In Simple Terms: Alzheimer’s Disease

Alzheimer’s Disease occurs when there is an increase in neuronal cell death in the hippocampus. The hippocampus is the part of the brain that is involved in learning, memory, as well as with emotional responses. If you are going to lose neurons in this part of the brain, this will obviously have an effect on your learning and memory. Brain imaging from Alzheimer’s patients shows atrophy (or degeneration) of the brain in areas that are involved in learning and memory.

Risk factors of Alzheimer’s include:

1. Age- risk increases after the age of 6o and doubles every decade after that

2. Genetics- if your relative has the disease, your chances of having it increase

3. Cholesterol-high levels of cholesterol are related to an increased risk

4. Injury- a head injury will likely increase the risk

5. Gender- this disease is more common in females than in males

6. Lack of mental stimulation

The critical and toxic molecule in Alzheimer’s disease patients is beta-amyloid, a protein that forms plaques in the brain. Beta-amyloid is formed when an Amyloid Precursor Protein (APP) is cleaved into Ab-40 and Ab-42 (both beta-amyloids) by an enzyme called gamma-secretase. Of the two, Ab-42 is the toxic substance that forms plaques in the brain. An increase in Ab-42 causes degeneration of neurons in the brain. Drugs that inhibit gamma-secretase activity have been found to be effective in reducing the progression of Alzheimer’s.

The mechanism by which beta-amyloid induces death of neurons is through its interference with the reuptake of glutamate. Glutamate binds to the NMDA receptor in the brain, which in turn lets calcium ions flow into the channel. However, if too much calcium comes in, it induces activation of calcium-activated proteases, which leads to cell death. Drugs that inhibit NMDA activity (like Memantine) are also used as treatment for Alzheimer’s.

DNA damage within neuronal cells is also prevalent during the course of the disease.
Even though the Alzheimer’s brain increases DNA repair enzymes as well as BCL-2 ( a component that protects against cell death), the battle between damage and repair is ultimately won by the degenerative neuronal cells. Thus, there is more damage than repair occurring in the brain of these patients.

Here’s what YOU can do to slow this degenerative process:

1. Crossword puzzles. Sudoku. Anything that keeps your mind alive.

Learning and mental stimulation enhances BDNF (brain derived neurotrophic factor), a neurotrophin that supports the cells and makes them ‘feel better’.

2. Take a hike.

Physical activity increases BDNF.

3. Eat healthy

Diets high in fats and sugars decrease BDNF activity.

4. SLEEP

Sleep enhances the activity of BDNF.

5. Quit stressing

6. Get your Vitamin E

Vitamin E slows the progression of Alzheimer’s.

Other interesting facts:

-Patients with rheumatoid arthritis that take Ibuprofen do not get Alzheimer’s because Ibuprofen affects the activity of gamma-secretase in such a way that it reduces the production of beta-amyloid.

-Bilinugals have a lower chance of getting Alzheimer’s

Reference Websites:
http://www.cmj.org/Periodical/paperlist.asp?id=LW7347&linkintype=pubmed
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772133/?tool=pmcentrez

*Lecture at University of California, Irvine

What was I talking about? Memory.

Humans have an extraordinary capability to remember faces, interactions, emotional experiences, and ‘interesting’ facts. Notice the wording-‘interesting’.

However, most of the time, our brain is bombarded with information that is useless and dull-think Calculus and Physics-and it has no other option, but to go into a hibernation mode when we are trying to study. For example, think about college students pulling all-nighters. (First of all, I never understood that. Sleep is such a precious time for me. Why would I want to wake up all night, cramming useless, pathetic facts in my brain that I won’t remember after turning in the exam?) Almost all of these students, either on the exam and most certainly after the exam, will forget 90% of what they tried to cram in their brains.

Obviously, when the topic of a recent Neurology of Learning lecture was on memory, I was thoroughly excited.

The process of consolidation (compiling information from short-term memory and putting it into long-term memory) is what limits our memory to a large extent. The brain does not see all things as memorable and hence, filters out all unimportant information. This is a mechanism that the brain evolved that works efficiently in terms of energy expenditure and usage.

Certain events, however, are stored by the brain relatively easily. Emotional responses associated with a memory will be retained much more likely than the same memory without the emotional cue. Bad memories can be prevented from consolidation by blocking norepinephrine receptors. (Norepinephrine affects our responses to stressful situations by increasing blood pressure, constricting blood vessels, etc.) This hormone also induces better cognitive function. Cognition refers to the process of learning, memory, and judgment. (A better cognitive ability would be an advantage in such situations)

There are interesting cases of people, called savants, that have an extraordinary memory, but limited mental abilities.

A patient called S. had a limitless memory; he could remember a table of 50 numbers horizontally, vertically, as well as diagonally. However, in other times, this ‘limitless’ power proved to be a curse. He was unable to forget bad events and was eventually unable to discern fantasy from reality. This shows us that our brain has the capability to remember an infinite number of things, but  it might not be a benefit in the long term.
There are two kinds of memories: declarative (facts) and non-declarative (perceptual and motor skills). A patient called H.M. had recurrent seizures that could not be fixed by medications alone. Doctors decided to remove his temporal lobes. His case gave an insight into the parts of the brain responsible for consolidation of memories.

The hippocampus (located within the temporal lobe) is responsible for the conversion of short-term memory into long-term memory, which affects our ability to recall information.

Following are a few tips that will help you with memory retention in the long-term (courtesy of the Professor):

-Right after class, write down the whole lecture by yourself. Then, look over the notes you took in class.

-Repetition. Look over the notes every couple of days.

-Get emotional. Memories linked to emotional events are retained much more easily than other non-emotionally associated events/facts. You might want to try associating the concepts with something that you encounter everyday.

-Listen to ‘Sonata for 2 pianos in D major K.448” by Mozart while on the way to the exam. (The only musical piece that has been shown to help with cognitive improvement). The research was done at University of California, Irvine and an excerpt from the paper can be found here (courtesy of the guy/gal who uploaded the video).

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