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Chapter 20 Neurocognitive Disorders

Gerald Goldstein 1

Introduction and Recent Developments

Most neurological disorders are ancient diseases, and developments in treatment and cure have been painfully slow. However, we continue to learn more about these disorders, and in previous versions of this chapter (Goldstein, 1997, 2007, 2014) we highlighted substantive developments. A new disorder, acquired immunodeficiency syndrome (AIDS) dementia, had appeared, and the marker for the Huntington's disease gene had been discovered. At the time of the 1997 writing, it was mentioned that a still mysterious and controversial disorder appeared, sustained by military personnel during the war with Iraq in the Persian Gulf area, popularly known as the Gulf War syndrome. An aspect of this syndrome has been said to involve impaired brain function (Goldstein, 2011; Goldstein, Beers, Morrow, Shemansky, & Steinhauer, 1996). A more readily understood condition emerging from the recent Iraq and Afghanistan wars involves the blast injuries caused largely by roadside bombs. These injuries appeared to have different characteristics from those associated with the open or closed head injuries associated with previous wars and accidents in civilian life (Belanger, Kretzmer, Vanderploeg, & French, 2010).

Another consequence of the Iraq and Afghanistan wars has been a reconsideration of the problem of mild traumatic brain injury (TBI), often called concussion. Concussion is a common sports injury, but it also appears to be a common consequence of sustaining a blast injury. It is sometimes complicated by its association with post-traumatic stress disorder (PTSD) acquired in reaction to the injury, and diagnostic difficulties have been created regarding whether the victim sustained brain injury, developed PTSD, or both. It was commonly accepted that concussion was a self-limiting disorder, and that essentially full recovery could be expected within no more than 90 days. Recently, however, it has been observed that some individuals with histories of concussion do not fully recover and continue to have complaints of cognitive problems, notably in attention, memory, and organizational abilities. Individuals with multiple concussions appear to experience a cumulative and long-lasting effect.

Initially, these symptoms were attributed to stress, but neuroimaging studies using advanced technologies have found that identifiable brain damage may result from concussion, involving the upper brain stem, base of the frontal lobe, hypothalamic–pituitary axis, medial temporal lobe, fornix, and corpus callosum. Bigler (2008) has written a review of this area, using the phrase “persistent postconcussive syndrome” to describe this condition. Substantial support for the neurological basis for this disorder comes from use of a technology that was just beginning its development and widespread use at the last writing, called diffusion tensor imaging (DTI). DTI is an magnetic resonance imaging (MRI)-related procedure that tracks axonal white matter, identifying misalignments.

In the Gulf War, concussion and more serious trauma were associated with blast injuries sustained mainly as a result of roadside bombing. Blast injuries remain a controversial area, with some authorities claiming they are no different from the commonly accepted types of brain injury (Hoge et al., 2008; Wilk et al., 2010), whereas others claim they are a unique form of trauma not identified previously. The matter is further complicated by the fact that the bombs used were sometimes loaded with depleted uranium or possibly infectious agents. Thus, the understanding of head injury has changed in recent years, with the development of methods that can detect persistent neurological consequences of concussion, producing a new diagnosis called persistent postconcussive syndrome, and the problem of blast injury among military personnel, which is still under intensive investigation.

Diagnostic Considerations

With the publication of DSM-5, there are substantial changes from DSM-IV in terminology and content. The name of the category “Delirium, Dementia, Amnestic, and Other Cognitive Disorders” has been replaced by the phrase “Neurocognitive Disorders.” The term delirium remains as part of a set of three major subcategories: major neurocognitive disorder, minor neurocognitive disorder, and delirium. The term dementia has been eliminated.

It may be useful to review the rationale for the changes made in DSM-5. The DSM-5 Neurocognitive Disorders Work Group prepared a document that contains their proposals for changes and their rationales for proposing them (American Psychiatric Association, 2010). We summarize some of their major points here:

1. Efforts were made to eliminate demeaning or stigmatizing terminology. Just as the term mental retardation has been replaced by intellectual disability in the neurodevelopmental disorders section, the term dementia has been replaced by major and mild neurocognitive disorders. These new terms are felt to reflect more accurately the nature of the disorder and a general attempt made by the writers of DSM-5 to correct for the demeaning, stigmatizing connotations of the names of some psychiatric disorders. The change from mental retardation to intellectual disability has already been widely accepted.

2. Diagnostic criteria wording was changed to increase precision. Thus, for example, the term consciousness has been changed to level of awareness. The changes in cognition specified in DSM-IV mention only memory, orientation, and language. In DSM-5 the domains of executive ability and visuospatial impairment are also specified.

3. Mention of severity is added to characterize development of a disturbance.

4. Specific symptoms of delirium are provided, such as hallucinations, delusions, and sleep–wake cycle disturbances.

5. Delirium is subcategorized into hyperactive, hypoactive, and mixed groups, again providing greater specificity.

6. There is a major reconceptualization regarding characterization of cognitive changes. The term cognitive decline replaces cognitive deficits to emphasize that major cognitive disorder is acquired and reflects a decline from previous level of performance. The previous model, based on Alzheimer's disease, requires that memory impairment must be present. However, data now indicate that in other neurocognitive disorders, other domains such as language or executive functions may be impaired first, and most prominently. The changed wording calls for decline from previous performance in one or more specified domains including memory, but also language (aphasia), disturbances of skilled movement (apraxia) or of recognition (agnosia) and executive function.

7. Emphasis is placed on objective assessment of performance that may include neuropsychological testing.

8. Emphasis is placed on independent performance of instrumental activities of daily living.

There have been changes in the number and description of the neurocognitive disorders. Dementia of the Alzheimer type has been renamed major or mild neurocognitive disorder due to Alzheimer's disease. The term vascular dementia has been replaced with major or mild vascular neurocognitive disorder. Other neurocognitive disorders/diagnoses now include frontotemporal, Lewy bodies disease, Huntington's disease, Parkinson's disease, TBI, substance/medication use, HIV infection, and prion disease neurocognitive disorders, each of which can be modified by a major or mild descriptor (see clinical presentation section).

The diagnosis of mild neurocognitive disorder is new to the DSM system. The distinction is a matter of severity. Cognitive decline is characterized as modest or mild, it should not interfere with capacity for independence in everyday living, and delirium or another mental disorder can make a better explanation of the condition. This change allows for the diagnosis of less disabling syndromes that may still benefit from treatment.

In general, the changes in DSM-5 have gone in the direction of increased specificity, including more detailed documentation of symptoms, description of cognitive domains involved, providing an etiological diagnosis, consideration of subtypes and use of more precise terminology. The distinction between major and mild disorders allows for diagnosis of individuals with mild impairment who would not meet criteria for a diagnosable neurological disorder, but who have experienced cognitive decline associated with brain dysfunction that would benefit from programs of treatment and management, such as cognitive rehabilitation.

Clinical Presentation

The theoretical approach taken here will be neuropsychological in orientation, and based on the assumption that clinical problems associated with brain damage can be understood best in the context of the relationship between brain function and behavior. Thus, we expand our presentation beyond the descriptive psychopathology of DSM-5 (APA, 2013) in order to provide some material related to basic brain–behavior mechanisms. There are many sources of brain dysfunction, and the nature of the source has a great deal to do with determining behavioral consequences: morbidity and mortality. Thus, understanding key neuropathological processes is crucial to understanding the differential consequences of brain damage, and, in turn, that requires an understanding of how the brain functions, and in some cases the genetics and neurochemistry of how memories and other cognitive abilities are preserved in brain tissue.

In recent years, knowledge of the neurological systems important for such areas as memory and language has been substantially expanded. It seems clear now that there are several separate memory systems located in different areas of the brain, notably the hippocampus, the amygdala, the neocortex, and the cerebellum. Each system interacts with the others but supports a different form of memory, such as immediate recall, remote recall, and the brief storage of information during ongoing cognitive activity known as working memory (Baddeley, 1986).

Initially, two major methodologies were used to assess brain dysfunction: direct investigations of brain function through lesion generation or brain stimulation in animal subjects; and studies of patients who had sustained brain damage, particularly localized brain damage. The latter method can be dated back to 1861 when Paul Broca produced his case report (Broca, 1861) on a patient who had suddenly developed speech loss. An autopsy revealed that he had sustained an extensive infarct in the area of the third frontal convolution of the left cerebral hemisphere. Thus, an important center in the brain for speech had been discovered, but perhaps more significantly, this case produced what many would view as the first reported example of a neuropsychological or brain–behavior relationship in a human. Indeed, to this day, the third frontal convolution of the left hemisphere is known as Broca's area, and the type of speech impairment demonstrated by the patient is known as Broca's aphasia.

Following Broca's discovery, much effort was devoted to relating specific behaviors to discrete areas of the brain. These early neuropsychological investigations not only provided data concerning specific brain–behavior relationships, but also explicitly or implicitly evolved a theory of brain function, now commonly known as classical localization theory. In essence, the brain was viewed as consisting of centers for various functions connected by neural pathways. In human subjects, the presence of these centers and pathways was documented through studies of individuals who had sustained damage to either a center or the connecting links between one center and another such that they became disconnected. To this day, the behavioral consequences of this latter kind of tissue destruction are referred to as a disconnection syndrome (Geschwind, 1965). For example, there are patients who can speak and understand, but who cannot repeat what was just said to them. In such cases, it is postulated that there is a disconnection between the speech and auditory comprehension centers.

Not all investigators advocated localization theory. The alternative view is that the brain functions as a whole in an integrated manner, currently known as mass action, holistic, or organismic theories of brain function. In contemporary neuropsychology the strongest advocates of holistic theory were Kurt Goldstein, Martin Scheerer, and Heinz Werner. Goldstein and Scheerer (1941) are best known for their distinction between abstract and concrete behavior, their description of the “abstract attitude,” and the tests they devised to study abstract and concrete functioning in brain-damaged patients. Their major proposition was that many of the symptoms of brain damage could be viewed not as specific manifestations of damage to centers or connecting pathways but as some form of impairment of the abstract attitude. The abstract attitude is not localized in any region of the brain but depends upon the functional integrity of the brain as a whole. Goldstein (1959) describes the abstract attitude as the capacity to transcend immediate sensory impressions and consider situations from a conceptual standpoint. Generally, it is viewed as underlying such functions as planning, forming intentions, developing concepts, and separating ourselves from immediate sensory experience.

