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Alzheimer's has become the fourth leading cause of death by disease and is affecting more and more families across the country. AgeNet is commited to being a resource for those affected by this disease.  We will continue to provide cutting-edge information on Alzheimer's as well as access to experts who have been successful in improving the quality of life of Alzheimer's patients and their families.

Alzheimer's disease is characterized by an impairment of memory and intellectual functioning. Memory loss associated with Alzheimer's should not be confused with normal memory loss tied to aging, known as benign senescent forgetfulness. In addition to memory, aspects of cognition that are affected by Alzheimer's disease are judgement, abstract thinking, language, personality and visual-spatial skills. Alzheimer's can be broken down into three levels of severity: mild, moderate and severe or advanced. Risk-factors for the development of Alzheimer's include: age, female gender, history of head trauma, family history, history of vascular disease, and low educational attainment.

Alzheimer's disease is one of several forms of dementia. There is no definitive test to diagnose the condition; its presence is determined by ruling out other forms of dementia or delirium. Dementia is defined as an organic mental syndrome that precipitates a significant deterioration of cognition and impairs performance of routine activities. The most prominent impairment is that of memory. It is not uncommon for an individual with Alzheimer's to forget how to drive home or who his or her relatives are.

Reversible forms of dementia

Since some forms of dementia are reversible, it is important to determine what type of dementia your family member has. Some forms of dementia are abrupt in onset, whereas others, like Alzheimer's, take hold more slowly. Dementia may be caused by the following: dehydration, electrolyte or glucose imbalances, infection, medications, neurologic causes such as a vitamin B-12 deficiency, hypothyroidism, hypoxia, alcoholism, psuedo-dementia secondary to depression, and others. These conditions must be ruled out before one can suspect that a person has an irreversible form of cognitive impairment.

Causes of irreversible dementia, other than Alzheimer's, include: HIV, head trauma, Parkinson's disease, Pick's disease, Huntington's disease. Next to Alzheimer's, one of the most frequent forms of dementia is multi-infarct or vascular dementia. Vascular dementia is abrupt in onset, resulting from a stroke or multiple strokes/infarcts.

Management options

Currently, there are no medications that halt or slow the progression of Alzheimer's. There are, however, medications that can improve cognition, and thereby delay Alzheimer's devastating effects on patients and families.

The medications known to improve cognition of those with Alzheimer's are Cognex (tacrine), Aricept (donepezil), Excelon (rivastigamine) and Reminyl (galantamine). These medications work by increasing the amount of acetylcholine in the brain. Acetylcholine affects memory and recall and is largely responsible for transmitting the brain signals that control cognition.

Because of its negative side effects, Cognex has been largely replaced by the other three drugs. Cognex not uncommonly causes liver impairment and significant gastrointestinal side effects. However, the other listed medications have a better side effect profile than Cognex.

Cognex, Aricept, Excelon, and Reminyl do not actually delay the progression of Alzheimer's, but they do lessen the decline in cognition in the mild and moderate stages of the disease. They are also known to lessen agitated behaviors. Although these drugs are not answers or cures, they do provide options for the daily management of Alzheimer's.

Prevention

Medications that can play a role in reducing the risk of Alzheimer's are reviewed as follows:

It has been shown that NSAIDs, otherwise known as non-steroidal anti-inflammatory drugs (e.g., Ibuprofen (Motrin and Advil)), are effective in reducing one's risk of developing Alzheimer's. These drugs are particularly important for those at high risk of developing Alzheimer's (i.e., strong family history).  Taking NSAIDs is not without risk. In certain individuals NSAIDs may induce gastrointestinal bleeding. More information is needed on the long-term use of NSAIDs in preventing Alzheimer's.

Another preventive measure is taking vitamin E on a daily basis. It has been shown that vitamin E reduces the risk of developing Alzheimer's. Doses of 1000 - 2000 I.U. per day are recommended. Also, vitamin E is beneficial in preventing cardiovascular disease. Caution is advised when taking vitamin E with Coumadin and/or aspirin since high doses of vitamin E can exacerbate bleeding.

