neurocognitive disorders

14 neurocognitive disorders

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learning objectives 14

· 14.1 What forms of neurocognitive disorders are recognized in DSM-5? What is presumed to be the cause of these disorders?

· 14.2 What are the clinical features of neurocognitive disorders?

· 14.3 What is delirium and how is it treated?

· 14.4 What are the risk factors for Alzheimer’s disease? What changes in the brain are found in patients with Alzheimer’s disease?

· 14.5 How is Alzheimer’s disease treated?

· 14.6 What is an amnestic disorder? What causes amnestic disorders?

· 14.7 What are some of the clinical consequences of head trauma? What factors are related to the degree of impairment that results?

A Simple Case of Mania? A highly successful businessman, age 45, with no previous history of psychiatric disorder, began to act differently from his usual self. He seemed driven at work. His working hours gradually increased until finally he was sleeping only 2 to 3 hours a night; the rest of the time he worked. He became irritable and began to engage in uncharacteristic sprees of spending beyond his means.

Although he felt extremely productive and claimed he was doing the work of five men, the man’s boss felt otherwise. He was worried about the quality of that work, having observed several recent examples of poor business decisions. Finally, when the man complained of headaches, his boss insisted that he seek help. Source: Adapted from Jamieson & Wells, 1979 .

The case you have just read concerns a man who, on first glance, looks as if he might be having an episode of mania. In fact, he is suffering from four tumorous masses in his brain. Clues that this man has a brain disorder rather than a mood disorder include the facts that he is experiencing headaches at the same time as a major change in behavior and that he has no prior history of psychopathology (see Taylor, 2000 ). Clinicians always need to be alert to the possibility that brain impairment itself may be directly responsible for their patients’ symptoms. Failure to do so could result in serious diagnostic errors, as when a clinician falsely attributes a mood change to psychological causes and fails to consider a neuropsychological origin such as a brain tumor.

The brain is an astonishing organ. Weighing around 3 pounds and having the consistency of firm jelly, it is the most complex structure in the known universe (Thompson, 2000 ). It is also the only organ capable of studying and reading about itself. It is involved in every aspect of our lives from eating and sleeping to falling in love. The brain makes decisions, and it contains all the memories that make us who we are. Whether we are physically ill or mentally disturbed, the brain is involved.

Because it is so important, the brain is protected in an enclosed space and covered by a thick outer membrane called the dura mater (literally, “hard mother” in Latin). For further protection, the brain is encased by the skull. The skull is so strong that, if it were placed on the ground and weight were applied very slowly, it could support as much as 3 tons (Rolak, 2001 , p. 403)! These anatomical facts alone indicate just how precious the brain is.

Even though it is highly protected, the brain is vulnerable to damage from many sources. When the brain is damaged, cognitive changes result, as you saw in the case study above. Although there may be other signs and symptoms (such as mood or personality changes) as well, changes in cognitive functioning are the most obvious signs of a damaged brain.

In this chapter we focus on disorders that arise because of changes in brain structure, function, or chemistry. In some cases, such as with Parkinson’s disease or Alzheimer’s disease, these are caused by internal changes that lead to destruction of brain tissue. In others, they result from damage caused by external influences such as trauma from accidents or from the repeated blows to the head that can occur in boxing, soccer, or football.

Why are neurocognitive disorders discussed at all in a textbook on abnormal psychology? There are several reasons. First, as their inclusion in the DSM indicates, these disorders are regarded as psychopathological conditions. Second, as you just saw in the case study , some brain disorders cause symptoms that look remarkably like other abnormal psychology disorders. Third, brain damage can cause changes in behavior, mood, and personality. You will recognize this more clearly later when we describe the case of Phineas Gage (who survived a metal bar being blown through his head). Understanding what brain areas are involved when behavior, mood, and personality change after brain damage may help researchers better understand the biological underpinnings of many problems in abnormal psychology. Fourth, many people who suffer from brain disorders (e.g., people who are diagnosed as having Alzheimer’s disease) react to the news of their diagnosis with depression or anxiety. Prospective studies also suggest that depressive symptoms may herald the onset of disorders such as Alzheimer’s disease by several years and that episodes of depression can double the risk for Alzheimer’s disease even 20 years later (Speck et al., 1995 ). Finally, neurocognitive disorders of the type we describe in this chapter take a heavy toll on family members, who, for many patients, must shoulder the burden of care. Again, depression and anxiety in relatives of the patients themselves are not uncommon.

research CLOSE-UP: Case Study

Case studies are descriptions of one specific case. Case studies can be a useful source of information and can help researchers generate hypotheses. Because of their highly selective nature, however, they cannot be used to draw any scientific conclusions.

Brain Impairment in Adults

The causes of neurocognitive disorders are often much more specific than is the case for many of the disorders we have discussed so far in this book. In DSM-5, the disorders that used to be known as “Delirium, Dementia, and Amnestic and Other Cognitive Disorders” are now grouped into a new diagnostic category called Neurocognitive Disorders. This term is more straightforward than its predecessor. It is also more conceptually coherent. Disorders in this category are those that involve a loss of cognitive ability that is presumed to be caused by brain damage or disease. Subsections of this diagnostic category include delirium, major neurocognitive disorder (formerly dementia), and a new category of mild neurocognitive disorder . The distinction between major and mild neurocognitive disorder is based on severity. As the “Thinking Critically About DSM-5” box illustrates, the inclusion of a mild neurocognitive disorder in DSM-5 raises some important issues.

Within each broad diagnostic category, the specific diagnosis is to be determined by what is thought to be the cause of the problem. For example, the diagnosis of major neurocognitive disorder associated with Alzheimer’s disease is used for patients thought to have Alzheimer’s. For patients whose brain damage is caused by a traumatic brain injury the diagnosis would be major (or mild) neurocognitive disorder associated with traumatic brain injury. In this way the diagnosis provides information about both the cause of the neurocognitive disorder as well as its degree of severity.

Clinical Signs of Brain Damage

With a few exceptions, cell bodies and neural pathways in the brain do not appear to have the power of regeneration, which means that their destruction is permanent. When brain injury occurs in an older child or adult, there is a loss in established functioning. Often, the person who has sustained this loss is painfully aware of what he or she is no longer able to do, adding a pronounced psychological burden to the physical burden of having the lesion. In other cases the impairment may extend to the capacity for realistic self-appraisal (a condition called anosognosia), leaving these patients relatively unaware of their losses and hence poorly motivated for rehabilitation.

The degree of mental impairment is usually related to the degree of damage to the brain. However, this is not invariably so. Much depends on the nature and location of the damage as well as the premorbid (predisorder) competence and personality of the individual. In some cases involving relatively severe brain damage, mental change is astonishingly slight. In other cases of seemingly mild and limited damage, there may be quite marked alterations in functioning, as in the following case example.

DSM-5 THINKING CRITICALLY about DSM-5: Is the Inclusion of Mild Neurocognitive Disorder a Good Idea?

An important addition to DSM-5 is the new diagnosis of mild neurocognitive impairment. This change reflects an effort to recognize that cognitive problems that do not reach the level of affecting everyday functioning may still warrant clinical attention. But this new diagnostic category is not without controversy.

Some people are concerned that the use of the word “mild” trivializes the cognitive impairments that are being experienced. It may also imply that there is no need for services to be provided. On the other hand, refraining from using a term like dementia until the cognitive impairment is more severe may alleviate anxiety and reduce stigma.

But if minor cognitive disorder is considered to be a prodromal stage before the onset of more severe impairment, will receiving the more mild diagnosis still not be a source of anxiety? People experiencing minor cognitive impairment (MCI) are thought to be at increased risk for the development of Alzheimer’s disease. If these people can now be formally diagnosed with a disorder (MCI is not a diagnosis but mild neurocognitive impairment is) will we be scaring large numbers of people needlessly? Many people with MCI do not go on to develop more severe cognitive problems. We also have no way to treat Alzheimer’s disease successfully, yet alone prevent it. So, from a practical perspective, how helpful will this new diagnosis be to those who will receive it?

Finally, how do we separate mild neurocognitive disorder from normal aging? This is all the more important because many examples of mild cognitive problems (e.g., finding that thinking is easier when not distracted by phone, TV, or other conversations or needing occasional reminders to keep track of characters in a movie or a novel) are problems that are hardly unusual for older adults. Every time we lose our keys or forget whether or not we have paid a bill should we now be worried that we have mild neurocognitive impairment?

Hit on the Head With a Rake A 17-year-old girl was referred by her father for neuropsychiatric evaluation because of the many changes that had been observed in her personality during the past 2 years. She had been an A student and had been involved in many extracurricular activities during her sophomore year in high school. But now, as a senior, she was barely able to maintain a C average, was “hanging around with the bad kids,” and was frequently using marijuana and alcohol. A careful history revealed that 2 years before, her older brother had hit her in the forehead with a rake, which stunned her but did not cause her to lose consciousness. Although she had a headache after the accident, no psychiatric or neurological follow-up was pursued.

Neuropsychological testing at the time of evaluation revealed a significant decline in intellectual functioning from her “preinjury” state. Testing revealed poor concentration, attention, memory, and reasoning abilities. Academically, she was unable to “keep up” with the friends she had had before her injury. She began to socialize with a group of students who had little interest in academics, and she began to see herself as a rebel. When the neuropsychological test results were explained to the patient and her family as a consequence of the brain injury, she and her family were able to understand the “defensive” reaction to her changed social behavior.

Source: Adapted from Silver et al., 2002 .

Diffuse Versus Focal Damage

The disorders discussed in this section are characterized by neurocognitive problems, although psychopathological problems (such as psychosis or mood change) may also be associated with them. Some of these disorders are generally well understood, with symptoms that have relatively constant features in people whose brain injuries are comparable in location and extent. For example, attention is often impaired by mild to moderate diffuse—or widespread—damage, such as might occur with moderate oxygen deprivation or the ingestion of toxic substances such as mercury. Such a person may complain of memory problems due to an inability to sustain focused retrieval efforts, while his or her ability to store new information remains intact.

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The brain can be damaged by exposure to solvents. Nail studios frequently use a variety of organic solvents that are known to be potentially damaging to the central nervous system.

In an illustration of this, LoSasso, Rapport, and Axelrod ( 2001 , 2002 ) found that nail salon technicians reported significantly more cognitive and neurological impairments than controls did. The nail salon technicians also performed more poorly than the controls on tests of attention and information processing. This is likely due to routine exposure to (meth)acrylates and a variety of organic solvents such as toluene, acetone, and formaldehyde that are known to be potentially damaging to the central nervous system. Such findings highlight the consequences of even low-level exposure to neurotoxic substances that can be found in places where many people work and where many others routinely visit.

In contrast to diffuse damage, focal brain lesions involve circumscribed areas of abnormal change in brain structure. This is the kind of damage that might occur with a sharply defined traumatic injury or an interruption of blood supply (a stroke) to a specific part of the brain. Figure 14.1 explains how a stroke occurs.

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FIGURE 14.1 How a Stroke Occurs. Most strokes occur when an artery in the brain is blocked by a clot. The others, about 13 percent of strokes, occur when a brain artery bursts. Both types can be disastrous.

