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Alzheimer’s disease, or AD, a form of dementia associated with memory loss, affects an estimated 5.3 million Americans, a number that has more than doubled since 1980. Among people age 65 and older, AD is the most common cause of dementia. AD is now the sixth leading cause of death in the United States, with death typically occurring four to six years after diagnosis. Whether you are getting older yourself and worried about the prospect of developing AD, or you are trying to understand the disease so that you can care for and support your loved one who has been diagnosed with it, facing Alzheimer’s is no easy task.

The good news is that AD is an urgent research priority, through funding from the National Institutes of Health (NIH) National Institute on Aging (NIA). So, while there is no current cure for AD, research on the causes, detection, and treatment continues at a rapid pace. Indeed, as the population age 85 and older is the fastest-growing segment of the population, AD is becoming even more of a problem.

Signs of Mild AD

As AD spreads through the brain, shrinkage progresses, the number of tangles and plaques grows, and more of the cerebral cortex is affected. Memory loss continues and other cognitive problems begin to emerge. It is at this point that a clinical diagnosis of AD is made. Signs of mild AD include:

• Memory loss

• Confusion about the location of familiar places (getting lost occurs)

• Taking longer than before to accomplish normal daily tasks

• Difficulty handling money and paying bills

• Poor judgment leading to bad decisions

• Loss of spontaneity and sense of initiative

• Personality and mood changes, increased anxiety and/or aggression

In a person with mild AD, they look healthy and appear normal, but they’re actually having trouble dealing with the world and things happening around them. Realization that something is wrong gradually occurs to the person and his or her family. But acceptance of these signs of mild AD as something as other than normal aging is a huge hurdle for all involved, especially the person experiencing it. Experts say that once families know what is causing the problems, they often feel a sense of relief. Despite the diagnosis of early AD, they are comforted that the individual will still be able to make meaningful contributions to society for some time to come.

Signs of Moderate AD

In this stage of AD, damage has spread to the cerebral cortex areas that control language, conscious thought, reasoning, and sensory processing. Signs and symptoms of the disease become more pronounced as ventricles enlarge and affected regions increase. New behavioral problems of wandering and agitation can occur. The person with moderate AD may require more intensive care and supervision, which is difficult for many spouses and families. Symptoms of moderate AD include:

• Increasing confusion and memory loss

• Inappropriate outbursts of anger

• Shortened attention span

• Problems recognizing family members and friends

• Repetitive statements or movement

• Occasional muscle twitches

• Language difficulty, problems with reading, writing, and working with numbers

• Difficulty organizing thoughts and thinking logically

• Inability to learn something new or to cope with situations that are new or unexpected

• Loss of impulse control (manifested through vulgar language or undressing at inappropriate times or places)

• Anxiety, agitation, fearfulness, restlessness, and wandering (especially in late afternoons or at night)

• Delusions, hallucinations, irritability, paranoia or suspiciousness

• Inability to carry out actions that require multiple, sequenced steps (such as getting dressed, making coffee, or setting the table)

It is important to understand that complex brain processes are disturbed in a person with AD. What takes seconds in a person with a healthy brain takes longer or is disrupted in someone with AD. This may result in distressing or inappropriate behaviors. Someone with AD may follow around a caregiver. Since they are not able to remember the past or anticipate the future, the world around them is a strange and frightening place. Sticking close to a caregiver gives the person a measure of security. They may also refuse to take a bath, not understanding what the caregiver is saying or not remembering how to accomplish the task.

Signs of Severe AD

At this stage of the disease, the person with severe AD cannot recognize family members and friends and cannot communicate in any way. The person is completely dependent on others now. The plaques and tangles are more widespread throughout the brain, the brain areas have shrunk even more, and ventricles are even more enlarged. Signs of severe AD include:

• Difficulty swallowing

• Groaning, grunting, or moaning

• Increased sleeping

• Loss of bladder and bowel control

• Seizures

• Skin infections

• Weight loss

Near the end of this final stage of AD, the person is in bed all or most of the time. Death usually occurs as a result of aspiration pneumonia. This type of pneumonia develops when the person is unable to swallow properly and takes food or liquid into the lungs instead of air.

Searching for the Cause of AD

Scientists and researchers are aggressively searching for what causes AD. They want to know why it begins in the first place, what causes it to get worse over time, why the number of people with AD increases with age, and why some people get it and others remain healthy. The consensus is that AD occurs when genetic, lifestyle and environmental factors work together to start the disease process. AD develops because of a complex series of events that occur in the brain over a long period of time.

