Alzheimer's Disease

Alzheimer’s disease is a progressive condition in which nerve cells in the brain degenerate and the brain shrinks. Alzheimer’s disease is the most common cause of dementia (a general decline in all areas of mental ability). Its onset is uncommon before the age of 60, but incidence increases steadily with age thereafter.

Causes

Early onset Alzheimer's disease, in which symptoms develop before the age of 60, is often inherited as a dominant trait. Late onset Alzheimer's disease is associated with one of the genes that is responsible for the production of the blood protein apolipoprotein E. Genetic factors also result in the abnormal deposition of a protein in the brain called beta amyloid. Other chemical abnormalities include deficiency of the neurotransmitter acetylcholine.

Symptoms and signs 

The features of Alzheimer’s disease vary, but there are three broad stages. At first, the affected individual becomes increasingly forgetful; and problems with memory may cause anxiety and depression. Some deterioration in memory is a feature of normal aging, and this alone is not evidence of dementia. In the second stage of the disease, loss of memory, particularly for recent events, gradually becomes more severe, and there may be disorientation as to time or place. The person’s concentration and numerical ability decline, and there is noticeable dysphasia (inability to find the right word). Anxiety increases, mood changes are unpredictable, and personality changes may occur. If the patient is left unsupervised, he or she may repeatedly wander off. Finally, confusion becomes profound. There may be symptoms of psychosis, such as hallucinations and delusions. Signs of nervous system disease, such as abnormal reflexes (involuntary actions) and faecal or urinary incontinence, begin to develop.

Diagnosis 

Alzheimer’s disease is usually diagnosed from the symptoms, but tests including blood tests and CT scanning or MRI (techniques that produce cross-sectional or three-dimensional images) of the brain may be needed to exclude other causes of dementia.

Treatment 

The most important aspect of treatment for Alzheimer’s disease is the provision of suitable nursing and social care for sufferers and support for their relatives. Tranquillizer drugs can often improve difficult behaviour and to help with sleep. Treatment with acetylcholinesterase inhibitors, such as rivastigmine and donepezil, may slow the progress of the disease for a time, but will not improve mental ability. Side effects such as nausea and dizziness may occur.

Alzheimer’s Disease in more detail - non-technical

Definition 

Alzheimer’s disease (AD) is the most common form of dementia in those aged 65 and older. It is an irreversible and incurable progressive neurological disease caused by the degeneration and eventual death of a large number of neurons (nerve cells) in several areas of the brain, accompanied by diminished brain size. AD usually occurs in old age and begins with short-term memory loss. This is followed by the slow progressive loss of memory and cognitive and intellectual functions, leading to the deterioration of physical functioning and incapacitation.

Demographics

Alzheimer’s disease is the most common degenerative brain disorder. It accounts for 50–70% of all cases of dementia in the United States and for about 75% of all dementias in people over age 65. An estimated 5.1 million Americans have AD. The exact number is difficult to determine since AD is often misdiagnosed or not diagnosed until the disease is in its later stages. About 350,000 new cases of Alzheimer’s disease are diagnosed each year in the United States and approximately 65,800 people die from AD each year. It is the fourth leading cause of death in American adults after heart disease, cancer, and stroke.

Alzheimer’s rarely occurs before the age of 60. Early-onset AD, affecting people in their 30s, 40s, and 50s, accounts for only about 5% of total cases. About 3–5% of men and women aged 65–74 have AD. About 19–20% of those between 75 and 84 and nearly half of those over 85 have the disease. Slightly more women than men develop AD, but this may be because women tend to live longer. About half of all nursing home patients in the United States have AD.

Alzheimer’s disease appears to be more prevalent among African Americans, with estimates ranging from 14% to almost 100% higher than among Caucasian Americans. One study reported that the onset of AD in Hispanics occurs at an age that is, on average, five years younger than its onset in Caucasians.

The incidence of Alzheimer’s in other developed countries is about the same as in the United States. In countries such as Japan that have a rapidly aging population with a higher percentage of people over 65, the incidence of AD is even higher than in the United States. In developing countries the percentage of the population with AD is lower because fewer people live to age 65. However more than 50% of people with AD live in developing countries and by 2025 this is expected to be above 70%.

The number of people afflicted with Alzheimer’s is expected to more than triple by 2050, as the population ages and more people live longer. The number may be even higher than predicted, since recent research suggests that mild cognitive impairment observed in many elderly people may be early-stage Alzheimer’s disease.

Description

In 1906 Alois Alzheimer (1864–1915), a German psychiatrist and neuroanatomist, was studying slides prepared from the brain of a 51-year-old woman, known as Frau D., who had died after suffering from dementia for several years. Her symptoms did not fit those of any brain disorder known at the time. Alzheimer found abnormal clumps of material—now called beta-amyloid plaques—and tangled bundles of fibers—neurofibrillary tangles—in Frau D.’s brain tissue.

These plaques and tangles, found upon brain autopsy, constitute the diagnostic signature of Alzheimer’s disease. The plaques, sometimes called senile plaques, are sticky clumps or clusters of dead and dying neurons and other cellular debris surrounding insoluble deposits of beta-amyloid. The latter are fragments of a larger protein called amyloid precursor protein (APP) that was not processed properly. These plaques are located in between neurons. They are believed to interfere with normal communication between neurons, eventually causing the nerve cells to die. The tangles are accumulations of twisted fragments of tau proteins inside neurons. Tau proteins normally bind and stabilize neurons. When tau proteins are damaged by the addition of phosphorus, a process called hyperphosphorylation, they form filaments that twist around each other to form neurofibrillary tangles that can no longer stabilize the neurons. Increased beta-amyloid may cause the formation of neurofibrillary tangles. However it is not known whether the plaques and tangles cause AD or are the result of it.

Plaques and tangles occur as part of the normal aging process, but are far less prevalent in normal brains than in the brains of AD patients. Because dementia had been associated with the elderly and Frau D. had been middle-aged, her disease was named presenile dementia and was thought to be a very rare disorder. It was not until the early 1950s that researchers at St. Elizabeth’s Hospital in Washington, D.C. came to realize that Alzheimer’s disease is the single most common cause of dementia.

Scientists have since found other changes in the brains of AD patients. Connections between nerve cells are disrupted and nerve cells die in areas of the brain that are vital for memory and learning, including the hippocampus, which is a structure deep in the brain that controls short-term memory. Later, AD affects the cerebral cortex, particularly the areas responsible for language and reasoning. Eventually many areas of the brain become involved and atrophied (shrunken and dysfunctional).

The levels of the brain neurotransmitters serotonin, norepinephrine, and acetylcholine are also lower in AD. These chemicals transmit signals across the synapses or gaps between nerve cells. Many of the behavioral and psychiatric problems associated with AD are thought to result from low levels of these neurotransmitters. Acetylcholine and norepinephrine are important for many processes in the body including digestion, blood vessel dilation and constriction, and regulation of heartbeat.

