TOC  |   Neurology  |  Dementia  

Alzheimer's Dementia         Alzheimer2010.pdf  |   Early Alzheimer2010.pdf   

Alzheimer's Association

Diagnosis, Management, and Treatment of Alzheimer Disease -  A Guide for the Internist
Stephanie S. Richards, MD; Hugh C. Hendrie, MB, ChB
Arch IM April 26, 1999;159:789

What is Alzheimer’s disease?

Alzheimer’s is a degenerative disease that usually begins gradually, causing a person to forget recent events or familiar tasks. How rapidly it advances varies from person to person, but the brain disease eventually causes confusion, personality and behavior changes and impaired judgment. Communication becomes difficult as the affected person struggles to find words, finish thoughts or follow directions.

Eventually, most people with Alzheimer’s become unable to care for themselves.

What are the warning signs?

The Alzheimer’s Association has developed a list of warning signs that include common symptoms of Alzheimer’s disease (some also apply to other dementing illnesses). Individuals who exhibit several of these symptoms should see a physician for a complete examination.

1. Memory loss that affects job skills. It’s normal to occasionally forget an assignment, deadline or colleague’s name, but frequent forgetfulness or unexplainable confusion at home or in the workplace may signal that something’s wrong.

2. Difficulty performing familiar tasks. Busy people get distracted from time to time. For example, you might leave something on the stove too long or not remember to serve part of a meal. People with Alzheimer’s might prepare a meal and not only forget to serve it, but also forget they made it.

3. Problems with language. Everyone has trouble finding the right word sometimes, but a person with Alzheimer's disease may forget simple words or substitute inappropriate words, making his or her sentences difficult to understand.

4. Disorientation to time and place. It's normal to momentarily forget the day of the week or what you need from the store. But people with Alzheimer's disease can become lost on their own street, not knowing where they are, how they got there or how to get back home.

5. Poor or decreased judgment. Choosing not to bring a sweater or coat along on a chilly night is a common mistake. A person with Alzheimer's, however, may dress inappropriately in more noticeable ways, wearing a bathrobe to the store or several blouses on a hot day.

6. Problems with abstract thinking. Balancing a checkbook can be challenging for many people, but for someone with Alzheimer's, recognizing numbers or performing basic calculation may be impossible.

7. Misplacing things. Everyone temporarily misplaces a wallet or keys from time to time. A person with Alzheimer's disease may put these and other items in inappropriate places – such as an iron in the freezer, or a wristwatch in the sugar bowl – then not recall how they got there.

8. Changes in mood or behavior. Everyone experiences a broad range of emotions – it’s part of being human. People with Alzheimer's tend to exhibit more rapid mood swings for no apparent reason.

9. Changes in personality. People's personalities may change somewhat as they age. But a person with Alzheimer's can change dramatically, either suddenly or over a period of time.  Someone who is generally easy going may become angry, suspicious or fearful.

10. Loss of initiative. It's normal to tire of housework, business activities, or social obligations, but most people retain or eventually regain their interest. The person with Alzheimer's disease may remain disinterested and uninvolved in many or all of his usual pursuits.


What causes Alzheimer's?

Scientists are still not certain. Age and family history have been identified as potential risk factors. Researchers are exploring the role of genetics in the development of Alzheimer’s, but most agree the disease is likely caused by a variety of factors.

How is Alzheimer's diagnosed?

There is no single, comprehensive diagnostic test for Alzheimer's disease. Instead, physicians or other specialists rule out other conditions through a process of elimination. Physical, psychological and neurological exams are usually conducted and a thorough medical history taken. A diagnosis of probable Alzheimer's disease can be obtained through evaluation with approximately 90% accuracy. The only way to confirm a diagnosis of Alzheimer's disease is through autopsy.

Steps to diagnosis

Currently, there is no one diagnostic test that can detect if a person has Alzheimer’s disease. However, new diagnostic tools and criteria make it possible for physicians to make a positive clinical diagnosis of Alzheimer’s with an accuracy of 85-90%. The diagnostic process may take more than one day, and will involve your primary care physician and possibly other specialty physicians, such as a psychiatrist, or a neurologist. Evaluations commonly performed during a diagnosis include:

A diagnosis of probable Alzheimer’s indicates that the physician has ruled out all other disorders that may be causing dementia, and has come to the conclusion that symptoms are most likely the result of Alzheimer’s disease.

