Alzheimer's Disease

Alzheimer's disease (AD) is a progressive, degenerative brain disease that results in impaired memory, thinking, and behavior. It is the most common cause of dementia in the elderly and affects at least three to four million people in the United States. People with AD experience gradual memory loss as well as impaired judgement, difficulty concentrating, loss of language skills, personality changes, and a decline in the ability to learn new tasks. Memory loss usually begins at about age 65 and symptoms tend to become severe within 8 to 10 years. In some cases, symptoms may appear earlier in life and advance at a faster or slower rate, but most people who develop symptoms before the age of 60 tend to have more severe forms of the disease. Currently, there is no cure for AD, but studies suggest that medications, herbs and supplements, and lifestyle adjustments may all help to slow the progression and improve the symptoms of the disease.

Signs and Symptoms

The early symptoms of AD are occasionally overlooked because they resemble signs that many people attribute to "natural aging." The following are the most common signs and symptoms of AD.

Psychological Symptoms

• Memory loss, including not recognizing friends and family members
• Difficulty concentrating
• Difficulty comprehending words, completing sentences, or finding the right words
• Loss of familiarity with surroundings, wandering aimlessly
• Depression
• Hallucinations, delusions, and psychosis
• Aggression, agitation, anxiety, restlessness
• Accusatory behaviors (such as accusations of spousal infidelity)
• Withdrawal, disinterest, hostility, loss of inhibitions

Physical Symptoms

• Impaired movement or coordination
• Muscle rigidity, shuffling or dragging feet while walking
• Insomnia or disturbances in sleep patterns
• Weight loss
• Incontinence
• Muscle twitching or seizures

Causes

The causes of AD are not entirely known but are thought to include genetics and environmental factors. New research indicates that free radicals (highly reactive molecules that can cause oxidation, or damage to cells) may play a role in the development of AD.

A gene for the protein epsilon apolipoprotein (Apo E)—especially Apo E3 and Apo E4 varieties—is thought to accelerate the formation of abnormal deposits (called plaques) in the brain and increase the risk for AD. Reports indicate that between 50% and 90% of those with the Apo E4 gene develop AD. However, even people without inherited genes for the disease can get AD.

Scientists also believe the environment may play a part in AD because people in different regions of the world have widely varying risks of developing the disease. For example, people living in Japan and West Africa have much less risk for AD than Japanese and Africans living in the United States.

People with AD have abnormal deposits, or plaques, in their brain tissue. These plaques contain beta amyloid, a protein that releases free radicals, or highly reactive molecules that can cause damage to cells through a process called oxidation. These free radicals are believed to lower levels of acetylcholine (a brain chemical that helps transmit impulses in the nervous system) and damage brain tissue, bringing on the symptoms of AD.

Although not confirmed by scientific studies, other factors that have been speculated to contribute to the development of AD include infections (such as herpesvirus type 1), exposure to metal ions (such as aluminum, mercury, zinc, copper, and iron), or prolonged exposure to electromagnetic fields.

Risk Factors

The causes and risk factors contributing to the development of AD are not entirely clear. The following all appear to have an association with AD to varying degrees.

• Family history of AD
• Older age — 20% to 40% of people with AD are older than 85
• Female gender—while women tend to develop AD more than men, this may be related to the tendency for women to live longer
• Americans are more likely to get AD than Asians or Native Americans
• Long-term high blood pressure
• History of head trauma—one or more serious blows to the head may put a person at an increased risk
• Down Syndrome
• Elevated levels of homocysteine (a body chemical that contributes to chronic illnesses such as heart disease, depression, and AD)
• Aluminum or mercury poisoning
• Prolonged exposure to electromagnetic fields

Diagnosis

There is no definitive test for AD, and a true diagnosis of AD can only be made after a person dies and an autopsy is performed on the brain. All individuals with AD have an accumulation of abnormal deposits (called plaque) and tangled nerve cells in their brains. The physician will try to narrow down a diagnosis, however, by eliminating the possibility of other illnesses. He or she will ask the individual (or a close family member) to describe the primary symptoms, and how long they have been noticeable.

The following tests may also be used to aid in the diagnosis.

• Psychological tests — assess the individual's memory and attention span. They may also reveal difficulties in problem-solving, social, and language skills.
• Electroencephalograph (EEG) — traces brain-wave activity. This test sometimes reveals "slow waves" in people with AD. Although other diseases may reveal similar brain-wave activity, EEGs help distinguish a person with AD from a severely depressed person, whose brain waves are normal.
• Imaging tests (such as CT, MRI, or PET) — computerized tomography (CT) or magnetic resonance imaging (MRI) can detect the presence of stroke, blood clots, and tumors (problems that cause AD-like symptoms but are not themselves related to AD). MRI, positron emission tomography (PET) scans, and other advanced imaging techniques may eventually be able to diagnose AD by identifying altered blood flow patterns in the brain.
• Blood test for Apo E4 — although the presence of Apo E4 gene in the blood may suggest AD, it does not always make an accurate diagnosis.