The notion of a nonlocalized generalized deficit underlying many of the specific behavioral phenomena associated with brain damage has survived to some extent in contemporary neuropsychology, but in a greatly modified form. Similarly, some aspects of classical localization theory are still with us, but also with major changes (Mesulam, 1985). None of the current theories accepts the view that there is no localization of function in the brain, and correspondingly, none of them would deny that some behaviors cannot be localized to some structure or group of structures. This synthesis is reflected in several modern concepts of brain function, the most explicit of these probably being that of Luria (1973). Luria has developed the concept of functional systems as an alternative to both strict localization and mass action theories. Basically, a functional system consists of several elements involved in the mediation of some complex behavior. For example, there may be a functional system for auditory comprehension of language. Thus, no structure in the brain is only involved in a single function. Depending upon varying conditions, the same structure may play a role in several functional systems. With regard to clinical neuropsychology, the main point is that there are both specific and nonspecific effects of brain damage. Evidence for this point of view has been presented most clearly by Teuber and his associates (Teuber, 1959) and by Satz (1966). The Teuber group was able to show that patients with penetrating brain wounds that produced very focal damage had symptoms that could be directly attributed to the lesion site, but they also had other symptoms that were shared by all patients studied, regardless of their specific lesion sites.

An old principle of brain function in higher organisms that has held up well and that is commonly employed in clinical neuropsychology involves contralateral control: the right half of the brain controls the left side of the body and vice versa. The contralateral control principle is important for clinical neuropsychology because it explains why patients with damage to one side of the brain may become paralyzed only on the opposite side of their body or may develop sensory disturbances on that side. We see this condition most commonly in individuals who have had strokes, but it is also seen in some patients who have open head injuries or who have brain tumors.

Although aphasia, or impaired communicative abilities as a result of brain damage, was recognized before Broca (Benton & Joynt, 1960), it was not recognized that it was associated with destruction of a particular area of one side of the brain. Thus, the basic significance of Broca's discovery was the discovery not of aphasia, but of cerebral dominance. Cerebral dominance is the term that has been commonly employed to denote the fact that the human brain has a hemisphere that is dominant for language and a nondominant hemisphere. In most people, the left hemisphere is dominant, and left hemisphere brain damage may lead to aphasia. However, some individuals have dominant right hemispheres, while others do not appear to have a dominant hemisphere. Although it remains unknown why most people are left-hemisphere dominant, what is clear is that for individuals who sustain left hemisphere brain damage, aphasia is a common symptom, while aphasia is a rare consequence of damage to the right hemisphere.

Following Broca's discovery, other neuroscientists discovered that just as the left hemisphere has specialized function in the area of language, the right hemisphere also has its own specialized functions. These functions seem to relate to nonverbal abilities such as visual-spatial skills, perception of complex visual configurations, and, to some extent, appreciation of nonverbal auditory stimuli such as music. Some investigators have conceptualized the problem in terms of sequential as opposed to simultaneous abilities. The left hemisphere is said to deal with material in a sequential, analytic manner, while the right hemisphere functions more as a detector of patterns or configurations (Dean, 1986). Thus, while patients with left hemisphere brain damage tend to have difficulty with language and other activities that involve sequencing, patients with right hemisphere brain damage have difficulties with such tasks as copying figures and producing constructions, because such tasks involve either perception or synthesis of patterns. In view of these findings regarding specialized functions of the right hemisphere, many neuropsychologists now prefer to use the expression functional asymmetries of the cerebral hemispheres rather than cerebral dominance.

With this basic brain–behavior background in mind, we now turn to a clinical description of the individual disorders that are included in the broad diagnostic category of neurocognitive disorders. This includes delirium and a number of individual disorders included under the major categories of major or mild neurocognitive disorders.

Delirium

The first disorder listed in the DSM-5 is delirium. This temporary condition is basically a loss of capacity to maintain attention with corresponding reduced awareness of the environment. Tremors and lethargy may be accompanying symptoms. Delirium is reversible in most cases but may evolve into a permanent neurocognitive or other neurological disorder. DSM-5 allows for the specification of the cause of delirium, whether it is due to substance intoxication, substance withdrawal, medication-induced delirium due to another medical condition, or delirium due to multiple etiologies. Typically, delirium is an acute phenomenon and does not persist beyond a matter of days. However, delirium, notably when it is associated with alcohol abuse, may eventually evolve into permanent disorders in the form of a persistent neurocognitive disorder (formerly dementia). The behavioral correlates of delirium generally involve personality changes such as euphoria, agitation, anxiety, hallucinations, and depersonalization.

Major and Mild Neurocognitive Disorders

There are several types of neurocognitive disorders, but they all involve the usually slowly progressive deterioration of intellectual function. The deterioration is frequently patterned, with loss of memory generally being the first function to decline, and other abilities deteriorating at later stages of the illness. As noted in DSM-5, the term major or mild neurocognitive disorder replaces the term dementia in an effort to eliminate stigmatization. The DSM-5 approach to the diagnosis of the major and mild neurocognitive disorders is that there is first a determination of whether the individual is suffering from a major or mild type of cognitive impairment, and then the reason for the impairment is added (e.g., due to Alzheimer's disease) to indicate the distinct behavioral features and likely etiology. Furthermore, for either the major or mild types, there are “probable” or “possible” specifiers depending upon the strength of the evidence for the etiological factor (genetics, neuroimaging).

Major or Mild Neurocognitive Disorders of the Alzheimer's Type

One class of neurocognitive disorders, major or mild neurocognitive disorder of the Alzheimer's type, arises most commonly in late life, either during late middle age or old age, although it may occur at any age. In children it is differentiated from intellectual disability on the basis of the presence of deterioration from a formerly higher level. These disorders are defined as those conditions in which, for no exogenous reason, the brain begins to deteriorate and continues to do so until death. As indicated in the psychological and biological assessment section, a diagnostic method has recently become available to specifically diagnose Alzheimer's disease in the living patient. Its presence also becomes apparent on examination of the brain at autopsy.

Clinically, the course of the Alzheimer's type generally begins with signs of impairment of memory for recent events, followed by deficits in judgment, visual-spatial skills, and language. The language deficit has become a matter of particular interest, perhaps because the communicative difficulties of patients with major or mild neurocognitive disorders of the Alzheimer's type are becoming increasingly recognized. Generally, the language difficulty does not resemble aphasia, but can perhaps be best characterized as an impoverishment of speech, with word-finding difficulties and progressive inability to produce extended and comprehensible narrative speech as illustrated in the descriptive writing of Alzheimer's disease patients (Neils, Boller, Gerdeman, & Cole, 1989). The patients wrote shorter descriptive paragraphs than did age-matched controls, and they also made more handwriting errors of various types. The end state is generalized, severe intellectual impairment involving all areas, with the patient sometimes surviving for various lengths of time in a persistent vegetative state.

Criteria for the Alzheimer's disease subtype include meeting criteria for major or minor neurocognitive disorder, early and prominent impairment in memory, deficits in at least one other domain in the case of the major form of the disorder, a course of gradual onset and continuing cognitive decline, and a ruling out of the condition being attributable to other disorders (APA, 2013). The diagnosis may indicate whether it occurs with or without behavioral disturbance. Separate criteria for psychosis and depression have been written.

Major or Mild Frontotemporal Neurocognitive Disorder

In this disorder, there is specific impairment of social judgment, decision-making, and particular language and memory skills. The decline in language can take the form of speech production, word finding, object naming, grammar, or word comprehension (APA, 2013). Frontotemporal neurocognitive disorder is only diagnosed when Alzheimer's disease has been ruled out, and the patient must have symptoms that can be characterized as forming a “frontal lobe syndrome” (Rosenstein, 1998). The generic term commonly used to characterize the behaviors associated with this syndrome is executive dysfunction, a concept originally introduced by Luria (1966). Executive function is progressively impaired, and personality changes involving either apathy and indifference or childishness and euphoria occur. Compared with patients with Alzheimer's disease, frontal dementia patients have greater impairment of executive function but relatively better memory and visuoconstructional abilities. The outstanding features may all be viewed as relating to impaired ability to control, regulate, and program behavior. This impairment is manifested in numerous ways, including poor abstraction ability, impaired judgment, apathy, and loss of impulse control. Language is sometimes impaired, but in a rather unique way. Rather than having a formal language disorder, the patient loses the ability to control behavior through language. There is also often a difficulty with narrative speech, which has been interpreted as a problem in forming the intention to speak or in formulating a plan for a narrative. Such terms as lack of insight or of the ability to produce goal-oriented behavior are used to describe the frontal lobe patient. In many cases, these activating, regulatory, and programming functions are so impaired that the outcome looks like a generalized dementia with implications for many forms of cognitive, perceptual, and motor activities. Frontal dementia may occur as a result of several processes, such as head trauma, tumor, or stroke, but the syndrome produced is more or less the same.

Major or Mild Neurocognitive Disorder With Lewy Bodies

This disorder has a different pathology from Alzheimer's disease, being associated more with Parkinson's disease (Becker, Farbman, Hamilton, & Lopez, 2011; McKeith et al., 2004). The major symptoms are variations in alertness, recurrent hallucinations, and Parkinsonian symptoms (e.g., tremor, rigidity). Lewy bodies are intraneuron inclusion bodies first identified in the substantia nigra of patients with Parkinson's disease.

Major or Mild Vascular Neurocognitive Disorder

This is a progressive condition based on a history of small strokes associated with hypertension. Patients with vascular neurocognitive disorder experience a stepwise deterioration of function, with each small stroke making the dementia worse in some way. There are parallels between this disorder and the older concept of cerebral arteriosclerosis in that they both relate to the role of generalized cerebral vascular disease in producing progressive brain dysfunction. However, vascular neurocognitive disorder is actually a much more precisely defined syndrome that, although not rare, is not extremely common either. Furthermore, although it continues to be a separate diagnosis, there is substantial evidence that vascular neurocognitive disorder overlaps a great deal with Alzheimer's disease. Autopsy studies often show that there is evidence of vascular pathology in individuals diagnosed with Alzheimer's disease, and the reverse is also true. It has been suggested that cardiovascular illness may be a risk factor for Alzheimer's disease. Moreover, there appears to have been an increased focus of interest in the specific vascular disorders, including heart failure, stroke, and arteriovenous malformations, each of which has different cognitive consequences (Festa, 2010; Lantz, Lazar, Levine, & Levine, 2010; Pavol, 2010).

