includes 3 percent of people between the ages of 65 and 74, 17 percent of people ages 75 to 84, and almost one-third (32 percent) of individuals over the age of 85. According to the National Institute on Aging, it is the most common cause of dementia among older Americans and the sixth-leading cause of death in the US. It is the fifth-leading cause of death among Americans over the age of 65, and afflicts women far more often than men.

Though the prevalence of AD among seniors is not on the rise, the number of people suffering from the affliction is expected to increase as members of the baby boom generation enter their sunset years. Furthermore, many believe that it is irreversible. However, new research may indicate that there is a line of defense that will at least help prevent AD from developing.

What Alzheimer’s Disease Does to the Brain?

AD affects the connections between the cells in the brain, which are known as neurons. When these networks are disrupted, individual neurons begin to lose functionality, lose connectivity with other neurons, and eventually die.

Typically, the first part of the brain to be affected by the disease is the entorhinal cortex and the hippocampus, two regions associated with the creation and storage of memory. Recent episodic memories are typically the first to be impacted by the disease, with more distant memories remaining unadulterated until subsequent stages of the disease.

As AD progresses, it will also affect the cerebral cortex, which is the area of the brain responsible for language, problem-solving, praxis, planning, and organization. Consequently, it may become difficult for individuals with AD to perform tasks that require concentration, visuospatial skills, or abstract thinking, and it may be very difficult for them to live independently. As the disease progresses, more parts of the brain become affected, thereby making it virtually impossible to live without constant supervision. Ultimately, it is fatal.

These connections are not merely disrupted due to old age. Researchers hypothesize that neural networks are gradually bogged down by a buildup of proteins in the brain. One of these proteins, known as beta-amyloid, begins to collect between neurons, thereby disrupting communication between the cells. Beta-amyloid is a naturally occurring protein that is derived from the cellular metabolism (technically known as the proteolytic cleavage) of a larger protein known as amyloid precursor protein [APP], which is responsible for performing a range of neuronal activities. Amyloid deposition oftentimes begins twenty years prior to the first clinical symptoms of AD.

Another protein, tau, normally facilitates the exchange of nutrients and other molecules between neurons by strengthening microtubules, which play a key role in the intracellular transport of materials. In brains with AD, these tau proteins begin to bind together in abnormal patterns, creating what are known as neurofibrillary tangles. These tangles block the flow of molecules between neurons. Research suggests that the buildup of beta-amyloid proteins is a precursor to these neurofibrillary tangles, though it is not the sole precursor, as such tangles are not exclusive to AD.

In healthy brains, microglia, a type of glial cell, clears out waste from the brain. This includes excess beta-amyloid and tau proteins. As the brain becomes increasingly cluttered with buildups of beta-amyloid and tau proteins, however, microglia can’t do their job. When microglia fail to do their job, the brain releases another type of glial cell (which are known as astrocytes) to get rid of the plaque. They too get bogged down by the plaque and release chemicals that lead to inflammation. This can also lead to vascular problems within the brain.

What Causes the Plaque Associated with Alzheimer’s Disease to Form?

There are a variety of factors that influence beta-amyloid plaque growth. On the one hand, heritability of AD is considered to be between 60 percent and 80 percent, largely due to genetic variation. When the gene TREM2 functions improperly due to mutation, for example, it can inhibit microglia from effectively clearing the brain of excess beta-amyloid proteins, which, in turn, can set in motion a chain of events leading to AD. The e4 allele of the APOE gene, as another example, is associated with the increased presence of amyloid plaque in the brain. Mutations in the APP gene may produce similar phenomena.

While it is doubtless that genetics does play a role in the development of AD, several new studies have indicated that a diet high in sugar and simple carbohydrates can also affect the probability that one will be afflicted by the disease. More studies will have to be conducted to determine to what extent diet influences the development of the disease—if diet can independently trigger AD or if diet only compounds hereditary risks associated with AD.

There are numerous types of proteins that work in conjunction and clear the brain of debris—including dead or damaged cells, foreign material, or the tangles and beta-amyloid buildup described above. In some cases, diet has an influence over how effective some of these proteins can be. This correlation became clear as researchers found that patients with diabetes are more likely to develop AD.

In some circles, AD has become known as “type 3” diabetes because of how common it is that individuals with chronically high blood sugar develop late-onset AD. A longitudinal study published in the journal Diabetologia in 2018 followed 5,189 people in the United Kingdom over the course of a decade and found that this is true for all diabetics. People with type 2 diabetes and people with type 1 diabetes are more likely to develop AD than those who do not have insulin problems. The study’s authors, Zheng et al, wrote that “memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes.”

A study conducted by Melissa Schilling of New York University found that the link between diabetes and AD is not due to insulin problems per se, but due to the enzyme that breaks down insulin in the blood stream, aptly known as insulin-degrading enzyme [IDE], also helps break up clumps of beta-amyloid proteins in the brain. This would explain why an individual with type 1 diabetes, who does not make enough of the enzyme in the first place, and an individual with type 2 diabetes, who often ends up with excess insulin in the blood, both have a higher risk of developing AD. As Schilling writes, “If IDE preferentially targets insulin and insulin levels are outpacing IDE production, IDE’s ability to breakdown other amyloidogenic proteins will be markedly reduced.” On top of affecting diabetics, the phenomenon could also impact individuals who are prediabetic, i.e. those who have a glucose intolerance caused by chronically high levels of blood glucose (hyperglycemia).

Given that most non-diabetic instances of hyperglycemia are associated with a diet that is high in sugars and simple carbohydrates, and that hyperglycemia is associated with increased amyloid deposits in the brain, it stands to reason that diet can play a role in the development of AD. Zheng et al has found that efforts to control blood sugar levels may prevent brain function decline. “Future studies are required to determine the long-term effects of maintaining optimal glucose control on cognitive decline in people with diabetes,” they wrote. “Our findings suggest that interventions that delay diabetes onset, as well as management strategies for blood sugar control, might help alleviate the progression of subsequent cognitive decline over the long-term.”

These findings suggest that the rise in the prevalence of AD and the increase in the number of individuals with diabetes are related, and that the primary mechanism driving both trends is a diet that is frequently associated with hyperglycemia, which, in turn, inhibits IDE from naturally breaking down both insulin and beta-amyloid proteins in the brain. Though more research is necessary to better support these findings, they present yet another reason why people should avoid a diet that is high in sugar and simple carbohydrates. Diets that contain whole grains, lean meats, fish, green leafy vegetables, and fruits keep blood sugar levels from spiking, on top of providing the body with the necessary vitamins, minerals, and fiber it needs to stay healthy. While there is no one singular diet that is ideal for everyone, eating meals comprised of mostly non-processed foods like those described above are preferable to meals consisting of starches, sugars, refined flours, and additives.

Dr. Ahmad reports no conflict of interest. He is not a speaker, advisor or consultant and has no financial or commercial relationship with any bio-pharmaceutical entity whose product/device may have been mentioned in this article.