Source: Dr. Steven Warach, National Institute of Neurological Disorders and Stroke; American Heart Association.

image4 Watch the Video Special Topics: The Plastic Brain in MyPsychLab.

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Cross sections of damaged brains. The brain on the left shows damage from a stroke. Damage from a bullet is shown on the right.

The location and extent of the damage determine what problems the patient will have. As you are aware, the brain is highly specialized. Although the two hemispheres are closely interrelated, they are involved in somewhat different types of mental processing. At the risk of oversimplifying, it is generally accepted that functions that are dependent on serial processing of familiar information, such as language and solving mathematical equations, take place mostly in the left hemisphere for nearly everyone. Conversely, the right hemisphere appears to be generally specialized for grasping overall meanings in novel situations; reasoning on a nonverbal, intuitive level; and appreciating of spatial relations. Even within hemispheres, the various lobes and regions mediate specialized functions (see Figure 14.2 ).

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FIGURE 14.2 Brain Structures and Associated Behaviors

image7 Watch the Video The Basics: How The Brain Works Part 2 in MyPsychLab

TABLE 14.1 Impairments Associated With Brain Disorders

The following types of difficulties are often the consequences of brain disease, disorder, or damage.

· 1. Impairment of memory. The individual has trouble remembering recent events, although memory for past events may remain more intact. Some patients with memory problems may confabulate—that is, invent memories to fill in gaps. In severe instances, no new experience can be retained for more than a few minutes.

· 2. Impairment of orientation. The individual may not know where he or she is, what the day is, or who familiar people are.

· 3. Impairment of learning, comprehension, and judgment. The individual’s thinking becomes clouded, sluggish, or inaccurate. The person may lose the ability to plan with foresight or to understand abstract concepts and hence to process complex information (described as “thought impoverishment”).

· 4. Impairment of emotional control or modulation. The individual is emotionally overreactive: laughing, crying, or flying into a rage with little provocation.

· 5. Apathy or emotional blunting. The individual is emotionally underreactive and seems indifferent to people or events.

· 6. Impairment in the initiation of behavior. The individual lacks self-starting capability and may have to be reminded repeatedly about what to do next, even when the behavior involved remains well within the person’s range of competence. This is sometimes referred to as “loss of executive function.”

· 7. Impairment of controls over matters of propriety and ethical conduct. The individual may manifest a marked lowering of personal standards in areas such as appearance, personal hygiene, sexuality, or language.

· 8. Impairment of receptive and expressive communication. The individual may be unable to comprehend written or spoken language or may be unable to express his or her own thoughts orally or in writing.

· 9. Impaired visuospatial ability. The individual has difficulty coordinating motor activity with the characteristics of the visual environment, a deficit that affects graphomotor (handwriting and drawing) and constructional (e.g., assembling things) performance.

Although none of these relationships between brain location and behavior can be considered universally true, it is possible to make broad generalizations about the likely effects of damage to particular parts of the brain. Damage to the frontal areas, for example, is associated with one of two contrasting clinical pictures: (1) being unmotivated and passive and with limited thoughts and ideas or (2) featuring impulsiveness and distractibility. Damage to specific areas of the right parietal lobe may produce impairment of visual-motor coordination, and damage to the left parietal area may impair certain aspects of language function, including reading and writing, as well as arithmetical abilities. Damage to certain structures within the temporal lobes disrupts an early stage of memory storage. Extensive bilateral temporal damage can produce a syndrome in which remote memory remains relatively intact but nothing new can be stored for later retrieval. Damage to other structures within the temporal lobes is associated with disturbances of eating, sexuality, and emotion. Occipital damage produces a variety of visual impairments and visual association deficits, the nature of the deficit depending on the particular site of the lesion. For example, a person may be unable to recognize familiar faces. Unfortunately, many types of brain disease are general and therefore diffuse in their destructive effects, causing multiple and widespread interruptions of the brain’s circuitry. Some consequences of brain disorders are described in Table 14.1 above.

The Neurocognitive/Psychopathology Interaction

Most people who have a neurocognitive disorder do not develop psychopathological symptoms such as panic attacks, dissociative episodes, or delusions. However, many show at least mild deficits in cognitive processing and self-regulation. Similarly, some people who suffer from psychopathological disorders also have cognitive deficits. For example, patients with bipolar disorder have persistent cognitive deficits that can be detected even during periods of illness remission (Bora et al., 2011 ). This highlights the close link between psychopathological and neuropsychological conditions.

The psychopathological symptoms that do sometimes accompany brain impairment are not always predictable and can reflect individual nuances consistent with the patient’s age (see Tateno et al., 2002 ), her or his prior personality, and the total psychological situation confronting the patient. We should also never just assume that a psychological disorder—for example, a serious depression that follows a brain injury—is always attributable to the patient’s brain damage. Certainly that could be the case. However, it is also possible that the depression might be better explained by the patient’s awareness of dramatically lessened competence and the loss of previous skills. After a traumatic brain injury caused by an accident or a fall, for example, around 18 percent of patients make a suicide attempt (Simpson & Tate, 2002 ).

People with more favorable life situations tend to fare better after brain injury than people whose lives are more disorganized or disadvantaged (Yeates et al., 1997 ). Intelligent, well-educated, mentally active people have enhanced resistance to mental and behavioral deterioration following significant brain injury (e.g., see Mori et al., 1997a ; Schmand et al., 1997 ). Because the brain is the organ responsible for the integration of behavior, however, there are limits to the amount of brain damage that anyone can tolerate or compensate for without exhibiting abnormal behavior.

in review

· • Describe some of the major ways in which the brain can become damaged.

· • What kinds of clinical symptoms are often associated with damage to the frontal, parietal, temporal, and occipital lobes of the brain?

· • List nine impairments that are typical of focal and diffuse brain damage.

Delirium

Delirium is a state of acute brain failure that lies between normal wakefulness and stupor or coma (see Figure 14.3 ). The word comes from the Latin delirare, meaning to be out of one’s furrow or track.

Clinical Picture

A commonly occurring syndrome, delirium is characterized by confusion, disturbed concentration, and cognitive dysfunction (see the DSM-5 table on page 489 for diagnostic criteria). Although the DSM-IV-TRcriteria stated that delirium involved a disturbance in consciousness, this word was removed in DSM-5. This is because the essence of delirium is better captured by the idea of a disturbance in awareness. Think of delirium as a condition with a sudden onset that involves a fluctuating state of reduced awareness. Delirium is treated as a distinct disorder in DSM-5 (rather than as a type of major or mild neurocognitive disorder) because it can quickly fluctuate in severity. It can also coexist with a major or mild neurocognitive disorder (such as Alzheimer’s disease). It therefore does not fit well with being categorized as a major or mild form of neurocognitive disorder.

In addition to a disturbance in level of awareness, delirium also involves impairments of memory and attention as well as disorganized thinking. Hallucinations and delusions are quite common (see Trzepacz et al., 2002 ). In addition, the syndrome often includes abnormal psychomotor activity such as wild thrashing about and disturbance of the sleep cycle. A delirious person is essentially unable to carry out purposeful mental activity of any kind. The intensity of the symptoms also fluctuates over the course of a 24-hour period, as described in the following case study.

Delirium Following a Routine Operation Mrs. Patterson was 75 years old when she was admitted to the hospital. A widow who lived alone, she had broken her leg, and she needed a routine operation. The operation was successful. However, shortly afterward, Mrs. Patterson began to show signs of confusion. She had problems with awareness and attention, and she had no idea of what had happened to her or why she was in the hospital. During the day, she seemed agitated and aimlessly wandered around. She was unable to focus enough to watch television or to read. She was also unable to recognize friends and relatives who came to visit her. On several occasions, nursing staff saw her staring at an imaginary spot on the ceiling of her room and having conversations with imaginary people. Mrs. Patterson refused to take any medications. She would knock her meals onto the floor when they were brought to her. Between these outbursts, Mrs. Patterson was able to calm down, sleeping for short periods of about 30 minutes at a time. However, at night, she could hardly sleep at all. Instead, she wandered around the hospital ward. She went into the rooms of other patients, waking them up, and sometimes even trying to get into their beds. On a number of occasions, she was found in her nightdress, trying to leave the hospital. However, the staff always stopped her and carefully escorted her back to her room.

Source: Based on Üstün et al., 1996.

Delirium can occur in a person of any age. However, the elderly are at particularly high risk, perhaps because of brain changes caused by normal aging that lead to reduced “brain reserve.” As described in the case of Mrs. Petersen, delirium is very common in the elderly after they have had surgery, with patients over 80 being particularly at risk (Trzepacz et al., 2002 ). At the other end of the age spectrum, children are also at high risk of delirium, perhaps because their brains are not yet fully developed. In addition to advanced age, other risk factors for delirium include dementia, depression, and tobacco use (Fricchione et al., 2008 ).

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FIGURE 14.3 Continuum of Level of Awareness .

DSM-5 criteria for: Delirium

· A. A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment).

· B. The disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day.

· C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception).

· D. The disturbances in Criteria A and C are not better explained by another preexisting, established, or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma.

· E. There is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e., due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple etiologies.

Estimates of the prevalence of delirium vary widely with the age of the population studied. However, somewhere between 10 and 51 percent of patients who have had surgery will experience delirium; patients who have had cardiac surgery seem to be at especially high risk. The presence of delirium is also a bad prognostic sign. Delirium is correlated with cognitive decline, longer hospital stays, more health problems, and increased mortality; 25 percent of elderly patients with delirium die within the following 6 months (Fricchione et al., 2008 ; Witlox et al., 2010 ).

Delirium may result from several conditions including head injury and infection. However, the most common cause of delirium is drug intoxication or withdrawal. Toxicity from medications also causes many cases of delirium. This may explain why delirium is so common in the elderly after they have had surgery.

Treatments and Outcomes

Delirium is a true medical emergency, and its underlying cause must be identified and managed. Most cases of delirium are reversible, except when the delirium is caused by a terminal illness or by severe brain trauma. Treatment involves medication, environmental manipulations, and family support. The medications that are used for most cases are neuroleptics (Fricchione et al., 2008 ; Lee et al., 2004 ). These are the same drugs that are used to treat schizophrenia. For delirium caused by alcohol or drug withdrawal, benzodiazepines (such as those used in the treatment of anxiety disorders) are used (Trzepacz et al., 2002 ). In addition, environmental manipulations that help patients stay oriented, such as good lighting, clear signage, and easily visible calendars and clocks, can be helpful. It is also important that staff members introduce themselves when they work with patients, explain what their role is, and provide reorienting prompts whenever necessary. Some patients, however, especially elderly ones, may still have orientation problems, sleep problems, and other difficulties even months after an episode of delirium.

in review

· • What clinical features characterize the syndrome of delirium?

· • Describe some common causes of delirium. Who is most at risk of developing this clinical condition?

· • How is delirium treated?

Major Neurocognitive Disorder (Dementia)

In DSM-5 the broad diagnostic category of dementia has been renamed. The term major neurocognitive disorder is now used. One reason for this is to reduce stigma. It is also the case that, although the term dementia is widely accepted for older adults it is not a very appropriate term for younger adults who have cognitive problems (e.g., those who have sustained damage from head injuries).

