ALZHEIMER’S DISEASE DEFINITION
Alzheimer’s disease (AD) is an age-related, non-reversible brain disorder that develops over a period of years. Initially, people experience memory loss and confusion, which may be mistaken for the kinds of memory changes that are sometimes associated with normal aging. However, the symptoms of AD gradually lead to behavior and personality changes, a decline in cognitive abilities such as decision-making and language skills, and problems recognizing family and friends. AD ultimately leads to a severe loss of mental function. These losses are related to the worsening breakdown of the connections between certain neurons in the brain and their eventual death. AD is one of a group of disorders called dementias that are characterized by cognitive and behavioral problems. It is the most common cause of dementia among people age 65 and older.There are three major hallmarks in the brain that are associated with the disease processes of AD.Amyloid plaques, which are made up of fragments of a protein called beta-amyloid peptide mixed with a collection of additional proteins, remnants of neurons, and bits and pieces of other nerve cells.Neurofibrillary tangles (NFTs), found inside neurons, are abnormal collections of a protein called tau. Normal tau is required for healthy neurons. However, in AD, tau clumps together. As a result, neurons fail to function normally and eventually die.Loss of connections between neurons responsible for memory and learning. Neurons can’t survive when they lose their connections to other neurons. As neurons die throughout the brain, the affected regions begin to atrophy, or shrink. By the final stage of AD, damage is widespread and brain tissue has shrunk significantly.
ALZHEIMER’S DISEASE CAUSES
Scientists believe that for most people, Alzheimer’s disease results from a combination of genetic, lifestyle and environmental factors that affect the brain over time.
Less than 5 percent of the time, Alzheimer’s is caused by specific genetic changes that virtually guarantee a person will develop the disease.
Although the causes of Alzheimer’s are not yet fully understood, its effect on the brain is clear. Alzheimer’s disease damages and kills brain cells. A brain affected by Alzheimer’s disease has many fewer cells and many fewer connections among surviving cells than does a healthy brain.
As more and more brain cells die, Alzheimer’s leads to significant brain shrinkage. When doctors examine Alzheimer’s brain tissue under the microscope, they see two types of abnormalities that are considered hallmarks of the disease:
- Plaques. These clumps of a protein called beta-amyloid may damage and destroy brain cells in several ways, including interfering with cell-to-cell communication. Although the ultimate cause of brain-cell death in Alzheimer’s isn’t known, the collection of beta-amyloid on the outside of brain cells is a prime suspect.
- Tangles. Brain cells depend on an internal support and transport system to carry nutrients and other essential materials throughout their long extensions. This system requires the normal structure and functioning of a protein called tau.
In Alzheimer’s, threads of tau protein twist into abnormal tangles inside brain cells, leading to failure of the transport system. This failure is also strongly implicated in the decline and death of brain cells.
ALZHEIMER’S DISEASE PATHOPHYSIOLOGY
A continuum exists between the pathophysiology of normal aging and that of AD. Pathologic hallmarks of AD have been identified; however, these features also occur in the brains of cognitively intact persons. For example, in a study in which neuropathologists were blinded to clinical data, they identified 76% of brains of cognitively intact elderly patients as demonstrating AD.
AD affects the 3 processes that keep neurons healthy: communication, metabolism, and repair. Certain nerve cells in the brain stop working, lose connections with other nerve cells, and finally die. The destruction and death of these nerve cells causes the memory failure, personality changes, problems in carrying out daily activities, and other features of the disease.
The accumulation of SPs primarily precedes the clinical onset of AD. NFTs, loss of neurons, and loss of synapses accompany the progression of cognitive decline.
Considerable attention has been devoted to elucidating the composition of SPs and NFTs to find clues about the molecular pathogenesis and biochemistry of AD. The main constituent of NFTs is the microtubule-associated protein tau (see Anatomy). In AD, hyperphosphorylated tau accumulates in the perikarya of large and medium pyramidal neurons. Somewhat surprisingly, mutations of the tau gene result not in AD but in some familial cases of frontotemporal dementia.
Since the time of Alois Alzheimer, SPs have been known to include a starchlike (or amyloid) substance, usually in the center of these lesions. The amyloid substance is surrounded by a halo or layer of degenerating (dystrophic) neurites and reactive glia (both astrocytes and microglia).