Ginkgo Biloba, a natural remedy, has been shown to improve cognition. When taken daily it seems to improve recall and increase mental acuity. It is unknown how Ginkgo Biloba works.  Some researchers cite its ability to improve blood flow to the brain. This understanding seems inadequate as other cerebral vasodilators do not yield the same benefits as Ginkgo.  More research must be done.  Caution is advised when taking Ginkgo concurrently with Coumadin because Ginkgo has an aspirin-like effect. 

Lastly, there are studies that suggest that smoking helps to reduce the risk of developing Alzheimer's. It is sometimes thought that smoking has a "protective effect" because nicotine mimicks the effects of acetylcholine. (They both work on the same receptor in the brain to enhance recall and cognition.)  However, a recent study conducted by the Emasmus University Medical School in Rotterdam and the University of Antwerp in Belgium concludes that smoking more than doubles the risk of dementia and Alzheimers.

Investigational drugs

Although therapy options for Alzheimer's are few, there are many investigational drugs that are showing promise. We will keep you posted on our web page as new drugs near FDA approval. One such drug is metrifonate. It is manufactured by the Bayer Corporation. Metrifonate is in the same class as Cognex and Aricept.

Managing depression, anxiety and aggression

Not uncommonly, the path traveled by one with Alzheimer's is littered with bouts of anxiety, depression and agitated behaviors. When managing these conditions one must be cautious to select a drug therapy that does not negatively affect cognition and result in a worsening of clinical status.

Depression

Alzheimer's patients suffer from depressed mood at a rate of nearly 50%, with 10-20% suffering from major depression. Depression is thought to be underdiagnosed and undertreated in this sub-group, resulting in a poorer quality of life.   People with depression often experience insomnia or hypersomnia, increased agitation, anxiety and irritability. It is believed that these behavioral symptoms are more debilitating to a person with Alzheimer's than impaired cognition. In fact, these behavioral problems are the primary reason for institutionalization of those with Alzheimer's. Thus, depression needs to be identified and treated in order to improve the overall quality of life for those with Alzheimer's.

Diagnosis of depression in one with impaired cognition is more difficult because symptoms may be expressed as somatic complaints. There are, however, several assessment scales used to help define and diagnose depression in the elderly. One example is the Cornell Depression Scale. Assessments should be performed by an experienced medical professional.

Treatment of depression in the elderly should take a different approach than treatment of younger patients since some of the more traditional antidepressants (e.g., Elavil (amitriptyline), Tofranil (imipramine), Sinequan (doxepin)) can produce additional complications for seniors.   These problems include: urinary retention with subsequent bladder infection and/or incontinence, constipation (which may also cause incontinence), delirium (a form of dementia), aggravation of glaucoma, cardiac arrhythmias, sedation, dizziness, among others.

Antidepressants that are better tolerated in the elderly are: Celexa (citalopram), Prozac (fluoxetine), Zoloft (sertraline), and Paxil (paroxetine). Although these drugs are not without side effects (such as anxiety, anorexia, insomnia, dry mouth), they have been shown to be better tolerated than more traditional antidepressants.

AgeNet prefers Celexa and Prozac, a conclusion founded on several studies. Celexa, the newest agent of the class called SSRI's (Selective Serotonin Re-uptake Inhibitors) is the most utilized antidepressant in Europe, but is rather new to the U.S. market. Data suggests that Celexa is well suited for the elderly. Prozac has been shown to produce fewer side-effects in the elderly than Zoloft. The previous assumption about Prozac was that its long half-life and duration of action lead to accumulation, making it an undesirable SSRI for the management of depression in the elderly. However, when dosed appropriately (e.g., 10mg daily or every other day), it appears to be very well tolerated and effective.

Another antidepressant that is fairly well tolerated in the elderly is Serzone.  It should be noted that Serzone has an anti-anxiety effect.  Remeron is another acceptable alternative and may be preferred by those who are below a desirable weight; weight increases are not uncommon with the use of Remeron.  The consumption of SSRIs by those who are underweight could cause further weight loss and lead to complications.  

Anxiety

Anxiety may be managed with an agent called Buspar, a drug that has fewer side effects than its alternatives. More traditional agents, such as Valium, Xanax, Librium, and Ativan, cause significant sedation and impairment of cognition. Also, Valium, and drugs in the benzodiazepine class, may cause a paradoxical rage reaction. If an anti-anxiety agent is needed for an acute episode of anxiety, the smallest dose of Ativan or Serax is recommended, and only on an "as needed" basis. These drugs are metabolized more favorably in the elderly and ,as a result, are recommended over drugs like Valium.