A diagnosis of possible Alzheimer’s indicates the presence of another disorder that may be affecting the known progression of Alzheimer’s, so that the disease process is somewhat different than what is seen normally. In this case, however, it is still Alzheimer’s disease that is the primary cause of dementia symptoms.

A diagnosis of definite Alzheimer’s only can be made at time of autopsy and requires examination of brain tissue. Autopsy allows for confirmation of the presence of plaques and tangles, which are the characteristic lesions of Alzheimer’s, and is the only way to diagnose the disease with 100% accuracy. A brain autopsy confirming Alzheimer’s can provide a vital record for your family’s medical history.


How does it progress?

Alzheimer’s disease causes the formation of abnormal structures in the brain called plaques and tangles. As they accumulate in affected individuals, nerve cells connections are reduced. Areas of the brain that influence short-term memory tend to be affected first. Later, the disease works its way into sections that control other intellectual and physical functions.

Alzheimer’s disease affects people in different ways, making it difficult for medical professionals to predict how an individual’s disease will progress. Some experts classify the disease by stage (early, middle and late). But specific behaviors and how long they last vary greatly, even within each stage of the disease.

Does Alzheimer's disease run in families?

The evidence is not clear. Cases where several members of a single family have been diagnosed with Alzheimer’s is rare (except in families who have a history of early onset Alzheimer’s, a form of the disease that typically strikes middle-aged members of the same family). Much more common is the situation where a single family member is diagnosed with Alzheimer’s late in life.

Does Alzheimer's disease occur in younger adults?

Yes, though less frequently. The disease can occur in people in their 30s, 40s and 50s, however, most people diagnosed with Alzheimer’s are older than 65. The early onset form of the disease that strikes younger people accounts for less than 10 percent of all reported cases and is considered quite rare.

Isn't memory loss a natural part of aging?

Yes and no. Many healthy individuals are less able to remember certain kinds of information as they get older. But the symptoms of Alzheimer’s disease involve more than simple lapses in memory.  People with Alzheimer’s experience difficulties communicating, learning, thinking and reasoning, that can have an impact on a person’s work, social and family life. Alzheimer’s is a disease that destroys brain cells – which is not a normal part of aging.

What is dementia?

Dementia is an umbrella term used to describe the loss of cognitive or intellectual function. Many conditions can cause dementia.  Dementia related to depression, drug interaction, thyroid and other problems may be reversible if detected early. That’s one of the reasons why it’s important that a professional assessment takes place, so that the actual cause can be identified and proper care provided. Several other diseases also cause dementia, such as Parkinson’s, Creutzfeldt-Jakob, Huntington’s and Multi-Infarct or vascular disease, caused by multiple strokes in the brain.


What treatment is available?

There is no medical treatment currently available to cure or stop the progression of Alzheimer’s disease.

These drugs –
Donepezil (Aricept)
Memantine (Namenda)
tacrine (Cognex), &
Rivastigmine (Exelon) ,
Reminyl (Glantamine)
-- may temporarily relieve some symptoms of the disease and have been approved by the FDA. Many other new promising drugs are now being developed – some which may be available within the next few years. Medication and non-drug therapies are also available to reduce some of the behavioral symptoms associated with Alzheimer’s, such as depression, sleeplessness and agitation.

Neither tacrine nor donepezil will cure Alzheimer’s, nor do they stop the progression of the disease. Both are indicated for the treatment of individuals with mild to moderate Alzheimer’s and may not be as effective for those in the advanced stages of the disease.

Donepezil (Aricept):

Tacrine (Cognex):

Rivastigmine (Exelon) 1.5 - 3 - 4.5 -6 mg cap bid PO
It works in the brain the same way as the other two Alzheimer's drugs, Aricept and Cognex. They inhibit the breakdown of acetylcholine, a brain chemical vital for nerve cells to communicate with each other. The longer acetylcholine remains in the brain, the longer those cells can call up memories.

The drugs offer modest relief for mild to moderate Alzheimer's symptoms. While the products have not been compared directly, Exelon's effectiveness is believed to be "pretty much in the same league" as Aricept and Cognex, said FDA official Dr. Russell Katz.

