Increasingly, as the number of elderly in our population rises, the neurologist is consulted because an otherwise healthy person begins to fail mentally and loses his capacity to function effectively at work or in the home. This may indicate the development of a degenerative brain disease, a brain tumor, multiple strokes, chronic subdural hematomas, drug intoxication, chronic meningoencephalitis (such as caused by HIV or syphilis), normal-pressure hydrocephalus, or a depressive illness. Formerly, when there was little that could be done about these clinical states, no great premium was attached to diagnosis. But there are now effective means of treating several of these conditions, and in some instances, of restoring the patient to normal mental competence. Moreover, diagnostic technologies allow earlier recognition of the underlying pathologic process, thus improving the chances of recovery or of preventing the disease’s progression.

The definitions of normal and abnormal states of mind were considered in Chap. 20, where it was pointed out that the term dementia denotes a persistent deterioration of intellectual or cognitive function with little or no disturbance of consciousness or perception. In current neurologic parlance, the term is used to designate a syndrome of failing memory and impairment of other intellectual functions as a result of chronic progressive degenerative disease of the brain. Such a definition may be too narrow. The term more accurately includes a number of closely related syndromes characterized not only by intellectual deterioration but also by certain behavioral abnormalities and changes in personality. Furthermore, dementia can be the result of a static encephalopathy such as head trauma or cerebral anoxia or of a progressive degenerative disease, but it differs from “encephalopathy” in its chronicity. Thus, it is not possible to determine if a confused, amnestic person is demented until some time has passed and the deficits have perished. Encephalopathies, by contrast, are largely reversible.

Beyond the need to properly define these terms, the two entities have different causes. There are several states of dementia of differing causes and mechanisms and that a degeneration of certain systems of cerebral neurons, albeit common, is only one of the many types. Thus, it is more correct to speak of the dementias or the dementing diseases.

To understand the phenomenon of intellectual deterioration, it is helpful to have some idea of how intellectual functions, particularly intelligence and memory, are normally organized and sustained, and the manner in which deficits in these functions relate to diffuse and focal cerebral lesions. The neurology of intelligence is considered in this chapter as a prelude to a discussion of the dementias and the neurology of memory.

Intelligence, or intelligent behavior, has been variously defined as a “general mental efficiency,” as “innate cognitive ability,” or as “the aggregate or global capacity of an individual to act purposefully, to think rationally, and to deal effectively with his environment” (Wechsler) in other words, the capacity to have ideas and reason about them. It is global because it characterizes an individual’s behavior as a whole; it is an aggregate in the sense that it is composed of a number of independent and qualitatively distinguishable cognitive abilities. This topic should be of interest to neurologists because intelligence is disturbed by many disorders of the brain but cannot be easily attributed to any cerebral region or particular cognitive function. In the dementias and in developmental delays, intelligence is affected in a way that cannot be explained except by some global aspect of brain function.

As every educated person knows, intelligence has something to do with normal cerebral function. It is also apparent that the level of intelligence differs widely from one person to another, and members of certain families are exceptionally bright and intellectually accomplished, whereas members of other families are just the opposite. If properly motivated, intelligent children excel in school and score high on intelligence tests. Indeed, the first intelligence tests, devised by Binet and Simon in 1905, were for the purpose of predicting scholastic success. The term intelligence quotient, or IQ, was introduced by the German psychologist Stern and used by Terman in 1916 for the development of intelligence testing. It denotes the figure that is obtained by dividing the subject’s mental age (as determined by the Binet-Simon scale) by his chronologic age (up to the 14th year) and multiplying the result by 100. The IQ correlates, but only broadly, with achievement in school and eventual success in professional work. IQ increases with age up to the 14th to 16th years and then remains stable, at least until late adult life. At any given age, a large sample of normal children attains test scores of a normal, or gaussian, distribution.

The original studies of pedigrees of highly intelligent and mentally less-able families, which revealed a striking concordance between parent and child, lent support to the idea that intelligence is to a large extent inherited. However, it became evident that the tests were also greatly influenced by the environment in which the child was reared. Moreover, tests were less reliable in identifying talented children who were not offered optimal opportunities. This led to the widespread belief that intelligence tests are only achievement tests and that environmental factors fostering high performance are the important factors determining intelligence.

