What is Alzheimer’s Disease?
Alzheimer's disease, which is named for the German physician who first identified it in 1906, is the most common form of dementia, accounting for 60 to 70% of cases. It is a progressive degenerative disorder of the brain and is characterized by a gradual deterioration of mental faculties caused by a loss of nerve cells and the connections between them. The disease is often accompanied by changes in behavior and personality.
The symptoms of Alzheimer’s disease usually appear very slowly, get progressively worse over years, and are irreversible. Minor forgetfulness becomes more pronounced; speech deteriorates; and the ability to do everyday things, such as dressing, bathing, and eating, is increasingly difficult. In the final stages, severe cognitive impairment results in complete dependence upon caregivers. On average, patients die within 5 to 10 years of onset of symptoms, often from complications such as malnutrition or pneumonia.
Who Gets Alzheimer’s Disease?
Alzheimer’s disease is slightly more common in women, affecting about 10 percent of people over the age of 65, more than 10 percent of those between 75 and 85, and by some estimates, upward of 50 percent of those over 85. Nearly all people with Down syndrome who live into their 40s develop the disease.
Alzheimer's disease advances slowly through three stages, ranging from mild forgetfulness to severe dementia. In the first stage of Alzheimer's, symptoms include impaired memory of recent events, faulty judgment, and poor insight. People may forget important appointments, recent family events, and highly publicized news stories. Other symptoms include losing or misplacing possessions, repetition of questions or statements, and minor or occasional disorientation.
In the second stage of Alzheimer's disease, memory problems grow worse and basic self-care skills begin to decline. Patients have trouble expressing themselves verbally or in writing and may be unable to perform everyday activities, such as dressing, bathing, using a knife or fork, or brushing their teeth. They may also suffer from delusions or hallucinations.
In the third stage of Alzheimer's, almost all reasoning capacity is lost. Individuals become completely dependent on others for their care. The disorder eventually becomes so debilitating that most patients cannot walk or feed themselves and become susceptible to other diseases.
Lung and urinary tract infections are common. Pneumonia is the most common cause of death among Alzheimer's patients.
Specific symptoms include:
Increasing forgetfulness and short-term memory loss.
Difficulty making decisions.
Impaired judgment; new difficulty making mathematical calculations or handling money.
Decreased knowledge of current events.
Anxiety, withdrawal, and depression as awareness of deficits becomes frightening and embarrassing.
Language difficulties, including rambling speech, frequent inability to name familiar objects, long pauses to find the right word, and repetition of the same words, phrases, or questions.
Loss of ability to communicate verbally or to write and understand written language.
Delusions, hallucinations, paranoia, or irrational accusations.
Agitation and combativeness.
Unusual quiet and social withdrawal.
Wandering or getting lost in familiar places.
Urinary and fecal incontinence.
Inappropriate social behavior; indifference to others.
Failure to recognize friends and family.
Inability to dress, eat, bathe, or use a bathroom without assistance.
Walking difficulty or multiple falls.
Despite tremendous advances in the understanding of Alzheimer's disease, scientists have yet to pinpoint a true cause of the disorder.
The leading theory is that Alzheimer's disease is caused by an accumulation of insoluble fragments of a protein called beta-amyloid in the brain. Because these fragments are not dissolved, researchers suspect that this form of beta-amyloid more readily builds up and forms plaques.
The two most significant physical findings in the cells of brains affected by Alzheimer's disease are neuritic plaques and neurofibrillary tangles. Another significant factor is the greatly reduced presence of acetylcholine in the cerebral cortex. Acetylcholine is necessary for cognitive function.
While some neuritic plaques, or patches, are commonly found in brains of elderly people, they appear in excessive numbers in the cerebral cortex of Alzheimer's disease patients. Beta-amyloid occupies the center of these plaques. Surrounding the protein are fragments of deteriorating neurons, especially those that produce acetylcholine, a neurotransmitter essential for processing memory and learning. Neurotransmitters are chemicals that transport information or signals between neurons.
Neurofibrillary tangles are twisted remnants of a protein called tau, which is found inside brain cells and is essential for maintaining proper cell structure and function. An abnormality in the tau protein disrupts normal cell activity.
Alzheimer's Risk Factors. Risk factors for Alzheimer's disease increase the likelihood that an individual will develop the disorder but are not believed to directly cause it. The distinction between risk factors and cause is sometimes unclear because the biology of the disease is not fully understood. Risk factors for Alzheimer's include:
- Older age.
- Being female.
- Genetic predisposition.
- The presence of a specific form (ε4) of the gene that makes a protein called apolipoprotein E (APOE).
- Elevated levels of lipoprotein(a) (a type of very-low-density cholesterol).
- Cardiovascular disorders (such as high blood pressure, high cholesterol, and heart attack).
- Down syndrome.
Head injury and depression are other possible risk factors for Alzheimer's.