Major neurocognitive disorders are those that involve marked deficits in cognitive abilities. These may be apparent in such areas as attention, executive ability, learning and memory, language, perception, and social cognition (skills required for understanding, interpreting, and responding to the behavior of others). What is crucial is that there is a decline from a previously attained level of functioning (see the DSM-5 table for diagnostic criteria for major neurocognitive disorder).

In older people the onset of cognitive deficits is typically quite gradual. Early on, the individual is alert and fairly well attuned to events in the environment. Even in the early stages, however, memory is affected, especially memory for recent events. As time goes on, patients show increasingly marked deficits in abstract thinking, the acquisition of new knowledge or skills, visuospatial comprehension, motor control, problem solving, and judgment. These are often accompanied by impairments in emotional control and in moral and ethical sensibilities; for example, the person may engage in crude solicitations for sex. Deficits may be progressive (getting worse over time) or static, but is more often the former. Occasionally a major neurocognitive disorder is reversible if it has an underlying cause that can be removed or treated (such as vitamin deficiency). Some treatable causes of major neuro-cognitive disorder are listed in Table 14.2 . image9 Watch the Video Alvin: Dementia (Alzheimer’s Type) on MyPsychLab.

DSM-5 criteria for: Major Neurocognitive Disorder (Dementia)

· A. Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition) based on:

· 1. Concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function; and

· 2. substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing or, in its absence, another quantified clinical assessment.

· B. The cognitive deficits interfere with independence in everyday activities (i.e., at a minimum, requiring assistance with complex instrumental activities of daily living such as paying bills or managing medications).

· C. The cognitive deficits do not occur exclusively in the context of a delirium.

· D. The cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia).

TABLE 14.2 Some Treatable Causes of Major Neurocognitive Disorder

Medications

Certain tumors or infections of the brain

Clinical depression

Blood clots pressing on the brain

Vitamin B12 deficiency

Metabolic imbalances (including thyroid, kidney, or liver disorders)

Chronic alcoholism

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At least 50 different disorders are known to cause the types of cognitive deficits that are now included in the category of major neurocognitive disorders (Bondi & Lange, 2001 ). They include degenerative diseases such as Hunting-ton’s disease and Parkinson’s disease (which are described below). Other causes are strokes (see Ivan et al., 2004 ); certain infectious diseases such as syphilis, meningitis, and AIDS; intracranial tumors and abscesses; certain dietary deficiencies (especially of the B vitamins); severe or repeated head injury; anoxia (oxygen deprivation); and the ingestion or inhalation of toxic substances such as lead or mercury. As Figure 14.4 on page 491 illustrates, the most common cause of major neurocognitive disorder is degenerative brain disease, particularly Alzheimer’s disease. In this chapter we will focus primarily on this greatly feared disorder. We will also briefly discuss neurocognitive disorders that result from HIV infection and stroke (vascular dementia).

Parkinson’s Disease

Named after James Parkinson, who first described it in 1817, Parkinson’s disease is the second most common neurodegenerative disorder (after Alzheimer’s disease). It is more often found in men than in women, and it affects between 0.5 and 1 percent of people between ages 65 and 69 and 1 to 3 percent of people over 80 (Toulouse & Sullivan, 2008 ). However, the actor Michael J. Fox developed Parkinson’s disease when he was only 30 years old. His book Lucky Man ( 2002 ) offers a moving personal account of his struggle with the illness and well describes some of its major symptoms.

Parkinson’s disease is characterized by motor symptoms such as resting tremors or rigid movements. The underlying cause of this is loss of dopamine neurons in an area of the brain called the substantia nigra. Dopamine is a neurotransmitter that is involved in the control of movement. When dopamine neurons are lost, a person is unable to move in a controlled and fluid manner. In addition to motor symptoms, Parkinson’s disease can involve psychological symptoms such as depression, anxiety, apathy, cognitive problems, and even hallucinations and delusions (Chaudhuri et al., 2011 ). Later on in the illness, cognitive deficits may also become apparent Over time, 25 to 40 percent of patients with Parkinson’s disease will show signs of cognitive impairment (Marsh & Margolis, 2009 ). The causes of Parkinson’s disease are not clear, although both genetic and environmental factors are suspected. Genetic factors may be more important in cases where the Parkinson’s disease develops earlier in life, and environmental factors may be more relevant in later onset cases (Wirdefeldt et al., 2011 ). Interestingly, smoking and drinking coffee may provide some protection against the development of Parkinson’s disease, although the reasons for this remain unclear (Toulouse & Sullivan, 2008 ; Wirdefeldt et al., 2011 ).

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FIGURE 14.4 Causes of Dementia (major neurocognitive disorder). Causes are presented according to the percentage of all cases they account for .

The symptoms of Parkinson’s disease can be temporarily reduced by medications, such as Mirapex (pramipexole), that increase the availability of dopamine in the brain. However, once the medications wear off, the symptoms return. Another treatment approach that is now being tried is deep brain stimulation (described in Chapter 16 ). In the future, stem cell research may also offer some hope for patients with this disease.

Huntington’s Disease

Huntington’s disease is a rare degenerative disorder of the central nervous system that afflicts about 1 in every 10,000 people (Phillips et al., 2008 ). It was first described in 1872 by the American neurologist George Huntington. The illness begins in midlife (the mean age of onset is around 40 years), and it affects men and women in equal numbers. Huntington’s disease is characterized by a chronic, progressive chorea (involuntary and irregular movements that flow randomly from one area of the body to another). However, subtle cognitive problems often predate the onset of motor symptoms by many years. These cognitive problems are no doubt due to the progressive loss of brain tissue (detectable with brain imaging) that occurs as much as a decade before the formal onset of the illness (Shoulson & Young, 2011 ). Patients eventually develop dementia, and death usually occurs within 10 to 20 years of first developing the illness. There are currently no effective treatments that can restore functioning or slow down the course of this terrible and relentless disorder. American folk singer Woody Guthrie, whose song “This Land Is Your Land” is well known, died of the disease in 1967 when he was 55 years of age.

Huntington’s disease is caused by a single dominant gene (the Huntingtin gene) on chromosome 4. This genetic mutation was discovered as a result of intense research on people living in villages around Lake Maracaibo in Venezuela, where this disease is extremely common (Marsh & Margolis, 2009 ). Because the Huntingtin gene is a dominant gene, anyone who has a parent with the disease has a 50 percent chance of developing the disease himself or herself. A genetic test can be given to at-risk individuals to determine whether they will eventually develop the disorder. However, in the United States, only about 10 percent of people who are eligible for testing choose to know what their genetic destiny is (Shoulson & Young, 2011 ). If you were in this situation, what would you do? One interesting finding here is that the majority of people who have asked to be tested are women (Hayden, 2000 ).

Alzheimer’s Disease

Alzheimer’s disease is a progressive and fatal neurodegenerative disorder. It takes its name from Alois Alzheimer (1864–1915), the German neuropathologist who first described it in 1907. It is the most common cause of dementia (Jalbert et al., 2008 ). In the DSM-5 it is called “major (or mild) neurocognitive disorder associated with Alzheimer’s disease.” Alzheimer’s disease is associated with a characteristic dementia syndrome (see the case study below) that has an imperceptible onset and a usually slow but progressively deteriorating course, terminating in delirium and death.

The Forgetful Mail Carrier At the age of 60, Harold took early retirement from his government job because, for the previous 5 years, he had been having difficulty performing his work properly. A mail carrier, he was constantly making errors and delivering mail to the wrong places. He also began to become more withdrawn, gradually giving up hobbies that had been important to him. At first, his increasing forgetfulness was not very noticeable when he was at home. Then, one day when he was 62, Harold was hiking in an area he knew well and was unable to find his way home. Since that time, his memory problems have grown increasingly worse. He loses things, forgets appointments, and can no longer find his way around his home-town. Now, at the age of 66, Harold no longer recognizes his close friends and is uninterested in reading or watching television. Things are so bad that his wife is afraid to leave him alone in the house because he is so forgetful.

Source: Based on Üstün et al., 1996.

CLINICAL PICTURE

The diagnosis of Alzheimer’s disease is made after a thorough clinical assessment of the patient. However, the diagnosis can only be confirmed after the patient’s death. This is because an autopsy must be performed to see the brain abnormalities that are such distinctive signs of this disease. In the living patient, the diagnosis is normally given only after all other potential causes of dementia are ruled out by medical and family history, physical examination, and laboratory tests.

Alzheimer’s disease usually begins after about age 45 (Malaspina et al., 2002 ). Contrary to what many people believe, it is characterized by multiple cognitive deficits, not just problems with memory. There is a gradual declining course that involves slow mental deterioration. Figure 14.5 shows the performance of two men on a battery of cognitive tests repeated over a period of several years. Both men were of similar age and level of education, and both were initially free of Alzheimer’s disease. However, for the man who subsequently developed Alzheimer’s disease (confirmed on autopsy), a progressive, downward course in his cognitive performance is apparent (see Storandt, 2008 ).

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FIGURE 14.5 Test Performance in a Healthy Man and a Man Who Developed Alzheimer’s Disease .

Source: Figure 1 on page 198 from Martha Storandt. (2008). Cognitive deficits in the early stages of Alzheimer’s disease. Current Directions in Psychological Science, 17(3), 198–2202 (Copyright © 2008). Association for Psychological Science. Reproduced with permission of Blackwell Publishing Ltd.

In its earliest stages, Alzheimer’s disease involves minor cognitive impairment. For example, the person may have difficulty recalling recent events, make more errors at work, or take longer to complete routine tasks. In the later stages, there is evidence of dementia; deficits become more severe, cover multiple domains, and result in an inability to function. For example, the person may be easily disoriented, have poor judgment, and neglect his or her personal hygiene. Because they have impaired memory for recent events, many patients have “empty” speech in which grammar and syntax remain intact but vague and seemingly pointless expressions replace meaningful conversational exchange (e.g., “It’s a nice day, but it might rain”). The case study below, which involves a man who had retired some 7 years prior to his hospitalization, is typical.

Restless and Wandering During the past 5 years, the patient had shown a progressive loss of interest in his surroundings and during the last year had become increasingly “childish.” His wife and eldest son had brought him to the hospital because they felt they could no longer care for him in their home, particularly because of the grandchildren. They stated that he had become careless in his eating and other personal habits and was restless and prone to wandering about at night. He could not seem to remember anything that had happened during the day but was garrulous concerning events of his childhood and middle years.

After admission to the hospital, the patient seemed to deteriorate rapidly. He could rarely remember what had happened a few minutes before, although his memory for remote events of his childhood remained good. When visited by his wife and children, he mistook them for old friends, and he could not recall anything about the visit a few minutes after they had departed. The following brief conversation with the patient, which took place after he had been in the hospital for 9 months (and about 3 months before his death), shows his disorientation for time and person.

· DOCTOR: How are you today, Mr. _______?

· PATIENT: Oh … hello [looks at doctor in rather puzzled way as if trying to make out who he is].

· DOCTOR: Do you know where you are now?

· PATIENT: Why yes … I am at home. I must paint the house this summer. It has needed painting for a long time but it seems like I just keep putting it off.