Because this disorder is known to be associated with hypertension and a series of strokes, the end result is substantial deterioration in cognitive functioning. However, the course of the deterioration is not thought to be as uniform as is the case in Alzheimer's disease, but rather is generally described as stepwise and patchy. The patient may remain relatively stable between strokes, and the symptomatology produced may be associated with the site of the strokes. It should be noted that whereas these distinctions between vascular and Alzheimer's type dementia are clearly described, in individual patients it is not always possible to make a definitive differential diagnosis. Even such sophisticated radiological methods as the computed tomography (CT) scan and MRI do not always contribute to the diagnosis. DSM-5 recognizes the significance of comorbidity with the statement “Most individuals with Alzheimer's disease are elderly and have multiple medical conditions that can complicate diagnosis and influence the clinical course. Major or mild NCD [neurocognitive disorder] due to Alzheimer's disease commonly co-occurs with cerebrovascular disease which contributes to the clinical picture” (p. 614).

Major or Mild Neurocognitive Disorder due to Huntington's Disease

The progressive cognitive deterioration seen in Huntington's disease also involves significant impairment of memory, with other abilities becoming gradually affected through the course of the illness. However, it differs from Alzheimer's disease in that it is accompanied by choreic movements and by the fact that the age of onset is substantially earlier than is the case for Alzheimer's disease. Because of the chorea, a difficulty in speech articulation is also frequently seen, which is not the case for Alzheimer's patients.

There are other major or minor neurocognitive disorders listed in the DSM-5, including major or mild neurocognitive disorder due to TBI, substance/medication-induced major or mild neurocognitive disorder, major or mild neurocognitive disorder due to HIV infection, major or mild neurocognitive disorder due to prion disease, and major or mild neurocognitive disorder due to Parkinson's disease. Patients diagnosed with these syndromes do not have the specific syndromes of the type described earlier. The deficit pattern tends to be global in nature, with all functions more or less involved, even though some investigators have attempted to identify syndromal subtypes, with some having more deficit in the area of abstraction and judgment, some in the area of memory, and some in regard to affect and personality changes. This typology has recently received support from studies delineating frontotemporal dementia, semantic dementia, and Lewy body dementia as separate entities, but most patients have difficulties with all three areas.

Other Conditions Important for Understanding Brain Functioning

In this section we will provide descriptions of the more commonly occurring disorders associated with structural brain damage. It is clear that what is common in one setting may be rare in another. Thus, we will focus on what is common in an adult neuropsychiatric setting. The neuropsychological syndromes found in childhood are often quite different from what is seen in adults and deserve separate treatment. Furthermore, the emphasis will be placed on chronic rather than acute syndromes because, with relatively rare exceptions, the psychologist and psychiatrist encounter the former type far more frequently than the latter.

The Communicative Disorders

In general, aphasia and related language disorders are associated with unilateral brain damage to the dominant hemisphere, which in most individuals is the left hemisphere. Most aphasias result from stroke, but they can be acquired on the basis of left hemisphere head trauma or from brain tumor. Whereas the definition has changed over the years, the most current one requires the presence of impairment of communicative ability associated with focal, structural brain damage. Thus, the term is not coextensive with all disorders of communicative ability and does not include, for example, the language disorders commonly seen in demented individuals with diffuse brain damage. The study of aphasia has in essence become a separate area of scientific inquiry, having its own literature and several theoretical frameworks. The term aphasia does not convey a great deal of clinically significant information, because the various subtypes are quite different from each other.

Numerous attempts have been made to classify the aphasias, and there is no universally accepted system. Contemporary theory indicates that perhaps the most useful major distinction is between fluent and nonfluent aphasias. To many authorities, this distinction is more accurate than that previously more commonly drawn between expressive and receptive aphasias. The problem is that people with aphasia with primarily expressive problems do not generally have normal language comprehension, and it is almost always true that people with aphasia with major speech comprehension disturbances do not express themselves normally. However, there are individuals with aphasia who talk fluently and others whose speech is labored, very limited, and halting, if present at all in a meaningful sense. In the case of the former group, while speech is fluent, it is generally more or less incomprehensible because of a tendency to substitute incorrect words for correct ones—a condition known as verbal paraphasia. However, the primary disturbance in these patients involves profoundly impaired auditory comprehension. This combination of impaired comprehension and paraphasia is generally known as Wernicke's aphasia. The responsible lesion is generally in the superior gyrus of the left temporal lobe. In nonfluent aphasia, comprehension is generally somewhat better, but speech is accomplished with great difficulty and is quite limited. This condition is generally known as Broca's aphasia, the responsible lesion being in the lower, posterior portion of the left frontal lobe (i.e., Broca's area). Several other types of aphasia are relatively rare and will not be described here. However, it is important to point out that most aphasias are mixed, having components of the various pure types. Furthermore, the type of aphasia may change in the same patient, particularly during the course of recovery.

The disorders of reading, writing, and calculation may also be divided into subtypes. In the case of reading, our interest here is in the so-called acquired alexias, whereby an individual who was formerly able to read has lost that ability because of focal, structural brain damage. The ability to read letters, words, or sentences may be lost. Handwriting disturbances, or agraphia, might involve a disability in writing words from dictation or a basic disability in forming letters. Thus, some agraphic patients can write, but with omissions and distortions relative to what was dictated.

However, some can no longer engage in the purposive movements needed to form letters. Calculation disturbances, or acalculias, are also of several types. The patient may lose the ability to read numbers, to calculate even if the numbers can be read, or to arrange numbers in a proper spatial sequence for calculation. The various syndromes associated with communicative disorders, while sometimes existing in pure forms, often merge together. For example, alexia is frequently associated with Broca's aphasia, and difficulty with handwriting is commonly seen in patients with Wernicke's aphasia. However, there is generally a pattern in which there is a clear primary disorder, such as impaired auditory comprehension, with other disorders, such as difficulty with reading or writing, occurring as associated defects. Sometimes rather unusual combinations occur, as in the case of the syndrome of alexia without agraphia. In this case, the patient can write but cannot read, often to the extent that the patient cannot read what she or he just wrote. Based upon recent research, we would add that academic deficits that are not the product of brain damage acquired during adulthood, or of inadequate educational opportunity, are frequently seen in adults. Rather, people with these deficits have developmentally based learning disabilities that they never outgrew. The view that learning disability is commonly outgrown has been rejected by most students of this area (Katz, Goldstein, & Beers, 2001).

Disorders of Perception and Motility

The disorders of perception can involve perception of one's body as well as perception of the external world. In the case of the external world, the disorder can involve some class of objects or some geographic location. The disorders of motility to be discussed here will not be primary losses of motor function as in the cases of paralysis or paresis, but losses in the area of the capacity to perform skilled, purposive acts. The set of impairments found in this area is called apraxia. There is also the borderline area in which the neuropsychological defect has to do with the coordination of a sense modality, usually vision, and purposive movement. These disorders are sometimes described as impairment of constructional or visual-spatial relations ability. In some patients, the primary difficulty is perceptual, whereas in others it is mainly motoric. The body schema disturbances most commonly seen are of three types. The first has to do with the patient's inability to point to his or her own body parts on command. The syndrome is called autotopognosia, meaning lack of awareness of the surface of one's body. A more localized disorder of this type is finger agnosia, in which, while identification of body parts is otherwise intact, the patient cannot identify the fingers of his or her own hands, or the hands of another person. Finger agnosia has been conceptualized as a partial dissolution of the body schema. The third type of body schema disturbance is right–left disorientation, in which the patient cannot identify body parts in regard to whether they are on the right or left side. For example, when the patient is asked to show the right hand, he or she may become confused or show the left hand. More commonly, however, a more complex command is required to elicit this deficit, such as asking the patient to place the left hand on the right shoulder. The traditional thinking about this disorder is that both finger agnosia and right–left disorientation are part of a syndrome, the responsible brain damage being in the region of the left angular gyrus. However, Benton (1985) has pointed out that the matter is more complicated than that, and the issue of localization involves the specific nature of these defects in terms of the underlying cognitive and perceptual processes affected.

The perceptual disorders in which the difficulty is in recognizing some class of external objects are called gnostic disorders or agnosias. These disorders may be classified with regard to modality and verbal or nonverbal content. Thus, one form of the disorder might involve visual perception of nonverbal stimuli, and would be called visual agnosia. By definition, an agnosia is present when primary function of the affected modality is intact, but the patient cannot recognize or identify the stimulus. For example, in visual agnosia, the patient can see but cannot recognize what he or she has seen. In order to assure oneself that visual agnosia is present, it should be determined that the patient can recognize and name the object in question when it is placed in his or her hand, so that it can be recognized by touch, or when it produces some characteristic sound, so that it can be recognized by audition. The brain lesions involved in the agnosias are generally in the association areas for the various perceptual modalities. Thus, visual agnosia is generally produced by damage to association areas in the occipital lobes. When language is involved, there is obviously a great deal of overlap between the agnosias and the aphasias. For example, visual-verbal agnosia can really be viewed as a form of alexia. In these cases, it is often important to determine through detailed testing whether the deficit is primarily a disturbance of perceptual recognition or a higher-level conceptual disturbance involving language comprehension. There is a wide variety of gnostic disorders reported in the literature involving such phenomena as the inability to recognize faces, colors, or spoken words. However, these are relatively rare conditions and, when present, they may only persist during the acute phase of the illness. In general, agnosia has been described as “perception without meaning,” and it is important to remember that it is quite a different phenomenon from what we usually think of as blindness or deafness.

