Memory and Demetia
The definition of Alzheimer's is changing in response to growing research on normal aging. By studying the brain tissue of normal adults, researchers have determined that Alzheimer's disease likely starts decades before the symptoms of the disease are recognized.
In fact, it is hypothesized that the disease actually begins in the third, fourth or fifth decade of life. What used to be considered a disease of advanced age is now viewed as a disease that develops across the lifespan. Read more about its diagnosis and treatment.
Alzheimer's disease is not a normal part of aging. It is a disease. While it is true that growing older increases your risk for developing AD, it does not mean that you will develop AD. We now know that changes in the brain's structure and neurochemical system occur with age, and that these changes may affect aspects of thinking and memory. However, these age-related changes are considered normal and do not represent AD.
With age, nerves and other tissues in the brain are lost or shrink, causing the brain to shrink in size. As nerves die or function less effectively, the availability of various neurotransmitter systems or chemical neurotransmitters (i.e., chemical substances in the brain which allow the nerves to communicate with each other) may diminish. Consequently, this may or may not result in observable but often subtle, age-related cognitive changes, including more difficulty recalling names or proper nouns, slowed processing speed, or the need for more time or more repetitions to learn new information.
What is not a normal part of aging is forgetfulness. Research shows that older adults are capable of learning new information as well as younger adults if given more time to learn and a greater number of learning "trials." While it may take longer to retrieve the information that has been learned, once learned, it is not forgotten.
Mild cognitive impairment is a term used to describe an abnormal cognitive state in which memory ("Amnestic MCI") or non-memory cognitive functions ("Atypical MCI") are affected. Having MCI means that there has been a decline in memory or thinking abilities beyond what is considered normal for someone's age, but the decline is isolated and not diagnostically indicative of AD or another form of dementia.
Someone with Amnestic MCI has difficulty remembering, but experiences no significant difficulty in other areas of thinking, and no serious decline in daily activities. Conversely, someone with Atypical MCI usually has normal memory functions, but experiences problems in a non-memory related ability (i.e., attention, concentration, processing speed, language, perceptual ability, problem solving, reasoning, etc.) or has a more subtle memory change. In both types of MCI, the decline is not sufficiently severe to cause disruption in day to day functioning.
One conceptualization of MCI is that it is a stage of cognitive functioning between normal aging and dementia. Alternatively, it has been proposed that Amnestic MCI actually represents very early AD. It is suspected that everyone who develops AD will first experience MCI for some period of time. However, researchers do not know if everyone who develops MCI will eventually develop AD.
Longitudinal studies are currently underway to answer this question, and drug trials are underway to determine if a diagnosis of AD can be delayed or avoided for those already experiencing MCI.
For those persons with MCI who do later develop AD, it is important to know that the rate at which someone passes through the MCI stage to AD varies from person to person. Clinical observation of patients with carefully documented Amnestic MCI suggests that 10 to 15 percent per year will eventually go on to develop AD.
MCI is a concept that is still evolving and is not yet a clinical diagnosis. However, the concept reflects the growing interests of researchers and clinicians in identifying non age-related changes in memory and cognition that may predict AD or other dementias.
According to guidelines published by the American Academy of Neurology, persons with MCI are considered to be "at risk" for developing dementia, and should therefore receive ongoing clinical monitoring post-evaluation (see Petersen, R.C. et al., Practice parameter: early detection of dementia: mild cognitive impairment, Neurology, 2001; 56:1133-1142; Peterson, R.C., Doody, R., Kurz, A., et al., Current concepts in mild cognitive impairment, Archives of Neurology, 2001; 58:1985-1992).
Rarely is Alzheimer's disease inherited. The genetic or "inherited" type of AD (also referred to as "familial" AD) accounts for only 1 to 5 percent of all cases of AD. People with the inherited form of AD are born with specific genetic mutations on either Chromosome 1, 14 or 21. Essentially, these individuals are born with the disease, and if they live long enough, they will develop AD. Typically, these individuals will develop AD before the age of 65. To date, there are only about 200 families known worldwide who carry the chromosomal mutations which cause this form of AD. Therefore, to have the inherited form of AD, you must be a descendant of one of these families.