Neither of these views is likely to be entirely correct. Studies of monozygotic and dizygotic twins raised in the same or different families have put the matter in a clearer light. Identical twins reared together or apart are more alike in intelligence than nonidentical twins brought up in the same home (see reviews of Willerman, of Shields, and of Slater and Cowie). A study of elderly twins by McClearn and colleagues has shed further light on the issue; even in twins who were older than 80 years of age, a substantial part (an estimated 62 percent) of cognitive performance could be accounted for by genetic traits. These findings suggest that life experience alters intelligence, but in only a limited way. There can be little doubt, therefore, that genetic endowment is the more important factor—a view that was championed by Piercy and more recently by Herrnstein and Murray. However, there is also evidence that early learning modifies the level of ability that is finally attained. The latter should be looked upon not as the sum of genetic and environmental factors but as the product of the two. More importantly, it is generally appreciated that nonscholastic achievement or success is governed by factors other than intellectual ones, such as curiosity, a readiness to learn, interest, persistence, sociability, and ambition or motivation—factors that vary considerably from person to person and are not measured by tests of intelligence.

As to the genetic mechanisms involved in the inheritance of intelligence, a limited amount is known. There is an excess of males with mental retardation, and there are several well-characterized syndromes in which the inheritance of mental retardation is X-linked as described in Chaps. 28 and 38. Also notable is the somewhat different patterns of subtest performance between males and females (males perform better on subtests of spatial ability and certain mathematical tasks). Males may be more likely to be affected by advantageous or aberrant genes on a single X chromosome, whereas females benefit from the mosaic provided by two X chromosomes. In some families, high intelligence segregates to certain individuals through an X-linked pattern. Further study will determine the validity of this view and its contribution to our understanding of what will certainly prove to be a polygenic inheritance of intellectual traits.

One would think that neurologic structure and function would correlate in some way with intelligence, but with the exception of the pathologically developmentally delayed (Chaps. 28 and 38), such an association has been difficult to document. Brain weight and the complexity of the convolutional pattern are not correlated with intelligence—despite popular notions to the contrary, including a widely criticized analysis of the brain of Albert Einstein. (In regard to Einstein’s brain, Witelson and colleagues proposed that an enlarged inferior parietal lobule, a crossmodal association area, accounted for his visuospatial and mathematical genius, but this has been disputed.) Only laboratory measures of vigilance and facility of sensory registration (speed of motor responses/reaction time and rapid recognition of differences between lines, shapes, or pictures) have a definite but still modest correlation with IQ. However, it is of interest that morphometric features of the regions of the cortex that are presumed to underlie IQ and verbal skills, such as the frontal and language areas, show a heritable component when measured on high-resolution MRI scans in twins (see Thompson et al).

As to psychologic theories of intelligence, several have traditionally been held at different historical periods. One is the two-factor theory of Spearman, who noted that all the separate tests of cognitive abilities correlated with each other, suggesting that a general factor (g factor) enters into all performance. Because none of the correlations between subtests approached unity, he postulated that each test measures not only this general ability (commonly identified with intelligence) but also a subsidiary factors specific to the individual tests, which he designated the s factors. A second theory, the multifactorial theory of Thurstone, proposed that intelligence consists of a number of primary mental abilities, such as memory, verbal facility, numerical ability, visuospatial perception, and capacity for problem solving, all of them more or less equivalent. These primary abilities, although correlated, are not subordinate to a more general ability. For Eysenck, intelligence exists in three forms: biologic (the genetic component), social (development of the genetic component in relation to personal relationships), and a number of specific abilities subject to measurement by psychometric tests.