Sometimes a perceptual disorder does not involve a class of objects but a portion of geographic space. The phenomenon itself is described by many terms, the most frequently used ones being neglect and inattention. It is seen most dramatically in vision, where the patient may neglect the entire right or left side of the visual world. It also occurs in the somatosensory modality, in which case the patient may neglect one side or the other of his or her body. Neglect can occur on either side, but it is more common on the left side, because it is generally associated with right hemisphere brain damage. In testing for neglect, it is often useful to employ the method of double stimulation, for example, in the form of simultaneous finger wiggles in the areas of the right and left visual fields. Typically, the patient may report seeing the wiggle in the right field but not in the left. Similarly, when the patient with neglect is touched lightly on the right and left hands at the same time, he or she may report feeling the touch in only one hand or the other. As in the case of the gnostic disorders, neglect is defined in terms of the assumption of intactness of the primary sensory modalities. Thus, the patient with visual neglect should have otherwise normal vision in the neglected half field, while the patient with tactile neglect should have normal somatosensory function. Clinically, neglect may be a symptom of some acute process and should diminish in severity or disappear as the neuropathological condition stabilizes. For example, visual neglect of the left field is often seen in individuals who have recently sustained right hemisphere strokes, but it can be expected to disappear as the patient recovers.

The apraxias constitute a group of syndromes in which the basic deficit involves impairment of purposive movement occurring in the absence of paralysis, weakness, or unsteadiness. For some time, the distinction has been made among three major types of apraxia: ideomotor, limb-kinetic, and ideational. In ideomotor apraxia, the patient has difficulty in performing a movement to verbal command. In the case of limb-kinetic apraxia, movement is clumsy when performed on command or when the patient is asked to imitate a movement. In ideational apraxia, the difficulty is with organizing the correct motor sequences in response to language. In other words, it may be viewed as a disability in regard to carrying out a series of acts. In addition, there are facial apraxias, in which the patient cannot carry out facial movements to command. These four types are thought to involve different brain regions and different pathways. However, they are all generally conceptualized as a destruction or disconnection of motor engrams or traces that control skilled, purposive movement. Certain of the visual-spatial disorders are referred to as apraxias, such as constructional or dressing apraxia, but they are different in nature from the purer motor apraxias described earlier.

The basic difficulty the patient with a visual-spatial disorder has relates to comprehension of spatial relationships, and, in most cases, coordination between visual perception and movement. In extreme cases, the patient may readily become disoriented and lose his or her way when going from one location to another. However, in most cases, the difficulty appears to be at the cognitive level and may be examined by asking the patient to copy figures or solve jigsaw or block design type puzzles. Patients with primarily perceptual difficulties have problems in localizing points in space, judging direction, and maintaining geographic orientation, as tested by asking the patient to describe a route or use a map. Patients with constructional difficulties have problems with copying and block building. So-called dressing apraxia may be seen as a form of constructional disability in which the patient cannot deal effectively with the visual-spatial demands involved in such tasks as buttoning clothing. Whereas visual-spatial disorders can arise from lesions found in most parts of the brain, they are most frequently seen, and seen with the greatest severity, in patients with right hemisphere brain damage. Generally, the area that will most consistently produce the severest deficit is the posterior portion of the right hemisphere. In general, although some patients show a dissociation between visual-spatial and visual-motor or constructional aspects of the syndrome of constructional apraxia, most patients have difficulties on both purely perceptual and constructional tasks.

Amnesia

Whereas some degree of impairment of memory is a part of many brain disorders, there are some conditions in which loss of memory is clearly the most outstanding deficit. When the loss of memory is particularly severe and persistent, and other cognitive and perceptual functions are relatively intact, the patient can be described as having an amnesic syndrome. Dementia patients are often amnesic, but their memory disturbance is embedded in significant generalized impairment of intellectual and communicative abilities. The amnesic patient generally has normal language and may be of average intelligence. As in the case of aphasia and several of the other disorders, there is more than one amnesic syndrome. The differences among them revolve around what the patient can and cannot remember. The structures in the brain that are particularly important for memory are the limbic system, especially the hippocampus, and certain brain stem structures, including the mammillary bodies and the dorsomedial nucleus of the thalamus.

There are many systems described in the literature for distinguishing among types of amnesia and types of memory. With regard to the amnesias, perhaps the most basic distinction is between anterograde and retrograde amnesia. Anterograde amnesia involves the inability to form new memories from the time of the onset of the illness producing the amnesia, whereas retrograde amnesia refers to the inability to recall events that took place before the onset of the illness. This distinction dovetails with the distinction between recent and remote memory. It is also in some correspondence with the distinction made between short-term and long-term memory in the experimental literature. However, various theories define these terms somewhat differently, and it is perhaps best to use the more purely descriptive terms recent and remote memory in describing the amnesic disorders. It can then be stated that the most commonly appearing amnesic disorders involve dramatic impairment of recent memory with relative sparing of remote memory. This sparing becomes greater as the events to be remembered become more remote. Thus, most amnesic patients can recall their early lives, but they may totally forget what occurred during the last several hours. This distinction between recent and remote memory possibly helps to explain why most amnesic patients maintain normal language function and average intelligence. In this respect, an amnesic disorder is not so much an obliteration of the past as it is an inability to learn new material.

Probably the most common type of relatively pure amnesic disorder is alcoholic Korsakoff's syndrome. These patients, while often maintaining average levels in several areas of cognitive function, demonstrate a dense amnesia for recent events with relatively well-preserved remote memory. Alcoholic Korsakoff's syndrome has been conceptualized by Butters and Cermak (1980) as an information-processing defect in which new material is encoded in a highly degraded manner leading to high susceptibility of interference. Butters and Cermak (1980), as well as numerous other investigators, have accomplished detailed experimental studies of alcoholic Korsakoff's patients in which the nature of their perceptual, memory, and learning difficulties has been described in detail. The results of this research help to explain numerous clinical phenomena noted in Korsakoff's patients, such as their capacity to perform learned behaviors without recall of when or if those behaviors were previously executed, or their tendency to confabulate or “fill in” for the events of the past day that they do not recall. It may be noted that although confabulation was once thought to be a cardinal symptom of Korsakoff's syndrome, it is only seen in some patients. Another type of amnesic disorder is seen when there is direct, focal damage to the temporal lobes, and most important, to the hippocampus. These temporal lobe or limbic system amnesias are less common than Korsakoff's syndrome, but they have been well studied because of the light they shed on the neuropathology of memory. These patients share many of the characteristics of Korsakoff's patients but have a much more profound deficit in regard to basic consolidation and storage of new material. When Korsakoff's patients are sufficiently cued and given enough time, they can learn. Indeed, sometimes they can demonstrate normal recognition memory. However, patients with temporal lobe amnesias may find it almost impossible to learn new material under any circumstances.

In some cases, amnesic disorders are modality specific. If one distinguishes between verbal and nonverbal memory, the translation can be made from the distinction between language and nonverbal abilities associated with the specialized functions of each cerebral hemisphere. In fact, it has been reported that patients with unilateral lesions involving the left temporal lobe may have memory deficits for verbal material only, whereas right temporal patients have corresponding deficits for nonverbal material. Thus, the left temporal patient may have difficulty with learning word lists, while the right temporal patient may have difficulty with geometric forms. In summary, whereas there are several amnesic syndromes, they all have in common the symptom of lack of ability to learn new material following the onset of the illness. Sometimes the symptom is modality-specific, involving only verbal or nonverbal material, but more often than not it involves both modalities. There are several relatively pure types of amnesia, notably Korsakoff's syndrome, but memory difficulties are cardinal symptoms of many other brain disorders, notably the progressive dementias and certain disorders associated with infection. For example, people with herpes encephalitis frequently have severely impaired memories, but they have other cognitive deficits as well.

Pseudodementia

Although alterations in brain function can give rise to symptoms that look like functional personality changes, the reverse can also occur. That is, a nonorganic personality change, notably the acquisition of a depression, can produce symptoms that look like they have been produced by alterations in brain function. The term generally applied to this situation is pseudodementia, and it is most frequently seen in elderly people who become depressed. The concept of pseudodementia or depressive pseudodementia is not universally accepted, but it is not uncommon to find elderly patients diagnosed as demented when in fact the symptoms of dementia are actually produced by depression. The point is proven when the symptoms disappear or diminish substantially after the depression has run its course or the patient is treated with antidepressant medication. Wells (1979, 1980) has pointed out that this differential diagnosis is a difficult one to make, and it cannot be accomplished satisfactorily with the usual examinational, laboratory, and psychometric methods. He suggests that perhaps the most useful diagnostic criteria are clinical features. For example, patients with pseudodementia tend to complain about their cognitive losses, whereas patients with dementia tend not to complain. In a more recent formulation, Caine (1986) pointed to the many complexities of differential diagnosis in the elderly, referring in particular to the abundant evidence for neuropsychological deficits in younger depressed patients, and to the not uncommon coexistence of neurological and psychiatric impairments in the elderly.

In recent years there has been substantial rethinking about the concept of pseudodementia in the direction of characterizing it as a neurobiological disorder associated with demonstrable changes in brain structure. Clinicians have observed that depression may sometimes be the first indicator of Alzheimer's disease, and Nussbaum (1994), based on an extensive review of the literature, concluded that pseudodementia or late-life depression has a neurological substrate involving subcortical structures and the frontal lobes. He indicated that the probable pathology is leukoaraiosis, diminution in the density of white matter, which particularly involves the subcortex in this disorder. Leukoaraiosis is frequently seen in the MRIs of elderly depressed individuals.

Epidemiology

Returning to the DSM-5 disorders, the epidemiology of the neurocognitive disorders varies with the underlying disorder, and so is unlike what is found for most of the other diagnostic categories in the DSM system. Here, we will only sample from those disorders in which epidemiological considerations are of particular interest. There are some exceptionally interesting and well-documented findings for multiple sclerosis, in which prevalence is directly related to the latitude at which one resides; the further from the equator, the higher the prevalence (Koch-Henriksen & Sørensen, 2010). Further study of this phenomenon has tended to implicate an environmental rather than an ethnic factor.

