As the Baby Boomers age, illnesses associated with aging are taking up more of our budgets. They also place a great burden on the quality of life of patients and their caregivers.
Alzheimer’s disease is a particularly difficult disease. According to the Alzheimer’s Association, over 6 million Americans suffer from AD. Over 11 million individuals provide unpaid care for a loved one with AD. This is a tremendous burden. Yet experts predict that 16 million people will have AD by 2050 with associated costs expected to exceed $1 trillion.
Currently, AD has no cure, and therapies are largely ineffective. Thus, discovering the causes and exacerbating factors behind AD is crucial. Prevention and early detection would help decrease or delay the symptoms and difficulties this illness causes. Prevention is critical because AD symptoms often do not appear until the loss of functional neurons is so widespread that irreversible damage has already occurred.
An increasing body of evidence indicates that AD is a “disease of civilization” caused by our modern, industrialized lifestyles. High intake of refined carbohydrates and omega-6-rich polyunsaturated oils, low antioxidant intake, lack of physical activity, and misguided avoidance of cholesterol and saturated fats promote glycation and oxidative stress in the brain. This leads to severe cognitive decline.
Our modern lifestyle has been linked to conditions like diabetes, heart disease, polycystic ovarian syndrome, rheumatoid arthritis, and schizophrenia. Research shows that our brains are particularly susceptible to the detrimental effects of our modern diets despite the blood-brain barrier.
While it is difficult to differentiate which factors are causative and which are correlative, current literature points to an increased risk for AD due to genetic and environmental factors. The risk profile has a strong basis in epigenetics—the influence of diet and lifestyle on how particular genotypes are expressed. The two most important risk factors appear to be hyperinsulinism and possession of one or two E4 alleles for the apolipoprotein E gene (ApoE4), which is involved in lipid processing.
Having the E4 allele is strongly correlated with AD, and people with ApoE4 heterozygotes have a five-fold increased risk of developing AD. Having homozygotes (two alleles) means a lifetime risk of between 50% and 90%.
The other known risk factor is hyperinsulinism, which increases the risk of developing AD by 43%. Hyperinsulinemia occurs in approximately 40% of people over the age of 60. Type 2 diabetes (T2D) is considered an additional risk factor for developing AD.
Type 2 diabetics who carry ApoE4 alleles are at the greatest risk for AD, with an even more severe risk reserved for those treated with insulin. This suggests that insulin may be a key factor in the development of AD.
Still, not all type 2 diabetics develop AD and not all AD patients are diabetic. Research seems to support some relation between them, but not necessarily causative factors. They result from the same underlying metabolic imbalances but manifest differently depending on which parts of the body are affected.
AD patients experience decreased cognitive function and lapses in memory that progress and negatively impact daily life. AD patients have several physical hallmarks including insoluble extracellular plaques made of beta-amyloid peptide (Aβ); intracellular neurofibrillary tangles (NFTs) resulting from the hyperphosphorylation of tau (a microtubule-associated protein); loss of hippocampal neurons; a decrease in the production of brain acetylcholine; and a marked decline in glucose usage in regions of the brain associated with memory and learning.
All of these hallmark physiological symptoms result from long-term dysregulation of glucose metabolism and insulin signaling. Their damaging effects are exacerbated by the Western diet and lifestyle: consumption of refined carbohydrates, imbalance between n-3 and n-6 essential fatty acids, a lack of physical activity, and a lack of micronutrient and antioxidant-rich vegetables and fruits.
The Role of insulin in alzheimer’s disease
Because the common brain glucose transporters, GLUT1 and GLUT3, are non-insulin sensitive, scientists believed that the brain was independent of insulin. Now we know that there are insulin receptors and insulin-sensitive glucose transporters (GLUT4) at the blood-brain barrier. They are very abundant in areas of the brain involved in learning and memory.
One feature of AD is the combination of hypoinsulinism in the central nervous system and hyperinsulinism in the periphery. Patients with advanced AD show higher plasma but lower CSF insulin concentrations than healthy controls. The lower concentration of insulin in the brain is not due to lower circulating levels in the blood. Somehow the brain becomes insulin-resistant, most likely due to long-term overconsumption of refined carbohydrates.
Insulin plays a role in cognitive function in different ways. Acute administration of insulin improves performance on tests of memory and cognition, but chronically elevated insulin levels have the opposite effect. This is similar to T2D. Normal doses of insulin help regulate blood glucose, but chronically higher levels result in hyperglycemia, insulin resistance, inflammation, and vascular damage.
For non-ApoE4 carriers, diabetes alone is a significant risk factor for AD. Having both diabetes and an ApoE4 allele increases the risk even further—five-fold over non-diabetic, non-E4 carriers. Glycemic control is crucial for better cognitive performance in type 2 diabetics. The question is whether diabetes plays a causal role in the development of Alzheimer’s disease. However, not all AD patients are diabetic, and not all diabetics develop AD. Research suggests that Alzheimer’s and type 2 diabetes are different manifestations of the same underlying causes. In Alzheimer’s, the damage is located in the brain. In type 2 diabetes, the damage is in the organs and peripheral muscles.
Final thoughts
There is a growing body of evidence suggesting that glucose dysfunction, mitochondrial dysfunction, T2D, and hyperinsulinemia result from the classic Western diet heavy in refined carbohydrates. Research shows that Alzheimer’s disease may also be linked to the modern diet. It’s time for significant changes in the standard diet and lack of exercise. Combined with stressful and sedentary lifestyles, and particularly when complicated by cholesterol-lowering medication, this raises the risks of developing Alzheimer’s and other forms of neurological degeneration.