Dr. Sharlin explains many common questions and facts as it pertains to
Late Onset Alzheimers Disease.
Late Onset Alzheimers Disease.
Late Onset Alzheimer’s Disease is defined as the onset of Alzheimer’s disease after the age of 65.
An estimated 5.4 million Americans of all ages have Alzheimer’s disease (2016 estimate). According to the Alzheimer’s Association this number includes an estimated 5.2 million people age 65 and older and approximately 200,000 individuals under the age of 65 who have younger-onset Alzheimer’s.
Significantly more women than men have Alzheimer’s disease. When looking at the lifetime risk it is important to keep in mind these gender differences. The risk of Alzheimer’s disease increases with age (% men/ %w omen): at age 65 (9% / 17%), age 75 (10% / 19%), age 85 (12% / 20%).
- The estimates of the number and proportion of people who have Alzheimer’s disease is based on the number of people who are symptomatic (after the onset of symptoms). However, the current criteria and guidelines by the National Institute on Aging and the Alzheimer’s Association propose that Alzheimer’s begins before the onset of symptoms. In fact, there is now strong evidence that the changes which lead up to Alzheimer’s disease begin in the brain decades before the onset of symptoms.  
- In fact, if we consider the number of Americans who are too young to know they are going to get Alzheimer’s disease later in life the estimated number of Americans affected by Alzheimer’s disease balloons from 5.4 million to about 45 million (about 15% of the population).
- The National Institute on Aging and the Alzheimer’s Association have proposed three stages of Alzheimer’s disease: Preclinical Alzheimer’s, Mild Cognitive Impairment (MCI), and Alzheimer’s disease.
Preclinical Alzheimer’s disease can be further divided into those with no symptoms or signs (Pre-symptomatic) and those with Subjective Cognitive Decline.
Pre-symptomatic refers to individuals without any noticeable symptoms of memory difficulty, but whose brains are already affected by characteristic changes of Alzheimer’s disease years before those symptoms appear.
Subjective Cognitive Decline describes the experience of worsening or more frequent confusion or memory loss and is one of the earliest warning signs of Alzheimer’s disease. Sometimes called SCI (“I” for Impairment) this stage is characterized by a ‘feeling’ or ‘sense’ that something is wrong and can be hard to describe to family, friends, or clinicians.
Mild Cognitive Impairment (MCI) is an intermediate stage between SCI and Alzheimer’s disease. It can involve problems with memory, language, thinking and judgement. At this stage the changes are serious enough to be noticed by the individuals experiencing them or to other people. But the changes are not severe enough to interfere with daily life or independent function. The type of MCI that is specifically associated with Alzheimer’s disease is called “Amnestic” MCI. With Amnestic MCI a person may start to forget important information that he or she would previously have recalled easily, such as appointments, conversations, or recent events. In MCI the changes are measurable.
- A risk factor is anything that increases the likelihood of developing a disease.
For example, lack of physical activity is a risk factor for the development of Alzheimer’s disease. One of the most important risk factors is a gene called ApoE4.
- A biomarker is a biological factor that can be measured to indicate the presence or absence of disease. An example of a biomarker in Alzheimer’s disease is a protein called amyloid beta.
- ApoE is the name for a protein that transports cholesterol and cholesterol-like molecules around the blood stream. There are three types of ApoE proteins: ApoE2, ApoE3, and ApoE4. Genes are the part of the DNA code that contain the information for cells to make specific proteins like the ApoE proteins. Everyone has two copies of the ApoE gene, one from their mother and one from their father.
It turns out that whether you have ApoE gene type 2, 3, or 4, and the number of copies of that type has a major impact on the risk for Late Onset Alzheimer’s disease.
More recent evidence suggests that ApoE4 can go inside the cell and bind to areas of its genetic code. The binding of ApoE4 to parts of the DNA activates specific instructions for cell behavior. Ultimately, ApoE4, responding to imbalances in other biomarkers, triggers an inflammatory state that magnifies the impact of those biomarkers on the cell. Put in another way ApoE4 interacts with the cell in ways that lead to Late Onset Alzheimer’s disease.