Thurstone’s multifactorial theory of intelligence has been periodically resurrected, most recently by Gardner who recognizes six categories of high-order cerebral ability but restates them in more modern terms: linguistic (encompassing all language functions); musical (including composition and performance); logical–mathematical (the ideas and works of mathematicians); spatial (including artistic talent and the creation of visual impressions); bodily–kinesthetic (including dance and athletic performance); and the personal (consciousness of self and others in social interactions). He refers to each of these as intelligences, defined as the ability to solve problems or resolve difficulties and to be creative within the particular field. Several lines of evidence are marshaled in support of this parceling of separable skills and abilities: (1) each may be developed to an exceptionally high level in certain individuals, constituting virtuosity or genius; (2) each can be destroyed or spared in isolation as a consequence of a lesion in a certain part of the nervous system; (3) in certain individuals, i.e., in prodigies, special competence in one of these abilities is evident at an unusually early age; (4) in the autism spectrum, one or more of these abilities may be selectively spared or developed to an abnormally high degree (idiot savant). Each of these entities appears to have a genetic basis in so far as musical, artistic, mathematical, and athletic ability often runs in families, but their full development is influenced by environmental factors.

There are only limited data regarding the highest levels of intelligence identified as genius. Terman and Ogden’s longitudinal study of 1,500 California school children who were initially tested in 1921 supported the idea that an extremely high IQ predicted future scholastic accomplishments (though not necessarily occupational and life success). On the other hand, most individuals recognized as geniuses have been especially skilled in one domain—such as painting, linguistics, music, chess, or mathematics—and such “domain genius” is not necessarily predicated on high IQ scores, although certain individuals display crossmodal superiorities—particularly in mathematics and music.

Chapter 28 discusses the developmental aspects of intelligence in detail. One of the leading theories has been that of Piaget, who proposed that this is accomplished in discrete stages related to age: sensorimotor, from 0 to 2 years; preconceptual thought, from 2 to 4 years; intuitive thought, from 4 to 7 years; concrete operations (conceptualization), from 7 to 11 years; and, finally, the period of “formal operations” (logical or abstract thought), from 11 years on. This scheme implies that the capacity for logical thought, developing as it does according to an orderly timetable, is coded in the genes. Surely, one can recognize these states of intellectual development in the child, but Piaget’s theory has been criticized as being too anecdotal and lacking the quantitative validation that could be derived only from studies of a large normal population. Furthermore, it does not take into account an individual’s special abilities, which do not usually develop and reach their maximum at the same time as the more general intellectual capacities.

One would suppose that in neurology, where one is exposed to so many diseases affecting the cerebrum, it might be possible to verify one of these several theories of intelligence and to determine the anatomy of this cognitive entity. Presumably, the g factor of intelligence would be maximally impaired, by diffuse lesions, in proportion to the mass of brain involved, an idea expressed by Lashley as the “mass-action principle.” Indeed, according to Chapman and Wolff, there is a correlation between the volume of brain tissue lost and a general deficit of cerebral function. Others disagree, claiming that no universal psychologic deficit can be linked to lesions affecting particular parts of the brain. Probably the truth lies between these two divergent points of view. According to Tomlinson and colleagues, who studied the effects of vascular lesions in the aging brain, lesions that involve more than 50 mL of tissue cause some general reduction in performance, especially in speed and capacity to solve problems. Piercy, on the other hand, found correlations only between specific intellectual deficits and lesions of particular parts of the left and right hemispheres. These problems are discussed in Chap. 22. It is surprising that lesions of the frontal lobes, and particularly the prefrontal regions, which so profoundly disorder planning and “executive” functions, do not measurably affect IQ except in subtests specific to these skills.

The authors conclude from experience and from evidence provided by neurologic studies that intelligence is a combination of multiple primary abilities, each of which seems to be inherited and each of which has a separate but as yet poorly delineated anatomy. Yet we would disagree with both Thurstone and Gardner that these special abilities are of equivalent weight with regard to what is generally considered as “intelligence.” When viewed in the light of the classics of literature, history, and science, we attach a disproportionate importance to some of them, namely linguistic and mathematical, and perhaps spatial–dimensional, abilities. These are integral to ideation and problem solving and are largely absent in the developmentally delayed and lost early in dementing diseases. To the extent that facility with general mental performance, that requiring the manipulation of abstract symbols and thoughts, marks an individual as “intelligent” and that these correlate with each other, we find Spearman’s g factor to be a credible but not completely satisfying concept for intelligence.