Public awareness of AD increased significantly when Ronald Reagan (1911–2004), the 40th president of the United States (1981–1989), was diagnosed with the disease in 1994. He died from complications of AD at the age of 93. Because of the growing numbers of people who are affected by AD, their increasing life expectancy, and the direct and indirect costs of their care, Alzheimer’s disease is now considered to be a major public health concern.

Alzheimer’s disease places severe emotional and financial burdens on patients and their families. In 2007 the annual cost of caring for a patient with AD was estimated at $18,400 for mild or early-stage conditions and at $36,100 for a patient with severe AD. The total annual cost of caring for AD patients in the United States was estimated to be at least $100 billion, including both direct patient costs and indirect costs, such as time lost from work by caregivers. On average, Medicare pays more than three times as much for the healthcare of a beneficiary with AD compared to a beneficiary without AD.

Risk factors

The most significant risk factor for Alzheimer’s disease is advancing age. The risk of developing AD begins to rise after age 65 and rises sharply after age 75. There are various other possible risk factors:

  • About 25% of AD cases are considered to be familial (FAD), defined as having symptoms of Alzheimer’s disease in at least three generations of a single family. About 2–5% of all AD cases are familial early-onset FAD of one of three types (AD1, AD3, and AD4), in which the disease develops before the age of 60, usually between the ages of 40 and 50, but sometimes as early as age 30. First-degree relatives of AD patients may have as much as a 20% lifetime risk of being affected by the disease. The risk to immediate relatives increases as more family members develop the disease. The remaining 75% of cases are sporadic Alzheimer’s disease (SAD) with no clear family history.
  • African American and Caribbean Hispanics who have mutations in a particular gene are at a higher than normal risk for AD, particularly if they have a family history of the disease.
  • A family history of Parkinson’s disease is a risk factor for AD.
  • There is some evidence that neuronal damage from small strokes may be linked to AD.
  • Studies have found a clear correlation between low educational and occupational attainment (employment in jobs that are not mentally challenging) and an increased risk for AD. Taking on less challenging rather than more challenging jobs as one grows older is also associated with a higher risk for AD.
  • Studies on special breeds of genetically engineered (transgenic) mice have suggested high blood cholesterol levels may increase the rate of plaque deposition.
  • Researchers suspect that a high-cholesterol, high-fat diet may increase the risk of AD. However, studies have not found cholesterol-lowering drugs to have any affect on AD onset.
  • High systolic blood pressure combined with high blood cholesterol levels increases the risk of AD by three-four fold.
  • Obesity is a risk factor for AD.
  • Mild cognitive impairment (MCI), which is characterized primarily by memory loss while other cognitive functions remain intact, increases the risk of AD. About 12% of people with MCI develop Alzheimer’s disease each year. About 40% of people diagnosed with MCI have clear symptoms of AD after four years.
  • High levels of an amino acid called homocysteine may be a risk factor for late-onset AD.
  • Symptoms of AD may develop faster in people who have had a head trauma or hypothyroidism.
  • Down syndrome patients over the age of 40 all develop the brain cell changes that are characteristic of Alzheimer’s disease. Down syndrome-associated AD accounts for less than 1% of Alzheimer’s cases.

Various environmental factors have been suspected of contributing to the development of AD. However, epidemiological studies have not borne out any links between AD and factors such as pollutants in drinking water, aluminum from commercial products, and metal dental fillings. Although higher-than- average levels of aluminum have been found in the brains of patients with AD, it now appears that this a result rather than a cause of the disease. Alzheimer’sdisease

Causes and symptoms

In most cases the cause of AD is unknown. It is most likely caused by a combination of genetic and environmental factors. Viral, immunological, and/or biochemical etiologies have also been proposed. Genetics almost certainly plays a role, even in sporadic AD. Brain inflammation and restriction of blood flow to the brain may play a role in the development of beta-amyloid plaques and neurofibrillary tangles. Highly reactive molecules called free radicals damage all types of cells through oxidative processes, especially brain cells, which have lower levels of protective antioxidants.

AD symptoms can be grouped into three categories: cognitive deficits or losses in brain function related to memory and learning; behavioral and psychiatric symptoms of dementia or BPSD; difficulties with activities of daily life or ADL. For most of the twentieth century studies of AD patients focused on cognitive symptoms. It was not until the 1980s and 1990s that researchers began to examine behavioral and psychiatric symptoms more closely.

There are four major cognitive deficits associated with AD:

  1. Amnesia or memory impairment, including a loss of the sense of time.
  2. Aphasia or loss of language. Patients may not remember the names of objects and use words like ‘‘thing’’ or ‘‘it’’ instead. They may echo what other people say or repeat a word or phrase over and over. Sometimes patients lose all language except curses.
  3. Apraxia—the inability to perform voluntary movements. Patients with apraxia may have trouble putting on a hospital gown or brushing their teeth.
  4. Agnosia—the inability to recognize familiar people and places. Agnosia comes from the Greek word meaning ‘‘to not know.’’ Patients with agnosia may even fail to recognize their own face in a mirror.

Symptoms associated with BPSD (behavioral and psychiatric symptoms of dementia) include:

  • Depression. Depression in AD is believed to result, at least in part, from lowered production of serotonin.
  • Delusions, or a false belief that is maintained even in the presence of evidence to the contrary. For example, AD patients may believe that someone is stealing from them when they cannot remember where they put something.
  • Wandering. This behavior may result from becoming disoriented or lost, but sometimes AD patients wander for no apparent reason.
  • Hallucinations, or sensory experiences that seem real. Although hallucinations can affect any of the senses, most are visual or auditory. For example, AD patients may say that they see Martians in the corner of the room or hear the voices of their long-dead parents. Like delusions, hallucinations are believed to be related to the deterioration of brain tissue. However sometimes they are caused by medications.
  • Aggression—hitting, shoving, pushing, or threatening behavior.
  • Agitation. Emotionally excited behavior (screaming, shouting, cursing, pacing, fidgeting, etc.) that is disruptive or unsafe may result from brain tissue damage or be a symptom of depression. It is thought that the emotional overreactions of AD patients are related to destruction of neurons in the amygdala of the brain.

ADL (activities of daily life) or personal-care symptoms include difficulties with:

  • eating, including simple cooking and washing dishes
  • shopping for groceries and other necessities
  • bathing, showering, or shaving
  • grooming and dressing in clothing appropriate for the weather and activity
  • toileting
  • other aspects of personal hygiene such as teeth brushing, denture cleaning, or washing hair

Although the rate of AD progression and specific symptoms vary with the individual, the general course of the progression is fairly consistent. Early-onset AD often progresses faster than the more common late- onset type. AD is generally considered to have seven stages:

  1. Stage 1: no decline in function yet noted. This includes individuals who may carry predictive gene mutations but have no symptoms and those who will develop AD by other mechanisms.
  2. Stage 2: generally normal functioning. The individual is aware of a subtle cognitive decline.
  3. Stage 3: early Alzheimer’s disease. Patients have difficulty performing complex tasks that require cognitive skills.
  4. Stage 4: mild Alzheimer’s disease. Patients require assistance with tasks such as paying bills or balancing a checkbook.
  5. Stage 5: moderate Alzheimer’s disease. Patients require assistance in making everyday personal decisions such as choosing appropriate clothing or ordering from a restaurant menu.
  6. Stage 6: moderately severe Alzheimer’s disease. Patients require assistance dressing, bathing, and using the toilet and may have urinary and/or bowel incontinence.
  7. Stage 7: severe Alzheimer’s disease. Vocabulary shrinks to a few words, followed by little or no verbal communication. The ability to walk is lost, followed by an inability to maintain a sitting posture in a chair. Eventually the patient experiences a profound lack of purposeful muscle control, is totally dependent for care, and cannot smile or hold up his or her head.