Scientists are looking at the genetic link to the two main types of AD: early-onset AD and late-onset AD. Early-onset AD is rare, affecting individuals between the ages of 30 and 60. Some early-onset AD cases are inherited. They are called familial AD (FAD). The far more common form of the disease is late-onset AD, which occurs in those aged 60 and older. Studies involving DNA, genes and chromosomes seek to unravel the mysteries of the genetic link with AD.

Since genetic material is critical to continued studies, in 2003, the National Institutes of Health (NIH) launched the Alzheimer’s Disease Genetics Study, and in 2007, the Alzheimer’s Disease Genetics Consortium. An important part of the NIA’s efforts to promote and accelerate AD genetics research is to make biological samples and data publicly available to approved researchers.

But there are other factors at work that cause AD.

• Beta-amyloid – While a lot is known about how beta-amyloid is formed, how the fragments stick together in aggregates (oligomers) and then gradually form into plaques, investigators are interested in the toxic effects of beta-amyloid, oligamers and plaques on neurons. Researchers are also looking into how beta-amyloid may disrupt cellular communications before the onset of plaques.

• Tau – The chief component of neurofibrillary tangles, tau is an exciting new area of study. This excitement is spurred by the finding that a mutant form of the protein is responsible for one form of frontotemporal dementia, the third most common cause of late-life dementia, after AD and vascular dementia. This suggests that abnormalities in the tau protein can cause dementia.

• Protein misfolding – Researchers have found that a number of neurodegenerative diseases (AD, Parkinson’s, Huntington’s, etc.) share a key characteristic – protein misfolding. When proteins form, they fold into unique, three-dimensional shapes that help them perform specific functions. When this process goes wrong – and it does for a variety of reasons, most commonly aging – the protein folds into an abnormal shape (misfolding). While cells can normally repair or degrade misfolded proteins, when these proteins are formed as part of age-related changes, the body’s repair mechanisms can become overwhelmed. Misfolded proteins stick together, form insoluble aggregates that build up, leading to disruption in cellular communication, metabolism, and even cell death. Learning how these processes occur and researching characteristics and actions of misfolded proteins may someday lead to new therapies.

The Aging Process and AD

The most basic of risk factors for AD is the aging process itself. Inflammation may make AD damage in the brain worse. Other important factors in the AD process include free radicals. Researchers are studying age-related changes in the working ability of synapses in certain areas of the brain. Age-related reductions in levels of particular growth factors, such as nerve growth factor and brain-derived neurotrophic factor, may also cause compromise to important cell populations.

Scientists are also looking into what happens with the brain’s blood vessels and aging in AD, and the relationship between AD and vascular problems in other parts of the body. Heart disease and stroke, for example, may contribute to the development or severity of AD or other types of dementia. In addition, studies show that high blood pressure that develops during middle age is associated with cognitive decline and dementia later in life. Another area of AD vascular research is the metabolic syndrome, a constellation of factors that increases risk of stroke, heart disease and type 2 diabetes. Nearly one in five Americans over 60 has type 2 diabetes, and studies suggest that these people may be more at risk for developing cognitive problems, including AD, as they age.

A growing body of evidence shows that lifestyle factors play an important role in the development of AD. Physical activity and a nutritious diet help people to remain healthy as they grow older. A healthy diet and exercise can reduce obesity, lower high blood pressure and cholesterol, and improve the action of insulin. Remaining active intellectually may also help reduce the risk of AD.

• Exercise – It is well known that exercise has many benefits. It improves heart and lung function, strengthens muscles, helps prevent osteoporosis, and improves overall well-being and mood. Scientists and researchers also believe exercise plays an important role in brain functioning. Animal studies show exercise increases the number of capillaries supplying blood to the brain, resulting in improved learning and memory in older animals. Epidemiologic studies show that higher levels of exercise or physical activity in older adults are associated with reduced risk of cognitive decline and dementia. This is true even with moderate exercise such as a brisk walk. Clinical trials show short-term positive effects of exercise on cognitive function (planning, organizing, and decision-making).

• Diet – Considerable attention has been paid to diet and its relationship to cognitive function preservation or reducing the risk of AD. Researchers have studied foods rich in antioxidants and anti-inflammatory properties to find out whether they affect age-related changes in brain tissue. Studies on curcumin (the main ingredient in the spice turmeric), DHA (a type of omega-3 fatty acid found in fish), vitamin E, vegetables (especially green, leafy and cruciferous ones), and other dietary items are showing exciting results, but they are not definitive. Clinical trials are being conducted to confirm the results.

