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) we highlighted substantive developments. A new disorder, 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 is 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 (mTBI), 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 posttraumatic 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 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 brainstem, 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 MRI-related procedure that tracks axonal white matter, identifying misalignments.

In the Gulf War, concussion and more serious trauma was 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), but with others claiming 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 since the last writing, 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, which is still under intensive investigation.

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, traumatic brain injury, 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.

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 understanding 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 (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 one 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 not the discovery 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 why most people are left-hemisphere dominant remains unknown, 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.

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.