The diagnosis of Alzheimer's disease involves taking a detailed history of symptoms and ruling out other treatable medical and psychological conditions that cause loss of cognitive function (dementia), such as the following:
- Head trauma.
- Infection (e.g., HIV, syphilis).
- Intoxication or withdrawal from medication, poison, or substance of abuse.
- Kidney disease.
- Liver disease.
- Neurodegenerative diseases (e.g., Creutzfeldt-Jakob, Huntington's).
- Seizures (epilepsy).
- Thiamine or vitamin B deficiency.
- Thyroid disease.
Except for an autopsy, no test or examination can definitively identify Alzheimer’s disease. Instead, diagnosis is based on patient history (including input from family members) and clinical examination, including tests of mental status to identify increasing forgetfulness, loss of judgment, difficulty with routine tasks, mood changes, and other warning signs. The primary criterion is loss in memory and other cognitive functions that clearly exceed what is a normal part of aging. Other disorders that can cause dementia must be ruled out; this may be facilitated by imaging of the brain and various laboratory tests, including:
- MRI (magnetic resonance imaging) or CT (computed tomography) brain scans to rule out cancer, subdural hematoma (a collection of blood), adult hydrocephalus (an accumulation of spinal fluid), or multiple small strokes due to vascular disease.
- Blood tests to rule out vitamin deficiencies, endocrine disorders (such as hypothyroidism), syphilis, HIV, and heavy-metal poisoning.
Researchers are examining several simple tests to predict the risk of Alzheimer's. One promising example is a smell test. The sense of smell begins to deteriorate early in the course of the disease, often many years before other symptoms arise. Researchers have found that people who are unable to identify more than two out of 10 common odors (such as lemon, smoke, and leather) are nearly five times more likely to be diagnosed with Alzheimer's disease in the ensuing years than people who perform better on the test. The "sniff test" will require further research, but in a large study it performed as well as memory tests and better than MRI scans in predicting which people would go on to develop Alzheimer's disease.
Likewise, imaging of the brain using various radiolabeled compounds is also promising. Many of these can demonstrate the presence of plaques, yet the accuracy of these tests has not yet been determined.
For now, no treatment can prevent or halt the mental deterioration associated with Alzheimer's disease. The search for effective drug therapy has focused on preventing the destruction of nerve cells, with the ultimate goal of preserving cognitive function for as long as possible and managing the disease's cognitive and behavioral symptoms.
One treatment approach is based on the theory that memory problems associated with Alzheimer's result in part from a deficiency of the neurotransmitter acetylcholine. Researchers have sought ways to boost the amount of acetylcholine in the brain by administering substances containing the chemical, stimulating the brain to manufacture more of it, or preventing the breakdown of the limited quantities of acetylcholine that the brain does produce.
Medications for Alzheimer’s disease include:
- Donepezil (Aricept), galantamine (Reminyl), and rivastigmine (Exelon), inhibitors of the enzyme acetylcholinesterase, can delay cognitive decline or even provide modest improvement in cognitive function in some patients with mild to moderate Alzheimer’s disease. Side effects of cholinesterase inhibitors include nausea and loss of appetite.
- Memantine (Namenda), approved for moderate to severe Alzheimer’s, blocks the activity of the neurotransmitter glutamate. Some patients will experience a modest delay in the deterioration of memory and the ability to perform daily activities.
- Insomnia, depression, aggression, and other psychological manifestations may be treated with various medications.
Much of the responsibility to care for a patient with Alzheimer’s falls into the hands of the primary caregiver. Supportive counseling, day care, visiting nurses, and eventual inpatient nursing facilities may help to ease the caregiver’s burden. Contact your local chapter of the Alzheimer’s Association for further information.
Despite the great strides that have been made in the past 20 years in understanding the nature of cognitive decline and Alzheimer's disease, many challenges remain, particularly in the area of prevention. While no adequately designed studies satisfactorily demonstrate that modifying risk factors like diet or physical activity can lower the incidence of dementia, there is some weak evidence suggesting protective effects from the Mediterranean diet, physical activity, and cognitive stimulation.
Current evidence is inadequate to support the use of any drugs or supplements to prevent these conditions.
Ongoing research efforts might lead to ways to prevent cognitive decline and Alzheimer's. Studies on the neurobiological basis for age-related cognitive decline and the role of behavioral disorders like depression will supplement existing research in these areas. More studies, especially large-scale, population-based investigations and randomized clinical trials, are essential for finding new strategies that will maintain cognitive function among at-risk individuals and delay or prevent the onset of cognitive decline and Alzheimer's.
When To Call Your Doctor
Occasional forgetfulness, such as misplacing the car keys, is normal and rarely anything to worry about. However, consult a doctor if you or a family member begins to show increasing signs of memory lapses; becomes lost in a familiar place; loses the ability to do everyday activities; or undergoes a change in personality.
Reviewed by Joseph V. Campellone, M.D., Division of Neurology, Cooper University Hospital, Camden, NJ. Review provided by VeriMed Healthcare Network.