Neurologic data certainly do not exclude the possibility of a general factor for intelligence—one that is unavoidably measured in many different tests of cerebral functions. It is expressed in thinking and abstract reasoning and is operative only if the connections between the frontal lobes and other parts of the brain are intact. Attention, drive, and motivation are noncognitive psychologic attributes of fundamental importance, the precise anatomy and physiology of which remain to be identified but are largely generated in the frontal and prefrontal region. It is also possible, if not likely, that the associative areas of the cerebrum are engaged in the apperception of sensory experiences and their manipulation in symbolic form. This applies equally to the ability to relate thoughts to each other and to stored concepts, but here, memory plays a central role. We view memory and capacity to learn as a separate cognitive entity, with its own neuroanatomic localizations. The interrelationships between some of these special abilities had been thoughtfully analyzed by Luria (see the section on frontal lobes in Chap. 22). An account of the subject of IQ and intelligence can also be found in the monograph by Mackintosh.

An even more complex problem arises in the neurologic analysis of the highest human achievement and the method of human advancement, namely creativity. In some ways, creativity is tied to special skills along the lines of Gardner’s modality-based intelligence, particularly as it relates to artistic work, but the brain structures involved in aesthetics and abstraction are entirely obscure, as Zeki points out. Some insight is gained from the fact that intelligence and problem-solving ability are innately but only roughly tied to creativity and that there are congenital absences and deficiencies of appreciation of visual, artistic, or mathematical skills. The capacity to be creative may be inhibited by other functions of the brain, as exposed in the case described by Seeley and colleagues of a woman with frontotemporal dementia whose artistic abilities emerged as her facility with language deteriorated. But, as pointed out in the following chapter, traits such as creativity almost certainly do not reside in a particular lobe or structure of the brain and may depend on the overdevelopment of certain associative areas, as well as on frontal lobe drive and, of course, are fully manifest only by educational exposure.

Dementia is a syndrome consisting of a loss of several separable but overlapping intellectual abilities and presents in a number of different combinations. These constellations of intellectual deficits constitute the preeminent clinical abnormalities in several cerebral diseases and are sometimes virtually the only abnormalities. Table 21-1 lists the most common types of dementing diseases and their relative frequency.

What is noteworthy about the figures in this table is the apparently high level of accuracy of diagnosis. Rather consistently, postmortem examination confirms that the accuracy of the clinical diagnosis of Alzheimer disease is in excess of 80 percent when rigid research criteria are used (Table 21-2). Of course, the high frequency of this disease in the older population makes the likelihood of correct diagnosis higher. In most cases, the degenerative diseases can be differentiated by one or two characteristic clinical features, but these distinctions may be difficult to discern early in the disease process. In particular, a proportion of patients thought to have Alzheimer disease are found to have another type of degenerative cerebral atrophy, such as Lewy-body disease, progressive supranuclear palsy, Huntington disease, Parkinson disease, corticobasal degeneration, Pick disease, or one of the frontotemporal lobar degenerative diseases (all described in Chap. 39). Or such patients have one of a variety of other processes, such as multiinfarct dementia or hydrocephalus alone or in combination with one of the other disorders. Of special importance is the fact that approximately 10 percent of patients who are referred to a neurologic center with a question of dementia prove to have a potentially reversible psychiatric or metabolic disorder. Emphasized again are the group of nonprogressive dementias that are the lasting result of a monophasic injury to the brain and do not appear in Table 21-2.

In the following pages, we consider the prototypic dementing syndromes. They are observed most frequently with degenerative diseases of the brain (Chap. 39) and less often as part of other categories of disease (vascular, traumatic, infectious, demyelinating), which are considered in their appropriate chapters.