AD usually starts slowly with a very gradual decline that is termed ‘‘insidious.’’ Some people are unaware of any impairment, blaming their forgetfulness on old age or ‘‘senior moments.’’ Often the earliest symptoms are recognized only in hindsight by a friend or family member. Furthermore, since the present generation at risk for AD is the first in history to understand the implications of the disease, there are very powerful emotional reasons for attributing early signs of AD to normal aging, job stress, adjusting to retirement, and other less troubling factors.

However the insidious nature of AD onset is a characteristic that helps physicians to distinguish it from other causes of dementia, including vascular dementia.

Key warning signs of early-stage AD include:

  • repeatedly asking the same question
  • repeatedly telling the same story, word for word
  • memory loss that affects job performance
  • loss of initiative inability to pay bills or balance a checkbook
  • misplacing commonly used personal or household objects
  • difficulty performing familiar tasks such as cooking, making repairs, or playing games like cards or checkers
  • poor or decreased judgment
  • problems with abstract thinking
  • getting lost in familiar surroundings
  • relying on others to make decisions or answer questions
  • disorientation of time and place
  • problems with language
  • mood or behavior changes
  • personality changes
  • neglecting personal hygiene—not bathing or changing clothes regularly

The first symptoms of early-stage AD usually include forgetfulness, short-term memory loss, temporary episodes of spatial disorientation, groping for words, minor problems with arithmetic, and small errors in judgment, often accompanied by some anxiety, agitation, mild depression, and withdrawal. The patient may light the stove under a saucepan while forgetting to add the food or water, but most ADL are unaffected. Some patients can continue to operate a motor vehicle safely, although many people with early-stage AD voluntarily give up driving.

Everyone has occasional memory lapses that do not signify any change in cognitive function. Early-stage AD may begin with routine memory lapses— forgetting where one left the car keys—but progresses to more profound or disturbing lapses, such as forgetting that one has a car. Some AD patients are unaware that their memory is failing. Other patients are keenly aware of their memory loss and may become anxious and frustrated. Becoming lost or disoriented on a walk around the neighborhood becomes more likely as the disease progresses. Individuals with AD may forget the names of family members or forget what was said at the beginning of a sentence by the time they hear the end. Although the progression of memory loss varies, it eventually begins to interfere with daily activities.

Middle-stage Alzheimer’s typically begins two to three years after the initial onset. Patients begin to lose awareness of their cognitive deficits. Memory loss, especially of recent events, becomes more severe and is accompanied by moderate spatial and temporal disorientation, loss of ability to concentrate, aphasia, and increased anxiety. Severe language problems develop. Patients cannot understand or remember the names of things. Their speech may not flow smoothly. Because of individual variation in disease progression, some patients may still be able to carry out routine behaviors and engage in generalized conversation. However they can no longer drive a car, cook a meal, or read a newspaper. They are unable to work, plan and execute familiar tasks, and reason and exercise judgment. They may get lost easily and find simple things confusing. The loss of cognitive functioning becomes impossible to ignore. Mood and personality are affected. Some people become angry or violent. Behavioral and psychiatric symptoms include agitation, wandering, temper tantrums, depression, and disorientation. Patients begin to lose their basic sense of personal identity. They may be at high risk for falls and other accidents. A small number of AD patients have vision problems. Although they frequently deny that they cannot see, autopsies confirm destruction in areas of the brain that process visual images.

Eventually spatial and temporal disorientation becomes profound and may be accompanied by delusions, hallucinations, and paranoia. Patients may not recognize a family member or may accuse a spouse of infidelity. They may become uninhibited and confrontational. Some patients exhibit inappropriate sexual behaviors. AD patients may have trouble sleeping and suffer from nighttime confusion or agitation called sunsetting or sundowner’s syndrome. Some patients repeat words, thoughts, or movements, a behavior known as perseveration. Eventually they are unable to feed, bathe, dress, or groom themselves and cannot be left unattended.

In end-stage Alzheimer’s disease patients undergo general physical decline and lose control of many physical functions. Seizures and hypertonicity (increased muscle movements) are common. Bladder and bowel control is lost and stiffening muscles prevent walking. Patients who can walk often wander aimlessly and must be monitored for night wandering due to altered sleep patterns. Although some patients may use a wheelchair temporarily, eventually they become completely bedridden, unable even to sit up. Many patients are unable to talk. Abnormal jerking movements may occur for no reason or in response to touch or noises. Reflexes may be exaggerated and some patients experience whole body contractions known as generalized seizures.

Once the disease affects the brain stem, the basic processes of digestion, respiration, and excretion shut down. Patients may be unable to eat or swallow and they sleep most of the time. Their hands and feet feel cold, breathing becomes shallow, and the patient is generally unresponsive. Death often results from infection, pneumonia, or malnutrition. Otherwise breathing simply stops. From the onset of initial symptoms, disease progression can last up to 25 years, although the typical duration is eight to 10 years.

Genetic profile

Familial early-onset Alzheimer’s disease accounts for fewer than 10% of AD cases. It can be caused by mutations in one of three genes. It is usually an autosomal dominant trait. Autosomal means that it affects males and females with equal frequency. Dominant means that it will affect individuals even if they inherited one copy of the mutated gene from one parent and a normal copy of the gene from the other parent. Individuals who have two copies of the mutant gene will pass on the gene to all of their children. If each parent has one copy of the mutant gene, there is a 75% that any of their children will inherit the gene. If only one parent has one copy of the gene, each of their children has a 50% of inheriting the gene.

Identification of these three genes has led to the subdivision of familial early-onset AD into three categories:

  1. AD1 is a genetic defect in the amyloid precursor protein (APP) gene located on chromosome 21. Mutations in the APP gene are associated with AD onset between the ages of 55 and 60.
  2. AD3 is a genetic defect in the presenilin 1 (PSEN1) gene located on chromosome 14. Presenilin 1 may be one of the enzymes that clips APP into beta-amyloid. It also may be important for the functioning of synaptic connections between neurons.
  3. AD4 is an extremely rare genetic defect in the presenilin 2 (PSEN2) gene located on chromosome 1. Presenilin 2 is also involved in processing APP. Mutations in PSEN1 and PSEN2 are associated with AD onset between the ages of 30 and 50. These three mutations result in the production of abnormal proteins and increased amounts of beta-amyloid. Together they account for approximately 50% of early-onset FAD.