· DOCTOR: Can you tell me the day today?

· PATIENT: Isn’t today Sunday … why, yes, the children are coming over for dinner today. We always have dinner for the whole family on Sunday. My wife was here just a minute ago but I guess she has gone back into the kitchen.

The temporal lobes of the brain are the first regions to be damaged in the person with Alzheimer’s disease. Because the hippocampus is located here, memory impairment is an early symptom of the disease. Loss of brain tissue in the temporal lobes may also explain why delusions are found in some patients (Lyketsos et al., 2000 ). Although delusions of persecution are predominant, delusional jealousy is sometimes seen. Here, the person persistently accuses his or her partner or spouse—who is often of advanced age and physically debilitated—of being sexually unfaithful. Family members may be accused of poisoning the patient’s food or of plotting to steal the patient’s funds. One study of physically aggressive patients with Alzheimer’s disease found that 80 percent of them were delusional (Gilley et al., 1997 ).

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Cognitive difficulties are not an inevitable consequence of aging. Betty White hosted Saturday Night Live when she was 89 years old.

With appropriate treatment, which may include medication and the maintenance of a calm, reassuring, and unprovocative social environment, many people with Alzheimer’s disease show some alleviation of symptoms. In general, however, deterioration continues its downward course over a period of months or years. Eventually, patients become oblivious to their surroundings, bedridden, and reduced to a vegetative state. Resistance to disease is lowered, and death usually results from pneumonia or some other respiratory or cardiac problem. The median time to death is 5.7 years from the time of first clinical contact (Jalbert et al., 2008 ).

PREVALENCE

Alzheimer’s disease is becoming a major public health problem, straining societal and family resources. It accounts for most cases of dementia (Lyketsos et al., 2000 ). Although this disease is not an inevitable consequence of aging (Betty White hosted Saturday Night Live when she was 89), age is a major risk factor.

It has been estimated that the rate of Alzheimer’s disease doubles about every 5 years after a person reaches the age of 40 (Hendrie, 1998 ). Whereas fewer than 1 percent of 60- to 64-year-olds have the disease, up to 40 percent those aged 85 and older do (Jalbert et al., 2008 ). In the United states, more than 5 million people are living with this disease. Worldwide, the figure is over 35 million (Selkoe, 2012 ). By 2030 it is expected that this number will rise to a staggering 66 million (Vreugdenhil et al., 2012 ). The future prospects are therefore somewhat alarming. If we have not solved the problem of preventing Alzheimer’s disease (or arresting it in its early stages) by around that time, society will be faced with the overwhelming problem of caring for millions of demented senior citizens.

For reasons that are not yet clear, women seem to have a slightly higher risk of developing Alzheimer’s disease than men (Jalbert et al., 2008 ). Indeed, Alois Alzheimer’s original case was a 51-year-old woman. Women tend to live longer than men, but this may not entirely explain the increased prevalence of women with Alzheimer’s disease. However, a relevant factor may be loneliness. In one study of 800 elderly people (the majority of whom were female), those who reported that they felt lonely had twice the risk of developing Alzheimer’s disease over the course of the 4-year follow-up. This association was independent of their scores on a measure of cognition, suggesting that loneliness is not an early sign of cognitive impairment or a consequence of impaired cognitive skill (Wilson, Krueger et al., 2007 ). It is reasonable to suggest that women are more likely to experience loneliness because they live longer and so outlive their husbands. This may be important when trying to understand sex differences in the risk for Alzheimer’s disease.

In addition to advanced age and being female, other risk factors for Alzheimer’s disease include being a current smoker, having fewer years of formal education, having lower income, and having a lower occupational status (Jalbert et al., 2008 ). Table 14.3 provides a summary of the most well-researched risk factors to date.

The prevalence of Alzheimer’s disease is higher in North America and Western Europe and lower in such places as Africa, India, and South East Asia (Ballard et al., 2011 ; Ferri et al., 2005 ). Such observations have led researchers to suspect that lifestyle factors such as a high-fat, high-cholesterol diet are implicated in the development of Alzheimer’s disease (Sjogren & Blennow, 2005 ). Also implicating diet, researchers have found that high levels of an amino acid called homocysteine (which is a risk factor for heart disease) seem to increase a person’s risk of developing Alzheimer’s disease later in life (Ravaglia et al., 2005 ). Levels of homocysteine in the blood can be reduced by taking folic acid and certain B vitamins. Taking statin drugs to lower cholesterol also seems to offer some protection against Alzheimer’s disease (Sparks et al., 2005 ).

TABLE 14.3 Summary of Risk Factors for Alzheimer’s Disease

Advanced age

Female

Current smoker

Fewer years of education

Lower income

Lower occupational status

Head trauma

CAUSAL FACTORS

When we picture a typical Alzheimer’s patient, we imagine a person of very advanced age. Sometimes, however, the disease begins much earlier and affects people in their 40s or 50s. In such cases, cognitive decline is often rapid. Considerable evidence suggests a substantial genetic contribution in early-onset Alzheimer’s disease, although different genes may be involved in different families (see Gatz, 2007 ). Genes also play a role in late-onset Alzheimer’s disease.

Cases of early-onset Alzheimer’s disease appear to be caused by rare genetic mutations. So far, three such mutations have been identified (Ballard et al., 2011 ). One involves the APP (amyloid precursor protein) gene, which is located on chromosome 21. Mutations of the APP gene are associated with an onset of Alzheimer’s disease somewhere between 55 and 60 years of age (Cruts et al., 1998 ).

The fact that a mutation of a gene on chromosome 21 has been found to be important is interesting because it has long been known that people with Down syndrome (which is caused by a tripling, or trisomy, of chromosome 21) who survive beyond about age 40 develop an Alzheimer’s-like dementia (Bauer & Shea, 1986 ; Janicki & Dalton, 1993 ). They also show similar neuropathological changes (Schapiro & Rapoport, 1987 ). In addition, cases of Down syndrome tend to occur more frequently in the families of patients with Alzheimer’s disease (Heyman et al., 1984 ; Schupf et al., 1994 ). One study has found that mothers who gave birth to a child with Down syndrome before age 35 had a 4.8 times greater risk of developing Alzheimer’s disease when they were older compared to mothers of children with other types of mental retardation (Schupf et al., 2001 ).

Other cases of even earlier onset appear to be associated with mutations of a gene on chromosome 14 called presenilin 1 (PS1) and with a mutation of the presenilin 2 (PS2) gene on chromosome 1. These genes are associated with an onset of Alzheimer’s disease somewhere between 30 and 50 years of age (Cruts et al., 1998 ). One carrier of the PS1 mutation is even known to have developed the disorder at age 24 (Wisniewski et al., 1998 ). Remember, however, that these mutant genes, which are autosomal dominant genes and so nearly always cause disease in anyone who carries them, are extremely rare. The APP, PS1, and PS2 genetic mutations probably account, together, for no more than about 5 percent of cases of Alzheimer’s disease.

A gene that plays an important role in cases of late-onset Alzheimer’s disease is the APOE (apolipoprotein) gene on chromosome 19. This gene codes for a blood protein that helps carry cholesterol through the bloodstream. We know that differing forms (genetic alleles) of APOE differentially predict risk for late-onset Alzheimer’s disease . Three such alleles have been identified, and everyone inherits two of them, one from each parent. One of these alleles, the APOE-E4 allele , significantly enhances risk for late-onset disease. Thus a person may inherit zero, one, or two of the APOE-E4 alleles, and his or her risk for Alzheimer’s disease increases correspondingly. For example, having two APOE-E4 alleles results in a sevenfold increase in a person’s chances of developing the disease (Ballard et al., 2011 ). Another such allele, APOE-E2, seems to convey protection against late-onset Alzheimer’s disease. The remaining and most common allele form, APOE-E3, is of neutral significance. The alleles differ in how efficient they are in clearing amyloid, with APOE-E2 being most efficient and APOE-E4 least efficient (Karran et al., 2011 ).

APOE-E4 has been shown to be a significant predictor of memory deterioration in older individuals with or without clinical dementia (Hofer et al., 2002 ). The APOE-E4 allele is relatively uncommon in Chinese people compared to its frequency in people from Europe or North America. In contrast, people of African descent are especially likely to have this allele (Waters & Nicoll, 2005 ). Table 14.4 summarizes the genes that have been implicated in Alzheimer’s disease.

The APOE-E4 allele (which can be detected by a blood test) is overrepresented in all types of Alzheimer’s disease including the early-onset and late-onset forms. Approximately 65 percent of patients have at least one copy of the APOE-E4 allele (see Malaspina et al., 2002 ). Exciting as they are, however, these discoveries still do not account for all cases of Alzheimer’s disease, not even all late-onset cases (e.g., Bergem et al., 1997 ). Many people who inherit the most risky APOE pattern (two APOE-E4 alleles) do not succumb to the disorder. One study found that only 55 percent of people who had two APOE-E4 alleles had developed Alzheimer’s disease by age 80 (Myers et al., 1996 ). And others with Alzheimer’s disease have no such APOE-E4 risk factor. In addition, substantial numbers of monozygotic twins are discordant for the disease (Bergem et al., 1997 ; Breitner et al., 1993 ).

TABLE 14.4 Genes Associated With Alzheimer’s Disease

Gene

Chromosome

Type

Amyloid precursor protein gene (APP)

mutation

Presenilin 1 (PS1)

mutation

Presenilin 2 (PS2)

mutation

Apolipoprotein E (APOE)

susceptibility gene

developments in RESEARCH: Depression Increases the Risk of Alzheimer’s Disease

Having a history of depression seems to put a person at higher risk for the later development of Alzheimer’s disease (Ownby et al., 2006 ). Although we are not yet sure why this is, researchers speculate that some of the changes in the brain that are known to be associated with depression and with stress may somehow leave the brain more vulnerable to problems down the road (Wilson et al., 2008 ).

Depression may also be an early warning sign of the onset of dementia. In a large, community-based prospective study of people aged 65 and older, researchers found that people who had no early (before age 50) history of depression but who developed symptoms of depression later in life were about 46 percent more likely to develop dementia over the course of the (approximately 7-year) follow-up period (Li et al., 2011 ). What this means is that late-life depression may be more than a risk factor for depression. Rather, it could be an early manifestation of the dementia itself. This raises the interesting question of whether treating depression might delay the clinical onset of dementia.

People with a genetic risk for Alzheimer’s disease because they carry the APOE-E4 gene may be especially vulnerable to developing Alzheimer’s disease if they also have a history of depression. In one study, depressed men who had the APOE-E4 gene were more than seven times more likely to develop Alzheimer’s disease over the course of a 6-year follow-up compared to men who had neither the gene nor a history of depression. For men who did not have the gene but did have a history of depression, the risk of later Alzheimer’s disease was also higher (1.6-fold increase), but not nearly as high as the risk for the men who had the gene and the history of depression (Irie et al., 2008 ). Having the APOE-E4 allele does not make a person more likely to develop depression; however, when the gene and depression occur together, the risk of later Alzheimer’s disease is especially high.