Preventive Care

• Consuming a low-fat, low-calorie diet may reduce the risk for AD.
• Higher intake of fatty, cold-water fish (such as tuna, salmon, and mackerel) has been associated with a lower risk of dementia. This may be due to the high level of omega-3 fatty acids found in such fish. Eating fish at least two to three times per week provides a healthy amount of omega-3 fatty acids.
• Reducing intake of linoleic acid (found in margarine, butter, and dairy products) may prevent cognitive decline.
• Antioxidants, such as vitamins A, E, and C (found in darkly colored fruits and vegetables) may help prevent damage caused by free radicals.
• Maintaining normal blood pressure levels may reduce the risk for AD.
• Hormone-replacement therapy in postmenopausal women may decrease production of chemicals that cause AD, stimulate growth of brain cells, and improve blood flow in the brain. However, the role of hormones in the prevention of AD is still controversial.
• Some studies suggest that certain medications may prevent AD, including "statin" drugs (such as pravastatin or lovastatin, used to lower cholesterol) and nonsteroidal anti-inflammatories (NSAIDs), with the exception of aspirin. More research is necessary, however, to determine how effective these medications are in reducing the risk of the disease.
• Keeping mentally and socially active may help delay the onset or slow the progression of AD.

Treatment Approach

Unfortunately, there is no cure for AD. The goal in treating AD is to slow the progression of the disease and improve symptoms. The most promising treatments for AD include medications that increase the amount of acetylcholine in the brain (such as donepezil), antioxidants that scavenge free radicals (such as vitamin E and ginkgo biloba), lifestyle modifications (such as walking programs and relaxation training) to reduce anxiety and improve behavior. Studies suggest that music therapy, the use of music to relax patients and bolster the immune system, may be healing for those with AD as well. It is also important that family members of people with AD get emotional support and assistance with the demanding tasks of caregiving.

Lifestyle

Research indicates that the following lifestyle modifications may help improve behavior in people with AD.

• A supervised walking program with a caregiver or other reliable companion may improve communication skills and diminish the risk of wandering.
• Bright light therapy may control insomnia and wandering.
• Calming music may reduce wandering and restlessness, boost brain chemicals, and improve behavior.
• Pet dogs can increase appropriate social behaviors.
• Relaxation training and other exercises that require focused attention (often used with refreshments as rewards) can improve social interaction and the ability to perform tasks.
• The Safe Return Program, implemented by the Alzheimer's Association, requires that a person with AD wear an identification bracelet. If he or she wanders, the caregiver can contact the police and the national Safe Return office, where information about the patient is stored and shared nationwide.

Individuals with AD may also have particular dietary concerns. They may require:

• Extra calories due to increased physical activity and restless wandering.
• Supervised meals and assistance with feeding. People with AD often forget to eat and drink, and, as a result, often become dehydrated.

Medications

The following medications increase the amount of acetylcholine, in the nervous system and slow the progression of AD:

• Donepezil—slows progression of AD in 30% to 50% of people with the disease; has few side effects
• Tacrine—10% to 20% of people who develop AD early in life show a positive response to this medication; not beneficial for people in the late stages of the disease; serious side effects include nausea, vomiting, diarrhea, and addiction
• Rivastigmine—side effects include dizziness, headache, nausea, vomiting, and diarrhea.

The following medications may ease the symptoms related to AD:

• Selective serotonin reuptake inhibitors (SSRIs)—increase activity of a brain chemical called serotonin; used to treat depression; because symptoms of depression often precede AD, SSRIs may slow the development of AD
• Methylphenidate—stimulates the brain to increase alertness; used to treat withdrawal and apathy
• Risperidone, olanzapine, or haloperidol—act as mood stabilizers and work on improving social interactions, mood, expression of mood, delusions, and paranoia; decreases aggression; haloperidol has serious side effects, including impaired control of movement
• Carbamazepine (or other antiseizure drugs)—stabilizes sodium levels in the brain; used to treat agitation

Nutrition and Dietary Supplements

Damage caused by free radicals is thought to play a major role in the development of AD. Many researchers have investigated whether antioxidants (agents known to scavenge free radicals) may ease the symptoms of dementia, increase the life span of those with AD, and help prevent the disease. Two antioxidants in particular, vitamins E and C, have shown promise in both the prevention and treatment of the disease. Research on other supplements is less convincing.

Vitamin E and Vitamin C
Vitamin E dissolves in fat, readily enters the brain, and helps slow down the cell damage that occurs naturally with age. In a well-designed study involving 341 people with AD who were followed for 2 years, researchers found that people who took vitamin E supplements had improvement in their symptoms and increased survival rates compared to those who took placebo.