One of the most important advances in recent decades has been the chemical characterization of this amyloid protein, the sequencing of its amino acid chain, and the cloning of the gene encoding its precursor protein (on chromosome 21). These advances have provided a wealth of information about the mechanisms underlying amyloid deposition in the brain, including information about the familial forms of AD. (See Amyloid Hypothesis Versus Tau Hypothesis, below.)
Although the amyloid cascade hypothesis has gathered the most research financing, other interesting hypotheses have been proposed. Among these are the mitochondrial cascade hypothesis.
In addition to NFTs and SPs, many other lesions of AD have been recognized since Alzheimer’s original papers were published. These include the granulovacuolar degeneration of Shimkowicz; the neuropil threads of Braak et all; and neuronal loss and synaptic degeneration, which are thought to ultimately mediate the cognitive and behavioral manifestations of the disorder.
ALZHEIMER’S DISEASE SYMPTOMS
Memory loss that disrupts daily life may be a symptom of Alzheimer’s or another dementia. Alzheimer’s is a brain disease that causes a slow decline in memory, thinking and reasoning skills. Every individual may experience one or more of these signs in different degrees.
One of the most common signs of Alzheimer’s is memory loss, especially forgetting recently learned information. Others include forgetting important dates or events; asking for the same information over and over; increasingly needing to rely on memory aids (e.g., reminder notes or electronic devices) or family members for things they used to handle on their own.
Some people may experience changes in their ability to develop and follow a plan or work with numbers. They may have trouble following a familiar recipe or keeping track of monthly bills. They may have difficulty concentrating and take much longer to do things than they did before.
People with Alzheimer’s often find it hard to complete daily tasks. Sometimes, people may have trouble driving to a familiar location, managing a budget at work or remembering the rules of a favorite game.
People with Alzheimer’s can lose track of dates, seasons and the passage of time. They may have trouble understanding something if it is not happening immediately. Sometimes they may forget where they are or how they got there.
For some people, having vision problems is a sign of Alzheimer’s. They may have difficulty reading, judging distance and determining color or contrast, which may cause problems with driving.
People with Alzheimer’s may have trouble following or joining a conversation. They may stop in the middle of a conversation and have no idea how to continue or they may repeat themselves. They may struggle with vocabulary, have problems finding the right word or call things by the wrong name (e.g., calling a “watch” a “hand-clock”).
A person with Alzheimer’s disease may put things in unusual places. They may lose things and be unable to go back over their steps to find them again. Sometimes, they may accuse others of stealing. This may occur more frequently over time.
People with Alzheimer’s may experience changes in judgment or decision-making. For example, they may use poor judgment when dealing with money, giving large amounts to telemarketers. They may pay less attention to grooming or keeping themselves clean.
A person with Alzheimer’s may start to remove themselves from hobbies, social activities, work projects or sports. They may have trouble keeping up with a favorite sports team or remembering how to complete a favorite hobby. They may also avoid being social because of the changes they have experienced.
The mood and personalities of people with Alzheimer’s can change. They can become confused, suspicious, depressed, fearful or anxious. They may be easily upset at home, at work, with friends or in places where they are out of their comfort zone.
ALZHEIMER’S DISEASE DIAGNOSIS
If a primary care doctor suspects mild cognitive impairment or possible Alzheimer’s, he or she may refer you to a specialist who can provide a detailed diagnosis, or you may decide to go to a specialist for further assessment. You can find specialists through memory clinics and centers or through local organizations or referral services. Specialists include:
Geriatricians, who manage health care in older adults. They know how the body changes as it ages and whether symptoms indicate a serious problem.
Geriatric psychiatrists, who specialize in the mental and emotional problems of older adults and can assess memory and thinking problems
Neurologists, who specialize in abnormalities of the brain and central nervous system and can conduct and review brain scans
Neuropsychologists, who can conduct tests of memory and thinking
ALZHEIMER’S DISEASE TREATMENT
Currently there are no medicines that can slow the progression of AD. However, four FDA-approved medications are used to treat AD symptoms. These drugs help individuals carry out the activities of daily living by maintaining thinking, memory, or speaking skills. They can also help with some of the behavioral and personality changes associated with AD. However, they will not stop or reverse AD and appear to help individuals for only a few months to a few years. Donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne) are prescribed to treat mild to moderate AD symptoms. Donepezil was recently approved to treat severe AD as well. The newest AD medication is memantine (Namenda), which is prescribed to treat moderate to severe AD symptoms.