What is Alzheimer’s disease?

Alzheimer’s disease is an age-related, non-reversible brain disorder that develops over a period of years.  Alzheimer’s disease is one of a group of disorders called dementias that are characterized by cognitive and behavioral problems. It is the most common cause of dementia among people age 65 and older.

At first, people with Alzheimer’s experience memory loss and confusion, which may be mistaken for the kinds of memory changes that are sometimes associated with normal aging. However, the symptoms of Alzheimer’s disease gradually lead to behavior and personality changes, a decline in cognitive abilities such as decision-making and language skills, and problems recognizing family and friends. Ultimately, Alzheimer’s disease leads to a severe loss of mental function. These losses are related to the worsening breakdown of the connections between certain neurons in the brain and their eventual death.

Alzheimer’s disease was discovered by, and named for, Dr. Alois Alzheimer. In 1906, Dr. Alzheimer noticed changes in the brain tissue of a woman who had died of an unusual mental illness. Her symptoms included memory loss, language problems, and unpredictable behavior. After she died, he examined her brain and found many abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary tangles). Plaques and tangles in the brain are two of the main features of Alzheimer’s disease. The third is the loss of connections between nerve cells (neurons) in the brain.

There are three major physical changes that occur in the brain that are associated with the disease process of Alzheimer’s disease.

  • Amyloid plaques, which are made up of fragments of a protein called beta-amyloid peptide mixed with a collection of additional proteins, remnants of neurons, and bits and pieces of other nerve cells.
  • Neurofibrillary tangles (NFTs), found inside neurons, are abnormal collections of a protein called tau. Normal tau is required for healthy neurons. However, in Alzheimer’s disease, tau clumps together. As a result, neurons fail to function normally and eventually die.
  • Loss of connections between neurons responsible for memory and learning. Neurons can't survive when they lose their connections to other neurons. As neurons die throughout the brain, the affected regions begin to atrophy, or shrink. By the final stage of Alzheimer’s disease, damage is widespread and brain tissue has shrunk significantly.

What changes happen to the brain in someone with Alzheimer’s?

Although we still don’t know what triggers the Alzheimer’s disease process, we do know that damage to the brain begins well before any problems are evident. In fact changes to the brain can start 10 to 20 years before any symptoms.  Tangles begin to develop deep in the brain, in an area called the entorhinal cortex, and plaques form in other areas. As more and more plaques and tangles form in particular brain areas, healthy neurons begin to work less efficiently. Then, the healthy neurons lose their ability to function and communicate with each other, and eventually they die. This damaging process spreads to a nearby structure, called the hippocampus.  The hippocampus is essential in forming memories. As the death of neurons increases, affected brain regions begin to shrink. By the final stage of Alzheimer’s disease, damage is widespread disease and brain tissue has shrunk significantly.

Very Early Signs and Symptoms

Memory problems are one of the first signs of Alzheimer’s disease. Some people with memory problems have a condition called amnestic mild cognitive impairment (MCI). People with this condition have more memory problems than normal for people their age, but their symptoms are not as severe as those with Alzheimer’s disease. More people with MCI, compared with those without MCI, go on to develop Alzheimer’s disease.

Other changes may also signal the very early stages of Alzheimer’s disease. For example, recent research has found links between some movement difficulties and MCI. Researchers also have seen links between some problems with the sense of smell and cognitive problems. Brain imaging and biomarker studies of people with MCI and those with a family history of Alzheimer’s disease are beginning to detect early changes in the brain like those seen in Alzheimer’s disease. These findings will need to be confirmed by other studies but appear promising. Such findings offer hope that some day, we may have tools that could help detect Alzheimer’s disease early, track the course of the disease, and monitor response to treatments.

Mild Alzheimer’s disease

As Alzheimer’s disease progresses, memory loss continues and changes in other cognitive abilities appear. Problems can include getting lost, trouble handling money and paying bills, repeating questions, taking longer to complete normal daily tasks, poor judgment, and mood and personality changes. People often are first diagnosed in this stage.

Moderate Alzheimer’s disease

In this stage, damage occurs in areas of the brain that control language, reasoning, sensory processing, and conscious thought. Memory loss and confusion increase, and people begin to have problems recognizing family and friends. They may be unable to learn new things, carry out tasks that involve multiple steps (such as getting dressed), or cope with new situations. They may have hallucinations, delusions, and paranoia, and may behave impulsively.

Severe Alzheimer’s disease

By the final stage, plaques and tangles have spread throughout the brain and brain tissue has shrunk significantly. People with severe Alzheimer’s disease cannot communicate and are completely dependent on others for their care. Near the end, the person may be in bed most or all of the time as the body shuts down.

What Causes Alzheimer’s disease?

Scientists don’t yet fully understand what causes Alzheimer’s disease, but it is clear that it develops because of a complex series of events that take place in the brain over a long period of time. It is likely that the causes include genetic, environmental, and lifestyle factors. Because people differ in their genetic make-up and lifestyle, the importance of these factors for preventing or delaying Alzheimer’s disease differs from person to person.