AD2 is familial late-onset Alzheimer’s disease, accounting for 15–25% of all AD cases. An association has also been found between AD2 and mutations in the gene encoding apolipoprotein E (APOE), located on chromosome 19. Apolipoprotein E is a major part of a lipoprotein that removes excess cholesterol from the blood. There are at least three forms or alleles of the APOE gene: e2, e3, and e4. Since each person inherits one APOE gene from each parent, it is possible to have two copies of one form of the APOE gene or two different forms of the gene. APOE e3 is the most common allele in the general population and does not appear to affect the development of AD. The relatively rare APOE e2 allele may be associated with a lower risk for AD or a later age of onset. Individuals with one copy of the e4 gene are three times more likely to develop late-onset AD than those without it. Those with two copies of APOE e4 gene are almost four times more likely to develop AD. APOE e4 can also lower the age of onset by as much as 17 years. Although APOE e4 increases the risk of developing AD, it does not cause the disease. Not everyone with e4 develops AD. However about 65% of all people with AD have at least one copy of e4. There are various theories as to why APOE e4 increases the risk of developing AD: it may facilitate beta-amyloid buildup in plaques, thereby lowering the age of AD onset, or it may interact with cholesterol levels and have effects on neuronal death that are independent of its effects on plaque buildup.

Sporadic AD is referred to as a polygenic disorder because it is believed to result from the effects of multiple genes combined with environmental factors. This view is supported by research involving identical twins. Only one-third of identical twins of those with AD develop AD themselves. This suggests that factors other than genetic predisposition affect the development of SAD.

AD researchers are also interested in the SORL1 gene, which encodes a protein that is involved regulating the transport of APP and lipoproteins in cells and may play a role in late-onset AD. Down syndrome-associated Alzheimer’s is another genetically determined form of AD. Normal individuals have two copies of each of the 22 human chromosomes, one copy from each parent. People with Down syndrome, also called trisomy 21, have three copies of chromosome 21, which results in brain changes that are similar to those that occur in both familial and sporadic AD. This is thought to be due to the over-production of APP from the extra chromosome 21 APP gene.

Diagnosis

An early and accurate diagnosis of AD is important for developing strategies for managing symptoms and helping patients and their families plan for treatment, long-term care, and financial concerns while the patient can still be involved in decision making. A diagnosis of AD also may help family members to avoid unnecessary anger and feelings of impotence when dealing with the progression of the disease.

A diagnosis of AD is based upon the finding of slowly progressive dementia, exclusion of other possible causes for dementia, and brain-imaging studies that show changes in the structure of the brain, usually in the form of shrinkage. Possible AD is diagnosed when AD is considered to be the primary cause of the symptoms, but the diagnosis is complicated by the presence of another disorder. Probable AD is diagnosed when physicians and psychiatrists have ruled out all other disorders that could produce similar symptoms.

Examination

Diagnosis of Alzheimer’s disease can be quite complex and require consultations with various specialists. It requires a complete physical examination and medical and family history, including family members who have had AD and their ages of onset. The results of neurological exams are generally normal in early-stage AD. A complete evaluation of alcohol use and prescription and over-the-counter medication history, including alternative remedies, vitamins, herbal supplements, or illicit drugs, is necessary to rule out other causes of dementia, because more than 150 drugs can cause AD-like symptoms. Diagnosis is based upon clinical findings of otherwise unexplained slowly progressing dementia. FAD is diagnosed if there is a family history of the disease. Although AD virtually always develops in Down syndrome patients over age 40, it may be difficult to determine whether further impairment is due to the Down syndrome or the progression of AD.

Other types of dementia, including some that are reversible, can cause symptoms similar to those of AD. Approximately 20% of patients originally suspected of having AD turn out to have some other disorder, about half of which are treatable:

  • Multi-infarct vascular dementia is caused by strokes (blood clots in the brain) that lead to stepwise destruction of mental capacities.
  • Diffuse white matter disease is a form of vascular dementia that can be diagnosed by magnetic resonance imaging (MRI) that reveals the generalized death of large parts of the brain.
  • Parkinson’s disease is a neurodegenerative condition that causes movement and functional abnormalities. Most Parkinson’s patients have tremors and rigidity in their arms and legs.
  • Alcohol-associated dementia is caused by nutritional deficiencies in alcoholics, especially malnutrition and deficiencies in vitamins B1 (thiamine) and B12 (cobalamin) and niacin (nicotinic acid). It is potentially reversible.
  • Chronic use of certain drugs such as tranquilizers, sedatives, and pain relievers, as well as drug interactions, can cause potentially reversible dementia.
  • Endocrine abnormalities (hormone imbalances), especially thyroid dysfunction, are less common causes of dementia. They can be diagnosed by blood tests.
  • Chronic infections of the central nervous system, tertiary syphilis, trauma or injury to the brain, brain tumors, psychiatric conditions such as depression (pseudodementia or dementia of depression), and genetic and degenerative disorders other than AD can also cause dementia.

Evaluations for depression and delirium (reduced consciousness or awareness of one’s environment) are particularly important components of the diagnostic process because, although they may be symptoms of AD, they can also be mistaken for AD. Depression and memory loss are both common among the elderly and a combination of the two can lead to a mistaken diagnosis of AD. Depression can be treated with drugs, although some antidepressants may worsen dementia, further complicating both diagnosis and treatment.

The clinical evaluation will assess cognitive impairment other than short-term memory loss. A family member or close friend of the patient often will be questioned about the onset and duration of symptoms. A neuropsychiatric examination may be performed to determine the pattern of cognitive impairment and probe the patient’s level of functioning. Patients may be asked to write a sample check, describe how they answer the telephone, interpret sample traffic signs, or pick out items on a shopping list from a display.

Tests

Blood and urine tests are used to help rule out other causes of dementia. Genetic tests are available to detect genes known to cause AD. However the APOE e4 gene is not used for diagnostic purposes, since even two copies of gene do not necessarily predict the development of AD.

Several types of oral and written tests are used to help diagnose AD and track its progression, including tests of mental status, functional abilities, memory, verbal fluency, and concentration. In early-stage AD the results of these tests are usually within the normal range. The widely used mini-mental status examination (MMSE) is a screening test. It is not particularly sensitive for detecting cognitive impairment in well-educated individuals who have previously functioned at a high level. It may also not yield accurate results for poorly educated individuals or cultural minorities. The clock test asks patients draw the face of a clock, possibly including a specific time such as 3:20. Patients with AD often put the numbers out of order, put them all in one part of the clock face instead of evenly spaced, or have difficulty drawing in the clock hands.

Occasionally the cerebrospinal fluid is tested for the levels of two proteins, Tau and a specific beta-amyloid protein fragment called A beta 42. Increased Tau protein and decreased A beta 42 in the cerebrospinal fluid are indicative of AD.

