The Pathological Cascade of Alzheimer's Disease

By the time you show symptoms of Alzheimer's disease, many irreversible changes have already occurred in your brain. This explains why early detection and timely intervention are so important. As described by the pathological cascade summarized in this post, treatment should ideally begin long before symptoms appear.  

The key features of the Alzheimer's disease pathological cascade include the accumulation of two types of abnormal proteins in the brain: amyloid beta (Aβ) plaques and tau tangles. The Aβ plaques are formed by the accumulation of a protein called amyloid beta, which is produced by the breakdown of a larger protein called amyloid precursor protein (APP). The tau tangles are formed by the abnormal accumulation of a protein called tau, which is essential for the normal functioning of the brain's nerve cells.

The accumulation of Aβ plaques in the brain disrupts the normal communication between brain cells and leads to inflammation and the activation of immune cells. As the disease progresses, tau proteins also start to accumulate in the brain, forming tangles that further contribute to the degeneration of brain cells. 

A simplified view of the process, which may take years, looks like this:
Protein Accumulation >> Inflammation >> Cell Death >> Symptoms

In an ideal scenario, patients would begin a regimen of disease modifying therapy (currently approved treatments can remove amyloid protein from the brain) as soon as amyloid plaques and tau tangles are present, and before inflammation, cell death, and cognitive symptoms emerge. 

Achieving such timely intervention on any meaningful scale will require a proactive mindset toward managing cognitive health along with inexpensive and non-invasive methods for detecting the early stages of the disease. Fortunately, such methods are now becoming available. One promising approach, from Embic Corporation, involves a brief cognitive test with sophisticated scoring that quantifies the unobservable cognitive processes of encoding and retrieval. These processes underly nearly all cognitive function and show clear changes in Alzheimer's patients long before symptoms of memory loss appear.

The good news is that the science of managing Alzheimer's disease, from detection to diagnosis to treatment, is moving forward quite rapidly. The bad news is that progress is happening faster than the healthcare system can embrace. Researchers need to keep racing forward and the care system needs to catch up!

Your Brain and Your New Year’s Resolutions


By Julie Russell, MA

The first of January marks the day many of us promise to do things differently, to make an improvement in our lives. Nowadays, New Year’s resolutions are typically personal health-related goals or a desired lifestyle change. 

Before we resolve to eat healthier, exercise more, lose weight, or any other lifestyle change goal that is commonly made each new year (though uncommonly maintained), we should focus first on changing our mindset to act differently. Mindset refers to our outlook; it is how we interpret what is happening around us. How we perceive our surroundings can determine whether we will make progress, or whether we will remain static. 

This year there are many external factors that may be contributing to a stuck or static mindset. Most Americans are literally stuck at home, working remotely and unable to go places where they used to get exercise and meet up with others who may be essential supporters to achieving their New Year’s resolution. Many people are also feeling emotionally overwhelmed by events occurring both in their personal lives and in the public sphere. These conditions may be creating a mindset that we cannot make progress until these other aspects of our lives are different. 

We might tell ourselves that we will make healthy lifestyle changes once life returns to the way it was, or to the way we expect it to become. As we settle into the waiting room of our aspirations, we can’t help but generate thoughts that the conditions may never be right and we defeat our ambitions before ever making any physical effort. 

Such a mindset can be generated through a simple focusing practice. Meditation is scientifically proven to focus attention and can be used to develop the mental language that empowers us to act with purpose. It is a technique to quiet mental distractions and concentrate thoughts towards a specific action. Often the breath is used as a way to begin focusing thoughts, as breathing is an automatic action that requires no effort. When paying attention to the breath, the meditator notices the in and out, the tempo, the sensations that accompany the flow of air, the subtle differences in each breath. When thoughts start to wander away from the breath, the meditator notices it and simply returns their attention to the breath again. Using the breath is the simplest way to practice focusing attention. 

From the breath, the meditation can move on to a new focus of action. If eating healthy for the day is a desire, the meditator can focus thoughts on a meal plan, and visualize the exact steps that will go into the action of preparing healthy food for the day and enjoying it. This visualization technique helps to prepare the mind for the act of eating healthy, and once the mind is set in motion, the body is primed for action. 