The remaining 95 to 99 percent of AD cases are not genetically transmitted, and it is not known what causes this form of the disease. The risk of developing the non-inherited form of AD (also called "sporadic" AD) increases significantly with age. By age 65, the lifetime risk for developing AD is approximately 12 percent. By age 75, the risk doubles to 24 percent. By age 85, the lifetime risk for developing AD is roughly 47 percent. In other words, if everyone sitting in the room with you lived to age 85, almost half would develop AD. Aging, not genetic heritability, is the primary risk factor for developing AD.
Researchers have identified a genetic risk factor which may increase a person's risk for developing AD. That risk factor is the Apolipoprotein E(ApoE) gene, which is located on chromosome 19. This gene is involved in determining what type of cholesterol carrying protein is inherited. There are three different forms of the ApoE gene (ApoE 2, ApoE 3, and ApoE 4). Each person inherits either a 2, 3 or 4 version of the gene from each parent, so that all people end up with either a 2/2, 2/3, 2/4 combination, a 3/3 or 3/4 combination, or a 4/4 combination.
Research indicates that inheriting an ApoE 2 version of the gene may help protect against developing AD, or perhaps delay the onset of the disease. The ApoE 3 gene is neutral and neither increases nor decreases risk for AD. Inheriting a type 4 version of the ApoE gene increases one's risk for developing AD. However, only about half of all patients with AD have a type 4 version of the gene, and among all persons who do inherit an ApoE 4 gene, only a subset will develop AD. Clearly, inheriting an ApoE 4 gene does increase risk for developing AD, but it does not cause AD.
It is important to keep in mind that inheriting the disease is not the same thing as inheriting a risk factor for the disease. Many risk factors for AD have been identified The ApoE gene is only one of those risk factors.
The issue of genetic testing for AD is often raised by family members of patients. Pursuing testing to determine if you have inherited an AD gene is not advised except under special circumstances. Genetic testing may be appropriate for family members who are descendants of one of the 200 known AD families, or for persons with an extensive family history of AD (multiple family members across multiple generations with onset at a young age) of AD. In these cases, genetic counseling should occur in conjunction with chromosomal testing.
For family members of persons with the non-inherited form of AD (sporadic AD), genetic testing should not be performed. Family members are also strongly discouraged from seeking ApoE testing to determine whether this risk factor has been inherited.
Why? First, the test has no predictive value and cannot determine whether AD will develop. Second, should you pursue testing and learn that you have inherited the ApoE risk factor for AD, it is possible that you would be viewed as having a greater risk for developing AD by insurance companies, including those providing long term care policies. Lastly, knowing that you carry a risk factor does not protect you from developing AD, and, in fact, may have a negative impact on your psychological or emotional well being.
Alzheimer's disease is a diagnosable and treatable condition. By applying standardized diagnostic criteria, a diagnosis of AD can be made with greater than 90 percent accuracy. In fact, the current diagnostic process is capable of detecting very subtle changes in thinking or memory which may actually precede the clinical onset of AD. Once diagnosed, AD can be effectively treated with Food and Drug Administration-approved medications capable of stabilizing the symptoms of AD for several years.
By seeking evaluation early, other possible causes of memory or thinking problems can be identified and properly treated. Identifying the presence of AD early on prevents misdiagnosis and unnecessary, sometimes costly or invasive work-ups, procedures or medications. For example, patients with AD are sometimes started unnecessarily on an anti-depressant medication before the correct diagnosis is made.
