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.
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 is related to obvious structural diseases of the cerebral cortex but the diencephalon and, as mentioned earlier, the basal ganglia are also implicated. Rarely, purely thalamic degenerations may be the basis of a dementia because of the integral relationship of the thalamus to the cerebral cortex, particularly as regards memory. Even when a particular disease disproportionately affects one part of the cerebrum, additional areas are often implicated and contribute to the mental decline. One such important example is found in Alzheimer disease, in which the main site of damage is in the hippocampus, but degeneration of the cholinergic nuclei of the basal frontal region, which project to the hippocampus, greatly augments the deterioration in memory function. Indeed, replacement of this lost cholinergic influence is one of the main approaches to the treatment of the disease.
Arteriosclerotic cerebrovascular disease, which pursues a different course than the neurodegenerative diseases, results in multiple foci of infarction throughout the thalami, basal ganglia, brainstem, and cerebrum, including the motor, sensory, and visual projection areas as well as the association areas. There is no evidence, however, that arteriosclerosis per se, without vascular occlusion and infarction, is a cause of progressive dementia as was thought in previous decades. Undoubtedly, the cumulative effects of recurrent strokes impair the intellect. Usually, but not always, the stroke-by-stroke advance of the disease is apparent in such patients (multi-infarct dementia). More uncertain in our opinion is the notion that a decline in mental function can be attributed to periventricular white matter changes (leukoaraiosis), which are observed on CT and MRI scans of many elderly patients and are presumed to be ischemic in nature (see review of van Gijn). Also, the construct that small strokes exaggerate or in some way biologically produce an Alzheimer neuropathologic process has been uncritically accepted in some quarters. The two processes do seem to coincide more often than chance. The special problem of arteriosclerotic or multi-infarct dementia is discussed in Chap. 34 on cerebrovascular disease.
The lesions of severe cerebral trauma, if they result in dementia, are found in the cerebral convolutions (mainly frontal and temporal poles), corpus callosum, and thalamus. In some cases, there is widespread degeneration of the deep cerebral hemispheres, because of a mechanical disruption of the deep white matter termed axonal shearing. Most traumatic lesions that produce dementia are quite extensive, making localization difficult. Our own experience suggests that the thalamic lesions are critical, but many authorities view the axonal shearing lesions as the primary cause of traumatic dementia. The special problem of chronic traumatic encephalopathy is addressed in Chap. 35.
Mechanisms other than the overt destruction of brain tissue may operate in some cases of dementia. Chronic hydrocephalus, regardless of cause, is often associated with a general impairment of mental function. Compression of the cerebral white matter is probably the main factor, but this has not been settled. The extrinsic compression of one or both of the cerebral hemispheres by chronic subdural hematomas may have the same effect. A diffuse inflammatory process is at least in part the basis of dementia in syphilis, cryptococcosis, other chronic meningitides, and viral infections such as HIV encephalitis, herpes simplex encephalitis, and subacute sclerosing panencephalitis; presumably, there is a loss of some neurons and an inflammatory derangement of function in the neurons that remain. The prion diseases (e.g., Creutzfeldt–Jakob disease) cause a diffuse loss of cortical neurons, replacement gliosis, and spongiform change and produce special patterns of cognitive dysfunction.
The adult forms of leukodystrophy (Chap. 37) also give rise to a dementing state, generally a "subcortical" syndrome with prominent frontal lobe features. Or extensive lesions in the white matter may be the result of advanced multiple sclerosis, progressive multifocal leukoencephalitis, or some of the vascular dementias already mentioned (Binswanger disease and CADASIL [cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy]). Last, several of the metabolic and toxic disorders discussed in Chaps. 37, 40, and 43 may interfere with nervous function over a period of time and create a clinical picture similar, if not identical, to that of one of the dementias. One must suppose in those cases that the altered biochemical environment has affected neuronal function.
Classification of the Dementing Diseases
Conventionally, the dementing diseases have been classified according to cause if known, to the pathologic changes, or more recently, to a genetic mutation. Another, more practical approach, which follows logically from the method by which much of the subject matter is presented in this book, is to divide the diseases into three categories on the basis of the neurologic signs and associated clinical and laboratory signs of medical disease: (1) dementia with medical disease, (2) dementia that is accompanied by other prominent neurologic signs, and (3) dementia as the sole or predominant feature of the illness (Table 21-3). Once it has been determined that the patient suffers from a dementing illness, it must then be decided from the medical, neurologic, and ancillary data into which category the case fits. This classification may at first seem somewhat dated and not based on newer genetic and molecular models, but it is likely to be more useful to the student or physician who must confront the many diseases that cause dementia.
