What’s Involved in Reaching an Alzheimer’s Diagnosis?

Learn which medical exams and screening tests may be needed before a clear diagnosis of Alzheimer’s disease can be made.

Diagnosing Alzheimer’s disease as early as possible can help patients and their families to better prepare for the progression of the disease. But diagnosing Alzheimer’s can be a complicated process, given that it is only one of a group of brain diseases known as dementia, meaning neurological disorders that rob the mind of its intellectual ability.

Alzheimer’s expert Malaz Boustani, MD, MPH, recommends that family members get a potential Alzheimer’s patient checked out, even if they just have a “gut feeling” something might be wrong. “That feeling in and of itself is a big red flag, and families need to get their loved one evaluated as soon as possible. If you have any doubt — even if it just crosses your mind — it’s worth investigating,” says Dr. Boustani, assistant professor at the Indiana University School of Medicine and a center scientist with the Indiana University Center for Aging Research.

Alzheimer’s Diagnosis: Finding a Doctor
If you or a family member needs to be evaluated for Alzheimer’s disease, medical experts say the first stop should be your primary care physician. Your family doctor will often coordinate the diagnostic process. If your doctor wants more input from a specialist, you could be referred to one of the following professionals:

  • A geriatrician, a medical doctor who specializes in the care of elderly patients
  • A neurologist, a medical doctor who specializes in diseases of the brain or nervous system and can assess different types of dementia
  • A psychiatrist, a medical doctor who specializes in mental disorders and can diagnose a mood disorder, such as severe depression that may mimic Alzheimer’s symptoms.
  • A psychologist, a licensed medical professional (a PhD or PsyD) who can test such mental functions as logic, memory, and concentration.

Boustani says that ideally, any specialist you see should have training in memory disorders and dementia. It can often be difficult, however, to find someone with those qualifications. “Our current health care system, unfortunately, doesn’t have enough memory-care practitioners capable of performing a full diagnostic assessment,” he says.

Screening Tests for Alzheimer’s
Currently, the only definitive way to diagnose Alzheimer’s disease is by looking at brain cells under a microscope after a person has died. But since that’s too late to do the person any good, physicians have come up with a battery of tests that can help determine the likelihood of an Alzheimer’s diagnosis. Experts believe that a skilled doctor using these tests can diagnose Alzheimer’s accurately in nine out of 10 cases.

Doctors can evaluate the possibility of Alzheimer’s disease by:

  • Taking a medical history. During this process, the doctor will learn whether anyone in the patient’s family has suffered from Alzheimer’s or other forms of dementia. The doctor will also ask about any medications or illnesses that could cause side effects that resemble Alzheimer’s symptoms. Both the patient and their family must be involved in this step, since short-term memory loss is an early symptom in 75 percent of people with Alzheimer’s and family members may have to help provide key information.
  • Administering a mental exam. A series of tasks will test the patient’s memory and problem-solving skills. Attention span is also assessed, as well as the ability to count and speak logically.
  • Performing a thorough physical examination. This hands-on exam includes a general check-up as well as a neurological exam that tests things like muscle tone, reflexes, and coordination. The doctor will also order blood work and urine test(s), and may order other, more specialized testing such as an MRI or CT scan of the brain.

Alzheimer’s Diagnosis: Ruling Out Other Causes
Most of the aforementioned tests aren’t just used to look for Alzheimer’s disease. They’re also aimed at ruling out other conditions that could be interfering with a person’s memory. For example, problems with memory or concentration can stem from an emotional disorder. “You might have depression, which can include memory complaints,” Boustani says.

A person with symptoms common to Alzheimer’s also might be suffering from a brain tumor, or bleeding inside the brain caused by a bad fall or a stroke. In other cases, memory loss could be caused by different forms of dementia, by a reaction to a medication the person is taking for an unrelated illness, or even by a vitamin deficiency. The important thing is to undergo the screening process so you know what’s wrong and can address it appropriately, Boustani says.

As with most medical conditions, an earlier diagnosis can bring quicker treatment and help ease the stress of dealing with a new illness. If you have any concerns about your risk of Alzheimer’s, do not hesitate to contact your doctor. Together you can decide on what, if any, testing is best for you or a loved one.

Citation

 

Is This Dementia and What Does It Mean?

Introduction

What does it mean when someone is said to have dementia? For some people, the word conjures up scary images of “crazy” behavior and loss of control. In fact, the word dementia describes a group of symptoms that includes short-term memory loss, confusion, the inability to problem-solve, the inability to complete multi-step activities such as preparing a meal or balancing a checkbook, and, sometimes, personality changes or unusual behavior.

Saying that someone has dementia does not offer information about why that person has these symptoms. Compare it to someone who has a fever: the person is ill from the fever, but the high temperature does not explain the cause or why this person is ill.

Does any loss of memory signify dementia? Isn’t memory loss a normal part of aging? We often hear that because someone is old, memory problems are “just natural” and are to be expected.  But we know that serious memory loss is not a normal part of aging, and should not be ignored. 

On the other hand, families might assume that a loved one’s noticeable loss of memory must be caused by Alzheimer’s disease. In many instances, Alzheimer’s is, in fact, the problem. But other conditions also can cause memory and cognitive problems severe enough to interfere with daily activities. These conditions can affect younger as well as older people. A clear diagnosis is needed.