Procedures

Brain neuroimaging studies such as positron emission tomography (PET), MRI, single photon emission computed tomography (SPECT) scans, or computed topography (CT) scans may be used to detect gross cerebral cortex atrophy due to brain cell death. PET scans can detect the earliest changes in brain structure. MRI scans are often performed on patients who are having problems with balance or gait. MRIs can detect diffuse atrophy that is often present in the cerebrum of the brain of AD patients. PET and SPECT scans can be used to evaluate patterns of glucose (sugar) metabolism in the brain to differentiate patterns characteristic of AD from those associated with vascular dementia and Pick’s disease. PET scans are more precise than SPECT scans but are more expensive. However imaging alone cannot diagnose AD. MRI and CT scans and electroencephalographs (EEGs), which measure the electrical activity in the brain, can be useful for excluding other causes of dementia such as stroke, subdural hematoma, and brain tumors.

Although a skilled physician can diagnose probable AD with 90% accuracy, a definitive diagnosis of Alzheimer’s disease requires a brain autopsy after death and examination of the brain tissue by a histopathologist. The presence of a large number of beta-amyloid plaques and intraneuronal neurofibrillary tangles are considered diagnostic of AD. Antibodies that bind to the specific amyloid proteins are tagged with a fluorescent or colorimetric molecule and visualized in a microscope. In addition, the longer the disease has progressed, the smaller the brain is at death.

A study published in The Archives of Neurology in August 2010 found that a spinal fluid test can be 100 percent accurate in identifying patients with significant memory loss who are on their way to developing Alzheimer’s disease. The test is one of many ways the the diagnosis of AD is moving from only being positive after death. Much work lies ahead, researchers say: making sure the tests are reliable if used in doctors’ offices, making sure the research findings hold up in real-life situations, getting doctors and patients comfortable with the notion of spinal taps, the method used to get spinal fluid. In addition to spinal fluid tests, new PET scans of the brain that show the telltale amyloid plaques are being developed, which are a unique feature of the disease. And researches are testing hundreds of new drugs that might change the course of the brain cell death associated with this disease. Breakthroughs in research have been rather stagnent, but as of 2010-2013, this research field had a flurry of new studies.

Treatment

Traditional

Although there is no cure for Alzheimer’s disease, early diagnosis and prompt intervention can slow its progression and enable patients to function independently for a longer period. Healthcare professionals usually assess a patient’s activites of daily living (ADL) to determine what type of care is needed. The mainstay of treatment is the establishment of daily routines, good nursing care and/or home-care strategies, and providing physical and emotional support. In the initial stages, counseling by a psychologist or an AD support group is recommended. The patient and caregiver should establish a relationship with a primary-care provider so that illnesses, such as urinary or respiratory infections, can be properly diagnosed and treated rather than being simply attributed to the inevitable decline of AD. Neurological and behavioral aspects of AD, including anxiety, agitation, defiant behavior, insomnia, hallucinations, and seizures are treated on an as-needed basis.

Treatment of AD is a very active area of research and the National Institutes of Health (NIH) and other agencies sponsor numerous clinical trials of new drugs and therapies. A list of current clinical trials enrolling volunteers can be found at http://clinicaltrials.gov

Drugs

The most common drugs prescribed for AD are inhibitors of acetylcholinesterase and butylcholinesterase, enzymes that break down the neurotransmitters acetylcholine and butylcholine, respectively. These medications increase levels of acetylcholine in the brain, thereby improving brain function in early-stage mild-to-moderate AD:

  • galantamine (Razadyne, formerly known as Reminyl)
  • rivastigmine (Exelon)
  • donepezil hydrochloride (Aricept)

Memantine (Namenda) is used to treat moderate-to-severe AD. It acts on glutamate, another brain neurotransmitter. It is used alone or in combination with donepezil.

These drugs can modestly increase attention span, concentration, mental acuity, and information processing and improve the ability to perform normal ADL. They slow the progression of symptoms for about six months to one year in one-third to one-half of patients with AD. All have side effects, most often mild diarrhoea, nausea, vomiting, muscle cramps, dizziness, headache, fatigue, and sleep disturbances. Tacrine (Cognex), the first such drug, is no longer prescribed because of the risk of liver toxicity.

The antioxidant vitamin E may delay AD onset by protecting neurons from free-radical damage. AD patients have lower blood levels of vitamin E than other adults of the same age. One large two-year study of moderately affected AD patients found that taking 2000 IU (international units) of vitamin E daily significantly delayed disease progression as compared with patients taking a placebo. However, high levels of vitamin E can put patients at higher risk for bleeding disorders. Vitamin E therapy, in combination with cholinesterase inhibitors, has become the standard treatment for AD.

Drugs previously used to treat AD—including selegiline (a drug for Parkinson’s disease), prednisone, estrogen, and nonsteroidal anti-inflammatory drugs (NSAIDs)—have been found to be ineffective.

Medications can be prescribed to manage the behavioral and psychiatric symptoms of AD, which are often very stressful for caregivers. These medications are usually prescribed for specific symptoms:

  • typical antipsychotics—usually haloperidol (Haldol), risperidone (Risperdal), olanzapine, or quetiapine— for anxiety, aggression, delusions, or hallucinations
  • short-term antianxiety drugs, usually lorazepam (Ativan) or buspirone (BuSpar), for agitation
  • a selective serotonin reuptake inhibitor (SSRI), such as citalopram or sertraline, at half the adult dosage, for depression, which is common in early-stage AD
  • acetaminophen or a very low dose of codeine for pain

Patients with AD are more susceptible to the side effects of medications, especially psychoactive drugs, and are usually given lower doses than younger adults. Physicians often recommend first trying to reduce behavioral symptoms with changes to the patient’s environment.

Alternative

Antioxidants have shown some degree of effectiveness in treating AD. Antioxidants, in addition to vitamin E, include:

  • vitamin C
  • selenium
  • green tea
  • ginkgo biloba extract

Derived from the leaves of the Gingko biloba tree, gingko also increases blood and oxygen flow to the brain and has anti-inflammatory and neuroprotective effects. It has been used for many years in China, is widely prescribed in Europe for circulatory problems, and is the most common herbal treatment for AD. However a large-scale, well-designed 2008 study found that Ginkgo extract neither prevented nor delayed AD.

Other supplements for treating AD include:

  • Huperzine A, from the club moss Huperzia serrata, is a natural cholinesterase inhibitor that has been reported to produce greater improvement than synthetic cholinesterase inhibitors at doses of 0.1–0.4 milligrams (mg) daily and has few side effects. Side effects may include nausea, muscle cramps, vomiting, and diarrhoea. Like ginkgo biloba, it is an unregulated herb and preparations may have widely varying amounts of active ingredients.
  • Thiamine (vitamin B1) in daily doses of 3 grams (g) for two to three months have been shown in small studies to improve mental function and AD assessment scores; however other studies have found no effect. Side effects can include nausea and indigestion.
  • Cobalamin (vitamin B12) improved memory and mental function in AD patients in some studies but not in others.
  • Acetyl L-carnitine is similar in structure to acetylcholine and some studies have indicated that 2–3 g daily slows the progression of AD in patients who developed the disease before age 66. Patients who developed AD after age 66 worsened with the treatment. Side effects include increased appetite, body odor, and rash.
  • DHEA (dehydroepiandrosterone) is a steroid hormone. Although a link between decreased levels of DHEA in the elderly and AD has been suggested, no studies have been performed. Side effects include acne, hair growth, irritability, insomnia, headache, and menstrual irregularities.
  • Melatonin is a hormone that helps regulate mood and sleep cycles. The usual dose is 3 mg one to two hours before bed. Side effects are drowsiness, confusion, headache, decreased sex drive, and decreased body temperature.