-  //www.jneurosci.org/content/36/3/685.long
- Amyloid beta comes from another protein called. Amyloid Precursor Protein (APP). APP is a specialized protein in nerve cells that is critical to growing and “pruning” nerve pathways (the connections between nerve cells). In a normal cell environment there is a balance. When this protein is cut in one way new proteins are created that promote thriving, healthy nerve cells, and the making of new connections (APP alpha and CTF alpha); when cut in another way new proteins are created that promote the pruning of nerve cell connections and nerve cell death. One of the protein involved in pruning nerve cell connections and nerve cell death is called amyloid beta.
- Those DNA instructions triggered by ApoE4 influence whether the amyloid precursor protein is cut in a way that produces too much amyloid beta.
- This imbalance is tied to factors involved with
- signals that prune connections between nerve cells (think memory loss);
- diabetes and energy management (think bad gasoline in the fuel tank);
- inflammation and infection;
- the processes that signals new nerve cells to be created,
- or signals them to self-destruct (known as “apoptosis” or programmed cell death).
-  //www.ncbi.nlm.nih.gov/pubmed/25774009
-  //www.ncbi.nlm.nih.gov/pubmed/27225182
-  //link.springer.com/referenceworkentry/10.1007%2F978-1-4614 5836-4_43
-  //www.nature.com/cdd/journal/v12/n1/full/4401528a.html
Yes. Of the three types of ApoE genes the ApoE4 significantly increases the risk of Late Onset Alzheimer’s disease, even if you have only one copy. ApoE3 confers average risk (about 15% lifetime risk overall), and ApoE2 appears to have a protective effect against Alzheimer’s disease. Here is a convenient table from the Alzheimer’s Drug Discovery Foundation: (The reason for two genes is you get one copy from your mother and one copy from your father.)In fact, if you have two copies of ApoE4, and do nothing to address your imbalances, you have a 91% chance of developing Alzheimer’s disease by the time you are 68 years old.
Here’s what you can do:
- Consider getting tested for your ApoE type. This can be performed as a blood test or a cheek swab.
- Change your diet. Diets high in sugary foods  and low in healthy fats like omega 3 polyunsaturated fatty acids are associated with chronic inflammation and an increased risk of Alzheimer’s disease. Adopt a diet that minimizes these simple carbohydrates and emphasizes anti-inflammatory “healthy” fats found in avocados, almonds, walnuts, flax, chia, and other seeds, extra virgin olive oil, coconut oil, grass-fed beef and wild-caught fish such as salmon, mackerel, and sardines. The best carbohydrates come from lots of leafy green vegetables, sulfur-rich vegetables, and a rainbow of colors.
- Exercise regularly. Exercise reduces brain inflammation, improves memory, and stimulates stem cells to become new nerve cells in the brain. You can make your brain grow (instead of shrink)!
- Optimize your sleep. Sleep is actually an active time for our bodies and our brains. Among the many functions of sleep is memory organization. Sleep is also critical for normal energy metabolism, tissue building and healing, hormone function, and immune function.
- Adopt a daily practice of relaxation, peace, and gratitude. It’s hard to escape the normal stresses of the day from work to family to finances. But just as important as exercise and proper nutrition is the brief time we take every day to detach from these responsibilities, and be in the moment with life. There are many “paths to the mountaintop.” This can include an easy bike ride, a walk with your dog, yoga, Tai chi, calming music, mindfulness meditation, rhythmic breathing, and listening to binaural beats.
- Engage your brain. Try out Brain HQ from Posit Science (www.brainhq.com). Do puzzles, read books, tinker, or build things. Take up a hobby.
- Connect with others. Maintaining social connections and leisure activities in late adulthood has been shown to lower the risk of dementia (such as Alzheimer’s disease) as much as 50%.