Certain conditions can cause reversible dementias. These include medication interactions, depression, vitamin deficiencies or thyroid abnormalities.  It is important that these conditions be identified early and treated appropriately so that symptoms can  be improved. 

The irreversible dementias are known as degenerative dementias, and Alzheimer’s disease is the most common.  There are a number of other degenerative dementias, however, that may look like Alzheimer’s, but have distinct or different features which need special attention and different treatment. Reversible and irreversible dementias are described in more detail below.

Importance of Obtaining a Diagnosis for Dementia

The diagnosis of dementia requires a complete medical and neuropsychological evaluation. The process is first to determine if the person has a cognitive problem and how severe it is. The next step is to determine the cause in order to accurately recommend treatment and allow patients and caregivers to plan for the future.

A medical evaluation for dementia usually includes the following:

  • Review of history or onset of symptoms. Questions you or your loved one might be asked include: What problems have been identified? In what order did things happen? How long have the symptoms been present? How is this affecting the person’s ability to function in daily life? Because the person being evaluated may not be able to recall accurately the sequence of events or may underestimate the problem, a caregiver or someone who knows the individual well needs to accompany the patient and provide this information to the doctor or nurse.
  • Medical history and medications. This will provide information about conditions that might indicate higher risk for a particular type of dementia or identify medications that may contribute to cognitive problems. Again, it is important that someone who can accurately provide this information be with the individual during the appointment.
  • Neurological exam. The neurological exam helps identify symptoms that may be present in particular kinds of dementia or other conditions that may increase the risk of cognitive problems, such a stroke or Parkinson’s disease.
  • Laboratory tests to rule out vitamin deficiencies or metabolic conditions. Although not common, sometimes a simple vitamin deficiency, infection or hormone imbalance can cause cognitive symptoms. These may include thyroid imbalances, Vitamin B12, and syphilis. In addition, some laboratory tests may indicate a condition that puts a person at risk for developing dementia, such as high cholesterol or high blood pressure.
  • Brain Imaging. A CT scan or MRI is done to evaluate the anatomy of the brain for conditions that might cause cognitive changes, such as a stroke or a brain tumor.  The tests also allow the determination of brain size and blood vessel changes which can be monitored over time. 
  • Mental status testing (also called cognitive or neuropsychological testing). These pencil-and-paper tests evaluate many areas of thinking, including memory, language, problem-solving and judgment. The results are used to compare an individual with others of his or her age, education and ethnicity to determine in what areas the individual has problems and how severe they are.

The process of diagnosing dementia has become more accurate in recent years, and specialists are able to analyze the large amount of data collected and determine if there is a problem, the severity, and, often, the cause of the dementia. Occasionally, there may be a combination of causes or it may take time to monitor the individual to be sure of a diagnosis. Determining whether the cause is a reversible or irreversible condition guides the treatment and care for the affected person and family.

Reversible Dementias

Deteriorating intellectual capacity may be caused by a variety of diseases and disorders in older persons. An illness and/or a reaction to medication may cause a change in mental status.  These are sometimes called “pseudodementias.” Detecting the underlying cause of changes through medical evaluation may lead to a determination that the cause is reversible or treatable. Examples of conditions that can cause reversible symptoms of dementia include:

  • Reactions to medications. Adverse drug reactions are one of the most common reasons older persons experience symptoms that mimic dementia. All medications, prescriptions, over-the-counter pills and herbal remedies should be monitored by a physician to reduce the possibility of side effects.
  • Endocrine abnormalities. The conditions of low or high thyroid levels, parathyroid disturbances or adrenal abnormalities can cause confusion that mimics dementia.
  • Metabolic disturbances. Confusion or appetite, sleep and emotional changes can be caused by medical conditions including renal and liver failure, electrolyte imbalances (blood chemistry levels), hypoglycemia (low blood sugar), hypercalcemia (high calcium), and diseases of the liver and pancreas.
  • Emotional Distress. Depression or major life changes such retirement, divorce or loss of a loved one can affect one’s physical and mental health.  A physician should be informed about major stressful life events.
  • Vision and Hearing. Undetected problems of vision or hearing may result in inappropriate responses and be misinterpreted.  Hearing and eye exams should be performed.
  • Infections. Confusion can be a symptom of an infection and needs to be brought to the attention of the physician.
  • Nutritional Deficiencies. Deficiencies of B vitamins (folate, niacin, riboflavin and thiamine) can produce cognitive impairment.

Degenerative (Irreversible) Dementias

If reversible dementias are ruled out and it is determined that the person has a degenerative or irreversible dementia, it is important that families and medical personnel  seek the cause of the problem. This will help ensure that the person affected receives proper medical care, and families can plan their caregiving and find appropriate support and resources.