The epidemiology of head trauma has been extensively studied, with gender, age, and social class turning out to be important considerations. Head trauma has a higher incidence in males than in females (274 per 100,000 in males and 116 per 100,000 in females in one study; Levin, Benton, & Grossman, 1982). It is related to age, with risk peaking between the ages of 15 and 24, and occurs more frequently in individuals from lower social classes. Alcohol is a major risk factor, but marital status, pre-existing psychiatric disorder, and previous history of head injury have also been implicated. The major causes of head injury are motor vehicle accidents, falls, assaults, and recreational or work activities, with motor vehicle accidents clearly being the major cause (50–60%; Smith, Barth, Diamond, & Giuliano, 1998). The epidemiology of Huntington's disease has also been extensively studied. The disease is transmitted as an autosomal dominant trait, and the marker for the gene has been located on the short arm of chromosome 4 (Gusella et al., 1983). Prevalence estimates vary between 5 and 7 per 100,000. There are no known risk factors for acquiring the disorder, the only consideration being having a parent with the disease. If that is the case, the risk of acquiring the disorder is 50%. A test is now available to detect carriers of the defective gene, and its availability and usage may eventually reduce the prevalence of Huntington's disease.

There is great interest in the epidemiology of Alzheimer's disease, because the specific cause of the disease is not fully understood, and prevention of exposure to risk factors for Alzheimer's disease and related disorders remains a possibility. General health status considerations do not appear to constitute risk factors, but some time ago there were beliefs that there was transmissible infective agent, and that exposure to aluminum might be a risk factor. The aluminum hypothesis has largely been discarded. Recently, episodes of head trauma have been implicated as a possible risk factor for Alzheimer's disease (Lye & Shores, 2000). A reasonably solid genetic association involving chromosome 21 trisomy has been formed between what appears to be an inherited form of Alzheimer's disease and Down syndrome.

Much of the epidemiology of the organic mental disorders merges with general considerations regarding health status. Cardiovascular risk factors such as obesity and hypertension put one at greater than usual risk for stroke. Smoking is apparently a direct or indirect risk factor for several disorders that eventuate in brain dysfunction. The association of alcoholism and diagnosis of substance/medication-induced major or mild neurocognitive disorder is now relatively widely accepted, although it was controversial at one time. Alcohol most clearly—and, perhaps, several other abused substances—make for significant risk factors.

Until recently, the risk of acquiring brain disease by infection had diminished substantially, but that situation has changed markedly with the appearance of human immunodeficiency virus, or HIV-1 infection, or AIDS dementia (Bornstein, Nasrallah, Para, & Whitacre, 1993; Grant et al., 1987; Van Gorp, Miller, Satz, & Visscher, 1989; Woods et al., 2009). It has become increasingly clear that AIDS is frequently transmitted to children during pregnancy or in association with breastfeeding. New anti-infection medication is in use or in the process of going through extensive clinical trials, and there is great promise of effectiveness.

In summary, the prevalence and incidence of the neurocognitive disorders vary substantially, ranging from very rare to common diseases. The number of risk factors also varies, ranging from complete absence to a substantial number. The genetic and degenerative diseases, notably Huntington's and Alzheimer's disease, possess little in the way of risk factors, and there is not much that can be done to prevent their occurrence. The development of a test for risk of transmitting Huntington's disease has opened up the admittedly controversial and complex matter of genetic counseling.

Psychological and Biological Assessment

In recognition of the complexities involved in relating structural brain damage to behavioral consequences, the field of clinical neuropsychology has emerged as a specialty area within psychology. Clinical neuropsychological research has provided specialized instruments for assessment of brain-damaged patients and a variety of rehabilitation methods aimed at remediation of neuropsychological deficits. This research has also pointed out that brain damage, far from being a single clinical entity, actually represents a wide variety of disorders.

Initially, neuropsychologists were strongly interested in the relationship between localization of the brain damage and behavioral outcome. In recent years, however, it has become evident that localization is only one determinant of outcome, albeit often a very important one. Other considerations include the individual's current age, age when the brain damage was acquired, the premorbid personality and level of achievement, and the pathological process producing the dysfunction. Furthermore, neuropsychologists are now cognizant of the possible influence of various nonorganic factors on their assessment methods, such as educational level, socioeconomic status, and mood states. There has been increasing interest in sociocultural aspects of neuropsychological assessment, particularly with reference to research and testing in cultures throughout the world that are experiencing significant effects of some brain disease, such as AIDS dementia (Heaton, 2006).

More recently, a third major methodology, neuroradiology is available for the study of neurocognitive disorders. Beyond the earlier development of the CT scan, positron emission tomography (PET) and functional MRI (fMRI) now allow direct observation of brain function in living individuals while they are engaged in some targeted activity. Using different technologies, these procedures can detect changes when the brain is behaviorally activated. It is now also possible to track conduction from one structure to another while some complex behavior is being performed, such as listening to a word and saying what it is. These methods are known as online procedures because the individual is having recordings made at the same time as the behavior is performed.

A second new development is magnetic resonance spectroscopy (MRS). MRS uses MRI technology, but instead of producing a visualization of brain structure or activity, it generates a chemical profile of the brain. While the individual lies under the magnet, a surface coil placed around the head generates various chemical spectra that provide data about underlying tissue at a microbiological level. In the brain, the phosphorous spectrum produces information about brain metabolism based on the activity of phospholipids that exist in cell membranes. The hydrogen spectrum is most often used to determine the level of a substance called N-acetylaspartate (NAA). NAA level has been found to be associated with integrity of neurons and thus provides an index of neuronal loss, deterioration, or maldevelopment. Therefore, we have a way of examining brain tissue at a molecular biological level in a living individual. PET, fMRI, and MRS have substantially advanced our capability of assessing brain function. DTI is an MRI-related technique that can evaluate misalignment of axonal white matter, as may be found with head injury or some developmental disorders. It evaluates anisotropy associated with diffusion of water mainly in white matter.

In this author's judgment, the major developments over recent years continue to be technological in nature. Increasingly sophisticated techniques have been developed to image the brain, not only structurally as in an X-ray but also functionally. We now have very advanced capacities to image brain activity while the individual is engaging in some form of behavior. At present, fMRI is the most widely used of these procedures. It involves performing MRI while the individual is given tasks to perform and recording changes in brain activity. Thus, for example, it is possible to observe increased activity in the language area of the brain while the person is performing a language task.

There have also been new developments in the techniques used to make a pathological diagnosis of Alzheimer's disease in a living person. Previously, the diagnosis could only be made at autopsy. Now there is a neuroimaging procedure that can visualize neurochemical changes in the brain which can make a specific diagnosis. It involves an amyloid-imaging PET tracer called Pittsburgh Compound B that detects amyloid in the brain. Amyloid is known to be central to the pathogenesis of Alzheimer's disease (Fagan et al., 2005; Klunk et al., 2004). There have been advances in the genetics of Alzheimer's disease, with great interest in the apolipoprotein E epsilon 4 allele (APOE4) which appears to be associated with age of onset of the disorder. There has also been substantial interest in mild cognitive impairment (MCI), the mild cognitive deficits that frequently appear in elderly people. The question raised has involved whether occurrence of MCI results in conversion to Alzheimer's disease. The degree of deficits noted on neuropsychological testing has been found to be significantly associated with conversion to Alzheimer's disease, thereby constituting a significant risk factor.

Etiological Considerations

The brain may incur many of the illnesses that afflict other organs and organ systems. It may be damaged by trauma or it may become infected. The brain can become cancerous or it can lose adequate oxygen through occlusion of the blood vessels that supply it. The brain can be affected by acute or chronic exposure to toxins, such as carbon monoxide or other poisonous substances. Nutritional deficiencies can alter brain function just as they alter the function of other organs and organ systems. The brain may mature abnormally during pregnancy for various reasons, producing different developmental disorders. Aside from these general systemic and exogenous factors, there are diseases that more or less specifically have the central nervous system as their target. These conditions, generally known as degenerative and demyelinating diseases, include Huntington's disease, multiple sclerosis, Parkinson's disease, and disorders associated with aging.

From the point of view of neuropsychological considerations, it is useful to categorize the various disorders according to temporal and topographical parameters. Thus, certain neuropathological conditions are static and do not change substantially; others are slowly progressive; and some are rapidly progressive. With regard to topography, certain conditions tend to involve focal, localized disease, others involve multifocal lesions, and still others involve diffuse brain damage without specific localization. Another very important consideration has to do with morbidity and mortality. Some brain disorders are more or less reversible, some are static and do not produce marked change in the patient over lengthy periods, and some are rapidly or slowly progressive, producing increasing morbidity and eventually leading to death. Thus, some types of brain damage produce a stable condition with minimal changes, some types permit substantial recovery, and other types are in actuality terminal illnesses. It is, therefore, apparent that the kind of brain disorder the patient suffers from is a crucial clinical consideration in that it has major implications for treatment, management, and planning.

Head Trauma

Although the skull affords the brain a great deal of protection, severe blows to the head can produce temporary brain dysfunction or permanent brain injury. The temporary conditions, popularly known as concussions, are generally self-limiting and involve a period of confusion, dizziness, and perhaps double vision. However, there seems to be complete recovery in most cases. In concussion, the brain is not thought to be permanently damaged, but there are exceptions. More serious trauma is generally classified as closed or open head injury. In closed head injury, which is more common, the vault of the skull is not penetrated, but the impact of the blow crashes the brain against the skull and thus may create permanent structural damage. In the case of open head injury, the skull is penetrated by a missile of some kind. Open head injuries occur most commonly during wartime as a result of bullet wounds. They sometimes occur as a result of vehicular or industrial accidents, if some rapidly moving object penetrates the skull. Open head injuries are characterized by the destruction of brain tissue in a localized area. It is generally thought that there are more remote effects as well, but the most severe symptoms are usually associated with the track of the missile through the brain. Thus, an open head injury involving the left temporal lobe could produce aphasia, whereas similar injury to the back of the head could produce a visual disturbance.

A major neuropsychological difference between open and closed head injury is that although the open injury typically produces specific, localized symptoms, the closed head injury, with the possible exception of subdural hematoma, produces diffuse dysfunction without specific focal symptoms. In both cases, some of these symptoms may disappear with time, whereas others may persist. There is generally a sequence of phases that applies to the course of both closed and open head injuries. Often, the patient is initially unconscious and may remain that way for an widely varying amount of time, ranging from minutes to weeks or even months. After consciousness is regained, the patient generally goes through a so-called acute phase, during which there may be confusion and disorientation.

