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To understand Alzheimer’s Disease and how it affects our loved one, we need to first understand the brain and how it functions.

Your brain is your most powerful organ, yet it only weighs about 3 pounds and is about the size of a head of cauliflower, but with the texture of firm jelly.  At any point in time, your brain holds about 20 to 25% of the blood in your body, and each heart beat carries about 25% of the oxygen taken in by your lungs to your brain.  When you are thinking hard, that percent can increase to up to 50% of your oxygen going to “feed the brain.”

The brain has 3 main parts.

The first is the brain stem.  This part of your brain sits just above your spinal column at the base of your neck, and connects your brain to your spinal column.  It is the control center for all your automatic functions such as breathing, digestion, heart rate and blood pressure.

The second main part of the brain is the cerebellum.  It sits at the back of your head under the cerebrum and controls your coordination and your balance.

The third main part of the brain is the cerebrum. It fills up most of your skull and is involved in remembering, problem solving, thinking and feeling.  It is comprised of several areas that have been mapped out my neuroscientists so we can see where some of the main activities are.  We’ll look more closely at those in a little bit.

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Your brain is enriched and nourished by a very rich network of blood vessels.  This is why wounds to the face, nose, head, and scalp bleed so profusely.  That is also why we’ve learned and heard so often what is good for your heart (and vascular system) is good for your brain.  A build up of plaque on the inside of your blood vessels in the brain could really plug up the works!  So, you can see how important it is to control your cholesterol levels in order to control the formation of vascular plaque.

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Now let’s go back and look at that 3^rd part of the brain, the cerebrum in detail.  Deep inside the cerebrum are two parts of the brain called the hippocampus and the hypothalamus.  The hippocampus is located under the base of the temporal lobe. It is a seahorse shaped section of matter that is responsible for forming short-term memories, and routing and sorting short=term memories into long term memories.  As part of the limbic system, it is also the seat of our emotions. 

The hypothalamus is located right in front of the hippocampus and a bit deeper in the brain. It is the part of our brain that controls our internal thermostat, our appetite, and our sleep regulator.

Our brain’s wrinkled outer surface is a specialized out layer of the cerebrum called the cortex.  Neuroscientists have mapped the cortex suing MRI images to identify areas strongly linked to specific functions.

The temporal lobes of our brain are the part of the brain that would be under our hands in “hear no evil”.  The right temporal lobe serves in time orientation.  The function of the left temporal lobe is understanding and speaking language.  Both the left and right temporal lobes house the auditory functions associated with hearing.

The parietal lobe of the brain would be the part of our brain that would be covered by our hands if we laced our fingers together and formed a “cap” or “beanie” with our hands.  It is the part of the brain that houses the motor functions or voluntary movements of our body, the sensory part of our brain that helps us interpret touch and pressure.  It is also the part of the brain that serves to put pieces of information together so that we can drive a familiar route, getting from a starting point to a planned destination. It is also the part that allows us to follow complex or multi-step directions.

The occipital lobe of the brain is located at the back of your head, near the base of your skull, just above your neck.  This is the part of the brain where vision is processed, allowing us to recognize what we see. It allows us to see in 3-D and perspective as well as gives us peripheral vision.

And finally the last major area of the cerebrum is the frontal lobe, located in the front of your head.  This part of the brain serves in the executive position. It is the boss. It is the part of our brain that makes you behave in a socially appropriate way. It helps you make decisions based on judgment.  It is the part that helps you generate thoughts, solve problems, and make plans.

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Your brain is divided into left and right halves, like a walnut. These halves are called hemispheres. Neuroscientists are not certain how the Left and Right hemispheres differ in function except that the left hemisphere controls the right side of the body, and the right hemisphere controls the left side of the body.  Most of the language function is in the left side of the brain, along with artistic function and perception. The right side of the brain appears to function with mathematics and logic.

Activities such as dancing and music appear to help build strong bridges between the left and right hemispheres, and help improve overall brain function.

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We’ve looked at the parts and function of the brain, but now we need to understand how the brain works.  The real work of your brain goes on in individual cells. An adult brain contains about 100 billion nerve cells, or neurons, with branches, called dendrites, that connect at more than 100 trillion points. Scientists call this dense, branching network a “neuron forest”. 

Signals traveling through the neuron forest form the basis of memories, thoughts and feelings.

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Signals that form memories and thoughts move through an individual nerve cell as a tiny electrical charge that pulses the length of the neuron to the dendrites or branches.  At the end of each branch is a small bulb that holds tiny pods of chemicals called neurotransmitters.  When the electrical impulse reaches the end of the dendrite, it triggers the release of tiny bursts of these neurotransmitters. The neurotransmitters travel across the small gap between the dendrites, called the synapse, and in turn stimulate the electrical impulse in other nerve cells.  Scientists have identified dozens of neurotransmitter.

Alzheimer’s disease disrupts both the way electrical charges travel within cells and the activity of the neurotransmitters.

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100 billion nerve cells, 100 trillion synapses, dozens of neurotransmitters.  This strength in numbers provides your brain’s raw material.  Over time, our experiences create patterns in signal type and strength.  These patterns of activity explain how, at the cellular level, our brains code our thoughts, memories, skills and sens of who we are.