Aggression

Since advancing Alzheimer's is wrought with bouts of aggression, it is important to understand how to effectively manage these outbursts. Most important to realize is that the intensity and frequency of aggressive episodes may be prevented by altering the patient's environment. Keeping lights low in intensity, minimizing distracting sounds, and reducing other stimuli lessen the likelihood of the patient becoming agitated. Remember, keep it simple. You may want to visit the National Alzheimer's Association web page to get more helpful hints on managing the environment of someone with Alzheimer's. Also, you may want to visit AgeNet's Alzheimer's Disease Links and Resources which includes an "Early Alzheimer's Patient & Family Resource Guide" and books on both Alzheimer's Disease and Dementia.

When a person suffering from Alzheimer's has an outburst, it may be desirable to use a pharmacologic agent to relax them. Drugs that have anti-cholinergic side effects may not be desirable since they may further impair cognition and result in increased combativeness (e.g., Thorazine or Mellaril). Likewise, we do we want to over-sedate the patient. Thus, selecting the proper agent is important in managing the acute episode.  One option may be small doses of Haldol (e.g., 0.5mg).

Although not to be used for acute episodes of agitation, Risperdal can be used to manage or reduce the incidence of agitation and hallucinations. Risperdal is known as an atypical anti-psychotic agent, which is more favorable in the elderly because of its association with a lower risk of movement disorders; this contrasts Risperdal with Thorazine, Mellaril and Haldol. If occasional use is needed for combative episodes, then one of the less expensive and more traditional agents may be justified. The movement disorder that results from the use of anti-psychotic agents is called EPS or pseudo-parkinsonism. It is very much like Parkinson's disease and involves stiffness, rigidity, tremors, altered gait, and postural imbalance. It is important to realize that postural and gait imbalances contribute to the incidence of falls.  Use these drugs cautiously!

Other atypical agents found to be useful for managing agitation are Seroquel and Zyprexa.  Seroquel is not as well studied in the elderly but appears to be effective at doses ranging from 100-300mg.  Seroquel may be a good choice for those with Parkinson's disease since it may not induce the Parkinson-like side effects seen with other agents.   Zyprexa may also be effective, but it has potent anti-cholinergic effects which must be considered when selecting an anti-psychotic agent for the elderly.

Alternative medications for aggressive behaviors

New information suggests that other medications seem to be effective at managing aggressive behaviors, especially those associated with "sundowning". Sundowning is a phenomenon linked to Alzheimer's in which episodes of agitation become more frequent and intense in the late afternoon and early evening (hence "sundowning").

Two medications that appear to be effective in managing aggressive behaviors are Desyrel (trazodone) and Sodium Valproate (Depakote). Trazodone was used originally as an antidepressant but seems to be more effective in the elderly as a hypnotic (or sleep) agent. It is now a favored drug in managing acute aggressive behaviors in Alzheimer's patients.  The drug Trazodone may cause dizziness and contribute to falls; thus it should be used only in individuals unlikely to fall.

Depakote (Sodium Valproate) is a commonly used anti-seizure medication that is showing success in managing aggressive behaviors. It appears effective in the elderly and has demonstrated good side effect tolerance.

We hope this review provided you with information that may help you to better care for someone with Alzheimer's. If you wish to seek more information regarding any of the medications we spoke of you may want to visit AgeNet's Alzheimer's Disease Links and Resources which includes an "Early Alzheimer's Patient & Family Guide" and books on both Alzheimer's Disease and Dementia.

Drugs for Managing Alzheimers

Drugs That May Help Reduce Risk of Developing Alzheimers

Preferred Drugs for Managing Depression

Acceptable Drugs for Managing Depression

Nonpreferred Drugs for Managing Depression

Preferred Drugs for Managing Anxiety

Excluded Drugs for Managing Anxiety

Preferred Drugs for Managing Aggression

Excluded Drugs for Managing Aggression

Alternative Drugs for Managing Aggression

2/04/2000