Naturopathic treatment for AD includes supplementation with antioxidant vitamins (A, C, and E), carotenoids, small amounts of selenium and zinc, and thiamine. Some alternative practitioners advise people with AD to also take supplements of phosphatidyl-choline, gotu kola, ginseng, St. John’s Wort, rosemary, saiko-keishi-to-shakuyaku (a Japanese herbal mixture), and folic acid. However none of these have met the safety and effectiveness standards of conventional Western medicine.

The incidence of AD is lower in countries with diets that are lower in calories and fats. There have been a few reports suggesting that diets rich in fish improve mental function in patients with AD or dementia and AD patients treated with essential fatty acids have shown greater improvement in mood and mental function than patients on placebos. Because of its disease-preventing properties, red wine in moderation may also benefit AD patients. Patients with AD should avoid environmental toxins such as tobacco smoke.

A variety of other therapies may be beneficial in the treatment of psychological symptoms of AD:

  • Music therapy has been found to calm agitated AD patients and improve mood, reduce chronic pain, depression, agitation, wandering, and feelings of isolation, and enhance long-term memory. Old familiar songs can be particularly effective in improving recall
  • Light therapy in the evening can help alleviate sleep-cycle disturbances
  • Supportive therapies include touch, compliments, and displays of affection
  • Sensory stimulation through massage and aromatherapy may be beneficial
  • Socio-environmental therapies include activities related to the patient’s previous interests and favorite foods, as well as pleasant surroundings
  • Cognitive therapy can reduce negative perceptions and teach coping strategies
  • Insight-oriented psychotherapy addresses patients’ awareness of their disease
  • Dance therapy, validation therapy, reminiscence therapy, and reality-oriented therapy have also been used with AD patients

Home remedies

About 70% of AD patients are cared for at home, with the remainder residing in various types of insti- tutions. Creative strategies are necessary to help the patient stay as independent as possible. Caregivers need their own support systems to minimize anger, despair, and burnout. Becoming familiar with likely future scenarios and considering financial and legal issues early on can ease the burden on both the patient and the family.

In the early stages of AD when memory loss is minimal, it is helpful for family and friends to interact with patients as much as possible, reminding them to eat, take their medication, keep their appointments, and help sustain daily living activities. Keeping records is helpful, particularly when there are several caregivers. The household should be organized so that important items can be found easily. The patient will need help in managing finances. Providing neighbors with a house key and setting up a schedule to check in on the patient are recommended. With the help of family, neighbors, and community resources, many people with early AD are able to maintain a successful lifestyle in their home environment for months or years.

Basic safety concerns for AD patients include:

  • falls
  • ingestion of dangerous substances
  • wandering from home and becoming lost
  • injuring one’s self or others with sharp objects, fire, or burns
  • the inability to respond rapidly to crisis situations

Often families have to modify their homes because of safety concerns:

  • grab bars in bathrooms, bed rails, and clutter-free passageways
  • electrical appliances that are unplugged and put away when not in use matches, lighters, knives, or weapons stored out of reach
  • lowered hot water heater temperature to avoid accidental scalding
  • a list of emergency numbers, including the poison control center and hospital emergency room, posted by the phone

Patients who have been diagnosed with AD should never be allowed to drive because of the danger of accidents or becoming disoriented. Some local chapters of the Alzheimer’s Association offer help with transportation.

A calm, structured environment with simple orientation aids such as calendars and clocks can help reduce anxiety and increase safety. Labeling cabinets and drawers can help patients focus their attention. Signs can be posted reminding patients of important phone numbers and to turn off appliances and lock doors. Scheduling meals, bathing, and other activities at regular times and places provides routine and emotional security, since unfamiliar places and activities can be disorienting. Caregivers should develop a daily routine and take advantage of periods during the day when the patient is less confused and more cooperative. The most severe symptoms often occur at night. Sleep disturbances may be minimized by keeping the patient engaged in activities during the day. Daily supervised walks are a good general exercise for people with AD.

A loss of grooming skills—mismatched clothing, unkempt hair, and decreased interest in personal hygiene—is often one of the early symptoms of AD. Caregivers, especially spouses, may find these changes socially embarrassing and difficult to cope with. The caregiver will increasingly assume grooming responsibilities as the disease progresses.

Feeding may require using a colored plate to focus the patient’s attention on the food. Finger foods may be preferable to the use of utensils. A nutritionist can give advice on well-balanced, easily prepared meals. Eventually the caregiver may need to feed the patient. As movement and swallowing become difficult, a feeding tube may be placed into the stomach through the abdominal wall.

Incontinence presents the most difficult problem for many caregivers and is a major reason for moving to nursing-home care. In the early stages, limiting fluid intake and increasing the frequency of toileting can help. Careful attention to hygiene is important to prevent skin irritation and infection from soiled clothing.

Family members or other caregivers have a difficult and stressful job, which becomes harder still as the disease progresses. Caring for dementia patients is significantly more demanding and time-consuming than caring for patients with other illnesses. Each day may bring new challenges as the patient’s ability levels decrease and new patterns of behavior develop. Many caregivers find the constant but unpredictable demands extremely difficult. The personality changes of AD can be heartbreaking for family members as a loved one deteriorates, seeming to become a different person. As the disease progresses, the patient’s behavior may become increasingly erratic. It may be impossible to leave a patient unattended for even a few minutes because they may wander off. Neighbors should always be informed of the person’s condition. However not all AD patients develop negative behaviors: some become gentle, spending increasing amounts of time in dreamlike states.

Caregivers often develop feelings of anger, resentment, guilt, and hopelessness. Depression is common and may need to be treated. Caregivers can become susceptible to illness, especially if they do not receive adequate support from family, friends, and community. Support groups can help caregivers deal with stress. The location and contact numbers for AD care-giver support groups are available from the Alzheimer’s Association, local social service agencies, physicians, and pharmaceutical companies that manufacture the drugs used to treat AD.

Most families eventually need outside help to care for the AD patient. Personal-care assistants, either volunteer or paid, may be available through local social service agencies. Adult daycare facilities are becoming increasingly common. Meal delivery, shopping assistance, or respite care may also be available. Special Alzheimer’s disease facilities are available for both respite daycare and permanent long-term care.