The cognitive residual symptoms of head trauma are extremely varied, because they are associated with whether the injury was open head or closed head and whether there was clear tissue destruction. Most often, patients with closed head injury have generalized intellectual deficits involving abstract reasoning ability, memory, and judgment. Sometimes, marked personality changes are noted, often having the characteristic of increased impulsiveness and exaggerated affective responsivity. Patients suffering from the residual of open head injury may have classic neuropsychological syndromes such as aphasia, visual-spatial disorders, and specific types of memory or perceptual disorders. In these cases, the symptoms tend to be strongly associated with the lesion site. For example, a patient with left hemisphere brain damage may have an impaired memory for verbal material such as names of objects, whereas the right hemisphere patient may have an impaired memory for nonverbal material such as pictures or musical compositions. In these cases there is said to be both modality (e.g., memory) and material (e.g., verbal stimuli) specificity. Head trauma is generally considered to be the most frequent type of brain damage in adolescents and young adults. Therefore, it generally occurs in a reasonably healthy brain. When the combination of a young person and a healthy brain exists, the prognosis for recovery is generally good if the wound itself is not devastating in terms of its extent or the area of the brain involved. For practical purposes, residual brain damage is a static condition that does not generate progressive changes for the worse, although there is some research evidence (Walker, Caveness, & Critchley, 1969) that, following a long quiescent phase, head-injured individuals may begin to deteriorate more rapidly than normal when they become elderly, and also that brain injury may be a risk factor for Alzheimer's disease (Lye & Shores, 2000). However, head-injured individuals may nevertheless have many years of productive functioning. There has been a strong interest in outcome following mild head injury (Levin, Eisenberg, & Benton, 1989), as well as in the specific problems associated with head injury in children (Noggle & Pierson, 2010). It has been frequently pointed out in recent years that trauma is the major cause of death in children, and head trauma among children is not uncommon. Most recently, a marked interest has developed in sports injuries (e.g., Schatz, Pardini, Lovell, Collins, & Podell, 2006), with most studies assessing athletes shortly after sustaining a concussion and evaluating future outcome.

Since the Persian Gulf War era, there has been a substantial increase in the study of head injury, particularly head injuries sustained by veterans and, more specifically, those who had blast injuries or concussions. Thus far, the results are mixed and the characteristics of persistent postconcussion syndrome and its association with PTSD are far from fully understood. Although standard neuroimaging procedures are typically normal following concussion, studies with DTI show some abnormal findings, as reviewed in Bigler (2008). However, in an individual study by Levin et al. (2010), there were no consequential findings with DTI, with head-injured subjects showing normal functional anisotropy, suggesting the absence of axonal misalignment. Wilk et al. (2010) found no or inconsistent association between self-reported concussion and the presence of persistent postconcussive symptoms. However, Mayer et al. (2010) did report finding white-matter abnormalities based upon DTI studies in patients with mild TBI. The roles of PTSD and depression as mediators of these associations have been stressed (Belanger et al., 2010).

Diseases of the Circulatory System

Current thinking about the significance of vascular disease has changed from the time when it was felt that cerebral arteriosclerosis, or “hardening of the arteries,” was the major cause of generalized brain dysfunction in the middle-aged and elderly. Although this condition is less common, the status of the heart and the blood vessels is significantly related to the intactness of brain function. Basically, the brain requires oxygen to function, and oxygen is distributed to the brain through the cerebral blood vessels. When these vessels become occluded, circulation is compromised and brain function is correspondingly impaired. This impairment occurs in several ways, perhaps the most serious and abrupt being stroke. A stroke is a sudden total blockage of a cerebral artery caused by blood clot or hemorrhage. The clot may be a thrombosis formed out of atherosclerotic plaques at branches and curves in the cerebral arteries, or an embolism, which is a fragment that has broken away from a thrombus in the heart and migrated to the brain. Cerebral hemorrhages are generally fatal, but survival from thrombosis or embolism is not at all uncommon. Following a period of stupor or unconsciousness, the most common and apparent postacute symptom is hemiplegia—paralysis of one side of the body. There is also a milder form of stroke known as a transient ischemic attack (TIA), which is basically a temporary, self-reversing stroke that does not produce severe syndromes or may be essentially asymptomatic. The phrase “silent stroke” or “silent cerebral infarction” is used when stroke-type neuropathology is detected by MRI or related procedures, but there are no apparent symptoms (Das et al., 2008).

Other relatively common cerebrovascular disorders are associated with aneurysms and other vascular malformations in the brain. An aneurysm is an area of weak structure in a blood vessel that may not produce symptoms until it balloons out to the extent that it creates pressure effects or it ruptures. A ruptured aneurysm is an extremely serious medical condition which may lead to sudden death. However, surgical intervention in which the aneurysm is ligated is often effective. Arteriovenous malformations are congenitally acquired tangles of blood vessels. They may be asymptomatic for many years, but they can eventually rupture and hemorrhage. They may appear anywhere in the brain, but they commonly occur in the posterior half. The symptoms produced, when they occur, may include headache and neurological signs associated with the particular site.

There are major neuropsychological differences between the individual with a focal vascular lesion, most commonly associated with stroke, and the patient with generalized vascular disease such as vascular dementia. The stroke patient is characterized not only by the hemiplegia or hemiparesis, but also sometimes by an area of blindness in the right or left visual fields and commonly by a pattern of behavioral deficits associated with the hemisphere of the brain affected and the locus within that hemisphere. If the stroke involves a blood vessel in the left hemisphere, the patient will be paralyzed or weak on the right side of the body, the area of blindness, if present, will involve the right field of vision, and there will frequently be aphasia. Right hemisphere strokes may produce left-sided weakness or paralysis and left visual field defects but no aphasia. Instead, a variety of phenomena may occur. The patient may acquire a severe difficulty with spatial relations—a condition known as constructional apraxia. The ability to recognize faces or to appreciate music may be affected. A phenomenon known as unilateral neglect may develop, in which the patient does not attend to stimuli in the left visual field, although it may be demonstrated that basic vision is intact. Sometimes affective changes occur in which the patient denies that he or she is ill and may even develop euphoria.

In contrast with this specific, localized symptom picture seen in the stroke patient, the individual with vascular dementia or other generalized cerebral vascular disease has a quite different set of symptoms. Generally, there is no unilateral paralysis, no visual field deficit, no gross aphasia, and none of the symptoms characteristic of patients with right hemisphere strokes. Rather, there is a picture of generalized intellectual, and to some extent physical, deterioration. If weakness is present, it is likely to affect both sides of the body, and typically there is general diminution of intellectual functions, including memory, abstraction ability, problem-solving ability, and speed of thought and action. In the case of the patient with vascular dementia, there may be localizing signs, but there would tend to be several of them, and they would not point to a single lesion in one specific site. The more common forms of cerebral vascular disease are generally not seen until at least middle age, and for the most part they are diseases of the elderly. Clinically significant cerebral vascular disease is often associated with a history of generalized cardiovascular or other systemic diseases, notably hypertension and diabetes. Some genetic or metabolic conditions promote greater production of atheromatous material than is normal, and some people are born with arteriovenous malformations or aneurysms, placing them at higher than usual risk for serious cerebral vascular disease. When a stroke is seen in a young adult, it is usually because of an aneurysm or other vascular malformation. Most authorities agree that stroke is basically caused by atherosclerosis, and so genetic and acquired conditions that promote atherosclerotic changes in blood vessels generate risk of stroke. With modern medical treatment there is a good deal of recovery from stroke with substantial restoration of function. However, in the case of the diffuse disorders, there is really no concept of recovery because they tend to be slowly progressive. The major hope is to minimize the risk of future strokes, through such means as controlling blood pressure and weight. An area of particular interest is the long-term effects of hypertension on cerebral function, as well as the long-term effects of antihypertensive medication. Reviews written some time ago (Elias & Streeten, 1980; King & Miller, 1990) have demonstrated that hypertension in itself, as well as antihypertensive medication, can impair cognitive function, but there are no definite conclusions in this area as yet, with studies reporting mixed as well as benign outcomes associated with prudent use of the newer antihypertensive medications (Goldstein, 1986).

Degenerative and Demyelinating Diseases

The degenerative and demyelinating diseases constitute a variety of disorders that have several characteristics in common but that are also widely different from each other in many ways. What they have in common is that they specifically attack the central nervous system, they are slowly progressive and incurable, and although they are not all hereditary diseases, they appear to stem from some often unknown but endogenous defect in physiology. Certain diseases, once thought to be degenerative, have been found not to be so, or are thought not to be so at present. For example, certain dementias have been shown to be caused by so-called slow viruses, whereas multiple sclerosis, the major demyelinating disease, is strongly suspected to have a viral etiology. Thus, in these two examples, the classification would change from degenerative to infectious disease.

The term degenerative disease means that, for some unknown reason, the brain or the entire central nervous system gradually wastes away. In some cases, this wasting, or atrophy, resembles what happens to the nervous system in very old people, but substantially earlier than the senile period, perhaps as early as the late 40s. The previous distinction between presenile and senile dementia is not currently used much, apparently based upon the understanding that it is the same disease, most often neurocognitive disorder of the Alzheimer's type, but the research literature continues to be controversial, showing some important neurobiological differences between those who demonstrate presence of the disease before and during late life.

Senile dementia is generally diagnosed in elderly individuals when the degree of cognitive deficit is substantially greater than one would expect with normal aging. In other words, not all old people become significantly demented before death. Most of those who do, but who do not have another identifiable disease of the central nervous system, are generally thought to have neurocognitive disorder of the Alzheimer's type, which is thought to account for more cases of cognitive dysfunction than does vascular disease. There is another disorder related to Alzheimer's disease called Pick's disease, but it is difficult to distinguish from Alzheimer's disease in living individuals. The distinction only becomes apparent on autopsy, as the neuropathological changes in the brain are different. Within psychiatry, there is no longer an attempt to differentiate clinically among Alzheimer's, Pick's, and some rarer degenerative diseases. DSM-5 considers all of these diseases as underlying the disorder known as major or mild neurocognitive disorder due to Alzheimer's disease.