Table 21-3 Bedside Classification of the Dementias ||Download (.pdf)
Table 21-3 Bedside Classification of the Dementias
Diseases in which dementia is associated with clinical and laboratory signs of other medical diseases
Endocrine disorders: hypothyroidism, Cushing syndrome, rarely hypopituitarism, Hashimoto encephalopathy
Nutritional deficiency states: Wernicke–Korsakoff syndrome, subacute combined degeneration (vitamin B12 deficiency), pellagra
Chronic meningoencephalitis: general paresis, meningovascular syphilis, cryptococcosis
Hepatolenticular degeneration—familial (Wilson disease) and acquired
Chronic drug and environmental intoxications (including CO poisoning)
Prolonged hypoglycemia or hypoxia
Paraneoplastic "limbic" encephalitis
Heavy metal exposure: arsenic, bismuth, gold, manganese, mercury
Dialysis dementia (now rare)
Diseases in which dementia is associated with other neurologic signs but not with obvious medical diseases
Invariably associated with other neurologic signs
Huntington chorea (choreoathetosis)
Multiple sclerosis, Schilder disease, adrenal leukodystrophy, and related demyelinative diseases (spastic weakness, pseudobulbar palsy, blindness)
Lipid-storage diseases (myoclonic seizures, blindness, spasticity, cerebellar ataxia)
Myoclonic epilepsy (diffuse myoclonus, generalized seizures, cerebellar ataxia)
Subacute spongiform encephalopathy; Creutzfeldt-Jakob disease; Gerstmann-Sträussler-Scheinker disease (prion, myoclonic dementias)
Cerebrocerebellar degeneration (cerebellar ataxia)
Cerebrobasal ganglionic degenerations (apraxia-rigidity)
Dementia with spastic paraplegia
Progressive supranuclear palsy (falls, vertical gaze palsy)
Amyotrophic lateral sclerosis (ALS) and ALS-Parkinson-dementia complex
Other rare metabolic diseases, including polyglucosan disease and leukodystrophies
Often associated with other neurologic signs
Multiple thrombotic or embolic cerebral infarctions and Binswanger disease
Brain tumor (primary or metastatic) or abscess
Brain trauma, such as cerebral contusions, midbrain hemorrhages, chronic subdural hematoma
Lewy-body disease (parkinsonian features)
Communicating, normal-pressure, or obstructive hydrocephalus (usually with ataxia of gait)
Progressive multifocal leukoencephalitis
Marchiafava-Bignami disease (often with apraxia and other frontal lobe signs)
Granulomatous and other vasculitides of the brain
Diseases in which dementia is usually the only evidence of neurologic or medical diseases
Some cases of AIDS
Progressive aphasia syndromes
Frontotemporal and "frontal lobe" dementias associated with tau deposition, Alzheimer change, or with no specific pathologic alteration
Degenerative disease of unspecified type
Although dementia per se does not indicate a particular disease, certain combinations of symptoms and neurologic signs are more or less characteristic and may aid in diagnosis. The age of the patient, the mode of onset of the dementia, its clinical course and time span, the associated neurologic signs, and the accessory laboratory data constitute the basis of differential diagnosis. It must be admitted, however, that some of the rarer types of degenerative brain disease are at present recognized mainly by pathologic examination or genetic testing. The correct diagnosis of treatable forms of dementia—subdural hematoma, certain brain tumors, chronic drug intoxication, normal-pressure hydrocephalus, HIV (reversible to some extent), neurosyphilis, cryptococcosis, pellagra, vitamin B12 and thiamine deficiency states, hypothyroidism, and other metabolic and endocrine disorders—is, of course, of greater practical importance than the diagnosis of the untreatable ones. Also important is the detection of a depressive illness, which may masquerade as dementia, and chronic intoxication with drugs or chemical agents, both of which are treatable.
The first task in dealing with this class of patients is to verify the presence of intellectual deterioration and personality change. It may be necessary to examine the patient serially before one is confident of the clinical findings and their chronicity. A mild aphasia from a focal brain lesion must not be mistaken for dementia. Aphasic patients appear uncertain of themselves, and their speech may be incoherent. Careful attention to the patient's language performance will lead to the correct diagnosis in most instances. It is a clinical truism that the abrupt onset of mental symptoms points to a delirium or other type of acute confusional state or to a stroke; inattention, perceptual disturbances, and often drowsiness are conjoined (Chap. 20). Also, progressive deafness or loss of sight in an elderly person may sometimes be misinterpreted as dementia.