Think of how you want to be, and then do what you have to do. 

2020: A Bad Year For Your Brain?

By Julie Russell, MA

On a global level, this has been a year of extraordinary change to daily life, an historic period during which humankind connected through a collective state of worry, isolation, and adaptation to the spread of the COVID-19 virus. While many have been directly affected by the virus, there are many more who live in fear that they will become personally affected before adequate treatment is available.

In addition to these worries about the virus, many families face significant stress related to:

• job security or loss
• managing working from home and remote schooling for children
• marital discord
• lack of social engagement with friends and loved ones
• poor quality sleep
• changes to eating habits
• disrupted exercise routines
• excessive screen time
• distress from headlines of political and social unrest

Taken together, these life stressors and lifestyle changes may be taking a significant toll on many people’s physical, psychological, and cognitive health.

How This Affects Your Brain
When life stressors and lifestyle changes co-occur and persist, it causes excessive release of stress hormones that can lead to inflammation in the body, which can eventually spread to the brain and adversely affect multiple domains of cognitive function1. Hormonal changes associated with chronic stress along with inflammation in the brain can impact both the reward-related brain regions that result in reduced motivation and loss of pleasure2 and reduced volume of the region of the brain involved in learning and memory3. This can result in noticeable difficulty concentrating, planning, problem-solving, reasoning, and making decisions, which then feeds an unrelenting cycle of increased anxiety and depression, and continues the release of stress hormones that maintains inflammatory processes1,2,3.

The stress response can manifest very differently on an individual level, but many will report symptoms such as headache, increased pain in the body, gastrointestinal changes, weight change, increased blood pressure, fatigue, irritability, and clouded thinking4. While these ongoing life challenges that we collectively face may feel overwhelming, there are numerous ways we can halt and even reverse their health-related and create the conditions for resilience and cognitive recovery5.

What Can You Do?
The best place to start is to prioritize rest, not just in the form of good sleep hygiene (see tips for better sleep), but also in the form of taking a rest from screen time. Excessive screen time impacts attention, energy, mood, and circadian rhythm6. As an alternative, consider listening to music after waking up and before bed rather than turning on a screen. Take a refreshing walk outdoors and stretch on a daily basis; the minimum recommendations for physical activity are 30 minutes a day, 5 days a week7. Ditch the junk food that leaves you feeling energy depleted and eat more foods from the MIND diet that has been shown to protect the vascular system and cognitive health.

Prioritizing better rest, less screen time, regular walks, and improved eating habits, will gradually reduce the stress response cycle and allow the body and the brain to recover from inflammation. Persistence is the key to recovery and for developing resilience.

Our minds and bodies are designed to adapt to the adversities we face, and the basic choices we make each day will either help or hinder our adaptability. Protecting and promoting our brain health has never been more important than it has been this year. While we may all be socially distanced, we are going through this together, and we can collectively adapt and recover.


  1. (1) Ménard, C., Pfau, M., Hodes, G. et al. Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience. Neuropsychopharmacol 42, 62–80 (2017).
  2. (2) Felger, J., Li, Z., Haroon, E. et al. Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. Mol Psychiatry 211358–1365 (2016).
  3. (3) Lupien SJ, Juster R-P, Raymond C, Marin M-F. The effects of chronic stress on the human brain: from neurotoxicity, to vulnerability, to opportunity. Frontiers in neuroendocrinology 49, 91-105. (2018). https://doi:10.1016/j.yfrne.2018.02.001
  4. (4) Wekenborg MK, von Dawans B, Hill LK, Thayer JF, Penz M, Kirschbaum C. Examining reactivity patterns in burnout and other indicators of chronic stress. Psychoneuroendocrinology 106, 195-205. (2019) https://doi:10.1016/j.psyneuen.2019.04.002
  5. (5) Ortiz JB, Conrad CD. The impact from the aftermath of chronic stress on hippocampal structure and function: is there a recovery? Frontiers in neuroendocrinology 49, 114-123. (2018). https://doi:10.1016/j.yfrne.2018.02.005
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