Is it Alzheimer's Disease, a Related Dementia or Nothing to Worry About?

Here are some hints that might help you decide if forgetfulness is normal or if it's a sign of something more significant:

Recent memory loss that affects job performance

It's normal to occasionally forget assignments, colleagues' names or a business associate's telephone number, but generally remember them later. Those with a dementia, such as Alzheimer's Disease, might forget things more often, and not remember them later. They might ask the same question many times, not remembering the answer, or that they already asked the question.

Difficulty in performing familiar tasks

Busy people can be distracted from time to time and leave the carrots on the stove, only to remember to serve them at the end of the meal. People with Alzheimer's Disease could prepare a meal, forget to serve it, and even forget they made it.

Problems with language

Everyone has trouble finding the right word sometimes, but can finish the sentence with another appropriate word. A person with Alzheimer's Disease might forget simple words, or substitute inappropriate words, making sentences incomprehensible.

Disorientation of time and place

It's normal to forget the day of the week or your destination for a moment. But people with Alzheimer's Disease can become lost on their own street or in a familiar shopping mall, not knowing where they are, how they got there or how to get home.

Poor or decreased judgement

People can become so immersed in an activity or telephone conversation they temporarily forget the child they're watching. A person with Alzheimer's Disease could entirely forget the child and leave the house to visit a neighbor.

Problems with abstract thinking

People who normally balance their checkbooks might momentarily be disconcerted when the task is more complicated than usual, but will eventually figure out the solution. Someone with Alzheimer's Disease could forget completely what the numbers are and what needs to be done with them.

Misplacing things

Anyone can misplace a wallet or keys, but eventually find them by reconstructing where they've left them. A person with Alzheimer's Disease might put things in inappropriate places -- an iron in the freezer, or a wristwatch in the sugar bowl -- and not be able to retrieve them.

Changes in mood

Everyone has a bad day once in a while, or might become sad or moody from time to time. Someone with Alzheimer's Disease can exhibit rapid mood swings for no apparent reason: i.e. from calm to tears to anger to calm in a few minutes.

Changes in personality

People's personalities ordinarily change somewhat at different ages, as character traits strengthen or mellow. But a person with Alzheimer's Disease can change drastically, becoming extremely irritable, suspicious of fearful.

Loss of Initiative

It's normal to tire of housework, business activities or social obligations, but most people regain their initiative. The person with Alzheimer's Disease might become very passive and require cues and prompting to get them involved in activities.

Source: Alzheimer's Association, San Diego Chapter

Herb For Alzheimer's Disease

Lisa Malak
Reporting

(CBS News) NEW YORK, NY Alzheimer's Is A Devastating Disease.. That Steals Away Memories.

But As C-B-S's Doctor Mallika Marshall Reports.. Doctor's Are Now Experimenting With A Chinese Herb.. Hoping It Can Slow Down The Memory Loss.

New York, NY
When You Hear Melvin Zuckerman Recall Events From The Past.

"I Moved Away From That House In 1938."

You Would Never Suspect He Has Alzheimeræs Disease.

That Changes When The Doctor Gives Him Three Things To Remember.

"Chair, Apple, Penny - (Melvin) Chair, Apple, Penny. (Doc) And Keep Them In Mind."

Just 45 Seconds Later..

"(Doc) Do You Remember Those Three Words I Mentioned To You Before (Melvin) Nope. (Doc) Any Hint Of Them (Melvin) Nope."

Dr. Mallika Marshall/CBS News
"How Does This Happen? Well When New Memories Travel Through Our Brain Theyære Led By A Chemical Called Acetylcholine. Alzheimeræs Detiorates The Production Of Acetylcholine... In Effect Stealing Memories."

But Researchers Are Hoping This Experimental Drug.... Derived From A Natural Chinese Herb.... Can Change That. It's Called Huperzine A.

Doctor Hillel Grossman Says It Works Similar To Drugs Currently On The Market That Boost Acetylcholine.

He's Testing It On Patients Like Melvin To See If It Works Better.
.
Dr. Hillel Grossman/Mt. Sinai School Of Med.
"If You Can Prop Up The Amount Of The Acetylcholine That Is There, That's Available, Flowing Through The Neurons Than Memory Can Be Sustained."

Melvin Just Started The Drug.

He Realizes It Won't Stop Alzheimer's But Hopes It Will Help Him Hold On To His Memories A Little Longer.

Doctor Mallika Marshall, CBS News.