The following are the most common degenerative dementias:

  • Alzheimer’s Disease. Alzheimer’s Disease is the most common cause of dementia in people over 65, although the disease also occurs in people much younger. Alzheimer’s affects approximately 50 percent of those over 85. Presently, researchers cannot definitely say what causes the disease, and there is no cure.  Symptoms differ from person to person, but declines in memory, thinking and ability to function gradually progress over of a period of years, ending in a severe loss of function.
  • Ischemic Vascular Dementia (IVD). IVD is the second most common dementia, characterized by an abrupt loss of function or general slowing of cognitive abilities that interferes with what are called “executive functions” such as planning and completing tasks. When symptoms appear suddenly, the person has usually experienced a stroke. For others, the condition develops slowly with a gradual loss of function and/or thinking.
  • Dementia with Lewy Bodies (DLB). Dementia with Lewy Bodies is a progressive degenerative disease that shares symptoms with Alzheimer’s and Parkinson’s.  People affected by this disease have behavioral and memory symptoms which can fluctuate, as well as motor problems which are commonly seen with Parkinson’s disease.
  • Frontotemporal Dementia (FTD). FTD is a degenerative condition of the front (anterior) part of the brain, which can sometimes be seen on brain scans. The frontal and anterior temporal lobes of the brain control reasoning, personality, movement, speech, language, social graces and some aspects of memory. Symptoms may lead to misdiagnosis as a psychological or emotionally-based problem. FTD frequently occurs after age 40 and usually before age 65.  Symptoms appear in two seemingly opposite ways: some individuals are overactive, restless, distracted and disinhibited (showing poor social judgment), while others are apathetic, inert and emotionally blunted.
  • Creutzfeldt-Jakob Disease. Creutzfeldt-Jakob Disease (CJD or Jakob-Creutzfeldt Disease) is a rapidly progressive, fatal brain disease. It is part of a family of diseases, called transmissible spongiform encephalopathies, that are caused by an agent known as a prion (“pree-on”). This condition can be very difficult to diagnose as it has many different symptoms, including behavioral changes, movement changes, cognitive changes and general changes in well-being such as sleep problems, loss of appetite and headaches.
  • Parkinson’s Dementia. Parkinsonism is the name given to a collection of symptoms and signs consisting of tremor, stiffness, slowness of movement, unsteady gait. Many neurological disorders have features of parkinsonism, including many of the dementias. When parkinsonism occurs without any other neurological abnormalities, and there is no recognizable cause, the disorder is termed Parkinson’s disease after the English physician who first described it fully in 1817.
  • Progressive Supranuclear Palsy (PSP). People with PSP usually show a group of three symptoms, including the gradual loss of balance and trouble walking, loss of control of voluntary eye movements, and dementia. Although these three features are considered to be the hallmarks of PSP, patients with this disorder also experience other symptoms common to degenerative diseases of the brain, including difficulties with movement, changes in behavior and difficulty with speech and swallowing. In part because it is relatively rare, PSP is frequently misdiagnosed as Parkinson’s Disease. However, its treatment response and clinical symptoms are different, making an accurate diagnosis very important.
  • Normal Pressure Hydrocephalus (NPH). Gait instability, urinary incontinence and dementia are the signs and symptoms typically found in patients who have NPH. Considered a rare cause of dementia, it primarily affects persons older than 60 years. The precise incidence of NPH is hard to determine because the condition does not have a formal, agreed-upon definition. Some physicians base the diagnosis strongly on radiographic evidence; another group of health care professionals relies more on clinical indications. Still others use a combination of signs and symptoms that they have found to be reliable. Traditionally, treatment is surgical implantation of a shunt to reduce the pressure caused by the build up of cerebrospinal fluid.
  • Huntington’s disease (HD). Huntington’s disease is a fatal disease typically characterized by involuntary movements (chorea) and cognitive decline (dementia). It is caused by a genetic mutation that can be passed down from generation to generation. HD is an illness with profound neurological and psychiatric features affecting certain structures deep within the brain, particularly the basal ganglia, responsible for such important functions as movement and coordination. Structures responsible for thought, perception and memory are also affected, likely due to connections from the basal ganglia to the frontal lobe of the brain. As a result, patients may experience uncontrolled movements (such as twisting and turning), loss of intellectual abilities, and emotional and behavior disturbances.
  • Mixed Dementias. At times, two of these conditions can overlap. This is commonly seen in Alzheimer’s disease and vascular dementia, and also in Alzheimer’s disease and Lewy Body dementia.

Medical Treatment for Dementia

There are no cures for degenerative or irreversible dementias, so medical treatments focus on maximizing the individual’s cognitive and functional abilities. Specific treatments for dementia vary depending on the cause of the dementia. For patients with Alzheimer’s disease and Lewy Body disease, for example, medications are available to slow the rate of decline and improve memory function. These medications are known as cholinesterase inhibitors and seem to be effective for some patients. For patients with Alzheimer’s disease, a newer medication, which prevents the buildup of chemicals thought to contribute to memory loss, has also been developed.  Treatment for vascular dementia includes controlling risk factors such as high blood pressure and high cholesterol. Additional medications are available to manage other symptoms associated with dementia, including sleep disorders, movement problems, depression, or behavioral symptoms such as irritability or agitation. Because treatments vary depending on the cause of dementia, an accurate diagnosis is critical.