Why should this be? Current thinking is that our genetic susceptibility interacts with other genetic factors and with environmental factors to determine whether we will succumb to any particular disorder. Clearly, other genes involved in the development of Alzheimer’s disease still remain to be found. However, environmental factors may also play a key role. As we have noted, the differences in the prevalence of Alzheimer’s disease across different parts of the world suggest that diet may be an important mediating environmental variable. Being overweight, having Type 2 diabetes, or not being physically active have also been implicated as risk factors. The association with diabetes is interesting because researchers have found that insulin levels are abnormally low in some of the brain areas that are most affected by Alzheimer’s disease. Other environmental factors under consideration include exposure to metals such as aluminum and experiencing head trauma. One prospective study has found that traumatic brain injury is associated, for up to 5 years after the injury, with a fourfold increase in risk of developing Alzheimer’s disease (see Malaspina et al., 2002 ). And, as illustrated in Developments in Research box above, depression also elevates risk of later Alzheimer’s disease). On the other hand, exposure to nonsteroidal anti-inflammatory drugs such as ibuprofen may be protective and lead to a lower risk of Alzheimer’s disease (Breitner et al., 1994 ; in’t Veld et al., 2001 ; Weggen et al., 2001 ). People with more cognitive reserve (a concept combining education, occupation, and mental engagement) also seem to be at reduced risk (Ballard et al., 2011 ). Recent research with mice further suggests that exposure to a more stimulating and novel environment slows down the development of Alzheimer-related changes in the brain (Li et al., 2013 ). In other words, it may be possible to reduce or delay the occurrence of Alzheimer’s disease by deliberately limiting exposure to risks, living a more interesting life, and taking other preventive measures.

NEUROPATHOLOGY

When Alois Alzheimer performed the first autopsy on his patient (she was known as Auguste D.), he identified a number of brain abnormalities that are now known to be characteristic of the disease. These are (1) amyloid plaques, (2) neurofibrillary tangles, and (3) atrophy (shrinkage) of the brain. Although plaques and tangles are also found in normal brains, they are present in much greater numbers in patients with Alzheimer’s disease, particularly in the temporal lobes.

Current thinking is that, in Alzheimer’s disease, neurons in the brain secrete a sticky protein substance called beta amyloid much faster than it can be broken down and cleared away. This beta amyloid then accumulates into amyloid plaques (see Figure 14.6 , p. 496). These are thought to interfere with synaptic functioning and to set off a cascade of events that leads to the death of brain cells. Beta amyloid has been shown to be neurotoxic (meaning it causes cell death). Amyloid plaques also trigger local chronic inflammation in the brain and release cytokines (see Chapter 5 ) that may further exacerbate this process.

Having the APOE-E4 form of the APOE gene is associated with the more rapid buildup of amyloid in the brain (Jalbert et al., 2008 ). Animal studies also suggest that stress makes the neurocognitive consequences of amyloid accumulation much worse (Alberini, 2009 ; Srivareerat et al., 2009 ). Insulin may also play a role in regulating amyloid. Although some scientists believe that the accumulation of beta amyloid plays a primary role in the development of Alzheimer’s disease, others suspect that it may be a defensive response rather than a causal factor. Importantly, amyloid deposits can be present as many as 10 years before clinical signs of Alzheimer’s disease first show themselves (Shim & Morris, 2011 ). It is not yet known if symptoms become apparent when the amyloid burden in the brain crosses a certain threshold or if amyloid buildup itself triggers other destructive processes that eventually culminate in symptoms (Karran et al., 2011 ).

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FIGURE 14.6 Brain Damage in Alzheimer’s Disease .

Watch the Video Alzheimer’s and Dementia in MyPsychLab

Neurofibrillary tangles are webs of abnormal filaments within a nerve cell. These filaments are made up of another protein called tau. In a normal, healthy brain, tau acts like a scaffolding, supporting a tube inside neurons and allowing them to conduct nerve impulses. In Alzheimer’s disease the tau is mis-shaped and tangled. This causes the neuron tube to collapse.

Although abnormal tau aggregation can occur independently, there is reason to believe that buildup of tau protein is accelerated by an increasing burden of amyloid in the brain (Shim & Morris, 2011 ). Animal studies of mice that have been genetically modified to be highly susceptible to developing Alzheimer’s disease (so-called transgenic mice) support this idea (Götz et al., 2001 ; Lewis et al., 2001 ). If correct, it suggests that the most promising drug treatments for Alzheimer’s disease may be those that can target and prevent amyloid buildup.

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This photomicrograph of a brain tissue specimen from an Alzheimer’s patient shows the characteristic plaques (dark patches) and neurofibrillary tangles (irregular pattern of strand-like fibers).

Another notable alteration in Alzheimer’s disease concerns the neurotransmitter acetylcholine (ACh). This neurotransmitter is known to be important in the mediation of memory. Although there is widespread destruction of neurons in Alzheimer’s disease, particularly in the area of the hippocampus (Adler, 1994 ; Mori et al., 1997b ), evidence suggests that among the earliest and most severely affected structures are a cluster of cell bodies located in the basal forebrain and involved in the release of ACh (Schliebs & Arendt, 2006 ). The reduction in brain ACh activity in patients with Alzheimer’s disease is correlated with the extent of neuronal damage (i.e., plaques, tangles) that they have sustained.

The loss of cells that produce ACh makes a bad situation much worse. Because ACh is so important in memory, its depletion contributes greatly to the cognitive and behavioral deficits that are characteristic of Alzheimer’s disease. For this reason, drugs (called cholinesterase inhibitors) that inhibit the breakdown of ACh (and so increase the availability of this neurotransmitter) can be clinically beneficial for patients (Winblad et al., 2001 ).

TREATMENT AND OUTCOME

Despite extensive research efforts, we still have no treatment for Alzheimer’s disease that will restore functions once they have been destroyed or lost. Current treatments, targeting both patients and family members, aim to diminish agitation and aggression in patients and reduce distress in caregivers as much as possible (Practice Guideline, 2007 ).

Some common problematic behaviors associated with dementia are wandering off, incontinence, inappropriate sexual behavior, and inadequate self-care skills. These can be somewhat controlled via behavioral approaches (see Chapter 16 ). Behavioral treatments need not be dependent on complex cognitive and communication abilities (which tend to be lacking in patients with dementia). Because of this, they may be particularly well suited for therapeutic intervention with Alzheimer’s disease. In general, reports of results are moderately encouraging in terms of reducing unnecessary frustration and embarrassment for the patient and difficulty for the caregiver (Fisher & Carstensen, 1990 ; Mintzer et al., 1997 ; Teri et al., 1997 ).

As we noted earlier, some patients with Alzheimer’s disease develop psychotic symptoms and are very agitated. Antipsychotic medications (like those used in the treatment of schizophrenia) are sometimes given to alleviate these symptoms. However, these medications must be used with great caution. The Food and Drug Administration has issued a warning that patients with dementia who receive atypical antipsychotic medications are at increased risk of death (Schultz, 2008 ). Moreover, although anti-psychotic medications may alleviate some symptoms to a very modest degree, there is no good evidence that they are better than placebo when it comes to patients’ overall daily functioning and cognition (Sultzer et al., 2008 ).

Treatment efforts to improve cognitive functioning have focused on the consistent findings of acetylcholine depletion in Alzheimer’s disease. The reasoning here is that it might be possible to improve functioning by administering drugs that enhance the availability of brain ACh. Currently, the most effective way of doing so is by inhibiting the production of acetylcholinesterase, the principal enzyme involved in the metabolic breakdown of acetylcholine. This is the rationale for administering drugs such as tacrine (Cognex) and donepezil (Aricept). Winblad and colleagues (2001) studied 286 patients who were randomly assigned to receive either medication (donepezil) or placebo for a 1-year period. Patients’ cognitive functioning and ability to perform daily activities were measured at the start of the study and again at regular intervals over the study period. Patients who received the medication did better overall than patients who received the placebo. However, all patients declined in their functioning over the course of the study. Furthermore, although donepezil does help patients a little, these gains do not mean that patients taking the drug are any less likely to avoid institutionalization than those who are not taking the medication (AD2000 Collaborative Group, 2004 ).

The newest medication that has been approved to treat Alzheimer’s disease is memantine, which is marketed as Namenda. Unlike other approved medications, memantine is not a cholinesterase inhibitor. Instead, it appears to regulate the activity of the neurotransmitter glutamate, perhaps by protecting cells against excess glutamate by partially blocking NMDA receptors. Memantine, which can be used alone or in combination with donepezil, appears to provide patients with some cognitive benefits (Forchetti, 2005 ; Reisberg et al., 2003 ). However, when it comes to day-to-day functioning, the improvements that come from taking medications are still very small (Ballard et al., 2011 ; Hansen et al., 2007 ).

Yet another line of treatment research is focused on developing vaccines that might help clear away any accumulated amyloid plaques. Although initial findings from animal research looked promising (e.g., McLaurin et al., 2002 ), human clinical trials of a vaccine were terminated prematurely because of dangerous side effects. Nonetheless, researchers continue to explore novel treatment approaches (Gestwicki et al., 2004 ; Hardy, 2004 ; Hutter-Paier et al., 2004 ). To date, however, all efforts to develop new drugs to treat Alzheimer’s disease have been unsuccessful. No new medications have become available since Namenda was approved in 2003. This is very disappointing for patients and for their families, who live in hope of major breakthroughs.

Unfortunately, once most types of neuronal cells have died they are permanently lost. This means that even if some new treatment could halt a patient’s progressive loss of brain tissue, he or she would still be left seriously impaired. This makes the research effort to detect Alzheimer’s disease in its earliest stages all the more important.

EARLY DETECTION

Most researchers believe that signs of Alzheimer’s disease might be detectable long before clinical symptoms appear. To explore this, they are using a range of brain-imaging techniques to study the brains of people at high risk for developing the disease. People at high risk include those who have the APOE-E4 allele as well as people who are experiencing minor cognitive impairment (MCI). MCI is thought to be on a continuum between healthy aging and the earliest signs of dementia (Risacher & Saykin, 2013 ). Some people with MCI report problems with memory. However, other (non-memory-related) cognitive problems are also predictive of later Alzheimer’s disease (Storandt, 2008 ).

the WORLD around us: Exercising Your Way to a Healthier Brain?

If you want to preserve your brain function as you age, you may be surprised to learn that one of the best things you can do is to exercise regularly. A growing amount of research suggests that exercise has considerable neurocognitive benefits. For example, in one prospective study of 299 elderly people (average age 78 years), those who walked 6 to 9 miles per week had much less loss of gray matter over time than did those who were more sedentary (Erikson et al., 2010 ). In another year-long study, people aged 55 to 80 years who had no dementia were randomly assigned to a program of 40-minute walks three times a week or a program of stretching and toning that lasted the same amount of time. At the end of 1 year, those who had exercised by walking showed a 2 percent increase in the size of their hippocampus. In contrast, those in the stretching and toning control group showed a decline in their hippocampal volume (which is expected with normal aging). In other words, exercise seemed to reverse the age-related loss whereas stretching and toning did not. What is also interesting is that increases in the volume of the hippocampus were also directly related to improvements in memory (Erikson et al., 2011 ).