Although much is still not known about the degenerative disorders, a lot has been discovered in recent years. The major discovery was that Alzheimer's and Huntington's disease (a frequently occurring degenerative disease found in younger adults) are apparently based on neurochemical deficiencies. In the case of Alzheimer's disease, the deficiency is thought to be primarily the group of substances related to choline, one of the neurotransmitters. The disease process itself is characterized by progressive death of the choline neurons—the cells that serve as receptor sites for cholinergic agents, and the presence of a gene that produces amyloid plaques in the brain. Huntington's disease is more neurochemically complex because three neurotransmitters are involved: choline, GABA, and substance P. The reasons for these neurochemical deficiency states remain unknown, but the states themselves have been described, and treatment efforts have been initiated based on this information. For example, some Alzheimer's patients have been given choline or lecithin, a substance related to choline, and other newer drugs such as Aricept, in the hope of slowing down the progression of the illness.

Most recently, an extensive literature has developed around progressive dementias that resemble but are pathologically or behaviorally different from Alzheimer's disease. One group is now known as prion diseases. Prions are proteins that are infectious and can transmit biological information. They also are apparently associated with Creutzfeldt–Jakob disease, a progressive dementia.

Alcoholism

The term alcoholism in the context of central nervous system function involves not only the matter of excessive consumption of alcoholic beverages, but also a complex set of considerations involving nutritional status, related disorders such as head trauma, physiological alterations associated with the combination of excessive alcohol consumption and malnutrition, and possible genetic factors. What is frequently observed in long-term chronic alcoholism is a pattern of deterioration of intellectual function not unlike that seen in patients with major or minor neurocognitive disorders of the Alzheimer's type. However, it is not clear that the deteriorative process is associated with alcohol consumption per se. Thus, although some clinicians use the term alcoholic dementia, this characterization lacks sufficient specificity, because it is rarely at all clear that the observed dementia is in fact solely a product of excessive use of alcohol. Looking at the matter in temporal perspective, there may, first of all, be a genetic propensity for the acquisition of alcoholism that might ultimately have implications for central nervous system function (Goodwin, 1979). Second, Tarter (1976) has suggested that there may be an association between having minimal brain damage or a hyperactivity syndrome as a child and the acquisition of alcoholism as an adult. These two considerations suggest the possibility that at least some individuals who eventually become alcoholics may not have completely normal brain function preceding the development of alcoholism. Third, during the course of becoming chronically alcoholic, dietary habits tend to become poor, and multiple head injuries may be sustained as a result of fights or accidents. As the combination of excessive alcohol abuse and poor nutrition progresses, major physiological changes may occur, particularly in the liver, and to some extent in the pancreas and gastrointestinal system. Thus, the dementia seen in long-term patients with alcoholism may well involve a combination of all of these factors in addition to the always-present possibility of other neurological complications.

The majority of alcoholics who develop central nervous system complications manifest it in the form of general deterioration of intellectual abilities, but some develop specific syndromes. The most common of these is the Wernicke–Korsakoff syndrome, which begins with the patient going into a confusional state, accompanied by difficulty in walking and controlling eye movements, and by polyneuritis, a condition marked by pain or loss of sensation in the arms and legs. The latter symptoms may gradually disappear, but the confusional state may evolve into a permanent, severe amnesia. When this transition has taken place, the patient is generally described as having Korsakoff's syndrome or alcohol amnestic disorder, and is treated with large dosages of thiamine, because the etiology of the disorder appears to be a thiamine deficiency rather than a direct consequence of alcohol ingestion. Data reported previously (Blass & Gibson, 1977) indicate that the thiamine deficiency must be accompanied by an inborn metabolic defect related to an enzyme that metabolizes thiamine and is associated with thiamine transport genes (Guerrini, Thomson, & Gurling, 2009). It should be noted that the amnesic and intellectual disorders found in chronic alcoholics are permanent and present even when the patient is not intoxicated. The acute effects of intoxication or withdrawal (e.g., delirium tremens [DTs]) are superimposed on these permanent conditions. These disorders are also progressive as long as the abuse of alcohol and malnutrition persist. Other than abstinence and improved nutrition, there is no specific treatment. Even thiamine treatment for the Korsakoff patient does not restore memory; it is used primarily to prevent additional brain damage.

It is probably fair to say that a major interest in recent years has been the genetics of alcoholism. There is a growing, probably well-justified, belief that a positive family history of alcoholism puts an individual at increased risk for becoming alcoholic, if exposed to alcoholic beverages. The body of supporting research done is broad-ranging, including extensive family adoption studies (Goodwin, Schulsinger, Hermansen, Guze, & Winokur, 1973); neuropsychological studies of relatives (Schaeffer, Parsons, & Yohman, 1984) and children of alcoholics (Tarter, Hegedus, Goldstein, Shelly, & Alterman, 1984); psychophysiological studies, emphasizing brain event-related potentials in siblings (Steinhauer, Hill, & Zubin, 1987) and children of alcoholics (Begleiter, Porjesz, Bihari, & Kissin, 1984); and laboratory genetic studies. In summary, an extensive effort is being made to find biological markers of alcoholism (Hill, Steinhauer, & Zubin, 1987) and to determine the transmission of alcoholism in families. At this time, several susceptibility genes have been identified (Hill et al., 2004). One reasonable assumption is that alcoholism is a heterogeneous disorder, and there may be both hereditary and nonhereditary forms of it (Cloninger, Bohman, & Sigvardsson, 1981).

Toxic, Infectious, and Metabolic Illnesses

Exogenous or endogenous agents may poison the brain or it may become infected. Sometimes these events occur with such severity that the person dies, but more often, the individual survives with a greater or lesser degree of neurological dysfunction. Beginning with the exogenous toxins, we have already discussed the major one: alcohol. However, excessive use of drugs such as bromides and barbiturates may produce at least temporary brain dysfunction, such as delirium.

In psychiatric settings, a fairly frequently seen type of toxic disorder is carbon monoxide poisoning. This disorder and its treatment are quite complex, because it usually occurs in an individual with a major mood or psychotic disorder who attempted to commit suicide by inhaling car fumes in a closed garage. The brain damage sustained during the episode may often be permanent, resulting in significant intellectual and physical dysfunction in addition to the previously existing psychiatric disorder. Other toxic substances that may affect central nervous system function include certain sedative and hypnotic drugs, plant poisons, heavy metals, and toxins produced by certain bacteria, leading to such conditions as tetanus and botulism. The specific effects of these substances themselves, as well as whether exposure is acute (as in the case of tetanus or arsenic poisoning) or chronic (as in the case of addiction to opiates and related drugs), are often crucial.

Many brain disorders are associated with inborn errors of metabolism. In some way, a fault in metabolism produces a detrimental effect on the nervous system, generally beginning in early life. There are so many of these disorders that we will only mention two of the more well-known ones as illustrations. The first is phenylketonuria (PKU). PKU is an amino acid uria, a disorder that involves excessive excretion of an amino acid into the urine. It is genetic and, if untreated, can produce intellectual disability accompanied by poor psychomotor development and hyperactivity. The treatment involves a diet low in a substance called phenylalanine. The second disorder is Tay–Sachs disease. The enzyme abnormality here is a deficiency in a substance called hexasaminidase A, which is important for the metabolism of protein and polysaccharides. It is hereditary, occurs mainly in Jewish children, and is present from birth. The symptoms are initially poor motor development and progressive loss of vision, followed by dementia, with death usually occurring before the age of 5 years. These two examples illustrate similarity in process, which is basically an inherited enzyme deficiency, but variability in outcome. PKU is treatable, with a relatively favorable prognosis, whereas Tay–Sachs is a rapidly progressive, incurable terminal illness.

Bacterial infections of the brain are generally associated with epidemics but are sometimes seen when there are no epidemics at large. They are generally referred to as encephalitis, when the brain is infected, or meningitis, when the infection is in the membranous tissue that lines the brain, known as the meninges. Infections, of course, are produced by microorganisms that invade tissue and cause inflammation. During the acute phase of the bacterial infections, the patient may be quite ill, and survival is an important issue. Headaches, fever, and a stiff neck are major symptoms. There may be delirium, confusion, and alterations in state of consciousness ranging from drowsiness, through excessive sleeping, to coma. Some forms of encephalitis were popularly known as “sleeping sickness.” Following the acute phase of bacterial infection, the patient may be left with residual neurological and neuropsychological disabilities and personality changes. Sometimes infections are local, and the patient is left with neurological deficits that correspond with the lesion site. The irritability, restlessness, and aggressiveness of postencephalitic children are mentioned in the literature. Jervis (1959) described them as overactive, restless, impulsive, assaultive, and wantonly destructive.

Neurosyphylis is another type of infection that has a relatively unique course. Most interesting, aside from the progressive dementia that characterizes this disorder, there are major personality changes involving the acquisition of delusions and a tendency toward uncritical self-aggrandizement. Although neurosyphilis or general paresis played a major role in the development of psychiatry, it is now a relatively rare disease and is seldom seen in clinical practice. Similarly, the related neurosyphilitic symptoms, such as tabes dorsalis and syphilitic deafness, are also rarely seen.

The incidence of and perhaps the interest in the bacterial infections and neurosyphilis have diminished, but interest in viral infections has increased substantially during recent years. There are perhaps four reasons for this phenomenon: (1) Jonas Salk's discovery that poliomyelitis was caused by a virus and could be prevented by vaccination; (2) the recent increase in the incidence of herpes simplex, which is a viral disorder; (3) the appearance of AIDS; and (4) the discovery of the “slow viruses.” The latter two reasons are probably of greatest interest in the present context. With regard to the slow viruses, it has been discovered that certain viruses have a long incubation period and may cause chronic degenerative disease, resembling Alzheimer's disease in many ways. Thus, some neurocognitive disorders may be produced by a transmittable agent. One of these disorders appears to be a disease known as kuru, and another is known as Creutzfeldt–Jakob disease. Recently, there has been an outbreak of a related disorder called mad cow disease, or bovine spongiform encephalopathy (Balter, 2001). The discovery of infection as the cause of disease is important because it opens up the possibility of the development of a preventive treatment in the form of a vaccine.