Prognosis---etc

Prognosis

There is considerable variability in the rate of Alzheimer disease progression. The Alzheimer Disease Association claims that the time from the onset of clinical symptoms to death can range from three to 20 years, with an average duration of eight years. There are probably many environmental and genetic factors that play a role in the progression of the disease. The accumulation of damage and loss of brain cells eventually results in the failure of many different organ systems in the body. According to the National Institute of Neurological Disorders and Stroke, the most common cause of death is due to infection.

Special concerns

Alzheimer disease should be distinguished from other forms of dementia. In some cases, depression can result in dementia-like symptoms. Other examples include chronic drug use, chronic infections of the central nervous system, thyroid disease, and vitamin deficiencies. These causes of dementia can often be treated. It is, therefore, important to obtain an accurate diagnosis to avoid complications associated with the inappropriate treatment and long-term care of these patients. There are also several genetically based syndromes in which dementia plays a role.

Genetic counseling

Genetic counseling is important for family members biologically related to patients with Alzheimer disease because each first-degree relative has as much as a 20% lifetime risk of also being affected. The risk to immediate relatives increases as more family members develop the disease. In the early-onset form of the disease, the inheritance pattern is thought to be autosomal dominant. This means that a carrier (who will eventually be affected) has a 50% chance of passing on the mutated gene to his or her offspring.

The general consensus in the scientific and medical community is to not test children or adolescents in the absence of symptoms for adult-onset disorders. There are many problems associated with predictive testing of asymptomatic individuals who are not yet adults. Children who undergo predictive testing lose the choice later in life (when they are capable of understanding the full ramifications of the disease) to know or not to know this information. It is, therefore, an important consideration that involves ethical and psychological implications.

Resources

BOOKS

Bird, T. D. "Memory Loss and Dementia." In Harrison's Principles of Internal Medicine, 15th ed. Edited by A. S. Franci, E. Daunwald, and K. J. Isrelbacher. New York: McGraw Hill, 2001.

Castleman, Michael, et al. There's Still a Person in There: The Complete Guide to Treating and Coping with Alzheimer's. New York: Perigee Books, 2000.

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. New York: Warner Books, 2001.

PERIODICALS

Campion, D., et al. "Early-onset Autosomal Dominant Alzheimer Disease: Prevalence, Genetic Heterogeneity, and Mutation Spectrum." Am J Hum Genet 65 (1999): 664–70.

Green, R.C. "Risk Assessment for Alzheimer's Disease with Genetic Susceptibility Testing: Has the Moment Arrived?" Alzheimer's Care Quarterly (2002): 3,208–14.

Rogan, S., and C. F. Lippa. "Alzheimer's Disease and Other Dementias: A Review." Am J Alzheimers Dis Other Demen (2002) 17: 11–7.

Romas, S. N., et al. "Familial Alzheimer Disease among Caribbean Hispanics: A Reexamination of Its Association with APOE." Arch Neurol (2002) 59: 87–91.

Rosenberg, R. N. "The Molecular and Genetic Basis of AD: The End of the Beginning: The 2000 Wartenberg Lecture." Neurology 54 (2000): 2045–54.

Treatment---etc

Treatment

 

Pharmacological treatment

Treatment of Alzheimer disease is mainly palliative (given for comfort) and focuses on mitigating symptoms. Each symptom is treated based on its severity and the other symptoms that are affecting the individual. Most affected individuals will eventually need professional care in assisted living or nursing homes. They require constant supervision as memory loss becomes incapacitating. There are several pharmacological interventions and treatment regimens that are suggested. Patients who have depression are treated with antidepressants. Tacrine is often prescribed to help with some of the behavioral problems and provides modest cognitive benefits in a small percentage of patients. Aricept, Galantamine, and Exelon are more recent drugs used for a similar purpose, and are not believed to cause liver toxicity; the liver must be monitored in those taking Tacrine. Non-steroidal anti-inflammatory drAIDs) are currently being investigated for their use in treating patients with Alzheimer disease.

Coping with the disorder

There are strategies to cope with this disorder and these should be considered in the beginning stages of the disease. Coping mechanisms depend on whether there are family members available for support. If an individual is without family members, relying on community support through neighbors or volunteers of Alzheimer disease organizations will be necessary.

Many precautions can be made early on to avoid difficult or life-threatening situations later, while maintaining everyday activities in the home environment. Dealing with a person with Alzheimer disease with patience is important. Daily tasks should be performed when the person with Alzheimer disease feels best. Informing neighbors of the person's condition is an important first step. Arranging for assistance, depending on the stage of the disorder, will become necessary. As the ability to drive may be compromised fairly early in the disorder, transportation may need to be arranged. There are local chapters of the Alzheimer's Association that offer help with transportation requirements.