If a diagnosis is made early on in the course of the disease, the patient and supportive others are given the opportunity to educate themselves about the condition. In turn, they are able to make informed choices and plan effectively for the future. Patients and caregivers can identify and make use of supportive services for those affected by AD, which is critical for long term management. Potential safety issues can be avoided before a crisis develops, and important social needs can be met if the condition is diagnosed early. Early diagnosis also ensures that the person with AD remains an active participant in their care by voicing preferences about important medical and financial issues, and appointing powers of attorney to ensure those preferences are upheld.
Because the current medications available for AD are intended to stabilize a patient's level of cognitive functioning at the time the medications are started, the earlier a diagnosis is made and treatment initiated, the better.
From a socio-economic standpoint, early diagnosis and treatment are cost effective. By diagnosing and stabilizing the condition at the earliest sign of difficulty, an individual is capable of functioning in much the same way he or she always has for a longer time. The use of specialized AD services, such as day activity programs, companion/escort or personal assistant services, home care, assisted living or nursing home services, or general medical care costs may be postponed or, in the case of diagnosis at a very advanced age, avoided in large part.
With the development of drugs to treat Alzheimer's disease, and a movement toward early identification and treatment, the definition of Alzheimer's disease is changing.
AD has historically been defined as a syndrome of cognitive and functional decline with associated but variable, non-cognitive, behavioral features, and specific neuropathological and chemical changes. AD is still considered a cognitive syndrome affecting memory and at least one other area of cognition (i.e., language ability, attention and concentration, orientation, judgment, problem solving, reasoning, or the ability to perform already learned motor skills). However, it is no longer believed that everyone who develops AD will necessarily show functional decline (i.e., a diminishing ability to independently perform activities necessary for daily living, such as the ability to manage finances, cook, use a telephone, bathe, dress oneself, etc.).
For those patients who are diagnosed with AD very late in life, but early in the course of their disease, the initiation of treatment may stabilize the condition before functional decline occurs, thereby allowing an individual to live the remainder of their natural life without significant change to their way of life.
The definition of AD is also changing in response to growing research on normal aging. By studying the brain tissue of normal adults, researchers have determined that Alzheimer's disease likely starts decades before the symptoms of the disease are recognized. In fact, it is hypothesized that the disease actually begins in the third, fourth, or fifth decade of life. What used to be considered a disease of advanced age is now viewed as a disease that develops across the lifespan.
There are many different conditions which cause "dementia." Dementia is a broad term used to describe a decline in cognitive function which is usually severe enough to disrupt daily life and activities. Alzheimer's disease is the leading cause of dementia among those aged 65 and older. However, unlike a dementia due to stroke, where the onset of memory and thinking problems is sudden, AD results in a slow but ongoing loss of memory and thinking abilities. It is a progressive disorder which, left untreated, will continue to cause declines in cognition and functional abilities over time.
Affects of Alzheimer's Disease
While AD always affects one of three primary domains (cognition), it may or may not impact the remaining two (functional ability and behavior). Depending on the age of the patient at the time of diagnosis, functional ability may be preserved in some cases. Most patients who live for a long time after an Alzheimer's disease diagnosis develop functional decline to variable degrees. The behavioral or "neuropsychiatric" features of AD may develop at any point in the course of the disease, or they may never develop. If behavioral symptoms of AD do occur, it does not necessarily mean that the disease is progressing. Examples of behavioral/neuropsychiatric features of AD include apathy (diminished interest, initiative, or feeling), anxiety, irritability, hallucinations (seeing or hearing things in the environment which aren't present) or delusions (holding false beliefs), disinhibition, agitation (restlessness, pacing, verbal or physical aggression), euphoria, or depression.
It is important to keep in mind that the behavioral or neuropsychiatric manifestations of AD vary widely from person to person. If behavioral symptoms occur, treatments (both non-pharmacological and pharmacological) are available, including the medications currently prescribed to treat the cognitive symptoms of AD. Originally thought to benefit cognition alone, research is demonstrating that cholinesterase inhibitors (e.g., Donepezil, Rivastigmine, Galantamine) and NMDA receptor antagonists (Memantine) may positively affect behavior and help maintain functioning for those with AD.