Communicating about Dementia with Health Care Providers

Good communication with the primary care provider affects the well-being of the person with dementia as well as the well-being of the  caregiver.  Communicating your concerns clearly and describing the changes you may have observed will help guide the provider to investigate further.  In some cases, you may find yourself “educating” medical staff about your loved one’s symptoms.

It is important that your concerns are taken seriously, and you are treated with respect and dignity.  If you are not receiving the attention you need, you should communicate your concerns to the provider and request a referral to a resource in the community that specializes in the evaluation of people experiencing cognitive changes.  The goal is to establish a partnership to both maintain the quality of health and to solve problems. 

Your Role as a Caregiver

Establishing a good working relationship with the primary care physician helps ensure good care and ongoing support. A comprehensive medical work-up that rules out treatable conditions and provides information on current status offers a foundation for care planning, now and in the future. 

An accurate diagnosis begins a process of education for caregivers and families so that needs can be met and resources located and put to use. Irreversible dementia requires a level of care that increases as the disease progresses. Through education and the use of available resources, families can learn new skills to handle shifting care needs.

Many families provide care at home for a person with dementia. While this can be an enriching and very rewarding experience, it can also be stressful. Studies have shown that caring for someone with a brain-impairing disorder can be more stressful than caring for someone with a physical impairment. It is essential that caregivers take the time to care for themselves physically and emotionally.

Support and assistance are very important throughout the months or years you are a caregiver. You will need respite from time to time—a break from caregiving demands. Help from friends, other family members or community agencies is invaluable so that you can continue to provide your loved one with good care without becoming exhausted, frustrated or simply burned out.

Safety-proofing the home, learning behavior management techniques and addressing legal and financial matters are important steps families can take to manage dementia, and resources are available to help. Many caregiver support groups–including some on the Internet–offer emotional and practical support. Caregivers may need to educate themselves about long-term care, and also to reach out in their communities to find the assistance they need. The list of resources below offers more information on where to start looking for help.

Every family is different. Whether care for someone with dementia is provided at home, in an assisted living center, an Alzheimer’s special care unit, or in a nursing home depends on family resources and patient needs. While placement in a facility is not uncommon in later stages of dementia, every family approaches the caregiving experience in a way that is best for them.

Research into the causes and treatments for dementia continues at a rapid pace. We all look forward to new developments that some day may postpone, cure or even prevent these debilitating disorders.

Recommended Reading

The Forgetting. Alzheimer’s: Portrait of an Epidemic, David Shenk, 2001, Random House, New York, NY.

Alzheimer’s Disease: Unraveling the Mystery, Anne Brown Rodgers, 2003, ADEAR (Alzheimer’s Disease Education & Referral Center, a service of the National Institute on Aging), Silver Spring, M.D.

Caregiving at Home, William Leahy, M.D., 2005, Hartman Publishing Inc. and William Leahy, M.D., 8529 Indian School Road NE, Albuquerque, NM 87112, (505) 291-1274.

FDA Report on Drugs: Coping With Memory Loss

Everyone has mild memory lapses from time to time. You go from the kitchen to the bedroom to get something, only to find yourself wondering what you needed. You can’t find your car keys one day and your reading glasses the next. Lapses such as these are usually just signs of a normal brain that’s constantly prioritizing, sorting, storing, and retrieving all types of information. So how do you know when memory loss is abnormal and warrants evaluation by a health professional? Here are some questions to consider:

  • Does the memory loss disrupt daily living? “If memory loss prevents someone from doing activities that they had no trouble handling before—like balancing a checkbook, keeping up with personal hygiene, or driving around—that should be checked,” says John Hart, Jr., M.D., professor of behavioral and brain sciences at the University of Texas at Dallas and medical science director at the Center for BrainHealth.
  • How often do memory lapses occur? It’s one thing to occasionally forget where you parked your car, but it’s not normal to forget where you parked every day or to forget appointments over and over. Frequent memory lapses are likely to be noticeable because they tend to interfere with daily living.
  • What kinds of things are being forgotten? “It’s normal to forget the name of someone you just met, but may not be normal to permanently forget the name of a close friend or relative,” Hart says. “It also may not be normal to never remember meeting a person after you have spent a great deal of time with them.” Most people have trouble remembering some details of a conversation, but forgetting whole conversations could signal a problem. Other red flags: frequently repeating yourself or asking the same questions in the same conversation.
  • Are there signs of confusion? Serious memory lapses may cause individuals to get lost in a familiar place or put something in an inappropriate place because they can’t remember where it goes. Putting the car keys in the refrigerator is an example.
  • Is the memory loss getting worse? Memory loss that gets progressively worse over time should be evaluated by a health professional.

back to top

What Can Cause Memory Loss?

Anything that affects cognition—the process of thinking, learning, and remembering—can affect memory. Doctors use a combination of strategies to gain better insight into what’s going on, says Ranjit Mani, M.D., a neurologist and medical reviewer in the Food and Drug Administration’s (FDA’s) Division of Neurology Products.

FDA neurologist and medical reviewer Dr. Ranjit Mani, M.D., sitting at his desk holding a neurology text book

Ranjit Mani, M.D., is a medical reviewer in FDA’s Division of Neurology Products.