In the early period of the disease when memory loss is minimal, it is helpful for family and friends to interact with the affected person, reminding him or her to take medication, eat, keep appointments, and so forth. Family and friends can help sustain the Alzheimer patient's daily living activities. Keeping records is also helpful, particularly if several people are overseeing the patient's care. Additionally, organizing the household so that it is easy to find important items is recommended.

Other helpful coping mechanisms include posting signs to remind patients of important phone numbers, to turn off appliances, and to lock doors. It is important that all electrical cords and appliances are arranged to minimize distraction, and to prevent danger of falling or misuse. Assistance in handling finances is usually necessary. Providing an extra house key for neighbors and setting up a schedule to check on persons with Alzheimer disease is very helpful for both the patient and the family. By utilizing these and other family, neighborhood, and community resources, many people with early Alzheimer disease are able to maintain a successful lifestyle in their home environment for months or years.

Recovery and rehabilitation

For a person with Alzheimer disease, emphasis is placed on maintaining cognitive and physical function for as long as possible. Currently, there is no cure for Alzheimer and, once the symptoms develop, patients do not recover. Instead, they progressively worsen, usually over a period of years. This has many psychosocial and financial ramifications for the patient and the patient's caretakers. Social service workers can help families plan for long-term care, as persons with Alzheimer disease most often eventually require 24-hour assistance with feeding, toileting, bathing, personal safety, and social interaction. Taking care of patients in the later stages can be financially and psychologically draining. Various support systems are available through community mental health centers and national support organizations.

Clinical trials

There are currently many clinical trials for the treatment or prevention of Alzheimer disease sponsored by the National Institutes of Health (NIH). Large multi-center clinical trials such as a Phase III clinical trail are aimed at determining whether anti-inflammatory drugs delay agerelated cognitive decline. (Contact information: UCLA Neuropsychiatric Institute, Los Angeles, California, 90024. Recruiter: Andrea Kaplan, (310) 825-0545 or her email: akaplan@mednet.ucla.edu.) A Phase III clinical trial is also organized to test the drug Risperidone for the treatment of agitated behavior in Alzheimer's patients. (Contact information: Palo Alto Veterans Administration Health Care System, Menlo Park, California, 94025. Recruiter: Erin L. Cassidy, PhD, (650) 493-5000, ext.27013 or her email: ecassidy@stanford.edu.)

Other trials include:

• A study on Valproate to prevent cognitive and behavioral symptoms in patients. Contact information: Laura Jakimovich, RN, MS, (585) 760-6578 or her email: laura_jakimovich@urmc.rochester.edu .
• The drug Simvastatin, a cholesterol-lowering medication, is being studied to learn if it slows the progression of Alzheimer disease. Contact information: Stanford University, Palo Alto, California, 94304. Recruiter: Lisa M. Kinoshita, PhD, (650) 493-0571 or her email: lisakino@stanford.edu.
• A study of the efficacy and dose of the drug NS 2330 to improve cognition. Contact information: Peter Glassman, MD, PhD, (800) 344-4095, ext. 4776 or his email: pglassma@rdg.boehringer-ingelheim.com.
• A study of investigational medications for the treatment of Alzheimer patients. Contact information: Eli Lilly and Company, (877) 285-4559.

There are also many other studies that are investigating various other pharmacological agents such as vitamin E and other currently available drugs.

Clinical diagnosis---etc

Clinical diagnosis

A physician can use a number of different tests to assess memory skills, and, combined with any observed changes in the individual's behavior, they can help make a diagnosis of Alzheimer disease. Other tests that are important in diagnosing the disorder can involve laboratory tests that require blood and urine or imaging studies of the brain. By using neuroimaging studies such as magnetic resonance imaging (MRI) scans, physicians have found that patients with Alzheimer disease often have diffuse atrophy (weakening or decrease in size) in a specific area of the brain called the cerebrum.

Genetic diagnosis

It has been shown that there is a significant association of a specific gene called APOE e4 with the development the early-onset form of the disease. There are three different types of Alzheimer disease that have been shown to be caused by mutations in three distinct genes known as APP, PSEN1, and PSEN2. However, determining the genotype (whether a patient carries this associated mutation) is not entirely conclusive. Currently, although APOE e4 mutation analysis can help in diagnosing a patient suspected of having Alzheimer disease, it is not used for predictive testing of these individuals.