Not surprisingly, researchers are now actively studying the effects of exercise in patients with Alzheimer’s disease. Recent findings suggest that even a short program of exercise for 4 months conducted at home under the supervision of a carer or other family member can improve cognitive and physical functioning in elderly patients with Alzheimer’s disease (Vreugdenhil et al., 2012 ). Inexpensive and easy to implement, exercise programs are now providing some much needed hope for patients and families coping with dementia.

Brain scans of people with MCI show that, like patients with Alzheimer’s disease, they have atrophy in a number of brain areas, including the hippocampus (which you may recall is involved in memory) (Chételat et al., 2003 ; Kubota et al., 2005 ; Devanand et al., 2007 ). Moreover, reduction in the size of the hippocampus predicts the later development of Alzheimer’s disease both in people with MCI and in elderly people who do not report any memory or cognitive impairments (De Leon et al., 2004 ; den Heijer et al., 2006 ). This suggests that atrophy of this brain area is an early sign of the disease.

Functional imaging techniques also show that the hippocampus is less active when patients with Alzheimer’s disease (compared to controls) are engaged in memory tasks (Kato et al., 2001 ; Sperling et al., 2003 ). Again, this is also true of people with MCI (Chételat et al., 2003 ; De Santi et al., 2001 ). These findings are in contrast to those found in people who are cognitively normal but who are at high risk because they carry the APOE-E4 allele. These people do not show a lack of activation in the hippocampus when they are involved in memory tasks. Instead, brain-imaging studies reveal the opposite. Rather than underactivity, people who are at genetic high risk show increased activity in various parts of the brain, including the hippocampus, when they engage in memory tasks (Bookheimer et al., 2000 ; Smith, Andersen et al., 2002 ).

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Atrophy of the hippocampus, a brain area critical for memory, is an early sign of Alzheimer’ disease. In these pictures, arrows highlight the body of the hippocampus. Note the atrophy in the image on the right.

How can we explain these rather contradictory findings? Current thinking is that the greater degree of brain activation in people who are cognitively normal but at high risk for developing Alzheimer’s disease reflects the greater effort they need to make to manage cognitive tasks. Simply put, carriers of the APOE-E4 allele may have to work harder. Because their brain tissue is still healthy (unlike in people with Alzheimer’s disease or MCI), we see an increase in brain activation in response to a cognitive challenge rather than the decrease in activation that is more typical of Alzheimer’s disease patients or those with MCI. A similar pattern of increased brain activation in certain key areas is also found in people with MCI who are able to perform better on cognitive tests compared to those who perform worse (Clément & Belleville, 2010 ).

Does brain-imaging research allow us to identify people who are going to develop dementia? Not yet. None of the changes found to date are specific enough to be used to make an early diagnosis. This, however, is the goal for the future. In the meantime, if you want to preserve your brain, you might consider reading The World Around Us box on page 498. And if you think this information is just for older people, keep in mind that the brain starts to decrease in size after about age 18. By the time we reach the age of 80, our brain has lost about 15 percent of its original weight (Perl, 1999 ).

SUPPORTING CAREGIVERS

In the past few decades there has been a sharp increase in the number of dementia special care units in nursing homes. The vast majority of patients with dementia will be institutionalized before they die. Until patients reach the stage of being severely impaired, however, most live in the community, cared for by their family members. Very often, the burden of care falls on a single person.

Any comprehensive approach to therapeutic intervention must consider the stresses experienced by caregivers. Some of the heartbreaking losses that they encounter are depicted in such movies as Iris and Away from Her. In 2008 former Supreme Court justice Sandra Day O’Connor disclosed that her husband, who suffered from Alzheimer’s disease, had found new happiness by developing a romantic relationship with a fellow Alzheimer’s sufferer in the facility in which he lived. Although this story garnered a great deal of media attention, it is far from a rare occurrence. Not all families are able to cope with this difficult situation with the love and grace that characterized Sandra Day O’Connor and her family.

image17

Why must therapeutic interventions also consider the caregivers of Alzheimer’s patients?

Not surprisingly, as a group, caregivers are at high risk for becoming socially isolated and for developing depression (Richards & Sweet, 2009 ). One study showed that in those caregivers who were not clinically depressed, cortisol levels were essentially similar to those in patients with major depression (Da Roza et al., 2001 ). Caregivers of patients with Alzheimer’s disease tend to consume high quantities of psychotropic medication themselves and to report many stress symptoms and poor health (Cummings, 2004 ; Hinrichsen & Niederehe, 1994 ). Providing caregivers with counseling and supportive therapy is very beneficial and produces measurable reductions in their levels of depression (Mittelman et al., 2004 ).

Neurocognitive Disorder Associated With HIV-1 Infection

Infection with the human immunodeficiency virus (HIV) wreaks havoc on the immune system. Over time, this infection can lead to acquired immune deficiency syndrome, or AIDS. Worldwide, the HIV type 1 virus has infected more than 36 million people and resulted in approximately 20 million deaths (Kaul et al., 2005 ).

In addition to devastating the body, the HIV virus is also capable of inducing neurological disease that can result in neuro-cognitive problems. This can happen in two ways. First, because the immune system is weakened, people with HIV are more susceptible to rare infections caused by parasites and fungi. However, the virus also appears capable of damaging the brain more directly, resulting in neuronal injury and destruction of brain cells (see Kaul et al., 2005 ; Snider et al., 1983 ).

The neuropathology of HIV-associated neurocognitive impairment involves various changes in the brain, among them generalized atrophy, edema (swelling), inflammation, and patches of demyelination (Adams & Ferraro, 1997 ; Sewell et al., 1994 ). No brain area may be entirely spared, but the damage appears to be concentrated in subcortical regions, notably the central white matter, the tissue surrounding the ventricles, and deeper gray matter structures such as the basal ganglia and thalamus. Ninety percent of patients with AIDS show evidence of such changes on autopsy (Adams & Ferraro, 1997 ).

The neuropsychological features of AIDS tend to appear as a late phase of HIV infection, although they often appear before the full development of AIDS itself. They begin with mild memory difficulties, psychomotor slowing, and diminished attention and concentration (see Fernandez et al., 2002 , for a review). Progression is typically rapid after this point, with clear-cut dementia appearing in many cases within 1 year, although considerably longer periods have been reported. The later phases also include behavioral regression, confusion, psychotic thinking, apathy, and marked withdrawal.

Estimates from the early 1990s suggested HIV-related dementia was present in 20 to 30 percent of people with advanced HIV disease. Fortunately, the arrival of highly active antiretroviral therapy has not only resulted in infected people living longer but has also reduced the prevalence of HIV-related dementia to around 10.5 percent (Kaul et al., 2005 ). However, although rates of frank dementia have decreased, around 30 percent of people who are infected with the HIV virus show some signs of MCI (Treisman et al., 2009 ). Moreover, for reasons that are not yet clear, women may be at especially high risk of HIV-related cognitive impairment.

Treatment with antiretroviral therapy does not fully prevent the HIV virus from damaging the brain (Kaul et al., 2005 ). This may be because HIV penetrates into the nervous system soon after a person becomes infected. What this means is that even though the new therapies have made HIV/AIDS a chronic but manageable condition (at least for those who have access to the necessary medications), prevention of infection remains the only certain strategy for avoiding the cognitive impairments associated with this disease.

Neurocognitive Disorder Associated With Vascular Disease

Neurocognitive disorder associated with vascular disease ( vascular dementia ) is frequently confused with Alzheimer’s disease because of its similar clinical picture of progressive dementia and its increasing incidence and prevalence rates with advancing age. However, it is an entirely different disease in terms of its underlying neuropathology. In this disorder, a series of circumscribed cerebral infarcts—interruptions of the blood supply to minute areas of the brain because of arterial disease, commonly known as “small strokes”—cumulatively destroy neurons over expanding brain regions. The affected regions become soft and may degenerate over time, leaving only cavities. Although vascular cognitive impairment tends to have a more varied early clinical picture than Alzheimer’s disease (Wallin & Blennow, 1993 ), the progressive loss of cells leads to brain atrophy and behavioral impairments that ultimately mimic those of Alzheimer’s disease (Bowler et al., 1997 ).

Vascular cognitive impairment tends to occur after the age of 50 and affects more men than women (Askin-Edgar et al., 2002 ). Abnormalities of gait (e.g., being unsteady on one’s feet) may be an early predictor of this condition (Verghese et al., 2002 ). Vascular cognitive impairment is less common than Alzheimer’s disease, accounting for only 19 percent of dementia cases in a community sample aged 65 years or older (Lyketsos et al., 2000 ). One reason for this is that these patients have a much shorter course of illness because they are vulnerable to sudden death from stroke or cardiovascular disease (Askin-Edgar et al., 2002 ). Accompanying mood disorders are also more common in vascular dementia than in Alzheimer’s disease, perhaps because subcortical areas of the brain are more affected (Lyketsos et al., 2000 ).

The medical treatment of vascular dementia, though complicated, offers slightly more hope than that of Alzheimer’s disease. Unlike Alzheimer’s disease, the basic problem of cerebral arteriosclerosis (decreased elasticity of brain arteries) can be medically managed to some extent, perhaps decreasing the likelihood of further strokes. The daunting problems that caregivers face, however, are much the same in the two conditions, indicating the appropriateness of support groups, stress reduction techniques, and the like.

in review

· • What is delirium? How is delirium different from major neurocognitive disorders?

· • List five diseases or clinical disorders that can cause major neuro-cognitive impairments.

· • What genes are implicated in Alzheimer’s disease?

· • Describe some of the major environmental risk factors for Alzheimer’s disease.

· • What kinds of neuropathological abnormalities are typical of the Alzheimer’s brain?

Amnestic Disorder

“Amnestic” is just another way of saying “amnesia,” and the characteristic feature of amnestic disorder is strikingly disturbed memory. Immediate recall (i.e., the ability to repeat what has just been heard) is not usually affected. Memory for remote past events is also usually relatively preserved. However, short-term memory is typically so impaired that the person is unable to recall events that took place only a few minutes previously. To compensate, patients sometimes confabulate, making up events to fill in the void that they have in their memories.

In contrast to patients with other forms of neurocognitive disorders, overall cognitive functioning in an amnestic disorder patient is often quite good. The affected person may be able to execute a complex task if it provides its own distinctive cues for each stage of the sequence.

Brain damage is the root cause of amnestic disorder. This damage might be caused by strokes, injury, tumors, or infections (Andreescu & Aizenstein, 2009 ). However, not all brain damage is permanent. Korsakoff’s syndrome is an amnestic disorder that is caused by deficiency in vitamin B1 (thiamine). Because of this, the memory problems associated with Korsakoff’s syndrome can sometimes be reversed if it is detected early enough and vitamin B1 is given. Korsakoff’s syndrome is often found in chronic alcoholics or in other people who do not eat healthily. It was the cause of the memory loss of the patient in the next case study.

He Forgot the Name of His Daughter A powerfully built six-footer, Charles Jackson still showed traces of a military bearing. Before he left the army a year before, he had been demoted to buck private; this was the culmination of a string of disciplinary actions for drunkenness.

For over a year he had had monthly consultations with the current interviewer. On this occasion, the interviewer asked when they had last met. Charles replied, “Well, I just don’t know. What do you think?” To the follow-up question, he said he guessed he had seen the interviewer before. “Maybe it was last week.”