The positron emission tomography (PET) scan on the left shows typical patterns of brain activity associated with 

reading words,

hearing words

thinking about words

saying words.

Activity is highest in the red areas and then decreases through the other colors of the rainbow from yellow to blue-violet

Specific activity patterns change throughout life as we meet new people, have new experiences, and acquire new skills.  The patterns also chance when Alzheimer’s disease or related disorder disrupts nerve cells and their connections to one another.

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Since Alzheimer’s early discoveries, scientists have studied the pathology that occurs in the inner and outer layers of the brain and is also found in brain tissue and nerve cells.  There are three characteristics that suggest brain changes. First and most important are neurofibrillary tangles, an accumulation of abnormal fibers concentrated in the cytoplasm of a cell. Under the electron microscope, these fibers appear as a tangle of filaments.  Tangles destroy a vital cell transport system made of proteins. This electron microscope picture shows a cell with some healthy areas and other areas where tangles are forming.

In the healthy area, the transport system is organized in orderly parallel strands somewhat like railroad tracks.  Food molecules, cell parts and other key materials travel along the tracks.

A protein called TAU helps the tracks stay straight.

In areas where tangles are forming, tau collapses into twisted strands called tangles.  The tracks can no longer stay straight. They fall apart and disintegrate.  Nutrients and other essential supplies can no longer move through the cells, which eventually die.

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The second change related to Alzheimer’s disease is a change within the brain cells themselves.  When brain tissue is observed through an electron microscope, one can see a granulovascular degeneration within the cell.  The cell becomes filled with vacuoles that have fluid and granular material, or plaque, made of a chemical called beta-amyloid protein.  These plaques look like loose bundles of long, thin fibers that gather in sticky clumps, and serve to interfere with the release and reception of the neurotransmitter, acetylcholine.  Acetylcholine, or ACH for short, is produced by the enzyme choline acetyltransferase, or CAT for short.  If the CAT levels in the brain drop to as much as 90 percent, the level of ACH in the hippocampus and the cerebral cortex is badly reduced; the brain does not have enough ACH for memory formation. 

The most damaging form of beta-amyloid may be groups of few pieces rather than the plaques themselves. The small clumps may block cell-to cell signaling at the synapses. They may also activate immune system cells that trigger inflammation and devour disabled cells.

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These plaques and tangles can be seen under a microscope.  The Alzheimer tissue has many fewer nerve cells and synapses than a healthy brain.

Plaques, the abnormal clusters of protein fragments, build up between nerve cells.

Dead and dying nerve cells contain tangles, which are made up of twisted strands of another protein.

Scientists are not absolutely sure what causes cell death and tissue loss in the Alzheimer brain, but plaques and tangles are prime suspects, and the target of most of the current drug therapies and drugs under development.

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The third characteristic of Alzheimer’s disease is the loss of brain tissue in the outer cortex.  If you look at the autopsied brain of a person with Alzheimer’s disease and the brain of a person without Alzheimer’s disease, you will see that the brain tissue of the person with Alzheimer’s disease has withered and is considerably smaller.  This relates back to the tangles and plaques.  As the tangles and plaques accumulate, not only cause the neurotransmitters to have more difficulty in relaying messages to the brain cells, they also cause some of the brain cells to die or to fragment.  This causes loss of brain tissue.  The constant loss of brain cells is so accelerated in the person with Alzheimer’s disease that the brain shrinks and appears to be a very aged brain.  At the same time, the ventricles (or inner spaces) of the brain increase in size and the outer layer of cells becomes less dense and thinner.

The first image shows a healthy brain.

The second image shows a brain with advanced Alzheimer’s disease

The third image shows how the two brains compare.

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Here is another view of how massive cell loss changes the whole brain in advanced Alzheimer’s disease. This slide shows a crosswise “slice” through the middle of the brain between the ears.

In the Alzheimer’s brain the cortex shrivels up, damaging areas involved in thinking, planning and remembering.

Shrinkage is especially severe in the hippocampus, the area of the cortex that plays a key role in formation of new memories

Ventricles (fluid-filled spaces within the brain) grow larger.

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Plaques and tangles (shown in the blue-shaded areas) tend to spread through the cortex in a predictable pattern as Alzheimer’s disease progresses.

The rate of progression varies greatly. People with Alzheimer’s live an average of eight years, but some people may survive up to 20 years. The course of the disease depends in part on age at diagnosis and whether a person has other health conditions.

Earliest Alzheimer’s starts in the very central part of the cortex.  Changes may begin 20 years or more before diagnosis.

Mild to moderate Alzheimer stages – generally last from 2 to 10 years.

Sever Alzheimer’s may last from 1 to 5 years.