The Basics of Alzheimer’s disease

Scientists are conducting studies to learn more about plaques, tangles, and other features of Alzheimer’s disease. They can now visualize plaques by imaging the brains of living individuals. They are also exploring the very earliest steps in the disease process. Findings from these studies will help them understand the causes of Alzheimer’s disease.

One of the great mysteries of Alzheimer’s disease is why it largely strikes older adults. Research on how the brain changes normally with age is shedding light on this question. For example, scientists are learning how age-related changes in the brain may harm neurons and contribute to Alzheimer’s disease damage. These age-related changes include inflammation and the production of unstable molecules called free radicals.

Genetics

In a very few families, people develop Alzheimer’s disease in their 30s, 40s, and 50s. These people have a mutation, or permanent change, in one of three genes that they inherited from a parent. We know that these gene mutations cause Alzheimer’s disease in these “early-onset” familial cases.

However, most people with Alzheimer’s disease have “late-onset” Alzheimer’s disease, which usually develops after age 60. Many studies have linked a gene called APOE to late-onset Alzheimer’s disease. This gene has several forms. One of them, APOE ε4, increases a person’s risk of getting the disease. About 40 percent of all people who develop late-onset Alzheimer’s disease carry this gene. However, carrying the APOE ε4 form of the gene does not necessarily mean that a person will develop Alzheimer’s disease, and people carrying no APOE ε4 forms can also develop Alzheimer’s disease.

Scientists think that other risk-factor genes exist as well. A possible new one, SORL1, was discovered in 2007. Large-scale genetic research studies are looking to find other genes.

Lifestyle Factors

A nutritious diet, exercise, social engagement, and mentally stimulating pursuits can all help people stay healthy. New research suggests the possibility that these factors also might help to reduce the risk of cognitive decline and Alzheimer’s disease. Scientists are investigating associations between cognitive decline and heart disease, high blood pressure, diabetes, and obesity. Understanding these relationships and testing them in clinical trials will help us understand whether reducing risk factors for these diseases may help with Alzheimer’s disease as well.

How is Alzheimer’s disease diagnosed?

Alzheimer’s disease can be definitively diagnosed only after death by linking clinical course with an examination of brain tissue and pathology in an autopsy. But doctors now have several methods and tools to help them determine fairly accurately whether a person who is having memory problems has “possible Alzheimer’s disease” (the symptoms may be due to another cause) or “probable Alzheimer’s disease” (no other cause for the symptoms can be found). To diagnose Alzheimer’s disease, doctors:    

  • ask questions about the person’s overall health, past medical problems, ability to carry out daily activities, and changes in behavior and personality 
  • conduct tests of memory, problem solving, attention, counting, and language
  • carry out medical tests, such as tests of blood, urine, or spinal fluid
  • perform brain scans, such as a computerized tomography (CT) scan or a magnetic resonance imaging (MRI) test

These tests may be repeated to give doctors information about how the person’s memory is changing over time.

Early diagnosis is beneficial for several reasons. Having an early diagnosis and starting treatment in the early stages of the disease can help preserve function for months to years, even though the underlying Alzheimer’s disease process cannot be changed. Having an early diagnosis also helps families plan for the future, make living arrangements, take care of financial and legal matters, and develop support networks.

In addition, an early diagnosis can provide greater opportunities for people to get involved in clinical trials. In a clinical trial, scientists test drugs or treatments to see which are most effective and for whom they work best.

How Is Alzheimer’s disease treated?

Alzheimer’s disease is a complex disease, and no single “magic bullet” is likely to prevent or cure it. That’s why current treatments focus on several different aspects, including helping people maintain mental function; managing behavioral symptoms; and slowing, delaying, or preventing Alzheimer’s disease.

Helping People with Alzheimer’s Disease Maintain Mental Function

Four medications are approved by the U.S. Food and Drug Administration to treat Alzheimer’s disease. Donepezil (Aricept®), rivastigmine (Exelon®), and galantamine (Razadyne®) are used to treat mild to moderate Alzheimer’s disease (donepezil can be used for severe Alzheimer’s disease as well). Memantine (Namenda®) is used to treat moderate to severe Alzheimer’s disease. These drugs work by regulating neurotransmitters (the chemicals that transmit messages between neurons). They may help maintain thinking, memory, and speaking skills, and help with certain behavioral problems. However, these drugs don’t change the underlying disease process and may help only for a few months to a few years.

Managing Behavioral Symptoms

Common behavioral symptoms of Alzheimer’s disease include sleeplessness, agitation, wandering, anxiety, anger, and depression. Scientists are learning why these symptoms occur and are studying new treatments—drug and non-drug—to manage them. Treating behavioral symptoms often makes people with Alzheimer’s disease more comfortable and makes their care easier for caregivers.

Slowing, Delaying, or Preventing Alzheimer’s disease

Alzheimer’s disease research has developed to a point where scientists can look beyond treating symptoms to think about addressing the underlying disease process. In ongoing Alzheimer’s disease clinical trials, scientists are looking at many possible interventions, such as cardiovascular treatments, antioxidants, immunization therapy, cognitive training, and physical activity.

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