Biochemical markers

Although there are no tests to definitively diagnose Alzheimer disease, there are useful biochemical markers that can help distinguish Alzheimer disease from other disorders that involve dementia, including dementia caused by vascular disorders, drugs, or thyroid disease. Fluid that is found in the brain and spinal cord called cerebrospinal fluid can be tested for levels of two proteins, Tau and A[.beta]42, in patients that develop symptoms of dementia. A[.beta]42 accumulation in the brain is associated with reduced levels in the cerebrospinal fluid. Accumulation of the Tau protein in the brain is associated with Alzheimer disease. Therefore, increased Tau protein levels and decreased A[.beta]42 in the cerebrospinal fluid can pinpoint which persons have Alzheimer disease, regardless of the cause or the age of onset.

The score for these tests is numerical and relies heavily on a reference range determined by a patient's age, sex, and the type of equipment used to perform the test. A positive result will only indicate that a patient is at high risk of having Alzheimer disease and requires further analysis for an accurate diagnosis. This test has yet to be widely performed and is, therefore, only available in certain reference laboratories.

Treatment team

Initially, a physician usually recommends counseling by a psychologist or a support group experienced with this disease. After the diagnosis, visits to the physician focus on treating mild behavioral changes such as depression. Eventually, treatment requires 24-hour supervision and nursing care. The caretakers are mostly nurses or professionals who are part of various assisted-living programs.

 

Late-onset familial Alzheimer disease

Late-onset familial Alzheimer disease

The late-onset familial form of Alzheimer disease (AD2) accounts for approximately 15–25% of all cases. These familial cases are seemingly indistinguishable from sporadic cases when observed clinically, but can be recognized based on molecular genetic testing. However, there is no clear chromosomal location for a gene directly responsible for the disease. Therefore, this complex type may involve many susceptibility genes. These familial cases are most likely due to multiple genes that make these individuals susceptible to developing the disease. For example, the APOE e4 gene on chromosome 19 associated with late-onset Alzheimer disease reduces the age in which symptoms develop by an unknown mechanism. There are many other candidate genes that are thought to modify Alzheimer disease risks and these genes, with various chromosomal locations, have been linked to the disease in different families.

Development (pathogenesis) of Alzheimer disease

Although scientists know how brain cells of persons with Alzheimer disease are affected, and additionally understand some of the genetic explanations of the disease, the precise cause of Alzheimer disease is still unclear. For example, it is known that accumulations of clumps of proteins called amyloid plaques outside brain cells and accumulation of altered proteins inside the cells called neurofibrillary tangles are characteristic of Alzheimer disease; however, it is unclear how these accumulated proteins cause brain cells to die.

According to the Alzheimer's Disease and Related Disorders Association, Inc., there are seven stages that characterize the disease:

• Stage 1: No decline in function is yet noted. This group includes individuals who may carry predictive gene mutations but have no symptoms, or those who will be affected by other unknown mechanisms.
• Stage 2: Normal function in general, although the person is aware of a subtle cognitive decline.
• Stage 3: Early Alzheimer disease. Persons experience difficulty in performing complex tasks that require cognitive skills.
• Stage 4: Mild Alzheimer disease. Persons require assistance with common tasks such as paying bills and balancing a checkbook.
• Stage 5: Moderate Alzheimer disease. Persons require assistance in making personal everyday decisions such as choosing appropriate clothing for the weather or ordering from a menu.
• Stage 6: Moderately severe Alzheimer disease. Persons require assistance dressing, bathing, and using the toilet. Urinary and bowel incontinence may be present.
• Stage 7: Severe Alzheimer disease. The vocabulary shrinks to only a few words; then little or no verbal communication is heard. The ability to walk is lost, followed by an inability to maintain a sitting posture in a chair. Eventually, the person experiences profound lack of purposeful muscle control, is totally dependent for care, and cannot smile or hold up his or her head.

Diagnosis

Alzheimer disease is diagnosed clinically by a physician, postmortem by a histopathologist (a scientist who studies diseased tissues by their various staining patterns), or genetically by identifying mutations in genes associated with the disease.

The gold standard for diagnosis of Alzheimer disease is through autopsy examination by an experienced pathologist. Detection of amyloid plaques in the brain by histopathology is the most conclusive diagnostic tool. This is performed using antibodies that bind to the particular amyloid proteins and can be visualized by microscopic evaluation, as the antibodies are tagged with a fluorescent or colorimetric molecule. A positive result would involve a significantly greater number of plaques compared to agematched controls. Other brain defects that characterize the disease, such as abnormal nerve cell configurations called intraneuronal neurofibrillary tangles, can also be detected by histopathology by the same methods. A clinical diagnosis by a physician accounts for 80–90% of patients diagnosed with Alzheimer disease.

