Alzheimer  >   3. The Changing Brain

During the progression of Alzheimer's disease (AD), brain damages occur first in entorhinal cortex and then spread to other regions.

Preclinical AD


AD begins in the entorhinal cortex, which is near the hippocampus and has direct connections to it. It then proceeds to the hippocampus, the brain region that plays a major role in learning and memories. Affected regions begin to atrophy (shrink). Ventricles, the fluid-filled spaces inside the brain, begin to enlarge as the process continues.

These brain changes may begin 10 to 20 years before any visible signs and symptoms appear. Memory loss, the first visible sign, is the main feature of mild cognitive impairment (MCI) which does not have other cognitive problems that characterize AD. MCI has several subtypes. The type most associated with memory loss is called amnestic MCI. About 8 of every 10 people who fit the definition of amnestic MCI go on to develop AD within 7 years.

Mild AD


As AD spreads through the brain, the number of plaques and tangles grows, shrinkage progresses, and more and more of the cerebral cortex is affected. Memory loss continues and changes in other cognitive abilities begin to emerge. The clinical diagnosis of AD is usually made during this stage.

Moderate AD

By this stage, AD damage has spread further to the areas of the cerebral cortex that control language, reasoning, sensory processing, and conscious thought. Affected regions continue to atrophy and signs and symptoms of the disease become more pronounced and widespread. Behavior problems, such as wandering and agitation, can occur. More intensive supervision and care become necessary, and this can be difficult for many spouses and families.

Behavior is the result of complex brain processes, all of which take place in a fraction of a second in the healthy brain. In AD, many of these processes are disturbed, and this is the basis for many distressing or inappropriate behavior. For example, a person may angrily refuse to take a bath or get dressed because he does not understand what his caregiver has asked him to do. If he does understand, he may not remember how to do it. The anger is a mask for his confusion and anxiety. Or, a person with AD may constantly follow her husband or caregiver and fret when the person is out of sight. To a person who cannot remember the past or anticipate the future, the world around her can be strange and frightening. Sticking close to a trusted and familiar caregiver may be the only thing that makes sense and provides security. Taking off clothes may seem reasonable to a person with AD who feels hot and doesn't understand or remember that undressing in public is not acceptable.

Severe AD


In the last stage of AD, plaques and tangles are widespread throughout the brain, and areas of the brain have atrophied further. Patients cannot recognize family and loved ones or communicate in any way. They are completely dependent on others for care. All sense of self seems to vanish.

At the end, patients may be in bed much or all of the time. Most people with AD die from other illnesses, frequently aspiration pneumonia. This type of pneumonia happens when a person is not able to swallow properly and breathes food or liquids into the lungs.

The following figure shows the spread of neurofibrillary tangles (in blue) throughout the brain as Alzheimer's disease progresses. Plaques also spread throughout the brain, starting in the entorhinal cortex.


[Adapted from: National Institute on Aging, USA]