Mild Cognitive Impairment and Early Dementia

It has become apparent that many individuals have memory complaints that are mild and do not interfere with daily functioning but are still disproportionate for the patient’s age and education. It is often difficult to differentiate this less-intrusive problem, which may be a result of the normal process of aging, from dementia. The former condition has been called mild cognitive impairment, age-associated memory impairment, and, in the past, benign senescent forgetfulness, as discussed in Chap. 29. When other aspects of mental functioning are affected, terms such as aging-associated cognitive decline are used. Defining the boundaries of such a condition has proved problematic, and determining the risk of progression to a dementing illness that does interfere with daily function, even more so. There is a further problem introduced by the premise that highly intelligent individuals would have to decline considerably on intelligence and memory tests to be identified as being below certain age-adjusted norms. However, a notion has evolved in which Alzheimer disease and mild cognitive impairment exist in a spectrum (see Petersen), and one of the main values to identifying such patients in a presymptomatic period of Alzheimer disease is the potential for early institution of treatment.

In most studies, 10 to 20 percent per year of such affected patients with mild cognitive decline will be found to have later acquired Alzheimer disease. A number of factors have been identified as associated with a progression to a state of indisputable dementia. These include elevated blood pressure, changes in the cerebral white matter on MRI, abnormality of gait, and—perhaps not surprisingly—certain biologic markers that are connected to Alzheimer disease. Other factors for the development of dementia, particularly the level of prior education and maintenance of an active mental life, have been studied in relation to Alzheimer disease (C.F. Willis et al) and are discussed in that section of Chap. 39.

At the moment, the clinician must simply counsel caution and reassurance in advising patients with mild memory impairment, and exclude treatable causes. Nonetheless, if the symptoms are progressive or begin to interfere in any consistent way with other mental functions or with the performance of daily activities, a dementing illness is likely.

Dementia Caused by Degenerative Diseases

The earliest signs of dementia caused by degenerative disease may be so subtle as to escape the notice of the most discerning physician. An observant relative of the patient or an employer may become aware of a certain lack of initiative or lack of interest in work, a neglect of routine tasks, or an abandonment of pleasurable pursuits. Initially, these changes may be attributed to depression, fatigue, or boredom in retirement. More often, gradual development of forgetfulness is the most prominent early symptom. Proper names are no longer remembered and cannot be recalled with time, to a far greater extent than can be attributed to “mild cognitive impairment.” Difficulty in balancing a checkbook and making change becomes evident. The purpose of an errand is forgotten, appointments are not kept, and recent conversations or social events have been overlooked. The patient may ask the same question repeatedly over the course of a day, having failed to retain the answers that were previously given.

Later, it becomes evident that the patient is easily distracted by every passing incident. He no longer finds it possible to think about or discuss a problem with customary clarity or to comprehend all aspects of complex situations. The ability to make proper deductions and inferences from given premises are greatly reduced. One feature of a situation or some relatively unimportant event may become a source of unreasonable concern or worry. Tasks that require several steps cannot be accomplished, and all but the simplest directions cannot be followed. The patient may get lost, even along habitual routes of travel. Day-to-day events are not recalled, and perseveration or impersistence in speech, action, and thought becomes evident.

In yet other instances, an early abnormality may be in the nature of emotional instability, taking the form of unreasonable outbursts of anger, easy tearfulness, or aggressiveness. A change in mood becomes apparent, deviating more toward depression than elation. Apathy is common. Some patients are irascible; a few are cheerful and facetious. The direction of the mood change is said to depend on the patient’s previous personality rather than on the character of the disease, but one can think of glaring exceptions from clinical experience. Excessive lability of affect may also be observed—for example, easy fluctuation from laughter to tears on slight provocation.

A considerable group of patients come to the physician with physical complaints, the most common being dizziness, a vague mental “fogginess,” and nondescript headaches. The patient’s inability to give a coherent account of his symptoms bears witness to the presence of dementia. Sleep disturbances, especially insomnia, are prominent in some cases and a particular disorder relating to the acting out of dreams during REM sleep marks some of the degenerative dementia. Sometimes the mental failure is brought to light more dramatically by a severe confusional state attending a febrile illness, a concussive head injury, an operative procedure, or the administration of some new medicine, as discussed below and in Chap. 20. As noted there, the family almost uniformly, but mistakenly, dates an abrupt onset of dementia to the time of the intercurrent illness.