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Alzheimer’s disease attacks the inside of the brain first.  The hypothalamus and the hippocampus.  The tangles occur most densely in an area of the brain known as the hippocampus.  Recent or short term memory is associated with this area, which is also part of a system called the limbic system, otherwise known as the seat of the emotions.  The onset of Alzheimer’s disease is insidious, meaning that its effects appear gradually.  At first there is no decrease in function and no sign of cognitive decline.  Then as the tangles increase, the person starts to complain of forgetting where he or she has put things.  The person may also have a bit less energy, drive, and initiative and be slower to react and to learn new things. 

The hypothalamus is the part of the brain that controls our internal thermostat, our appetite, and our sleep regulator.  So we may see the person with Alzheimer’s disease getting chilled or overheated easily.  They may also become frequently hungry and feel the need to snack a lot.  They may not remember that they have already eaten, or they may not remember they have NOT eaten and tell you they aren’t hungry.  And the person will experience a lot of sleep disturbances, waking up in the night and having difficulty getting back to sleep.

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In mild to moderate stages, brain regions important in memory and thinking and planning develop more plaques and tangles than were present in the early stages.  As a result, individuals develop problems with memory or thinking serious enough to interfere with work or social life.  They may also get confused and have some trouble handling money, expressing themselves, and organizing their thoughts.  Many people with Alzheimer’s are first diagnosed in these stages. 

The one of the functions of the right temporal lobe is to serve in time orientation.  As the disease begins to affect the right temporal lobe, the person may get lost in time, and frequently ask what day or time it is.  One of the functions of the left temporal lobe is language, so as the disease affects the left temporal lobe they may also have some early language problems such as “lost words”, or it’s on the tip of my tongue, so they may describe things rather than name them.

 The second area of the brain to be affected is the parietal lobe of the brain.  This is the area of the brain that serves to put pieces of information together.  It is the part of the brain that allows us to drive a familiar route and get from a starting point to a planned destination.  It is also the part of the brain that allows us to follow complex directions.  As the Alzheimer’s disease progress to this part of the brain, the person with Alzheimer’s disease will start getting lost or not recognizing how to get to a particular destination that they have always known how to get to.  The person will also have difficulty following multi-step directions. This is the point where often times families realize there is a problem and seek help if they haven’t already.

The third area of the brain to be affected is the occipital lobe of the brain.  This is the area of the brain where vision is processed. A person with Alzheimer’s disease may not be able to recognize what they see.  Initially the concept of 3 dimensions is affected, and that will show up as a problem seeing steps or changes in elevation when one walks.  Or differentiating the toilet from the floor and wall in a pastel bathroom with white fixtures.  As the disease progresses, the person’s peripheral vision is affected as well, leaving them with a sense of only central vision.  They can see only what is directly in front of them.  At this point, if someone comes up from their side, the person with Alzheimer’s disease may be startled, because they didn’t see or notice them coming.

The 4^th area of the brain to be affected is the Frontal lobe of the brain.  This area of the brain serves in the executive position.  It is the boss.  It is the part of the brain that makes you behave socially, it helps you reason and make decisions based on judgment.  When this area of the brain in affected, the person with Alzheimer’s disease may exhibit socially inappropriate behavior or make socially inappropriate comments.  They may exhibit poor judgment and leave the stove on, or go outside without a coat in cold weather.  They may stop caring about their appearance, and want to wear the same outfit all the time.  They lose their ability to make choices.  If you ask them what they would like for breakfast, they may respond “I’ll have what you are having” because they can’t make choices, they can’t process that much information.

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In advanced Alzheimer’s disease, most of the cortex is seriously damaged.  The brain shrinks dramatically due to widespread cell death. Individuals lose their ability to communicate to recognize family and loved ones, and to care for themselves.

The 5^th area or last area of the brain to be affected is the Motor area of the Parietal lobe.  This is the part of the brain that helps us move around, walk, feed ourselves, dress ourselves, talk and swallow.  As this area of the brain is affected, the person with Alzheimer’s disease begins to have trouble with walking.  They begin to shuffle their feet because they have trouble picking up their feet. They walk stooped over from the waist. They develop troubles feeding themselves.  You may have to put the food on the fork or spoon, put the utensil in their hand and raise their hand to their mouth.  Sometimes once you get them started, they can go from there.  But as the disease progresses, you will need to remind them to chew and to swallow.  It is in this stage that the person with Alzheimer’s disease will lose weight, and this weight loss is irreversible.  It is also in this stage that the person is very susceptible to pneumonia, particularly aspiration pneumonia, because of their swallowing difficulties.

Even though a lot of the brain is affected by Alzheimer’s disease as it progresses, one area that seems to not be affected is the sensory section of the parietal lobe of the brain.  This is the area of the brain that interprets the sense of hearing, taste, smell and touch.  It is also the part that interprets facial expressions and tone of voice.  To the very end, a person with Alzheimer’s disease will be able to sense that he or she is treated with love and respect, they will be able to hear and see and taste, and feel touch.

If you notice, there is a very predictable sequence in how the brain is affected by Alzheimer’s disease.  It is the reverse order that we gain skills and information as a baby, a child and a young adult. 

This predictable pattern of skills loss is what has allowed physicians to develop a rating scale for the various stages of Alzheimer’s disease.  We have a handout of those stages, that may help you understand what is going on with your loved one.