Major and mild neurocognitive disorder due to AIDS is another form of viral encephalopathy. It is a consequence of HIV infection and apparently represents an illness that has not appeared on the planet previously. It has been characterized as a progressive subcortical dementia of the type seen in patients with Huntington's disease and other neurological disorders in which the major neuropathology is in the subcortex. The syndrome has not been completely described, but there is substantial evidence of neuropsychological abnormalities. The first papers in this area appeared around 1987, with the best-known study being that of Grant et al. (1987). A review is contained in Bornstein et al. (1993), and recent updates have been provided by Heaton (2006) and Woods et al. (2009).

Genetic Factors

The neurocognitive disorders are based on some diseases of known genetic origin, some diseases in which a genetic or familial component is suspected, and some that are clearly acquired disorders. It is well established that Huntington's disease and certain forms of intellectual disability, notably Down syndrome, are genetic disorders. There appears to be evidence that there is a hereditary form of Alzheimer's disease, although the genetic contribution to Alzheimer's disease in general is not fully understood. A relatively rare genetic subtype has been identified consisting of patients who develop psychosis (DeMichele-Sweet & Sweet, 2010). The great majority of individuals with this subtype and other individuals with Alzheimer's disease have a gene on chromosome 14 called apolipoprotein E that promotes development of the amyloid plaques that constitute the major brain pathology associated with the disease. Whether multiple sclerosis has a genetic component remains under investigation, although it is clearly not a hereditary disorder like Huntington's disease.

Of great recent interest is the role of genetics in the acquisition of alcoholism, and subsequently dementia associated with alcoholism or alcohol amnestic disorder. Evidence suggests that having an alcoholic parent places one at higher than average risk for developing alcoholism. The specific genetic factors are far from understood, but there does appear to be an association in families. Whether having a family history of alcoholism increases the risk of acquiring dementia associated with alcoholism is not clear, but it has been shown that nonalcoholic sons of alcoholic fathers do more poorly on some cognitive tests than do matched controls. The matter is substantially clearer in the case of alcohol amnestic disorder or Korsakoff's syndrome. A widely cited study by Blass and Gibson (1977) showed that acquisition of Korsakoff's syndrome is dependent upon the existence of a genetic defect in a liver enzyme called transketolase in combination with a thiamine deficiency.

Other genetic and familial factors associated with the organic mental disorders relate largely to the genetics of underlying systemic disorders. Thus, the genetics of cancer might have some bearing on the likelihood of acquiring a brain tumor, while the genetics of the cardiovascular system might have some bearing on the risk for stroke. Disorders such as hypertension and diabetes appear to run in families and have varying incidences in different ethnic groups. Ethnic specificity is sometimes quite precise (but this is rare), as in the case of Tay–Sachs disease, a degenerative disorder of early childhood that is found almost exclusively in eastern European Jews.

Course and Prognosis

Course and prognosis for the neurocognitive disorders also vary with the underlying disorder. We will review the basic considerations here by first introducing some stages of acceleration and development. Then we will provide examples of disorders that have courses and prognoses consistent with various acceleration and developmental combinations. The acceleration stages are steady state, slow, moderate, and rapid. The developmental stages are the perinatal period, early childhood, late childhood and adolescence, early adulthood, middle age, and old age. The acceleration stages have to do with the rate of progression of the disorder, whereas the developmental stages characterize the age of onset of symptoms.

Intellectual disability would be a disorder with a course involving onset during the perinatal period and steady-state acceleration. Intellectual disability is one of those disorders in which there is little if any progression of neuropathology, but there may be a slowly progressive disability because of increasing environmental demands for cognitive abilities that the individual does not possess. Other developmental disorders, such as specific learning disability, do not have their onsets during the perinatal period but rather during early childhood when academic skills are first expected to be acquired.

In contrast to these disorders, stroke is typically characterized by onset during middle age. The acceleration of the disorder is extremely rapid at first and then slows down, gradually reaching steady state. Thus, the stroke patient, at the time of the stroke, becomes seriously ill very rapidly, and this is followed by additional destructive processes in the brain. Assuming a good outcome, a gradual recovery period follows, and there is restoration of the brain to a relatively normal steady state. On the other hand, malignant brain tumors, which also tend to appear during middle age, progress rapidly and do not decelerate unless they are successfully surgically removed.

The progressive dementias generally appear during middle or old age and accelerate slowly or moderately. Huntington's disease generally progresses less rapidly than Alzheimer's disease, and so the Huntington's patient may live a long life with his or her symptoms. Head trauma is a disorder that may occur at any age, but once the acute phase of the disorder is over, the brain typically returns to a steady state. Thus, the head trauma patient, if recovery from the acute condition is satisfactory, may have a normal life expectancy with an often dramatic picture of deterioration immediately following the trauma until completion of resolution of the acute phase, followed by substantial recovery. However, the degree of residual disabilities may vary widely.

Briefly summarizing these considerations from a developmental standpoint, the most common organic mental disorder associated with the perinatal period is intellectual disability and its variants. During early childhood, the specific and pervasive developmental disorders begin to appear. Head trauma typically begins to appear during late childhood and adolescence, and incidence peaks during young adulthood. Systemic illnesses, notably cardiovascular, cardiopulmonary, and neoplastic disease, most commonly impact negatively on brain functions during middle age. Dementia associated with alcoholism also begins to appear during early middle age. The progressive degenerative dementias are largely associated with old age.

With regard to acceleration, following the time period surrounding the acquisition of the disorder, developmental, vascular, and traumatic disorders tend to be relatively stable. Malignant tumors and certain infectious disorders may be rapidly progressive, and the degenerative disorders progress at a slow to moderate pace. Although the connotation of the term progressive is progressively worse, not all the neurocognitive disorders remain stable or get worse. There is recovery of certain disorders as a natural process or with the aid of treatment. In the case of head trauma, there is a rather typical history of initial unconsciousness, lapsing into coma for varying lengths of time, awakening, a period of memory loss and incomplete orientation called post-traumatic amnesia, and resolution of the amnesia. Rehabilitation is often initiated at some point in this progression, sometimes beginning while the patient is still in a coma. The outcome of this combination of spontaneous recovery and rehabilitation is rarely, if ever, complete return to pre-injury status, but often allows for a return to productive living in the community. Recovery from stroke is also common, and many post-stroke patients can return to community living. Among the most important prognostic indicators for head trauma are length of time in coma and length of post-traumatic amnesia. General health status is a good predictor for stroke outcome and potential for recurrence. Patients who maintain poor cardiac status, hypertension, inappropriate dietary habits, or substance abuse are poorer candidates for recovery than are post-stroke patients who do not have these difficulties. Some patients, particularly those with chronic, severe hypertension, may have multiple strokes, resolving into a vascular dementia.

There is increasing evidence that rehabilitation of head trauma may often have beneficial effects over and above spontaneous recovery. With regard to the developmental disorders, enormous efforts have been made in institutional and school settings to provide appropriate educational remediation for developmentally disabled children, often with some success. Effective treatment at the time of onset of acute disorder also has obvious implications for prognosis. Use of appropriate medications and management following trauma or stroke, and the feasibility and availability of neurosurgery, are major considerations. Tumors can be removed, aneurysms can be repaired, and increased pressure can be relieved by neurosurgeons. These interventions during the acute phase of a disorder are often mainly directed toward preservation of life, but they also have important implications for the outcomes of surviving patients.

Summary

The diagnostic category of neurocognitive disorders, formerly known as delirium, dementia, and amnestic and other cognitive disorders—and as organic mental disorders before that—consists of many conditions in which behavioral changes may be directly associated with some basis in altered brain function. Although the general diagnostic term organic brain syndrome has commonly been used to describe these conditions, the wide variability in the manifestations of brain dysfunction makes this term insufficiently precise in reference to clinical relevance, and it has been abandoned. It was pointed out that the variability is attributable to several factors, including the following considerations: (a) the location of the damage in the brain, (b) the neuropathological process producing the damage; (c) the length of time the brain damage has been present; (d) the age and health status of the individual at the time the damage is sustained; and (e) the individual's premorbid personality and level of function.

The neuropsychological approach to the conceptualization of these disorders has identified behavioral parameters along which the manifestations of brain dysfunction can be described and classified. The most frequently considered dimensions are intellectual function, language, attention, memory, visual-spatial skills, perceptual skills, and motor function. Some important concepts related to brain function and brain disorders include the principle of contralateral control of perceptual and motor functions and functional hemisphere asymmetries. In addition, studies of brain-damaged patients have shown that particular structures in the brain mediate relatively discrete behaviors. Neurologists and neuropsychologists have identified several syndromes in such areas as language dysfunction, memory disorder, and general intellectual impairment. It was pointed out that there are also major variations in the courses of neurocognitive disorders. Some are transient, leaving little or no residua; some are permanent but not progressive; while others are either slowly or rapidly progressive. Whereas these disorders most profoundly and commonly involve impairment of cognitive, perceptual, and motor skills, sometimes personality changes of various types are the most prominent symptoms. More often than not, personality and affective changes appear in brain-damaged patients along with their cognitive, perceptual, and motor disorders. Thus, a mood disorder or such symptoms as delusions and hallucinations may be sequelae of brain damage for various reasons.

During the years spanning the writing of the various editions of this chapter, there have been several major developments in the area of what was originally called the organic mental disorders. There has been the appearance of at least one new disorder, AIDS dementia, major discoveries in the genetics of Huntington's disease and alcoholism, enormous developments in the technology of neuroimaging, growth of a field of neurotoxicology producing knowledge about the epidemiology of neurodevelopmental disorders in particular, and a reconceptualization by psychiatry of the previously held distinction between functional and organic disorders. The work in neuroimaging is particularly exciting, because it goes beyond obtaining more refined pictures of the brain and now allows us to observe the working of the brain during ongoing behavior through fMRI, and to examine the molecular biology of brain function through MRS.

Note

1.  Editor's note: Sadly, Dr. Goldstein passed away in 2017 after completing a draft of this chapter and but before the editing process began.

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