Loss of social graces and indifference to social customs may occur, but usually later in the course of illness. Judgment becomes impaired, early in some, late in others. At certain phases of the illness, suspiciousness or frank paranoia may develop. Although more typical of advanced cases, on occasion the first indication of an oncoming dementia is the expression of paranoia—for example, relating to being robbed by employees or to the infidelity of a spouse. When the patient’s condition is probed by an examination, there are no signs of depression, hallucinations, or illogical ideas, but memory and problem solving are found to be deficient. The troublesome paranoid ideas then persist throughout the illness. Also more typical of late disease but an early feature of certain degenerative dementias, visual and auditory hallucinations, sometimes quite vivid in nature, may be added. Wandering, pacing, and other aimless activities are common in the intermediate stage of the illness, while other patients sit placidly for hours. By this point, these patients have little or no realization of the changes occurring within themselves; i.e., they lack insight into the problem.

As the condition progresses, all intellectual faculties become impaired; but in the most common degenerative diseases, memory is most affected. Deference to a spouse or child when the patient is unable to answer the examiner’s questions is characteristic. Up to a certain point in the illness, memories of the distant past are relatively well retained at a time when more recently acquired information has been lost (Ribot’s law). Eventually, patients also fail to retain remote memories, to recognize their relatives, and even to recall the names of their children.

Apraxias and agnosias are early and prominent in one special group of degenerative conditions, occurring only later in Alzheimer disease. These defects may alter the performance of the simplest tasks, such as preparing a meal, setting the table, or even using the telephone or a knife and fork, dressing, or walking. Or, language functions are impaired almost from the beginning of certain forms of dementia. Lost in these cases is the capacity to understand nuances of the spoken and written word, as are the suppleness and spontaneity of verbal expression. Vocabulary becomes restricted and conversation is rambling and repetitious. The patient gropes for proper names and common nouns and no longer formulates ideas with well-constructed phrases or sentences. Instead, there is a tendency to resort to clichés, stereotyped phrases, and exclamations, which hide the underlying defect during conversation. Paraphasias and difficulty in comprehending complex conversations become prominent. Subsequently, more severe degrees of aphasia, dysarthria, palilalia, and echolalia may be added to the clinical picture. As pointed out by Chapman and Wolff, there is loss also of the capacity to express feelings, to suppress impulses, and to tolerate frustration and restrictions.

However, several clinical variants of dementia in which memory is relatively spared have long been recognized, and in recent years three of them—frontotemporal dementia (Pick disease), primary progressive aphasia, and semantic dementia—have been subsumed under the summary term frontotemporal lobar degeneration. Several consensus statements on the clinical diagnostic criteria for these syndromes have been published, although not all writings on this subject are in agreement (see Morris).

The most common clinical syndrome in this group is characterized by features that would be expected of degeneration of the frontal lobes: early personality changes, particularly apathy or disinhibition, euphoria, perseveration in motor and cognitive tasks, ritualistic and repetitive behaviors, and laconic speech leading to mutism—all with relative preservation of memory, orientation, and visuospatial capability. With anterior temporal lobe involvement, hyperorality, excessive smoking, or overeating occur, and there may be added anxiety, depression, and anomia. Diminished capacity for abstraction, attention, planning, and problem solving may be observed as the degenerative process continues. These are subsumed under the term disorders of “executive functions.” To these features in some patients is added a parkinsonian syndrome.

In the advanced stages of some dementias, restraining the patient leads to disagreeable behavior, petulance, agitation, shouting, and whining. Well known to physicians is nighttime confusion and inversion of the normal sleep pattern, as well as increased confusion and restlessness in the early evening (“sundowning”), as described in Chap. 20. Any febrile illness, drug intoxication, anesthesia, surgery, or metabolic upset is poorly tolerated, leading to severe confusion and even stupor—an indication of the precarious state of cerebral compensation.

It would be an error to think that the abnormalities in the degenerative dementing diseases are confined to the intellectual sphere. The patient’s appearance and the physical examination yield highly informative data. The first impression is often revealing; the patient may be unkempt and unbathed. He may look bewildered, as though lost, or his expression may be vacant, and he does not maintain a lively interest or participate in the interview. There is a kind of psychic inertia. Movements may be slightly slow, sometimes suggesting an oncoming parkinsonian syndrome.