After 26 weeks of therapy, 81 percent of Exelon patients had stable or slightly better symptoms than patients given a dummy pill, Novartis said.   But Katz noted that Exelon's label bears a strong warning about a significant risk: It can cause nausea and vomiting severe enough that patients lose weight. In clinical trials, 26 percent of women and 18 percent of men who took high-dose Exelon lost at least 7 percent of their initial body weight.   The nausea and weight loss did end once affected patients stopped the drug.   Katz noted that Alzheimer's patients need options. "We just don't know who's going to respond to which drug" until they try one, he said.

Reminyl (Glantamine) 4-8 mg tab bid  

Memantine  (Namenda) in Moderate-to-Severe Alzheime
Results:  Two hundred fifty-two patients (67 percent women; mean age, 76 years) from 32 U.S. centers were enrolled. Of these, 181 (72 percent) completed the study and were evaluated at week 28. Seventy-one patients discontinued treatment prematurely (42 taking placebo and 29 taking memantine). Patients receiving memantine had a better outcome than those receiving placebo, according to the results of the CIBIC-Plus (P=0.06 with the last observation carried forward, P=0.03 for observed cases), the ADCS-ADLsev (P=0.02 with the last observation carried forward, P=0.003 for observed cases), and the Severe Impairment Battery (P<0.001 with the last observation carried forward, P=0.002 for observed cases). Memantine was not associated with a significant frequency of adverse events.
Conclusions:  Antiglutamatergic treatment (20 mg of memantine daily for 28 weeks) reduced clinical deterioration in moderate-to-severe Alzheimer's disease, a phase associated with distress for patients and burden on caregivers, for which other treatments are not available.
NEJM April 3, 2003 Volume 348:1333-1341

[Memantine is a substance developed by the Merz research organization and is successfully used to treat dementia. Clinical data show that Memantine provides rapid and enduring improvement in the cognitive, psychological, social and motor impairments of dementia. These symptomatic improvements lead to an increased quality of life of the patients and reduces home care efforts.
The efficacy of memantine is due to rapid, voltage-dependent interactions with the NMDA-receptor channel (Preclinical data). It is well-known that disturbances in brain function are associated with disturbances in glutamatergic neurotransmission and loss of specific glutamate receptors (Glutamate and Dementia).  As a NMDA receptor antagonist memantine protects the neuronal system from pathological activation while preserving or even restoring physiological activation (Mode of action).]


Treatment for Behavior Symptoms             

Damage to the brain from Alzheimer’s disease can cause a person to act in different or unpredictable ways. Some individuals with Alzheimer’s become anxious or aggressive, while others repeat certain questions or gestures. Often these behaviors occur in combination, making it difficult to distinguish one from another.

Behavioral problems do not always become apparent immediately after onset of disease, and often change as the disease progresses.

Challenging behaviors not only cause discomfort to individuals with the disease, but also can be frustrating and stressful for caregivers who cannot understand them.

When a problematic behavior surfaces, the individual with Alzheimer’s first needs to be evaluated by a physician for potential underlying causes. Behavioral symptoms often result from a variety of treatable problems that the individual cannot communicate, such as:

When behavioral symptoms are brought on by causes other than physical problems, they may be treatable through non-drug treatments or drug treatments.

Non-drug treatments             

Non-drug treatments of behavioral symptoms are recommended as a first option, since symptoms are best modified without the use of medication. Some suggestions for caregivers and families are:

Family education and counseling. Learn what to expect when afflicted with or caring for someone with Alzheimer’s. Family members who are familiar with the disease and know how to effectively communicate with their loved one may be able to better cope with challenging behaviors. Counseling and support for individuals with the disease and their families is available through local chapters of the Alzheimer’s Association.

Modifying the environment. Environmental factors such as lighting, color, and noise can greatly affect behavior.

Dim lighting, for example, makes some individuals uneasy, while loud or erratic noise often causes confusion and frustration. Modify the environment to reduce confusion, disorientation, and agitation. Keep familiar personal possessions visible to ensure comfort and feelings of warmth in your loved one’s surroundings.

Planning activities. Help individuals with Alzheimer’s organize their time and know what to expect each day.