Causes and symptoms---etc

Causes and symptoms

Although there are several known causes of Alzheimer disease, about 75% of cases are sporadic and occur without a clear cause; this percentage represents people without a family history of the disorder. Scientists assume that these cases are due to a combination of unknown genetic predisposing factors and environmental exposures. Although various narcotics, therapeutic drugs, viruses, and toxins have been implicated in the etiology of the disease, there is currently no proof that they can cause Alzheimer disease.

Genetic basis for Alzheimer disease

Of all persons with Alzheimer disease, up to 25% of cases are thought to be part of a familial-based inheritance pattern and therefore are only determined based on family history or genetic test results. In general, these forms of Alzheimer disease are inherited as an autosomal dominant disorder, meaning that affected individuals have a 50% chance of passing on the mutated gene to their offspring in each pregnancy. There is a late-onset familial form (AD2), three early-onset familial forms (AD1, AD3, AD4), and a form of Alzheimer disease associated with Down syndrome.

Down syndrome and Alzheimer disease

Less than 1% of all cases of Alzheimer disease are due to a chromosomal defect called trisomy 21 (also known as Down syndrome). This occurs when there are three copies of genes found on chromosome 21, usually due to a person having an extra chromosome 21. These individuals usually develop Alzheimer disease after the age of 40. The APP gene, which encodes the amyloid precursor protein and is implicated in the pathogenesis of Alzheimer disease, is localized to chromosome 21; it is felt that people with Down syndrome overproduce this protein, resulting in its accumulation in the brain. The excess protein is thought to cause the disease.

Early-onset familial Alzheimer disease

A low percentage (2%) of Alzheimer cases results from a familial form of the disease in which there is an early onset of symptoms (AD1, AD3, and AD4), usually occurring before the age of 60. Age of onset usually occurs around 40–50 years, but can occur as early as 30 yea majority of these persons have family members that are also affected. The clinical manifestations are similar to the adult-onset form, with loss of memory and cognitive ability. In this form of Alzheimer disease, there are several chromosomal locations of genes implicated in causing the disease.

AD1 accounts for approximately 10–15% of earlyonset Alzheimer disease and involves a protein called presenilin 1 that has a mutation in the gene that encodes it called PSEN1, which is found on chromosome 14. AD3 accounts for 20–70% of the early-onset familial form and is caused by mutations in APP found on chromosome 21, which encodes a protein called amyloid beta A4. AD4 is extremely rare and is caused by mutations in PSEN2, localized to chromosome 1, and encodes a protein called presenilin 2.

Definition---etc

Definition

Alzheimer disease is a neurological disorder characterized by slow, progressive memory loss due to a gradual loss of brain cells. Alzheimer disease significantly affects cognitive (thought) capabilities and, eventually, affected individuals become incapacitated. Alzheimer-related issues can cause emotional and financial upheaval for both the individuals with the disease and their families. Alzheimer disease is the most common form of dementia (loss of intellectual function) and, according to the National Institutes of Health (NIH), it is the fourth leading cause of death in adults.

Description

The condition was first described in 1906 by Alois Alzheimer, a German physician. Alzheimer characterized two abnormal structures in the brain of a woman with dementia that are now considered the hallmarks of the disease: amyloid plaques and neurofibrillary tangles. The nature of Alzheimer disease is progressive. Initially, dementia is manifested by barely noticeable memory deficits. Eventually, the memory loss becomes more severe until it is incapacitating. Other symptoms such as confusion, the inability to articulate words correctly, and hallucinations occur with varying degrees. Emotional problems such as easy agitation, poor judgment, and feelings of withdrawal are also common in the early stages. Affected individuals are also likely to develop seizures, hypertonicity (increased muscle movements), and incontinence. Without treatment or supervision, death often results from malnutrition or pneumonia. From the initial symptoms, disease progression can last up to 25 years, although typically the duration ranges from eight to 10 years.

Demographics

Dementia is thought to affect between 25–50% of individuals 85 years or older. The risk of developing Alzheimer disease increases with age and is independent of sex or geographical location (although there are environmental toxic agents that can impair various cognitive functions, including memory loss). A genetic association has been found for higher risk of developing Alzheimer disease in individuals with mutations in a particular gene who are also African American or Caribbean Hispanics. This association is greatest in individuals with a positive family history of dementia.

Approximately 10% of people 65 years or older are at risk for developing significant memory loss. More than half of these individuals (5% of all individuals 65 years or older) have Alzheimer disease. Approximately four in 10,000 individuals between the ages of 40 and 60 are at risk for having Alzheimer disease.