Alzheimer’s — To be, or not to be?

By Selin Sindel

Alzheimer’s Disease has disrupted the lives of countless families around the world. Characterized by severe memory and cognitive loss, Alzheimer’s Disease is progressive and has no cure. Current treatment for symptoms are available, but they cannot stop the progression of the disease, they just temporarily slow the worsening of symptoms, and work to improve the quality of life for patients.

Just like the rest of our bodies, our brains change as we get older. In Alzheimer’s, microscopic changes in the brain begin long before the first signs of memory loss. There are two anatomical hallmarks of Alzheimer’s: neurofibrillary tangles and amyloid-beta plaque. These plaques and tangles build up in the spaces between nerve cells as well as within the nerve cells. The role of these plaques and tangles are still not 100% certain, however, it is widely held that the excessive build-up blocks communication between neurons, and therefore disrupts processes that the cells need to survive.

Research into AD conducted by Fernandez, Santi, and Aleman, has sought to explore the lifestyle factors that engage the insulin pathways in the brain in order to provide a potential connection for lifestyle and AD risk. Although aging is one of leading risk factors of Alzheimer’s, the various lifestyle factors that are examined in this research, such as diet, physical exercise, mental engagement, exposure to stress, and sleep patterns are considered major modulators of AD pathology.

Before we dive deeper into these lifestyle factors, first it is important to understand the role of insulin in the brain and body. There are three families of related hormones in vertebrates: insulin and its related growth factors (IGF-I and IGF-II), relaxins, and insulin-like peptides (ILP). Faulty ILP function in the brain is a main pathogenic pathway in AD because all major disturbances associated with the pathology can be explained by altered ILP activity. IGF-I and IGF-II promote synapse formation and synaptic plasticity. Insulin and IGF-I are positive modulators of proteostasis (protein homeostasis), which includes the processing of amyloid beta. The functioning of the brains ILPs depend on input received from physical activity, mental engagement, diet, and sleep patterns, and in turn, ILPs regulate inflammation, oxidative stress, glucose metabolism, synaptic plasticity, tau phosphorylation, and amyloid beta clearance. For final emphasis: insulin is a vital hormone and plays a major role in modulating the development of AD.

It is important to understand the significance and effect that various lifestyle factors have on AD, and the ways they can influence insulin pathways, and how ultimately, we have the ability to manipulate them in order to prevent the onset of Alzheimer’s Disease.

Diet

A balanced diet is necessary for healthy cardio-metabolic status. Additionally, diet affects brain function by directing modulating ILPs in the brain which in turn modulate the entrance of circulating IGF-I and insulin through the blood-brain-barrier. The prototypical example of a beneficial diet is the Mediterranean diet, which emphasizes eating plant-based foods, whole grains, legumes, and nuts, although more research is needed to firmly establish its protective role. Moreover, an association of obesity with cognitive alterations and increased AD risk has been demonstrated, further supporting the importance of a balanced diet.

Physical Activity

In combination with a balanced diet, the proper amount of physical activity is probably the most modifiable lifestyle factor for populations at risk for AD. However easy it is to promote a healthy lifestyle that involves a balanced diet and sufficient exercise, it is just as easy to ignore these recommendations, even though they play a large role in thwarting the onset of AD. Regardless, research has proven that exercise is a preventive measure against AD, and there are studies looking to establish the baseline for it, and whether exercise can also be therapeutic after the establishment of AD pathology. The developed world must combat the sedentary lifestyle in order to promote the essential resources to maintain homeostatic brain function.

Stress

Patients with Alzheimer’s frequently experience depression as a comorbidity of the disease, and it seems as if psychiatric comorbidities are quite common, and of great impact in AD. Cognitive deterioration follows depression, and it is assumed that exposure to stress is a main triggering mechanism of depression. AD patients are usually prescribed with psychoactive drugs in order to help regulate their mood. Stress is linked to the development of AD by affecting the mechanisms of ILPs, ILP resistance, and ultimately results in pathological changes such as tau protein missorting, altered pro-inflammatory cytokines, and impaired mitochondrial function.

Mental Activity

Cognitive reserve, which is genetically acquired, as well as dependent on the environment, relies on the amount of neuronal resources that each individual has available, and has been linked to AD resilience. For example, an individual with higher education, or greater mental activity shows reduced incidence of dementia, and because the cognitive reserve is built through activity-dependent processes, cognitive activity protects against AD even at late stages in life.

Sleep/Wake Patterns

Altered patterns of sleep/wake is directly associated to AD, and although increased sleep fragmentation is linked to normal aging, AD patients present much more radical alterations in their sleep architecture. Levels of beta-amyloid are connected to the sleep/wake cycle, and a correlation between cerebral spinal fluid levels of orexin (a major hormone in sleep regulation) and biomarkers such as tau have been described in AD. Additionally, ILPs affect the activity of orexin neurons in the brain, which also affects the sleep/wake cycle.

Although it may seem as if we are powerless against Alzheimer’s, this is really not the case. Research has shown that by influencing the amount of ILPs circulating to the brain via diet, exercise, mental engagement, stress management, and sleep patterns, you can profoundly decrease the chances of developing this disease later in life.

References:

Fernandez, et al. “Insulin Peptides as Mediators of the Impact of Life Style in Alzheimer’s Disease.” Journal of X-Ray Science and Technology, IOS Press, 6 June 2018