Doctors evaluate memory loss by taking a medical history, asking questions to test mental ability, conducting a physical and neurological examination, and performing blood and urine tests. Brain imaging, using computerized axial tomography (CAT) scans or magnetic resonance imaging (MRI), can help to identify strokes and tumors, which can sometimes cause memory loss. “The goal is to rule out factors that are potentially reversible and determine if the memory loss is due to a more serious brain disease,” Mani says. Causes of memory loss, some of which can occur together, include the following:

  • Medications. Examples of medications that can interfere with memory include over-the-counter and prescription sleeping pills, over-the-counter antihistamines, anti-anxiety medications, antidepressants, some medications used to treat schizophrenia, and pain medicines used after surgery.
  • Alcohol and illicit drug use. Heavy alcohol use can cause deficiencies in vitamin B1 (thiamine), which can harm memory. Both alcohol and illicit drugs can change chemicals in the brain that affect memory.
  • Stress. Stress, particularly due to emotional trauma, can cause memory loss. In rare, extreme cases, a condition called psychogenic amnesia can result. “This can cause someone to wander around lost, unable to remember their name or date of birth or other basic information,” Mani says. “It usually resolves on its own.”
  • Depression. Depression, which is common with aging, causes a lack of attention and focus that can affect memory. “Usually treating the depression will improve mood and the memory problems may then also improve,” Mani says.
  • Head injury. A blow to the head can cause a loss of consciousness and memory loss. “Memory loss from head trauma typically stays the same or gradually gets better, but not worse,” Mani says.
  • Infections. People with HIV, tuberculosis, syphilis, herpes, and other infections of the lining or substance of the brain may experience memory problems.
  • Thyroid dysfunction. An underactive or overactive thyroid can interfere with remembering recent events.
  • Sleep deprivation. Lack of quality sleep—whether from stress, insomnia, or sleep apnea—can affect memory.
  • Nutritional deficiencies. Deficiencies of vitamins B1 and B12 can affect memory. Such deficiencies can be treated with a pill or an injection.
  • Normal aging. As part of the normal aging process, it can be harder for some people to recall some types of information, such as the names of individuals.
  • Mild cognitive impairment. Mild cognitive impairment (MCI) is a condition characterized by a memory deficit beyond that expected for age, which is not sufficient to impair day-to-day activities.
  • Dementia. Dementia is a term used for a condition in which there is increasing impairment of memory and other aspects of thinking that are sufficiently severe to impair day-to-day activities. There are many causes of dementia, but the most common by far is Alzheimer’s disease (AD), in which there is a progressive loss of brain cells accompanied by other abnormalities of the brain. A diagnosis of AD is made by confirming that a patient has dementia and by excluding other conditions, such as brain tumors, vitamin deficiencies, and hypothyroidism.

back to top

Mild Cognitive Impairment

People with MCI have memory impairments, but otherwise function well and don’t meet the clinical criteria for dementia. Whereas normal memory loss associated with aging may involve forgetting a name, memory loss associated with MCI is more severe and persistent. MCI is often a transition stage between normal aging and more serious problems caused by AD. Most, but not all, people with MCI get worse. According to some studies, each year about 12 to 15 percent of people with MCI develop AD. “Some people never decline in five years and with others, we might see a decline in the third year,” says Reisa Sperling, M.D., associate professor of neurology at Harvard Medical School and director of clinical research at the Memory Disorders Unit at Brigham and Women’s Hospital. “In older people with MCI, if the memory loss is slowly getting worse, the chances of developing AD are about 60 percent to 70 percent.” Research is under way on whether the drugs approved to treat symptoms of AD may help some people with MCI. Scientists hope that some day, accurate and early evaluation and treatment of people with MCI may help prevent further cognitive decline. back to top

Alzheimer’s Disease

AD is the most common form of dementia in people older than age 65, and affects more than 5 million Americans, according to the Alzheimer’s Association. AD is a progressive, neurodegenerative disease characterized in the brain by abnormal protein deposits (amyloid plaques) and tangled bundles of fibers within nerve cells (neurofibrillary tangles). The biggest risk factors are age and family history. Having a history of serious concussion is also a risk factor. AD gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate, and carry out daily activities. Memory loss becomes severe and is marked by disorientation, general confusion, and an inability to recall recent events. A person with mild-to-moderate AD may remember things that happened to them a long time ago, but they might get lost easily in a familiar place. People with AD may also experience changes in personality and behavior, such as withdrawal and suspicion. They eventually experience a loss of speech and movement, incapacitation, and death. Some facts about AD treatment follow:

  • Most clinical trials of drug treatments for memory loss focus on people with AD.
  • Five drugs are approved by FDA to treat the symptoms of AD, but there is no cure for the disease.
  • Four drugs are known as cholinesterase inhibitors and are thought to work in a similar way. Cognex (tacrine), Exelon (rivastigmine), and Razadyne (galantamine) are approved for mild-to-moderate AD. Aricept (donepezil) is approved to treat all degrees of severity of the disease—from mild to severe. Cholinesterase inhibitors prevent the breakdown of acetylcholine, a chemical that nerves use to communicate with each other. “These drugs may help delay or decrease the severity of symptoms for a limited time in some people,” says Susan Molchan, M.D., formerly program director for the Alzheimer’s Disease Neuroimaging Initiative project at the National Institute on Aging (NIA), part of the National Institutes of Health. Side effects of cholinesterase inhibitors are gastrointestinal, such as nausea and diarrhea.
  • Namenda (memantine), approved for moderate-to-severe AD, is believed to block the action of glutamate, a brain chemical that may be overactive in people with AD. Namenda may help some patients maintain certain daily functions a little longer. Common side effects include dizziness, headache, constipation, and confusion. Sometimes, Namenda is prescribed along with a cholinesterase inhibitor.
  • Behavioral symptoms of AD may include agitation, sleeplessness, anxiety, and depression, which can be treated.
  • Inhibiting and/or decreasing amyloid is an intense area of research because amyloid is the major component of the plaques that develop in the brains of people with AD and is associated with nerve cell death. Drugs called secretase inhibitors are being developed and tested to block beta-amyloid formation. Also under study is immunotherapy against beta amyloid—it’s possible that a vaccine may help reduce deposits of amyloid. NIA is recruiting patients for a study to determine if a type of protein to reduce brain amyloid slows the rate or prevents the decline of dementia in people with mild-to-moderate AD. For more information on the study, known as the Gammaglobulin Alzheimer’s Partnership Study (GAP), visit the Alzheimer’s Disease Education and Referral Center Web site or call the center at (800) 438-4380.

back to top

Other Diseases That Cause Dementia

Dementia is diagnosed when two or more brain functions, such as memory and language skills, are significantly impaired, according to criteria set forth by the National Institute of Neurological Disorders and Stroke. In practice, doctors use the same drugs that are used to treat AD to treat some other types of dementia. Vascular dementia. In people who have vascular dementia, also called multi-infarct dementia, arteries to the brain become blocked or narrowed. As a result, changes in the blood supply to the brain occur or multiple strokes disrupt blood flow to the brain. Symptoms may be similar to those of AD, although they usually occur more abruptly. Treatment focuses on preventing future strokes by controlling risk factors such as smoking, diabetes, and high blood pressure. Lewy body dementia. This progressive brain disease is caused by a buildup of protein deposits called Lewy bodies. It involves progressive cognitive decline, problems with alertness and attention, recurrent visual hallucinations, and motor problems similar to those seen with Parkinson’s disease, such as rigidity. Treatment aims to control symptoms of the disorder. Antipsychotic medications for hallucinations aren’t typically prescribed because there is a risk of the hallucinations becoming worse. Parkinson’s disease with dementia. Parkinson’s disease results from the loss of dopamine-producing brain cells. The primary symptoms are trembling in the hands, arms, legs, jaw, and face; body stiffness; and slowness of movement and impaired balance and coordination. Memory loss sometimes occurs with late-stage Parkinson’s disease. Exelon (rivastigmine), which is approved for mild-to-moderate AD, is also approved by FDA for the treatment of dementia with Parkinson’s disease. Frontotemporal dementia. This type of dementia is associated with the shrinking of the frontal and temporal anterior lobes of the brain. Symptoms involve either impulsive or listless behavior, and may include socially inappropriate behavior. Some forms of frontotemporal dementia consist of progressive loss of language functions. No treatment has been shown to slow the progression. Antidepressants and behavior modification may improve some symptoms. Huntington’s disease. This inherited brain disorder causes uncontrolled movements, loss of memory and other cognitive problems, and emotional disturbance. Some early symptoms are mood swings, depression, and difficulty learning new things and remembering facts. Medications help control emotional and movement problems. Creutzfeldt-Jakob disease (CJD). In the early stages of this rare, degenerative brain disorder, people may experience failing memory, behavioral changes, lack of coordination, and visual disturbances. Mental impairment becomes rapidly more severe as the illness progresses. There is no drug to cure or control CJD, but some drugs may help with symptoms. back to top

Resources for Coping

Coping with memory loss can be frustrating for both the person affected and family members and caregivers. Some families use memory aids to help quality of life, such as color coding and labeling items in the home with safety notes and directions for use, and using alarms and talking clocks to keep track of time and remember medication doses. Families also may experience anger, exhaustion, irritability, and other symptoms of caregiver stress. Alzheimer’s Association. Resources of the Alzheimer’s Association include an online message board; a 24/7 toll-free number; information on legal, financial, and living-arrangement decisions; and referrals to local community programs. Services include CareFinder, an interactive tool to help you choose home and residential care providers, and Safe Return, a program that helps when a person with AD or a related dementia wanders and becomes lost. Alzheimer’s Disease Education and Referral Center. A service of NIA. Information specialists can answer questions and offer free publications on home safety tips, caregiving tips, and information on the diagnosis and treatment of AD and related disorders, and ongoing research. A joint NIA and FDA effort maintains the Alzheimer’s Disease Clinical Trials Database. Family Caregiver Alliance. This alliance offers online discussion groups and caregiver information in English, Spanish, and Chinese, as well as fact sheets, including the Caregiver’s Guide to Understanding Dementia Behaviors. back to top

Can Memory Loss Be Prevented?

Two older women playing billiards

‘Social interaction … has been associated with a lower risk of dementia.’

