The improvement in overall health care has brought about an increase in the life span of the population and created the problem of dealing with the health care needs and diseases that affect the elderly. This situation has unmasked Alzheimer's disease, a formidable disease that will be discussed in detail later in this chapter. Show
10.1 Aging Is a Normal Biological Process Maximal and average life expectancy -- Aging is a normal biological process that is programmed into the genetics of all species. Thus aging, per se, is not caused by disease. Each animal species has a maximal life expectancy that is hypothesized to be unchangeable. Figure 10.1 is a survival curve for humans illustrating that the maximal life expectancy is approximately 90 years of age. In contrast to maximal life expectancy, the average life expectancy of individuals of a species can be dramatically influenced by environmental influences, especially disease. Thus, Figure 10.1 also shows that the average life expectancy has changed markedly. The figure shows that the average life expectancy, represented by “fifty percent survivors” has increased from 47 years in 1900 to 70+ years in 1989.
10.2 Biological Changes in the Absence of Disease in Aging Humans Below are listed some of the biological changes that occur in aging humans in the absence of disease. Reductions in the following sensory functions:
Examples of major changes in proteins with age:
General changes in aging:
Behavioral changes in aging (These usually are not marked):
CNS parameters that decrease in aging:
CNS parameters that increase in aging:
10.3 Alzheimer's Disease (AD) Alzheimer’s disease (AD) has become the most common neurodegenerative disorder, currently affecting nearly twenty five million worldwide. AD, which begins with mild memory deficits and modest neuronal death, is followed by progressive extensive neuronal death, eventually leading to severe dementia. In addition, AD is frequently accompanied by other neurological and personality impairments including slow movements, hampered motor coordination, general confusion and personality change. AD patients generally live for about 9 years after initial clinical diagnosis. Thus treatment is necessary for extensive time periods. This not only places a great burden on caregivers, but the economy as well, with an annual cost yearly of $160 billion worldwide. AD is estimated to affect over four million people in the USA (10% of the population over 65 and 47% of those over 85). The pathological features of Alzheimer’s disease, described below, are associated with profound degeneration of neurons and synapses in a few regions of the CNS, including the temporal, parietal, and frontal cortices, all of which are associated with learning and memory processes. The two most characteristic pathological inclusions found in the brains of AD patients are extracellular deposits of β-amyloid peptides (Aβ) that lead to senile plaque formation and intracellular neurofibrillary tangles of hyperphosphorylated tau. However, increasing evidence has suggested that inflammation may play a critical role in AD pathogenesis as well. 10.4 Diagnosis of Alzheimer's Disease In this chapter, the changes that occur with AD and the way to clinically diagnose the disease are summarized as a means to describe the disease and to illustrate how the physician must clinically evaluate the possibility of AD. According to the Psychiatric Manual three progressive stages or categories of AD diagnosis are defined. These include: 1) Suspected AD, 2) Probable AD, and 3) Definite AD. Definite AD can only be diagnosed after pathological brain specimens are examined by either biopsy or autopsy. The characteristics used to diagnose AD are listed below. Suspected AD. The following are changes that would lead to the diagnosis of Suspected AD (note that many of the behavioral changes overlap with those occurring in normal aging:)
Probable AD. Once a patient is determined to meet the criteria for diagnosis of suspected AD; further tests are conducted to establish the likelihood of AD. If the patient satisfies the criteria below, the diagnosis of Probable AD is made.
Definite AD. To make the diagnosis of Definite AD, morphological pathological inclusions must be present in the patient’s CNS. The nature of the pathological changes that occur in AD and the use of some of these features in the diagnosis of AS are described below.
10.5 Diagnosis of Definite AD With the above pathological features in mind, the physician examines the CNS biopsy or on autopsy to determine the presence of these histopathologic features. Following the examination of the histological sections, the age related criteria in Table I are used to establish the diagnosis of Definite AD. The areas where plaques and tangle are most abundant are usually the temporal- and neo-cortex. The histopathologic analysis requires multiple CNS samples for microscopic examination. Because these structures also occur in normal aging, the diagnosis of AD depends on the number of pathological features based on the patient’s age; with older age, more inclusions are required before AD is indicated. Other regions examined are the amygdala, hippocampus, basal ganglia, substantia nigra, cerebellum, and spinal cord.