Asking him to remain seated, the interviewer went into the waiting room to ask Mrs. Jackson how she thought her husband was doing. She said, “Oh, he’s about the same as before. He sketches some. But mostly he just sits around the house and watches TV. I come home and ask him what he’s watching, but he can’t even tell me.”

At any rate, Charles was no longer drinking, not since they had moved to the country. It was at least 2 miles to the nearest convenience store, and he didn’t walk very well anymore. “But he still talks about drinking. Sometimes he seems to think he’s still in the army. He orders me to go buy him a quart of gin.”

Charles remembered quite a few things, if they happened long enough ago—the gin, for example, and getting drunk with his father when he was a boy. But he couldn’t remember the name of his daughter, who was two and a half. Most of the time, he just called her “the girl.”

The interviewer walked back into the inner office. Charles looked up and smiled.

“Have I seen you before?” asked the interviewer.

“Well, I’m pretty sure.”

“When was it?”

“It might have been last week.”

Source: Adapted from Morrison, 1995 , pp. 50–51.

In DSM-IV amnestic disorder was a specific and distinct diagnosis. In DSM-5, patients who would have been given this diagnosis will now be diagnosed as having a major neurocognitive disorder. The cause of the disorder will also be listed (e.g., major neurocognitive disorder due to substance use). Unlike other forms of neurocognitive disorder, however, the substantial decline in functioning occurs in a single cognitive domain (memory).

Another common cause is head trauma. Stroke, surgery in the temporal lobe area of the brain, hypoxia (oxygen deprivation), and some forms of brain infections (such as encephalitis) can also lead to amnestic disorder. In these cases, depending on the nature and extent of damage to the affected neural structures and on the treatment undertaken, the disorder may remit with time. A wide range of techniques have been developed to assist the good-prognosis amnestic patient in remembering recent events (e.g., Gouvier et al., 1997 ). Moreover, because procedural memory (i.e., the ability to learn routines, skills, and actions) is often preserved in patients with amnesia, even patients without memory for specific personal experiences can still be taught to perform tasks that might help them reenter the workforce (Cavaco et al., 2004 ).

in review

· • What are the most striking clinical features of amnestic disorder?

· • What are some of the major causes of amnestic disorder?

· • How is amnestic disorder diagnosed in DSM-5?

Disorders Involving Head Injury

Traumatic brain injury (TBI) occurs frequently, affecting just under 2 million people each year in the United States. The most common cause of TBI are falls, followed by motor vehicle accidents. Other causes include assaults and sports injuries (although the vast majority of these are probably never even reported). Children aged 0 to 4, adolescents aged 15 to 19, and adults aged 65 years and older are most likely to experience a TBI. In every age group rates of TBI are higher for males than they are for females (Faul et al., 2010 ). In DSM-5 diagnostic terms such as major (or mild) neuro-cognitive disorder associated with head trauma are used to refer to the cognitive compromises that result from head injury.

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Former Arizona Congresswoman Gabrielle Giffords is recovering from a traumatic brain injury sustained after an assailant shot her in the head. She is receiving extensive therapy and is making considerable progress.

We are also now experiencing an escalation of cases of TBI caused by explosive blasts (Champion et al., 2009 ). Blasts seem to damage the brain in ways that are different from the brain damage seen in civilian cases of TBI. So many veterans have been injured by improvised explosive devices that TBI has been referred to as the signature injury of the Iraq War. Research suggests that around 15 percent of soldiers who have served in Iraq have experienced a TBI (Hoge et al., 2008 ). The military is now making efforts to improve screening and to increase rehabilitation service for veterans (see Munsey, 2007 ). However, for many, a full recovery may never be possible.

Clinical Picture

Clinicians categorize brain injuries as resulting from either a closed-head injury (where the cranium remains intact) or a penetrating head injury (where some object such as a bullet enters the brain). In closed-head injury, the damage to the brain is indirect—caused by inertial forces that cause the brain to come into violent contact with the interior skull wall or by rotational forces that twist the brain mass relative to the brain stem. Not uncommonly, closed-head injury also causes diffuse neuron damage because of the inertial force. In other words, the rapid movement of the rigid cranium is stopped on contact with an unyielding object. However, the softer brain tissue within keeps moving, and this has a shearing effect on nerve fibers and their synaptic interconnections.

Severe head injuries usually cause unconsciousness and disruption of circulatory, metabolic, and neurotransmitter regulation. Normally, if a head injury is severe enough to result in unconsciousness, the person experiences retrograde amnesia , or inability to recall events immediately preceding the injury. Apparently, the trauma interferes with the brain’s capacity to consolidate into long-term storage the events that were still being processed at the time of the trauma. Anterograde amnesia (also called posttraumatic amnesia) is the inability to store effectively in memory events that happen during variable periods of time after the trauma. It is also frequently observed and is regarded by many as a negative prognostic sign.

A person rendered unconscious by a head injury usually passes through stages of stupor and confusion on the way to recovering clear consciousness. This recovery of consciousness may be complete in the course of minutes, or it may take hours or days. Following a severe injury and loss of consciousness, a person’s pulse, temperature, blood pressure, and important aspects of brain metabolism are all affected, and survival may be uncertain. In rare cases, an individual may live for extended periods of time without regaining consciousness, a condition known as coma. The duration of the coma is generally related to the severity of the injury. If the patient survives, coma may be followed by delirium, marked by acute excitement and disorientation and hallucinations. Gradually the confusion may clear up and the individual may regain contact with reality. Individual courses of recovery are highly variable and difficult to predict (Waters & Nicoll, 2005 ).

Large numbers of relatively minor closed-head brain concussions and contusions (bruises) occur every year as a result of car accidents, athletic injuries, falls, and other mishaps. Even riding roller coasters that generate high G-forces may cause brain injury in some people (see Fukutake et al., 2000 ). It is estimated that two deaths per year can be attributed to brain hemorrhages that result from roller coaster rides (Pelletier & Gilchrist, 2005 ). Although these statistics are unlikely to dissuade you from heading to a theme park the next time you want to have some fun, they have prompted some calls for greater oversight of the industry.

image19

Exposure to high G-forces, such as those experienced on some theme park rides, can cause neurological injury in some individuals by creating small tears in delicate blood vessels in the brain.

TABLE 14.5 Signs of a Concussion

Temporary loss of consciousness

Confusion or foggy feeling in the brain

Amnesia for the period surrounding the event/injury

Headache that gets worse and doesn’t go away

Nausea or vomiting

Excessive drowsiness

Slurred or incoherent speech

Difficulty remembering new information

Dizziness

These symptoms may not be immediately apparent.

Some symptoms may develop several days after the injury.

People who play certain sports are at high risk of experiencing concussions and brain injuries. For males, the greatest risk comes from playing football; for females, the greatest risk comes from playing soccer (Lincoln et al., 2011 ). Signs of concussion are listed in Table 14.5 . However, the majority of concussions do not involve a loss of consciousness. It is important to know that, after a concussion, the brain is four or five times more vulnerable to a second impact and that this increased vulnerability lasts for several weeks. As described in The World Around Us box on page 504, and as illustrated in the following case study, athletes at every level sometimes want to get back into the game without adequate recovery time, often with devastating consequences. In an effort to deal with this problem, many States now require that young people who have sustained a sports-related brain injury must see a doctor before they can be allowed to play again. Return to play protocols are also being established (Sahler & Greenwald, 2012 ).

Zack’s Story Zack, a gifted athlete who played both offense and defense on his junior high school football team, was injured at 13 when his head struck the ground after tackling an opponent. The official called a time out, and Zack was sidelined for just three plays before half-time. Despite the blow, Zack shook it off and by the start of the third quarter he was back in the game. “He always wanted to be part of the play” his father recalls.

After a hard-played second half, Zack collapsed on the field. He was airlifted to a medical facility where he underwent emergency life-saving surgery to remove the left and right side of his skull to relieve pressure from his injured and swelling brain. He experienced numerous strokes, spent 7 days on a ventilator, and was in a coma for 3 months before he awoke to a new reality. It was 9 months before Zack spoke his first word, 13 months before he could move a leg or an arm, and he spent 20 months on a feeding tube. Confined to a wheelchair, it was nearly 3 years until Zack was able to stand, with assistance, on his own two feet.

In 2009 the state of Washington passed a new law named after Zack. It requires that any young athlete who shows signs of a concussion be examined and cleared for play by a licensed health care provider. The law protects young athletes from the kind of life-threatening and potentially life-long consequences that can be caused by shaking off an injury and returning to play. Source: Adapted from CDC, 2010 .

We are also learning something about the factors that may increase a person’s susceptibility to having problems after a brain injury. One important risk factor appears to be the presence of the APOE-E4 allele that we discussed earlier (Waters & Nicoll, 2005 ). In one study of boxers, the presence of the APOE-E4 genetic risk factor was associated with more chronic neurological deficits (Jordan et al., 1997 ). A study of patients being treated in a neurosurgical unit found that APOE-E4 predicted patients doing more poorly at a 6-month follow-up. This was true even after controlling for such factors as severity of the initial injury (Teasdale et al., 1997 ).

Perhaps the most famous historical example of TBI is the case of Phineas Gage (Harlow, 1868 ). Gage, 25 years old, was the foreman of a gang of men who were building a railroad in Cavendish, Vermont. On September 13, 1848, there was an accident, and an iron rod (3 feet 7 inches in length, about an inch in diameter, and weighing just over 13 pounds) was blown through Gage’s skull, entering through his lower cheek. Gage was thrown back by the force of the explosion but started to speak a few minutes later. His men put him in an ox cart and took him to his hotel, whereupon he walked, with a little assistance, to his room, bleeding profusely. Miraculously, Gage survived the accident and eventually made a full physical recovery. However, in other respects he was a different man. What was most striking was the change in his personality. As his doctor noted, “He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operations, which are no sooner arranged than they are abandoned in turn for others” (Harlow, 1868 , p. 327). As others have noted, changes such as this (emotional dyscontrol, personality alterations, and impairment of self-awareness) are fairly characteristic of severe damage to the frontal lobes (Stuss et al., 1992 ).

image20

Though Phineas Gage survived when a tamping iron entered his face and shot through his head, his personality was altered such that his friends found that he was “no longer Gage.”

the WORLD around us: Brain Damage in Professional Athletes

For athletes, collisions are often part of the game. But new evidence is forcing many in collegiate and professional sports to consider the potential for long-term brain damage that may come from heading the ball or tackling another player. This issue came to the attention of sports fans when Ted Johnson, a former Super Bowl champion and linebacker for the New England Patriots, went public about the crippling depressions and headaches he now experiences (MacMullan, 2007). Johnson, who has been diagnosed with a chronic postconcussion syndrome (involving fatigue, irritability, memory loss, and depression), is also showing signs of early brain damage. He believes that his problems are a direct result of the multiple hits to the head he sustained during his playing career.