There is no conclusive evidence that the herb ginkgo biloba prevents memory loss. And research has shown that the combination of estrogen and progestin increased the risk of dementia in women older than age 65. So what can you do to prevent memory loss? Clinical trials are under way to test specific interventions. While those tests are being conducted, you may want to consider hints from animal and observational studies of promising approaches. These steps are already beneficial in other ways and may help reduce the risk of developing memory problems.

  • Lower cholesterol and high blood pressure. A number of studies in recent years have suggested that vascular diseases—heart disease and stroke—may contribute to the development of AD, the severity of AD, or the development of multi-infarct dementia (also called vascular dementia).
  • Don’t smoke or abuse alcohol. According to a research report from Harvard Medical School, “Improving Memory: Understanding Age-Related Memory Loss,” smokers perform worse than nonsmokers in studies of memory and thinking skills. Heavy alcohol use can also impair memory.
  • Get regular exercise. Physical activity may help maintain blood flow to the brain and reduce risk factors associated with dementia.
  • Maintain healthy eating habits. According to a study published in the Oct. 24, 2006, issue of Neurology, eating vegetables may help slow down the rate of cognitive change in adults. Researchers studied 3,718 residents in Chicago who were older than age 65. Of the types of vegetables, green leafy vegetables had the strongest association with slowing the rate of cognitive decline. Also reducing foods high in saturated fat and cholesterol and eating fish with beneficial omega-3 fatty acids, such as salmon and tuna, may benefit brain health. An NIA-funded clinical trial to test the effects of omega-3 fatty acids in people with AD is now recruiting patients nationwide.
  • Maintain social interactions. Social interaction can help reduce stress levels and has been associated with a lower risk of dementia. In the February 2007 issue of the Archives of General Psychiatry, researchers found that loneliness is associated with an increased risk of late-life dementia.
  • Keep your brain active. Some experts suggest that challenging the brain with such activities as reading, writing, learning a new skill, playing games, and gardening stimulates brain cells and the connections between the cells, and may be associated with a lower risk of dementia.
Citation

Red glow test that could catch Alzheimer’s before it strikes

The breakthrough gives new hope for catching the illness in its earliest stages, even before symptoms fully develop – and
also means there will be less chance of misdiagnosis, so those with other forms of dementia can be given the correct treatment.

The test has entered final clinical trial stages. Should results continue to prove successful, it could be rolled out by the end of 2012.

Pioneering: The new brain scan will show the early signs of Alzheimer's and gives off a red glow
Pioneering: The new brain scan will show the early signs
of Alzheimer’s and gives off a red glow

Until now, the only way to diagnose Alzheimer’s (AD) was by ruling out other conditions such as cancer, depression or even a vitamin deficiency. Definitive confirmation came after death when brain samples containing high levels of beta amyloid plaques, the growths that characterise AD, are found.

But now a new compound called Flutemetamol, which highlights areas of the brain that are affected by the disease when scanned, is showing promising results in clinical studies.

The compound is injected into the arm and the patient exhibiting symptoms of AD undergoes a positron emission tomography (PET)
scan. If beta amyloid plaques are present in the brain, Flutemetamol makes them glow red, which confirms the patient has AD.

The second phase of the Flutemetamol study was completed earlier this year. In the trial, 65 patients suffering with AD and other degenerative mental-health conditions with less than a year to live were given Flutemetamol to see what PET scans revealed.

Colour code: A brain scan which has a healthy glow to it
Colour code: A brain scan which has a healthy glow to it

Post-mortem results showed that when a specialist alone tried to diagnose each case, 15 per cent of diagnoses were incorrect. However, by using Flutemetamol there was only a seven per cent failure rate.

Any mistakes during the scan were because low levels of beta amyloid plaques do not necessarily mean a patient has developed
full-blown AD. However, many experts believe that having a positive amyloid scan may indicate risk of developing AD in the future.

Dr Francois Nicolas, director of neurology for PET Medical Diagnostics, at GE Healthcare, the company that is developing Flutemetamol, says: ‘What makes the results so revolutionary is that it makes both a correct and an earlier diagnosis possible for the first time. This could significantly increase the quality and even the length of a patient’s life. Equally, those whose scan shows no signs of AD can be given the appropriate treatment they need too.’

Difference: The two sets of scans clearly show the difference between the infected brain and the healthy one
Difference: The two sets of scans clearly show the difference between the infected brain and the healthy one

AD affects about 342,000 Britons but the symptoms – forgetfulness, sudden mood changes, confusion and speech problems,
among others – are vague and difficult to measure or attribute to a specific condition.

Dementia is most common in adults over the age of 65 although why it develops is not entirely understood, though age, family
history, serious head injuries and even excessive exposure to aluminium have been linked to AD. Professor Leslie Findley, consultant neuroscientist at the Essex Neuroscience Unit, is heartened by the results but still believes a lot more research needs to be done into how dementia presents itself.

He says: ‘The study is very positive but we don’t know the full picture yet. To be able to detect AD as a very early diagnosis really would be ground-breaking.’

Published by Associated Newspapers Ltd.