Sooner or later, gait is characteristically altered in many of the dementias (Chap. 7). Passive movements of the limbs encounter a fluctuating resistance or paratonia (gegenhalten). Mouthing movements and a number of abnormal reflexes—grasping and sucking (in response to visual as well as tactile stimuli), inability to inhibit blink on tapping the glabella, snout reflex (protrusion of the lips in response to perioral tapping), biting or jaw clamping (bulldog) reflex, corneomandibular reflex (jaw clenching when the cornea is touched), and palmomental reflex (retraction of one side of the mouth and chin caused by contraction of the mentalis muscle when the thenar eminence of the palm is stroked)—all occur with increasing frequency in the advanced stages of the dementia. Many of these abnormalities are considered to be motor disinhibitions that appear when the premotor areas of the brain are involved.

In the very later stages, physical deterioration is inexorable. Food intake, which may be increased at the onset of the illness, sometimes to the point of gluttony, is in the end reduced, with resulting emaciation. Finally, these patients remain in bed most of the time, oblivious of their surroundings, and succumb at this stage to pneumonia or some other intercurrent infection. Some patients, should they not die in this way, become virtually decorticate—totally unaware of their environment, unresponsive, mute, incontinent, and adopting a posture of flexion. They lie with their eyes open but do not look about. Food and drink are no longer requested but are swallowed if placed in the patient’s mouth. The term persistent vegetative state is appropriately applied to these patients, although it was originally devised to describe patients in this inert state after cardiac arrest or head injury. Occasionally, diffuse choreoathetotic movements or random myoclonic jerking can be observed, and seizures occur in a few advanced cases. Pain or an uncomfortable posture goes unheeded. The course of the prototype of dementia, Alzheimer disease, extends for 5 to 10 years or more from the time that the memory defect becomes evident. The clinical course of advanced dementia has been studied by Mitchell and colleagues in nursing homes. Those who acquired pneumonia, a febrile episode or an eating disorder, not surprisingly, had high rates of mortality, approaching half, in the subsequent 6 months.

Naturally, every case does not follow the exact sequence outlined here. Often, a patient is brought to the physician because of an impaired facility with language. In other patients, impairment of memory with relatively intact reasoning power may be the dominant clinical feature in the first months or even years of the disease; or low impulsivity (apathy and abulia) may be the most conspicuous feature, resulting in obscuration of all the more specialized higher cerebral functions. Gait disorder, although usually a late development, may occur early, particularly in patients in whom the dementia is associated with or superimposed on frontal lobe degeneration, Parkinson disease, normal pressure hydrocephalus, cerebellar ataxia, or progressive supranuclear palsy. Insofar as the types of degenerative disease do not affect certain parts of the brain equally, it is not surprising that their symptomatology varies. Moreover, frank psychosis with delusions and hallucinations may be woven into the dementia and are particularly characteristic of certain diseases such as Lewy-body dementia. Chapter 39 discusses these variations and others more fully.

The aforementioned alterations of intellect and behavior are the direct consequence of neuronal loss in certain parts of the cerebrum. In other words, the symptoms are the primary manifestations of neurologic disease. However, some symptoms are secondary; i.e., they may represent the patient’s reactions to his mental incapacity. For example, a demented person may seek solitude to hide his affliction and thus may appear to be asocial or apathetic. Again, excessive orderliness may be an attempt to compensate for failing memory; apprehension, gloom, and irritability may reflect a general dissatisfaction with a necessarily restricted life. According to Goldstein, who has written about these “catastrophic reactions,” as he calls them, even patients in a state of fairly advanced deterioration are still capable of reacting to their illness and to persons who care for them.

In the early and intermediate stages of the illness, special neuropsychologic tests aid in the quantitation of some of these abnormalities, as indicated in the later part of this chapter.