There is always a tendency to assume that mental function is normal if a patient complains only of anxiety, fatigue, insomnia, or vague somatic symptoms, and to label the patient as anxious. This will be avoided if one keeps in mind that these disorders rarely have their onset in middle or late adult life.
Clues to the diagnosis of depression are the presence of frequent sighing, crying, loss of energy, psychomotor underactivity or its opposite, agitation with pacing, persecutory delusions, persistent hypochondriasis, and a history of depression in the past and in the family. Although depressed patients may complain of memory failure, scrutiny of their complaints will show that they can usually remember the details of their illness and that little or no qualitative change in other intellectual functions has taken place. Their difficulty is either a lack of energy and interest or preoccupation with personal worries and anxiety, which prevents the focusing of attention on anything except their own problems. Even during mental tests, their performance may be impaired by "emotional blocking," in much the same way as the worried student blocks during an examination ("experiential confusion"). When such patients are calmed by reassurance and encouraged to try harder, their mental function improves, indicating that intellectual deterioration has not occurred. Conversely, it is helpful to remember that demented patients rarely have sufficient insight to complain of mental deterioration; if they admit to poor memory, they do so without conviction or full appreciation of the degree of their disability. The physician must not rely on the patient's statements alone in gauging the efficiency of mental function and should seek corroboration from family members. Yet another problem is that of the impulsive, cantankerous, and quarrelsome patient who is a constant source of distress to employer and family. Such changes in personality and behavior (as, for example, in Huntington disease) may precede or mask early intellectual deterioration.
The neuropsychiatric symptoms associated with metabolic, endocrine, or toxic disorders (e.g., Cushing syndrome, vitamin B12 deficiency, hypercalcemia, uremia) may present difficulties in diagnosis because of the wide variety of clinical pictures by which they manifest themselves. Drowsiness or stupor and asterixis are the surest signs of a metabolic or drug-induced encephalopathy, but they are not always present. Psychosis with hallucinations and a great deal of fluctuation in behavior also bespeak an exogenously caused confusional state, with the exception that Lewy-body dementia also has these characteristics. Whenever any such metabolic or toxic disorder is suspected, a thorough review of the patient's medications is crucial. Medications with atropinic activity, for example, can produce an apparent dementia or worsen a structurally based dementia, as discussed in Chap. 20. Occupational exposure to toxins and heavy metals should also be explored, but this is an infrequent cause of dementia; therefore, slight or even moderately elevated levels of these chemicals in the blood should be interpreted cautiously. It is also useful to keep in mind that seizures are not a usual component of the degenerative dementias; when they are present, they generally do not appear until a very late stage.
Once it is decided that the patient suffers from a dementing condition, the next step is to determine by careful physical examination, whether there are other neurologic signs or indications of a particular medical disease. This enables the physician to place the case in one of the three aforementioned categories in the bedside classification (see above and Table 21-3).
Experienced neurologists recognize that certain leading neurologic features are indicative of particular degenerative dementias. For example, prominent and early parkinsonian signs such as bradykinesia, tremor, and shortened gait step are parts of the subcortical dementias of Lewy body and Parkinson diseases. Rigidity of the limbs and apraxia may have a similar clinical appearance but point to corticobasal degeneration as the cause of mental decline. An early aphasia or visuospatial difficulty that is manifest as either geographic confusion or difficulty with drawing, copying, and recognizing faces and objects are characteristic of a focal degeneration of the parietal or inferior temporal lobes. Involuntary movements such as choreoathetosis, dystonia, ataxia, and myoclonus are each signs of particular degenerative disorders that include Huntington disease, acquired and inherited hepatocerebral degenerations, and prion disorder, all of which are discussed in later chapter. Frequent falls and a disorder of vertical eye movements are the core components of progressive supranuclear palsy that often has an attendant dementia. In the nondegenerative categories of dementia, spasticity and Babinski signs are typical of vascular dementias.
Ancillary examinations—such as CT, MRI, electroencephalography (EEG), lumbar puncture, measurement of blood urea nitrogen, as well as serum concentrations of calcium and electrolytes, and liver function tests—should be carried out in appropriate cases. Brain MRI and CT are of major importance in objectifying hydrocephalus, lobar atrophy, cerebrovascular disease, tumor, and subdural hematoma. Testing for syphilis, vitamin B12 deficiency, and thyroid function is also done in many clinics almost as a matter of routine because the tests are simple and the dementias they cause are reversible. These are supplemented in individual circumstances by serologic testing for HIV infection, measurement of copper and ceruloplasmin levels (Wilson disease), heavy metal concentrations in urine or tissues, serum cortisol levels, and drug toxicology screening. The final step is to determine, from the total clinical picture, the particular disease within any one category.