• Intellectually stimulating activities – Some studies have shown that keeping the brain active reduces AD risk. Doing puzzles, playing games, and spending time with family and friends is fun, and helps keep people alert and engaged in life. One study that tracked participants over a 4-year period found the risk of developing AD was 47 percent reduced lower who most frequently did activities involving significant information-processing (games, puzzles, etc.), than those who did them less frequently. Studies of nursing home residents and others living in the community suggest a link between social engagement and cognitive process. Older adults who have a number of social contacts and participate in many social activities tend to have less cognitive decline and decreased risk of dementia than those who are less socially engaged.

Detecting AD

Using the arsenal of currently available tools, an experienced physician can be reasonably confident in making an accurate diagnosis of AD in an individual. These tools include:

• Detailed patient history – This includes a description of how and when symptoms developed, overall medical history of the person and his or her family, and an assessment of the person’s emotional state and living environment.

• Gathering information from family and close friends – Those who are closest to the individual being examined are in a position to provide valuable information and insights about how personality and behavior have changed. Often, these individuals know something is wrong before test results confirm it.

• Exams and tests – The physician will have the patient undergo various physical and neurological exams and laboratory tests.

• Neuropsychological testing – This involves Q&A tests and other tasks to measure language skills, memory, ability to do arithmetic, and other abilities related to brain functioning to show what kind of cognitive changes are happening.

• CT and/or MRI – Computed tomography (CT) or magnetic resonance imaging (MRI) may be performed. These scans can detect strokes or tumors or reveal changes in the brain’s structure indicating early AD.

Based on the results of the tests and findings, the experienced physician can diagnose or rule out other causes of dementia, or determine whether the person has MCI, possible AD (symptoms may be due to another cause), or probable AD (no other cause for the symptoms can be found).

New diagnostic tools center on the area of neuroimaging. Photon emission tomography (PET) and single photon emission computed tomography (SPECT) are the newest tools being studied for use with MRI to help identify the earliest changes in brain function and structure.

While they are still primarily research tools, one day they may be able to help physicians diagnose AD at the very earliest stages. They may also be used to monitor disease progress and assess responses to drug treatment.

Treatment for AD

Four medications, tested in clinical trials, have been approved by the Federal Drug Administration (FDA) for treatment of AD symptoms.

Three of the drugs used for mild to moderate AD symptoms are donezepil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). Donezepil was recently approved to treat severe AD as well. These drugs, known as cholinesterase inhibitors, help persons maintain abilities to carry out activities of daily living. They may also help maintain some skills in speaking, memory, or thinking, and may help with certain behavioral symptoms. They will not stop or reverse AD’s progression and appear to only work for a period of months or a few years.

Memantine (Namenda) is the newest approved AD drug, and is prescribed to treat moderate to severe AD symptoms. Like the cholinesterase inhibitors, memantine also will not stop or reverse AD.

Coping Tips for Caregivers

Caring for loved ones with AD takes a tremendous toll on caregivers – spouses, family members and close friends. The task is difficult and can be overwhelming at times. The handbook, Caring for a Person with Alzheimer’s Disease: Your Easy-to-Use Guide from the National Institute on Aging, may help caregivers overcome some of those difficult challenges. In particular, the handbook covers:

• Understanding AD

• Caring for a Person with AD

• Caring for Yourself

• When You Need Help

• The Medical Side of AD

• Coping with the Last Stages of AD

• Other Information (participating in clinical trials)

The NIA site also has a wealth of other links and resources on daily coping, websites and planning.

Other Resources on AD

The Alzheimer’s Association website, at http://www.alz.org/index.asp, is a great resource for information about AD, living with AD, and finding help. The Alzheimer’s Association is the leading voluntary health organization in the AD support, research, and care.

The NIA/NIH/HBO collaboration film, The Alzheimer’s Project, is an Emmy Award winning, multi-platform (print, DVD, Web and television) public health series that takes a look at groundbreaking scientific discoveries and seeks to bring a wider understanding of AD research and care.

The Alzheimer’s Disease and Cooperative Study (ADCS), is a collaborative effort between the NIA and the University of California San Diego. The ADCS is a major initiative for AD clinical studies in the federal government, addressing treatment for both cognitive and behavioral symptoms.

Bottom line, whether you have Alzheimer’s disease or you are caring for someone who does, the important thing to know is you are not alone. There is help and support available to you. Take advantage of all the information and assistance that you can. Educate yourself, ask questions, and do not be afraid to seek help.

One day, there may be a cure for AD. There is, for example, much promising research involving stem cell research and the disease. In the meantime, know that there is a wealth of goodwill and resources surrounding AD that can benefit you.