The decision to move the patient to a nursing home is often one of the most difficult for the family, who may consider that they have failed in their obligations and are abandoning their loved one. Counseling with a physician, clergy, or other trusted adviser can ease this transition. Selecting a nursing home may require a difficult balancing of costs, services, location, and availability. Keeping the entire family involved in the decision may help prevent further stress later.

Social Security Disability, Medicare, Medicaid, or Supplemental Security Income may provide financial assistance, but will not usually cover nursing home care indefinitely. Long-term care insurance, if purchased prior to diagnosis, reverse mortgages, or other financial devices may be appropriate.

Prognosis

There is no cure for Alzheimer’s disease and once the symptoms develop patients do not recover. The goal is to maintain cognitive and physical function for as long as possible. Although there is considerable variation in the rate of disease progression, symptoms continue to worsen, usually over a period of years. Eventually loss of brain cells and brain damage result in the impairment of autonomic body functions, the failure of various organ systems, coma, and death. Most AD patients die within eight to 10 years of diagnosis, although that interval can be as short as one year or as long as 20 years. The life expectancy of AD patients is increasing because the disease is generally being diagnosed at an earlier stage.

The most common cause of death among AD patients is infection. People with AD are often in poor health and may be malnourished, which puts them at increased risk of life-threatening infections such as pneumonia. They are also susceptible to other conditions and diseases of old age. The consequences of cancer, stroke, and heart disease can be more severe in patients with AD than in otherwise healthy people. Alzheimer’s disease

Prevention

There is no known prevention for Alzheimer’s disease. Several studies have suggested that high-fat and high-calorie diets may increase the risk of developing AD. Other possible risk factors include alcohol, salt, and refined carbohydrates. Some studies have found that fish consumption reduces the incidence of AD in Europe and North America, possibly due to the omega-3 fatty acids found in fish. It is also possible that staying physically and mentally active throughout life may lower the risk of AD.

Individuals with a history of Alzheimer’s disease in their families may want to consider genetic counseling to clarify possible risk factors and determine the appropriateness of available genetic tests. Since the APOE e4 gene is merely a risk factor for AD, it is not considered useful for predicting whether a person will develop the disease.

The US National Institute on Aging does not recommend using the test to screen people because:

  • it does not predict whether an individual will develop AD
  • there are ethical implications to testing for a disease that is currently incurable
  • it may have adverse psychological consequences for patients and their families
  • it could lead to discrimination in employment or health insurance for carriers of the gene

Research on the prevention of AD has focused on blocking the production of amyloid protein in the brain and on breaking down beta-amyloid after it is released from cells but before it has a chance to aggregate into insoluble plaques.

Health care team roles

Treatment of AD is a team effort, involving primary-care physicians, nurses, imaging and laboratory technicians, gerontology specialists, psychiatrists, psychologists, and caregivers. Educating patients and care-givers about the nature of the disease and its progression usually falls on the nursing staff. Nurses are also the first line of access for medical care and support groups. Social workers, counsellors, and support group facilitators may provide emotional support, practical advice, and information about community resources. Specialized Alzeimer’s disease facilities may be used for either respite daycare or permanent long-term care.

Key terms

  • Acetylcholine—A neurotransmitter with effects that are generally opposite those of dopamine and norepinephrine. Acetylcholine dilates blood vessels, lowers blood pressure, and slows heartbeat.
  • Agitation—Excessive restlessness or emotional disturbance that is often associated with anxiety or psychosis; common in middle-stage AD.
  • Agnosia—Inability to recognize familiar people, places, and objects.
  • Amnesia—Partial or complete loss of memory or gaps in memory.
  • Amygdala—An almond-shaped brain structure of the limbic system that is activated in stressful situations and triggers fear.
  • Antioxidant—A substance that prevents the destructive effects of oxidative chemicals in the body.
  • Aphasia—Loss of language abilities.
  • Apolipoprotein E (APOE)—A protein that transports cholesterol throughout the body. One form of this protein, APOE e4, is associated with a 60% risk of late-onset AD.
  • Apraxia—An inability to perform purposeful movements that is not caused by paralysis or loss of feeling.
  • Autosomal dominant—A gene located on a chromosome other than the X or Y sex chromosomes, whose expression is dominant over that of a second copy of the same gene.
  • Beta-amyloid plaques—Senile plaques; structures in the brain, composed of dead or dying nerve cells and cell debris surrounding deposits of beta-amyloid protein, that are diagnostic of AD. Beta-amyloid forms when amyloid precursor protein (APP) is not broken down properly.
  • Brain stem—The part of the brain that connects to the spinal cord and controls most basic bodily functions. It is the last part of the brain to be destroyed by AD.
  • Cholinesterase inhibitors—Drugs that may slow the progression of AD by inhibiting the enzymes that break down acetylcholine.
  • Computed topography (CT) scan—A scan that used x rays and a computer to form detailed images of a part of the body.
  • Delirium—A disturbance of consciousness marked by confusion, inattention, delusions, hallucinations, and agitation. It is distinguished from dementia by its relatively sudden onset and variation in the severity of symptoms.
  • Delusion—A persistent false belief held in the face of strong contradictory evidence.
  • Dementia—A group of symptoms (syndrome) associated with a chronic progressive impairment of memory, reasoning ability, and other intellectual functions, personality changes, deterioration in personal grooming, and disorientation.
  • Donepezil hydrochloride (Aricept)—A drug that increases the levels of acetylcholine in the brain.
  • Down syndrome—A genetic disorder characterized by an extra chromosome 21 (trisomy 21), mental retardation, and susceptibility to early-onset AD.
  • Free radicals—Reactive atoms or molecules with unpaired electrons that damage cells, proteins, and DNA.
  • Genetic disease—A disease caused by genes inherited from one or both parents.
  • Ginkgo—An herb from Ginkgo biloba, a shade tree native to China with fan-shaped leaves and fleshy seeds with edible kernels. Some alternative practitioners recommend ginkgo extract for preventing and treating AD.
  • Hallucination—False sensory perceptions; hearing sounds or seeing people or objects that are not there. Hallucinations can also affect the senses of smell, touch, and taste.
  • Hippocampus—A part of the brain’s limbic system that is involved in memory formation and learning.
  • Insidious—Progressing gradually and inconspicuously, but with serious effects.
  • Magnetic resonance imaging (MRI)—An imaging technique that uses electromagnetic radiation and a computer to obtain detailed images of soft tissues such as the brain.
  • Mild cognitive impairment (MCI)—A transitional phase of memory loss in older people that precedes dementia or AD.
  • Neurofibrillary tangles—Accumulations of twisted protein fragments inside nerve cells in the brain that are diagnostic of AD.
  • Neuron—A nerve cell.
  • Neurotransmitters—Chemicals that carry nerve impulses from one nerve cell to another. AD causes a drop in the production of several important neurotransmitters.
  • Norepinephrine—A neurotransmitter and adrenal hormone and the precursor of epinephrine.
  • Perseveration—Continuous involuntary repetition of speech or behavior.
  • Polygenic—A trait or disorder that is determined by several different genes. Most human characteristics, including height, weight, and general body build, are polygenic. Schizophrenia and late-onset AD are considered polygenic disorders.
  • Positron emission tomography (PET)—A method of medical imaging capable of displaying the metabolic activity of organs and useful for investigating brain disorders.
  • Presenile dementia—The original name for Alzheimer’s disease.
  • Presenilin (PSEN)—Presenilin 1 and presenilin 2 are proteins that are involved in processing amyloid precursor protein (APP). Mutations in the genes encoding these proteins can cause early-onset AD.
  • Pseudodementia—Depression with symptoms resembling those of dementia. The term ‘‘dementia of depression’’ is now preferred.
  • Serotonin—A neurotransmitter found in the brain and blood. Low levels of serotonin are associated with AD.
  • Sunsetting—Confusion or agitation in the evening.
  • Systolic—Referring to the rhythmic contraction of the heart (systole) as the blood in the chambers is forced out. Systolic blood pressure is blood pressure measured during the systolic phase.
  • Tau protein—A protein involved in maintaining the internal structure of nerve cells. Tau protein is damaged in AD and forms neurofibrillary tangles.
  • Tomography—A technique for producing a focused image of the structures at a specific depth within the body, while blurring details at other depths.