Two large trials suggest that vitamins E and C may prevent the onset of AD, improve cognitive skills in healthy individuals, and decrease the symptoms of dementia. In one of the studies, more than 600 healthy individuals were followed for an average of 4 years. A total of 91 people developed AD, but none of the participants who took vitamin E or C supplements developed the disease.

S-adenosylmethionine (SAMe)
SAMe is a naturally occurring compound that increases the body's levels of serotonin, melatonin, and dopamine. Clinical studies suggest that people with AD and depression have depleted levels of SAMe in their brain tissue. While it has been reported that some people with AD have improved cognitive function from SAMe supplementation, further studies are needed to determine how safe and effective this supplement may be for individuals with the disease.

Beta-carotene and Vitamin A
Preliminary studies suggest that levels of vitamin A and its precursor, beta-carotene, may be significantly lower in people with AD compared to healthy individuals, but the effects of supplementation have not been studied.

Vitamin B9 (Folate) and Vitamin B12
Folate is a substance critical to the health of the nervous system and to a process that clears homocysteine from the blood. Homocysteine is a body chemical that contributes to chronic illness such as heart disease, depression, and AD. Elevated levels of homocysteine and decreased levels of both folate and vitamin B12 have been found in people with AD, but again, the benefits of supplementation for dementia are unknown.

Acetyl-L-carnitine
In addition to being structurally similar to the brain chemical acetylcholine, acetyl-L-carnitine is a scavenger of free radicals and is involved in the growth of brain cells. Several studies have examined the role of acetyl-L-carnitine in treating AD, but results have been conflicting. For example, one trial suggests that this supplement may help prevent the progression of AD in the early stages of the disease, but it may worsen symptoms in later stages of the disease. Use of this supplement for AD should be avoided, therefore, until more information is available. Reported side effects include increased appetite, body odor, and rashes.

Phosphatidylserine (PS)
PS is a naturally occurring substance found in the body that promotes cell health and boosts the activity of acetylcholine and other brain chemicals. Animal and laboratory studies suggest that this supplement may protect the brain from damage. Clinical trials have found that it may improve memory, ease symptoms in those with mild to moderate dementia, and prevent cognitive decline in middle-aged individuals.

Red Wine and Grape Juice
Resveratrol, a flavonoid or plant substance found in red wine and grape juice, is an antioxidant that may benefit people with AD. Because the alcohol in red wine may contribute to falls, interactions with medications, and sleepiness, it is not recommended for those with the condition.

Herbs

Ginkgo (Ginkgo biloba)

Ginkgo is widely used in Europe for treating dementia. It improves blood flow in the brain and contains flavonoids (plant substances) that act as antioxidants. Although many of the clinical trials have been scientifically flawed, the evidence that ginkgo may improve thinking, learning, and memory in people with AD has been highly promising.

Clinical studies indicate that gingko provides the following benefits for people with AD:

• Improvements in thinking, learning, and memory
• Improvements in daily living
• Improvements in social behavior
• Delayed onset of symptoms
• Reduced symptoms of depression

Recommended dosages for ginkgo range between 120 to 240 mg per day. Reported side effects have been minor, but ginkgo should not be taken with blood-thinning medications (such as warfarin), vitamin E, or a class of antidepressants called monoamine oxidase inhibitors (MAOIs).

Preliminary studies indicate that the following herbs may also slow the progression of AD and improve memory and behavior:

• Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolium)
• Nicotine (Nicotiana tobaccum)
• Huperzine (Huperzia serrata)
• Snowdrop (Galanthus nivalus)
• Physostigmine (Physostigma venenosa)

Although the following herbs have not been investigated in clinical studies, a professional herbalist may recommend the following for people with AD:

• Sage (Salvia officinalis)
• Lemon balm (Melissa officinalis)
• Rosemary (Rosmarinus officinalis)
• Peony (Paeonia suffruticosa)
• Guarana (Paullinia cupana)
• Gotu kola (Centella asiatica)

Other Considerations

Prognosis and Complications
A person with AD can experience the following complications:

• Falls (from impaired coordination)
• "Sundowning" (withdrawal or agitation in the evening)
• Malnutrition and dehydration
• Infection (from urinary tract infections or pneumonia)
• Asphyxiation (stopped breathing)
• Harmful or violent behavior toward self or others
• Suicide
• Poor health and support due to caregiver burnout
• Physical and emotional abuse, including neglect
• Coronary disease

There is no known cure for AD; the disease naturally progresses and worsens over time. People with the disease can survive for many years, however. While most people with AD die within 8 to 10 years, some live as long as 25 years. Some people decline steadily during their disease, while others reach major plateaus where their symptoms advance quite slowly. Men and people with a long-standing history of high blood pressure are more likely to decline rapidly. Additionally, the older a person with AD becomes, the more likely he or she is to decline rapidly. An accurate, early diagnosis gives affected individuals a greater chance of benefiting from existing treatments.

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