Repeat concussions are very serious. After a blow to the head, the brain remains in a vulnerable state for several weeks. A second injury during this time will cause an exponential amount of damage. Johnson’s cognitive functioning declined dramatically after he was involved in a serious collision during an exhibition game and had to be pulled off the field. Four days later, he was expected to engage in full contact during practice. Although he knew this was a bad idea, his pride, combined with the pressure not to appear weak, kept him from asking to be excused from the physical drills. During the practice he took a minor hit and experienced the warm and hazy sensation that signals a concussion. For Johnson, it was the beginning of the end.

Johnson decided to go public with his story after the suicide of former NFL defensive back Andre Waters. Waters, who was known to be a tough and hard-hitting player, suffered many repeat concussions during the course of his career. After his death at age 44, a neurologist examined his brain and reported that the tissue resembled that of an 85-year-old; Waters also had some signs of Alzheimer’s disease. Repeat concussions were suspected to be the cause of his brain damage.

Research supports this speculation. A study of 2,552 retired professional football players showed that the majority (61 percent) had experienced at least one concussion during their playing careers. Moreover, those players who had a history of three or more concussions were five times more likely to be diagnosed with cognitive problems and had three times more memory impairment than players with no concussion history (Guskiewicz et al., 2005 ). Players who had had repeat concussions were also more likely to later be diagnosed with depression (Guskiewicz et al., 2005 ).

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Sidney Crosby, captain of the Pittsburgh Penguins hockey team, experienced concussion-like symptoms for more than a year after being injured. He wisely took time to recover before returning to the ice.

The risks associated with concussions are now being taken very seriously in the NFL and also in the NHL. Several hockey players have had their careers cut short by concussions. In 2011, Sidney Crosby, captain of the Pittsburgh Penguins waited 10 months to return to the ice after experiencing two concussions only to be sidelined again shortly afterwards. He is now playing again. After taking a hit, staying out of future games until the brain has had enough time to heal is of critical importance.

Treatments and Outcomes

As illustrated in the case of Zack, prompt medical treatment of a brain injury may be necessary to save the person’s life and remove the pressure on the brain caused by intense swelling. Immediate medical treatment may also have to be supplemented by a long-range program of reeducation and rehabilitation involving many different professionals.

Although many TBI patients show few residual effects from their injury, particularly if they have experienced only a brief loss of consciousness, other patients sustain definite and long-lasting impairment. Common symptoms of minor TBI include headaches, memory problems, sensitivity to light and sound, dizziness, anxiety, irritability, fatigue, and impaired concentration (Miller, 2011 ). When the brain damage is extensive, a patient’s general intellectual level may be considerably reduced, especially if there is damage to the temporal lobe or parietal lobes. Most people have significant delays in returning to their occupations, and many are unable to return at all (Dikmen et al., 1994 ). Other losses of adult social role functioning are also common (Hallett et al., 1994 ). Some 24 percent of TBI cases, overall, develop posttraumatic epilepsy, presumably because of the growth of scar tissue in the brain. Seizures usually develop within 2 years of the head injury. For decades after a head injury, there is also an elevated risk of depression as well as other disorders such as substance abuse, anxiety disorders, and personality disorders (Holsinger et al., 2002 ; Koponen et al., 2002 ).

In a minority of brain injury cases, dramatic personality changes occur such as those described in the case of Phineas Gage. Other kinds of personality changes include passivity, loss of drive and spontaneity, agitation, anxiety, depression, and paranoid suspiciousness. Like cognitive changes, the kinds of personality changes that emerge in severely damaged people depend, in large measure, on the site and extent of their injury (Prigatano, 1992 ). However, even though more than half the people who sustain TBI develop psychological symptoms, and even though alleviation of such symptoms can improve rehabilitation outcome, there are currently few studies of risk factors, pathogenesis, and treatment of these disturbances (Rao & Lyketsos, 2002 ).

image22

Video games are now being used in the treatment of traumatic brain injury.

Children who undergo significant TBI are more likely to be adversely affected the younger they are at the time of injury and the less language, fine-motor, and other competencies they have. This is because brain damage makes it harder to learn new skills and because young children have fewer developed skills to begin with. The severity of their injury and the degree to which their environment is accommodating also affect children’s recovery (Anderson et al., 1997 ; Taylor & Alden, 1997 ; Yeates et al., 1997 ). When the injury is minor, most children emerge without lasting negative effects (Satz et al., 1997 ).

Treatment of TBI beyond the purely medical phase is often long, difficult, and expensive. It requires careful and continuing assessment of neuropsychological functioning and the design of interventions intended to overcome the deficits that remain. Many different treatment approaches are used including medication, rehabilitative interventions (such as occupational, physical, and speech/language therapy, cognitive therapy, behavior therapy, social skills training, vocational and recreational therapy) as well as individual, group, and family therapy (Hampton, 2011 ). Often, a treatment goal is to provide patients with new techniques to compensate for losses that may be permanent (Bennett et al., 1997 ). Research is also showing that patients with TBI may sometimes benefit from treatment with donepezil, an acetylcholinesterase inhibitor widely used in the treatment of Alzheimer’s disease (Zhang et al., 2004 ). Table 14.6 shows some of the variables that are associated with patients having a more favorable outcome after a TBI.

TABLE 14.6 Predictors of Clinical Outcome After Traumatic Brain Injury

Outcome is more favorable when there is:

· • only a short period of unconsciousness or posttraumatic anterograde amnesia

· • minimal cognitive impairment

· • a well-functioning preinjury personality

· • higher educational attainment

· • a stable preinjury work history

· • motivation to recover or make the most of residual capacities

· • a favorable life situation to which to return

· • early intervention

· • an appropriate program of rehabilitation and retraining

Sources: Bennett et al. ( 1997 ); Dikmen et al. ( 1994 ); Diller & Gordon ( 1981 ); Mackay ( 1994 ); and MacMillan et al. ( 2002 ).

in review

· • Why is it so important to take concussions very seriously?

· • What is the link between the APOE-E4 allele and problems after head injury?

· • What kinds of clinical problems are associated with head injury in the short and longer term?

· • What factors are associated with the degree of disability after head injury?

UNRESOLVED issues: Should Healthy People Use Cognitive Enhancers?

In the search for a cognitive advantage, many healthy people, young and old, are now turning to drugs that may provide cognitive benefits. Many of us routinely use caffeine, which improves vigilance, working memory, and incidental learning. Others use nicotine, which, although clearly detrimental to health when smoked, may enhance attention, working memory, and attention in the short term (Husain & Mehta, 2011 ; Lanni et al., 2008 ).

A more recent trend, however, involves the use of prescription stimulants. These include methylphenidate (Ritalin), which is used in the treatment of attention deficit disorder, and modafinil (Provigil), which is used as a wake-promoting agent for people with excessive daytime sleepiness. These compounds (which are not always legally prescribed) are now being used by students seeking better grades as well as by military personnel who need to remain awake during long missions.

Studies suggest that physicians are disinclined to prescribe these medications to young, cognitively healthy people (Banjo et al., 2010 ). In part, this reluctance stems from concerns about the safety of these compounds and beliefs that the benefits they provide are very small. Certainly, evidence suggests that the benefits of cognitive enhancers in healthy individuals are indeed very modest. But there are ethical issues, too (Hyman, 2011 ; Lanni et al., 2008 ). Should drugs developed as treatments be used as cognitive enhancers in people who do not have the disorders the drugs were designed to help? What do you think? Would you take a drug approved for Alzheimer’s disease if you thought it would help you do better on a test? Who is most likely to have access to these cognitive enhancers? And will their use lead to a “cognitive arms race” rather like that in some professional sports where athletes who do not take steroids are highly disadvantaged? Is it possible that students of the future might be required to provide a urine sample before taking a high-stakes exam?

14 summary

· 14.1 What forms of neurocognitive disorders are recognized in DSM-5 ? What is presumed to be the cause of these disorders?

· • The DSM-5 recognizes major and mild forms of neurocognitive disorders as well as delirium. These disorders are thought to result from transient or permanent damage to the brain. Chronic neurocognitive disorders involve the permanent loss of neural cells.

· 14.2 What are the clinical features of neurocognitive disorders?

· • Major neurocognitive disorders involves a loss of function and of previously acquired skills. Depending on the cause, the onset can be slow or gradual with a deteriorating course. The most common cause of major neurocognitive disorders is Alzheimer’s disease.

· • There is no simple relationship between the extent of brain damage and degree of impaired functioning. Some people who have severe damage develop no severe symptoms, whereas some with slight damage have extreme reactions.

· 14.3 What is delirium and how is it treated?

· • Delirium has a sudden onset. Common among the elderly, it is characterized by a state of awareness that fluctuates between wakefulness and stupor or coma. Delirium is treated with neuroleptic medications and also with benzodiazepines.

· 14.4 What are the risk factors for Alzheimer’s disease? What changes in the brain are found in patients with Alzheimer’s disease?

· • Age is a major risk factor for Alzheimer’s disease as well as for other forms of dementia such as vascular dementia.

· • Genes play a major role in susceptibility to and risk for Alzheimer’s disease. Genetic mutations of the APP, PS1, and PS2 genes are implicated in early-onset Alzheimer’s disease. The APOE-E4 allele of the APOE gene is also a risk factor for Alzheimer’s disease.

· • The characteristic neuropathology of Alzheimer’s disease involves cell loss, plaques, and neurofibrillary tangles. Plaques contain a sticky protein called beta amyloid. Neurofibrillary tangles contain abnormal tau protein.

· 14.5 How is Alzheimer’s disease treated?

· • Alzheimer’s disease causes the destruction of cells that make acetylcholine, a neurotransmitter important for memory. Drug treatments for Alzheimer’s disease include cholinesterase inhibitors such as donepezil (Aricept). These drugs help stop ACh from being broken down and so make more of it available to the brain.

· • Any comprehensive treatment approach for neurocognitive disorders should also involve caregivers, who are often under a great deal of stress and have difficulty coping. They may benefit from medications as well as from support groups.

· 14.6 What is an amnestic disorder? What causes amnestic disorders?

· • Amnestic disorders involve severe memory loss. The most common cause of amnestic disorders is chronic alcohol abuse.

· • Other causes include head trauma, stroke, surgery, infections, and hypoxia.

· 14.7 What are some of the clinical consequences of head trauma? What factors are related to the degree of impairment that results?

· • Head injuries can cause amnesia as well as other cognitive impairments. Retrograde amnesia is inability to recall events that preceded the trauma. Anterograde amnesia is inability to remember things that follow it.

· • Although such inconsistencies are not completely understood, it appears that an individual’s premorbid personality and life situation are important in determining his or her reactions to brain damage. The APOE-E4 genetic allele is also important. The severity of the trauma, age of the person who is injured, and site of the injury are also important.

key terms

· Alzheimer’s disease 491

· amnestic disorder 500

· amyloid plaques 495

· anterograde amnesia 502

· APOE-E4 allele 494

· delirium 488

· dementia 484

· early-onset Alzheimer’s disease 494

· HIV-associated neurocognitive impairment 500

· Huntington’s disease 491

· Korsakoff’s syndrome 501

· late-onset Alzheimer’s disease 494

· major neurocognitive disorder 484

· mild neurocognitive disorder 484

· neurofibrillary tangles 496

· Parkinson’s disease 490

· retrograde amnesia 502

· traumatic brain injury (TBI) 501

neurocognitive disorders

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