Citation

Advances in Research Into Alzheimer’s Disease

Advances in research into Alzheimer’s disease: transporter proteins at the blood CSF barrier and vitamin D may help prevent amyloid β build up in the brain.

Advancing age is a major risk factor for Alzheimer’s disease and is associated with build- up of the peptide amyloid β in the brain. New research published in BioMed Central’s open access journal Fluids and Barriers of the CNS shows that removal of amyloid β from the brain depends on vitamin D and also on an age-related alteration in the production of transporter proteins which move amyloid β in and out of the brain.

Low levels of vitamin D are thought to be involved in age-related decline in memory and cognition and are also associated with Alzheimer’s disease. Researchers from Tohoku University, Japan, looked at the mechanism behind this and found that vitamin D injections improved the removal of amyloid β from the brain of mice.

Prof Tetsuya Terasaki said, “Vitamin D appears increase transport of amyloid β across the blood brain barrier (BBB) by regulating protein expression, via the vitamin D receptor, and also by regulating cell signaling via the MEK pathway. These results lead the way towards new therapeutic targets in the search for prevention of Alzheimer’s disease.”

The transport of amyloid β across the BBB is known to be orchestrated by transporter proteins such as LRP-1 and P-gp, which move amyloid β out of the brain, and RAGE, which controls influx. Looking at the transport of amyloid β from blood to cerebrospinal fluid (CSF), and from CSF to blood, researchers from Rhode Island Hospital and The Warren Alpert Medical School, found that LRP-1 and P-gp at the blood-cerebrospinal fluid barrier (BCSFB), increased with age so increasing removal of amyloid β from the CSF and brain.

Prof Gerald Silverberg said, “While increased production of transporter proteins at the blood CSF barrier may help amyloid β removal from the older brain, production of these proteins eventually fails. This failure may be an important event in brain function as we age and for people with Alzheimer’s disease.”

 

Citation

 

High-dose B Vitamin Supplementation Not Effective in Alzheimer’s Disease

Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline.

Objective

To determine the efficacy and safety of B vitamin supplementation in the treatment of AD.

Design

Clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States.

Intervention

Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months.

Outcome

Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog).

Results

A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements.

Conclusion

This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD.

Citation

 

More Scientific Progress in Alzheimer’s Studies

Two new studies add to scientific efforts to find more accurate ways to determine whether a person’s brain is on a path toward Alzheimer’s disease.

Alzheimer’s, a brain-ravaging form of dementia, can now only be conclusively diagnosed after death. Beta amyloid plaques, physical hallmarks of the disease, can be seen in an autopsy.

In the first study, published in this week’s Journal of the American Medical Association (JAMA), older people without dementia whose blood showed lower levels of beta-amyloid 42/40 (proteins) had an increased rate of cognitive decline over nine years. The study found that participants with less education and lower levels of literacy had a stronger association with these biomarker levels. The study involved close to 1,000 participants with an average age of 74.

“What this implies — though we don’t know for sure, it’s just an association — is that even if you have this bad signature, you might be able to do something about it. Having a higher education appeared to be a sort of a buffer,” says study author Kristine Yaffe of the University of California-San Francisco and San Francisco Veterans Affairs Medical Center.

The second study, also in JAMA, suggests that a certain type of brain imaging procedure may help detect beta-amyloid in living patients.

For the study, researchers recruited 35 terminally ill participants from hospice, long-term care, and community health care facilities who were near the end of their lives, says Duke University Medical Center study investigator Murali Doraiswamy.

Doraiswamy and other researchers working with lead author, Christopher Clark of sponsor Avid Radiopharmaceuticals, used the chemical florbetapir F 18, which binds with beta-amyloid, in conjunction with positron emission tomographic (PET) imaging. The images were later compared with the quantity of beta-amyloid in the brain.

Comparisons agreed in 96% of 29 subjects, the study says.

Doraiswamy says this type of scan could be useful in ruling out Alzheimer’s.

“Many conditions can mimic Alzheimer’s — thyroid, vitamin deficiencies, depression, rarer dementias. Knowing someone doesn’t have amyloid in the brain can help a clinician focus on those other conditions,” he adds.

The 3-D overlay of the study results shows the hippocampal volume in patients with early Alzheimer's Disease.  The hippocampus is responsible for learning and memory in the brain, and is one of the first areas damaged by Alzheimer's disease.  It is also one of the only areas of the brain that can undergo adult neurogenesis, or new growth.
Enlarge image Enlarge Stock
The 3-D overlay of the study results shows the hippocampal volume in patients with early Alzheimer’s Disease. The hippocampus is responsible for learning and memory in the brain, and is one of the first areas damaged by Alzheimer’s disease. It is also one of the only areas of the brain that can undergo adult neurogenesis, or new growth.

The diagnostic uses of the scan aren’t clear yet, says William Thies of the Alzheimer’s Association. He says an FDA meeting this week will help determine how to move ahead with the findings.

While both studies are steps forward, “the field will still be waiting for something that will give us a more powerful discrimination between what is Alzheimer’s and what is not Alzheimer’s, and the severity of disease,” says William Klein, a professor of neurobiology at Northwestern University. “There’s still a lot of difficulty in making that connection between an imaging result or a clinical number and the state of the disease.”

Citation