Read a technical article about Alzheimer's disease and other types of dementia

Resources

Books 

Calo-oy, Starr, and Bob Calo-oy. Caregiving Tips A-Z, Alzheimer’s & Other Dementias. Fremont, CA: Orchard Publications, 2008.

Chan, A. P. Alzheimer’s Disease Research Trends. Hauppauge, NY: Nova Science, 2008.

Dawbarn, David, ed. Neurobiology of Alzheimer’s Disease, 3rd ed. New York: Oxford University Press, 2007.

Doraiswamy, P. M., et al. The Alzheimer’s Action Plan: The Experts’ Guide to the Best Diagnosis and Treatment for Memory Problems. New York: St. Martin’s Press, 2008.

Lerner, Adrienne. Alzheimer’s Disease. Farmington Hills, MI: Greenhaven Press, 2008.

Mace, Nancy L., and Peter V. Rabins. The 36-Hour Day: A Family Guide to Caring for Persons with Alzheimer Disease, Related Dementing Illnesses, and Memory Loss in Later Life, 3rd ed. New York: Warner Books, 2006.

McCann-Beranger, Judith. A Caregiver’s Guide to Alzheimer’s & Related Diseases. New York: Bunim & Bannigan, 2008.

Sabbagh, Marwan. The Alzheimer’s Answer: Reduce Your Risk and Keep Your Brain Healthy. Hoboken, NJ: Wiley, 2008.

Taylor, R. Alzheimer’s from the Inside Out. Baltimore: Health Professions Press, 2006.

Whitehouse, Peter J., and Daniel George. The Myth of Alzheimer’s: What You Aren’t Being Told About Today’s Most Dreaded Diagnosis. New York: St. Martin’s Press, 2008.

Periodicals

Arnst, Catherine. ‘‘Is Alzheimer’s a Form of Diabetes? If So, an Insulin-Centered Treatment Could Alter the Course of the Disease.’’ Business Week (December 17, 2007): 54.

Ault, Alicia. ‘‘Debate Continues Over Early Cognition Screening: Some Argue That Obtaining a Timely Baseline Could Offset Subsequent Delays in Diagnosing Alzheimer’s.’’ Family Practice News (December 15, 2007): 27.

Bain, L. J., et al. ‘‘Towards an Earlier Diagnosis of Alzheimer Disease.’’ Alzheimer Disease and Associated Disorders 22, no. 2 (April-June 2008): 99-110.

Christensen, Daniel D., and Peter Lin. ‘‘Practical Treatment Strategies for Patients with Alzheimer’s Disease.’’ Journal of Family Practice (December 2007): 17-23.

Frisoni, J. B., and J. L. Whitwell. ‘‘How Fast Will It Go, Doc? New Tools for an Old Question from Patients with Alzheimer Disease.’’ Neurology 70, no. 23 (June 2008): 2194-2195.

Grady, Denise. ‘‘Finding Alzheimer’s Before a Mind Fails.’’ New York Times (December 26, 2007): A1+.

Ji, Hong-fang, and Hong-yu Zhang. ‘‘Multipotent Natural Agents to Combat Alzheimer’s Disease: Functional Spectrum and Structural Features.’’ Acta Pharmacologica Sinica (February 2008): 143-151.

Kontush, Anatol, and Svetlana Schekatolina. ‘‘An Update on Using Vitamin E in Alzheimer’s Disease.’’ Expert Opinion on Drug Discovery (February 2008): 261-271.

Palmer, K., et al. ‘‘Mild Cognitive Impairment in the General Population: Occurrence and Progression to Alzheimer Disease.’’ American Journal of Geriatric Psychiatry 16, no. 7 (July 2008): 603-611.

Schwab, C., and P. L. McGeer. ‘‘Inflammatory Aspects of Alzheimer Disease and Other Neurodegenerative Disorders.’’ American Journal of Alzheimer’s Disease & Other Dementias 13, no. 4 (May 2008): 359-369.

Other

‘‘Alzheimer’s Disease.’’ American Health Assistance Foundation. http://www.ahaf.org/alzheimers

‘‘Alzheimer’s Disease.’’ MedlinePlus. http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html#cat25

‘‘Alzheimer’s Disease.’’ NIH Senior Health. http://nihseniorhealth.gov/alzheimersdisease/toc.html

The Alzheimer’s Disease Bookstore. http://www.alzheimersbooks.com

Organizations 

Alzheimer’s Association, 225 N. Michigan Ave., Fl. 17, Chicago, IL, 60601-7633 (312) 335-8700 (800) 272-3900 (866) 699-1246, info@alz.org, http://www.alz.org

Alzheimer’s Australia, PO Box 4019, Hawker, ACT, Australia, 2614 61 (2) 6254-4233 (1800) 100-500 (Australia only), http://www.alzheimers.org.au

Alzheimer’s Disease Education and Referral Center, National Institute on Aging, PO Box 8250, Silver Spring, MD, 20907-8250 (800) 438-4380, adear@nia. nih.gov, http://www.nia.nih.gov/Alzheimers

Alzheimer’s Foundation of America, 322 Eighth Avenue, 7th Floor, New York, NY, 10001 (866) 232-8484 (646) 638- 546, info@alzfdn.org, http://www.alzfdn.org

European Alzheimer’s Disease Consortium, Dept. of Internal Medicine and Clinical Gerontology, Toulouse University Hospital, 170 Avenue de Casselardit, Toulouse, France, 31300 33-5-6177-7649 33-5-6149- 7109, reynish.e@chu-toulouse.fr, http://eadc.alzheimer-europe.org

Fisher Center for Alzheimer’s Research Foundation, One Intrepid Square, West 46th Street & 12th Avenue, New York, NY, 10036 (800) ALZINFO (259-4636), http://www.alzinfo.org