Planned activities help individuals feel independent and needed by focusing their attention on pleasurable or useful tasks. Daily routines such as bathing, dressing, cooking, cleaning, and laundry can be turned into productive activities. Other more creative leisure activities can include singing, playing a musical instrument, painting, walking, playing with a pet, or reading. Planned activities may relieve depression, agitation, and wandering and help affected loved ones enjoy the best quality of life.

Drug Treatments

Non-drug treatments are not always effective, therefore, severe behavioral symptoms may be best treated with medication. In some cases, drugs that are available for the treatment of cognitive symptoms [such as donepezil HCl (Aricept®), or tacrine HCl (Cognex®)] also may improve behavioral problems.

Several drugs are available for treating problematic behaviors and many more are being studied for specific use in helping those who suffer from Alzheimer’s. Drugs commonly used to treat behavioral symptoms such as agitation, aggression, paranoia, delusions, or depression associated with Alzheimer’s include:

Antipsychotics (neuroleptics)

Anti-anxiety drugs


Like any other drugs, these treatments can cause undesirable side effects. Because individuals with Alzheimer’s may have difficulty identifying medication side effects, ask your physician or pharmacist about what to expect and warning signs to watch for with any drug that is prescribed.


Appendix: The Six Practice Recommendations Provided to the Intervention Group
Ref:  Annals of Internal Medicine, 17 August 1999  131:237-246

1. Use of neuroimaging in dementia evaluation .

"After performing a careful history and physical examination, the neurologist should consider whether or not to obtain a neuroimaging (MRI or CT scan) study in a patient diagnosed with dementia. Based on the AAN Practice Parameter, neuroimaging is usually indicated if any of the following criteria are present: duration of cognitive complaints <6 months, symptom onset before age 60 years, focal signs, focal symptoms, or papilledema, diagnosis by history of new onset seizures, or gait abnormalities (e.g. ataxic or apraxic gait).  
Neuroimaging need not be routinely obtained in every patient with dementia." Based on reference 15. Other organizations that support similar recommendations are the American College of Physicians (23), the Canadian Consensus Conference (25), the Department of Veterans Affairs (26), and New York State Department of Health (21).

2. Use of electroencephalography in dementia evaluation .

"Electroencephalography is not recommended as part of the routine evaluation in individuals with dementia unless the following criteria are present: (a) clinical history suggestive of seizure(s), including patients with fluctuating levels of consciousness (i.e. "sleepy demented") or transient brief episodes of behavior change, OR (b) Creutzfeldt Jakob Disease (CJD) is suspected, that is: rapid decline in cognitive function over 3 months or less, or ataxia, chorea, or myoclonus early in the course of dementia, AND any extrapyramidal or cerebellar features that are not attributable to some other diagnosis." Based on reference 15.

3. Detection and treatment of depression in dementia evaluation .

"(A) All patients diagnosed with dementia should be screened for depression initially and thereafter at least every 6 months using either: (a) questions to assess mood during the clinical history, or (b) a validated screening questionnaire for depression such as the Cornell Scale for Depression in Dementia. (B) Depression should be treated either when diagnosed or when highly suspected in patients with dementia." Based on references 19 to 21.

4. Testing for apolipoprotein E genotype in dementia evaluation .

"Apolipoprotein E genotype testing should not be ordered in routine office practice to diagnose Alzheimer's disease in individuals with dementia (or possible dementia). Apolipoprotein E genotype testing should not be ordered as a screening test to predict Alzheimer's disease in asymptomatic individuals. At present, apolipoprotein E genotype testing is only appropriate in the research setting, where data on its diagnostic utility can continue to be collected and analyzed, and where formal genetic counseling should be provided."   Based on reference 16.

5. Referral to the Alzheimer's Association.

(This recommendation also contained a description of the Alzheimer's Association and the Alzheimer's Disease Education and Referral Center.)
"At the time of diagnosis, patients with dementia (and their caregivers) should be referred by their physician to organizations that can provide educational information and resources, such as Alzheimer's Disease and Related Disorders Association (Alzheimer's Association) 1-800-272-3900.

6. Encouragement to enroll in the Safe Return Program.

(This recommendation also contained a description of the Safe Return Program.) "Patients with an established diagnosis of dementia should be encouraged to enroll in the Alzheimer's Association's Safe Return Program because of the potential for wandering and injury."

Alzheimer's Association Website 5-11-1999
Mayo Clinic Alzheimer Site