Causes & Symptoms of Disease - Alzheimer's Disease
Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks. In most people with Alzheimer’s, symptoms first appear after age 60.
Alzheimer’s disease is the most common cause of dementia among older people. Dementia is the loss of cognitive functioning—thinking, remembering, and reasoning—to such an extent that it interferes with a person’s daily life and activities. Estimates vary, but experts suggest that as many as 5.1 million Americans may have Alzheimer’s.
Alzheimer’s disease is named after 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.
Changes in the Brain in Alzheimer’s Disease
Although we still don’t know what starts the Alzheimer’s disease process, we do know that damage to the brain begins as many as 10 to 20 years before any problems are evident. 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, they 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, which is essential in forming memories. As the death of neurons increases, affected brain regions begin to shrink. By the final stage of Alzheimer’s, damage is widespread and brain tissue has shrunk significantly.
Very Early Signs and Symptoms of Alzheimer’s Disease
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. More people with MCI, compared with those without MCI, go on to develop Alzheimer’s.
Other changes may also signal the very early stages of Alzheimer’s disease. For example, brain imaging and biomarker studies of people with MCI and those with a family history of Alzheimer’s are beginning to detect early changes in the brain like those seen in Alzheimer’s. These findings will need to be confirmed by other studies but appear promising. Other 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. Such findings offer hope that some day we may have tools that could help detect Alzheimer’s 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 small mood and personality changes. People often are 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 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
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 differs from person to person.
The Basics of Alzheimer’s
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.
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 damage. These age-related changes include atrophy (shrinking) of certain parts of the brain, inflammation, and the production of unstable molecules called free radicals.
Genetics for Getting Alzheimer’s Disease
In a very few families, people develop Alzheimer’s disease in their 30s, 40s, and 50s. Many of 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 in these “early-onset” familial cases. Not all early-onset cases are caused by such mutations.
Most people with Alzheimer’s disease have “late-onset” Alzheimer’s, which usually develops after age 60. Many studies have linked a gene called APOE to late-onset Alzheimer’s. 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 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 the disease.
Most experts believe that additional genes may influence the development of late-onset Alzheimer’s in some way. Scientists around the world are searching for these genes. Researchers have identified variants of the SORL1, CLU, PICALM, and CR1 genes that may play a role in risk of late-onset Alzheimer’s.
A nutritious diet, physical activity, 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 vascular and metabolic conditions such as heart disease, stroke, 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 as well.
How Alzheimer’s Disease Is 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” (dementia may be due to another cause) or “probable Alzheimer’s disease” (no other cause for dementia can be found). To diagnose Alzheimer’s, 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 computerized tomography (CT) or magnetic resonance imaging (MRI)
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 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 Alzheimer’s Is 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 the disease.
Helping People with Alzheimer’s Maintain Mental Function
Four medications are approved by the U.S. Food and Drug Administration to treat Alzheimer’s. Donepezil (Aricept®), rivastigmine (Exelon®), and galantamine (Razadyne®) are used to treat mild to moderate Alzheimer’s (donepezil can be used for severe Alzheimer’s as well). Memantine (Namenda®) is used to treat moderate to severe Alzheimer’s. 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 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 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 clinical trials, scientists are looking at many possible interventions, such as cardiovascular and diabetes treatments, antioxidants, immunization therapy, cognitive training, and physical activity.
Supporting Families and Caregivers
Caring for a person with Alzheimer’s disease can have high physical, emotional, and financial costs. The demands of day-to-day care, changing family roles, and difficult decisions about placement in a care facility can be hard to handle. Researchers are learning a lot about Alzheimer’s caregiving, and studies are helping experts develop new ways to support caregivers.
Becoming well-informed about the disease is one important long-term strategy. Programs that teach families about the various stages of Alzheimer’s and about flexible and practical strategies for dealing with difficult caregiving situations provide vital help to those who care for people with Alzheimer’s.
Developing good coping skills and a strong support network of family and friends also are important ways that caregivers can help themselves handle the stresses of caring for a loved one with Alzheimer’s disease. For example, staying physically active provides physical and emotional benefits.
Some Alzheimer’s caregivers have found that participating in a support group is a critical lifeline. These support groups allow caregivers to find respite, express concerns, share experiences, get tips, and receive emotional comfort. The Alzheimer’s Association, Alzheimer’s Disease Centers, and many other organizations sponsor in-person and online support groups across the country. There are a growing number of groups for people in the early stage of Alzheimer’s and their families. Support networks can be especially valuable when caregivers face the difficult decision of whether and when to place a loved one in a nursing home or assisted living facility.
Advancing Our Understanding of Alzheimer’s Disease
30-years ago, we knew very little about Alzheimer’s disease. Since then, scientists have made many important advances. Research supported by NIA and other organizations has expanded knowledge of brain function in healthy older people, identified ways we might lessen normal age-related declines in mental function, and deepened our understanding of the disease. Many scientists and physicians are now working together to untangle the genetic, biological, and environmental factors that, over many years, ultimately result in Alzheimer’s. This effort is bringing us closer to the day when we will be able to manage successfully or even prevent this devastating disease.