Subcortical Dementia and Dementias Associated with Diseases of the Basal Ganglia

McHugh, who introduced the concept of subcortical dementia, pointed out that the cognitive decline of certain predominantly basal ganglionic diseases—such as progressive supranuclear palsy, Huntington chorea, and Parkinson disease—is different in several respects from the cortical dementia of Alzheimer disease. In addition to the obvious disorders of motility and involuntary movements, there are degrees of mild forgetfulness, slowed thought processes, lack of initiative, and depression of mood. Relatively spared, however, are vocabulary, naming, and praxis. By contrast, the “cortical dementias” (exemplified by Alzheimer disease) are distinguished by more severe disturbances of memory, language, and calculation, prominent signs of apraxia and agnosia, and impaired capacity for abstract thought.

The pathologic changes underlying the subcortical dementias predominate in the basal ganglia, thalamus, rostral brainstem nuclei, and mostly, in the ill-defined projections in the white matter from these regions to the cortex, particularly of the frontal lobes; however, it would be overly simplistic to attribute the dementia to changes in these areas. One of the problems with the concept of subcortical dementia is the name itself, implying as it does that symptoms of dementia are ascribed to lesions confined to subcortical structures. Anatomically, none of the neurodegenerative dementias is strictly cortical or subcortical. The attribution of dementia to subcortical gliosis, for example, has almost always proved to be incorrect; invariably there are cortical neuronal changes as well. In a similar way, the changes of Alzheimer disease may extend well beyond the cerebral cortex, involving the striatum, thalamus, and even cerebellum. Also, functionally, these lesions produce their effects by interrupting neural links to the frontal and other parts of the cerebral cortex. Similar ambiguity arises when one considers the dementias caused by Lewy-body disease (probably second in frequency only to Alzheimer disease) and by normal-pressure hydrocephalus; here there are parkinsonism and dementing features that could be construed as both cortical and subcortical in nature.

Certain authors, notably Mayeux and Stern and their colleagues as well as Tierney and coworkers, have been critical of the concept of subcortical dementia. They argue that the distinctions between cortical and subcortical dementias are not fundamental and that any differences between them are probably attributable to differences in the relative severity of the dementing processes. Nonetheless, a number of studies do indeed indicate that the constellations of cognitive impairments in the two groups of dementias differ along the lines indicated earlier (see Pillon et al). And, the clinical distinction between cortical and subcortical dementia based on a relative sparing of core cortical functions is very useful.

Pathogenesis of Dementia

Attempts to relate the impairment of general intellectual function to lesions in certain parts of the brain or a particular pathologic change have been largely unsuccessful. Lashley’s concept of loss of intelligence in proportion to brain damage has already been mentioned. This is not to say that certain parts of the cognitive apparatus are not localizable. It is the integrated capacity to think that defies easy attribution to a part of the brain. Two types of difficulty have obstructed progress in this field. First, there is the problem of defining and analyzing the nature of the intellectual functions as already discussed. Second, the pathologic anatomy of the dementing diseases is often so diffuse and complex that it cannot be fully localized and quantitated.

As described in Chap. 22, certain portions of the intellectual ensemble are controlled by circumscribed regions of the cerebrum. Memory impairment, which is a central feature of some dementias, may occur with extensive disease in several different parts of the cerebrum, but the integrity of certain discrete parts of the diencephalon and inferomedial parts of the temporal lobes is fundamental to memory. In a similar way, impairment of language function is associated specifically with disease of the dominant cerebral hemisphere, particularly the perisylvian parts of the frontal, temporal, and parietal lobes. Loss of capacity for reading and calculation is related to lesions in the posterior part of the left (dominant) cerebral hemisphere; loss of use of tools and imitation of gestures (apraxias) is related to loss of tissue in the dominant parietal region. Impairment in drawing or constructing simple and complex figures with blocks, sticks, picture arrangements, etc., is observed with parietal lobe lesions, more often with right-sided (nondominant) than with left-sided ones. And problems with modulation of behavior and stability of personality are generally related to frontal lobe degeneration. Thus, the clinical picture resulting from cerebral disease depends in part on the extent of the lesion, i.e., the amount of cerebral tissue destroyed, and in part on the region of the brain that bears the brunt of the pathologic change.

Dementia of the degenerative types

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