10.6 Classification of Alzheimer's Disease AD, in few cases, has been found to be associated with specific families. Although this happens rather infrequently, it has led to the classification of AD as either familial or sporadic. Sporadic AD refers to disease that has no clear-cut genetic basis. It is the majority of AD seen in the general population. However, a genetic predisposition may exist for even this disease, as will be discussed at the end of this chapter. Familian AD (FAD) refers to an inherited disease that is associated with families. Several examples of AD mapped to a specific gene exist. Based on the typical age of onset, familial AD has been sub-classified as early onset and late onset. Both of these will also be presented in more detail at the end of this chapter. 10.7 Observations
Concerning the Causes (Etiology) of Alzheimer's Disease Historically, several types of observations have been made concerning the cause of AD. Five of these include: 1) abnormally low levels of neurotransmitters, 2) accumulation of a pathological protein, β amyloid, 3) hyperphosphorylation of a microtubule associated protein, tau, 4) products of the presenilin genes and 5) alterations in a cholesterol shuttling protein (ApoE4). Several of these have been analyzed in genetic
studies.
10.8 Summary of the Genetics of Alzheimer’s disease The current information concerning the causes of AFD indicates that it is a genetically heterogeneous disorder. Although most cases of Alzheimer's disease do not exhibit familial inheritance, certain genes appear to act as risk factors for AD. Currently, the best known genetic risk factor for AD is the inheritance of the ε4 allele of the apolipoprotein E on chromosome 19. This gene is implicated in up to 50% of late-onset sporadic Alzheimer's cases. However, geneticists agree that numerous other genes probably also act as risk factors or have protective effects that influence the development of late onset AD. Over 400 genes have been tested for association with late-onset sporadic AD. There is also considerable evidence that Aβ and APP on chromosome 21 play an important role in the etiology of AD. The evidence for genetic basis in FAD and a role for Aβ in sporadic AD include the following: 1) Individuals with Down’s syndrome have three copies of chromosome 21 and consequently make large amount of APP. 2) Down’s syndrome patients exhibit brain pathology virtually identical to AD and suffer dementia. 2) A direct linkage has been made between chromosome 21 and a subset of FAD. 3) In addition a direct linkage has been made between mutations in the genes for presenilins and the facilitation of the abnormal processing of APP to produce Aβ. All of these observations support a role for amaloid in AD pathology. 10.9 Role of Risk Factors and the Environment Several clear risk factors exist for AD. These include being female, family history of neurodegenerative diseases, less education and less intellectually demanding jobs. How these factors fit into the etiology of AD is not known.
Test Your Knowledge
The following is evidence that Alzheimer’s disease is not merely exaggerated normal biological aging. Only Alzheimer’s disease brains have:
The following is evidence that Alzheimer’s disease is not merely exaggerated normal biological aging. Only Alzheimer’s disease brains have:
The following is evidence that Alzheimer’s disease is not merely exaggerated normal biological aging. Only Alzheimer’s disease brains have:
The following is evidence that Alzheimer’s disease is not merely exaggerated normal biological aging. Only Alzheimer’s disease brains have:
The following is evidence that Alzheimer’s disease is not merely exaggerated normal biological aging. Only Alzheimer’s disease brains have:
“Sporadic” Alzheimer’s disease has
“Sporadic” Alzheimer’s disease has
“Sporadic” Alzheimer’s disease has
“Sporadic” Alzheimer’s disease has
“Sporadic” Alzheimer’s disease has
The diagnosis “Definite Alzheimer’s Disease” is established by:
The diagnosis “Definite Alzheimer’s Disease” is established by:
The diagnosis “Definite Alzheimer’s Disease” is established by:
The diagnosis “Definite Alzheimer’s Disease” is established by:
The diagnosis “Definite Alzheimer’s Disease” is established by:
The diagnosis “Definite Alzheimer’s Disease” is established by:
Which of the following is not implicated via direct linkage to “Familial" Alzheimer’s Disease?
Which of the following is not implicated via direct linkage to “Familial" Alzheimer’s Disease?
Which of the following is not implicated via direct linkage to “Familial" Alzheimer’s Disease?
Which of the following is not implicated via direct linkage to “Familial" Alzheimer’s Disease?
Which of the following is not implicated via direct linkage to “Familial" Alzheimer’s Disease?
Which of the following is not implicated via direct linkage to “Familial" Alzheimer’s Disease?
Which is an age related change associated with the nervous system quizlet?Which of the following is a NORMAL age-related change of the nervous system? There is a decline in brain weight and a reduction in blood flow to the brain.
What are the normal effects of aging on the nervous system quizlet?Neurons decrease in number, neuroglial cells increase in size and number, axon thinning and decrease in number, dendrites decrease in number. Longer retrieval time for short term memory, categorization, and episodic memory.
Which statement is true regarding neurological changes in older adults?Which statement is true regarding neurologic changes in older adults? Older adults need more time to retrieve information due to the loss of cerebral neurons that occurs with aging.
What is the name for a condition in which the person is unconscious and can't be awakened by strong stimuli?The state of complete unconsciousness with no eye opening is called coma. The state of complete unconsciousness with some eye opening and periods of wakefulness and sleep is called the vegetative state.
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