Chapter 16 - Dementia

Dementia refers to a loss of higher intellectual (cognitive) and emotional function. It is a very common problem, particularly in the elderly, and it may go unrecognized for quite some time. Studies indicate that up to 20% or more of persons who have symptoms suggestive of dementia turn out to have treatable illness. About half of them will have psychiatric problems, but the remainder will have treatable organic disease. The proportion of treatable cases is lower the older the population and the more chronic the dementia. However, even in this group a significant number of persons may be helped. The clinical importance of this subject can hardly be exaggerated. Over the age of 65, 5-10% of the population has significant cognitive problems. Over the age of 80 this proportion rises to 15-20%, rising to nearly 40% by age 85. The incidence of dementia is fairly steady from 65 on, but the percentage of individuals with dementia climbs steadily with age due to accumulation. Recent data suggests that here is a possible decline in the incidence of dementia after one reaches the ninth decade. The importance of these statistics becomes immense considering the generally aging population. There were approximately 20 million over 65 in the late 1980's. By 2030, it is estimated that 60-70 million Americans will be over 65. The socio-economic consequences of having 5-10% of this population demented are staggering, particularly given the burden that dementia places on the individual, their families and society.

Is the Patient Demented?

Several problems often arise in trying to decide whether or not a patient is actually demented.

  1. Senescence: Mild defects in memory and other higher cortical functions occur normally with age. One may complain of these, but may be able to perform normally on clinical mental status testing and on formal psychological tests that take this normal deterioration into account. This has been described as mild cognitive impairment (MCI) and, although such patients are at increased risk of full-blown dementia, we have yet to develop a foolproof method for determining who will undergo such progression.
  2. Mental retardation: Because dementia is defined as a loss of function, the history should be adequate to document that the person was once capable of better performance. Educational and occupational histories are valuable in this regard. The patient should be asked at what age they achieved their highest educational grade, to ascertain whether they progressed normally through school.
  3. Psychiatric illness: Mistakes can be made in both directions. Organic illness can mimic many symptoms of psychiatric disease, especially the psychoses; and some psychiatric illness may prevent adequate evaluation of a patient's intellectual functioning. A few rules are useful:

Types of Dementia

Dementia is not a unitary condition. Findings differ greatly among patients, reflecting to a large extent, the regions of the brain involved or the nature of the biochemical insult. Localization of hemispheric function was discussed in Chapter 2.

Loss of recent memory

Loss of recent memory (as tested by a person's ability to remember three items after five minutes of distraction) in the absence of defects of attention (as tested, for example, by the digit span - the ability to repeat 7 numbers forward and 5 numbers backward) is indicative of bilateral lesions in the hippocampi or related structures (fornices, mamillary bodies, dorsomedial thalamus). A limited number of pathologic states, therefore, underlie this type of problem (Table 16-1). Unilateral damage to the hippocampal and adjacent neocortical regions may cause verbal memory defects if the lesion is in the dominant hemisphere. Difficulties learning visuospatial tasks have been seen in persons with damage or removal of the right temporal lobe. The defects with unilateral disease tend to be mild and patients often improve over time, whereas bilateral hippocampal-temporal lobe damage leaves devastating recent memory problems.

Difficulties with remembering ("absent mindedness") are a common complaint over the age of 60 and may represent an age related loss of hippocampal-temporal lobe function. As a rule, this mild and "benign" memory difficulty can be differentiated from pathologic loss of learning capacity. The patient with benign forgetfulness brings him- or herself to see the physician. They can "remember that they cannot remember" (i.e., insight is preserved). The patient with pathological or "malignant" memory loss is unable, as a rule, to imprint new memories and has little insight or concern about the problem (unless very mild). The patient is typically brought to the physician by a concerned family member and is found to have general intellectual deficits in addition to memory problems.

Frontal lobe dementia

Persons with frontal lobe lesions may have significant dementia with no abnormality of recent memory. Often intellectual function is intact on routine testing, but the patient's behavior is inappropriate, frequently disinhibited (see Chap. 2). Later, tests of manipulation of knowledge (calculations, proverbs, similarities) are poorly done. Regressive reflexes, which are often seen in infants but normally suppressed by the frontal lobe in adults (such as grasp reflex, gait apraxia, palmomental reflex, snout reflex, suck reflex) may reappear at this stage.

"Cortical" dementia

Cognitive functions such as language, praxis (the ability to synthesize and sequence motor tasks), and visuospatial functions can be impaired by diseases that affect the cortex, e.g., stroke, Alzheimer disease, frontotemporal dementia, diffuse Lewy body disease and Creutzfeldt-Jacob disease. Often these diseases affect other aspects of hemispheric function, such as memory (temporal lobe) and motivation (frontal lobes).

Subcortical dementia

Dementia can result from diseases that affect mainly subcortical structures. Some clues to this are the presence of severe motor abnormalities, significant difficulties with attention and concentration or improvement of memory with prompting (which usually doesn't happen with cortical disease such as Alzheimer disease). For example, patients with progressive supranuclear palsy (Steele-Richardson-Olchewsky disease, an uncommon disease affecting the midbrain and other subcortical structures) may show a remarkable slowness in performance; tests are performed well only if the patient is given a great deal of time. Often persons with subcortical disease (such as Parkinson disease) have dementias that resemble frontal lobe dementias. Some preliminary studies have shown that patients with Parkinson's who have dementia may have a slowed central reaction time. That is, the time between receiving a command for performance and the motor onset of that performance at the cortical level is delayed even though the performance is ultimately carried out correctly. In some patients with Parkinson disease, however, there is, in fact, diffuse loss of cortical neurons that best explains their more typical diffuse cognitive fall-off. Cortical and subcortical dementias can coexist.

Confusional states

Deficits in maintaining attention may markedly reduce intellectual functioning. Many metabolic dementias (such as hepatic encephalopathy, delirium tremens, and cognitive deficits produced by many drugs) are manifested principally by the inability to attend to important stimuli. Lesions affecting the brain stem or thalamic reticular formation, if insufficient to produce stupor or coma, result in an attentional deficit. In general, these are referred to as confusional states or "encephalopathy."

Organic psychoses

Diseases affecting the limbic system or related structures may produce a wide variety of psychiatric findings. Persons with temporal lobe epilepsy commonly have behavioral disturbances, with hyposexuality, hyper religiosity, and even paranoid psychosis being described as possible interictal phenomena. Temporal lobe lesions or damage to the medial hypothalamus may trigger aggressive behavior, potentially accompanied by changes in appetite for food and sex. Damage to the left frontal lobe often produces depression, while the right frontal lobe can trigger mania. Orbital and medial frontal cortex lesions can markedly alter personality, potentially producing apathy on the one hand, or disinhibition (with socially inappropriate behavior) on the other. Persons with Huntington disease may experience episodes that are indistinguishable from acute paranoid schizophrenia or manic-depressive illness. Diffuse Lewy body disease usually results in vivid hallucinations to go along with dementia. Obviously, the distinction between functional and organic disease can be difficult. It is, therefore, important to look for other indications of organic disease in these persons (for example, fever, incontinence, seizures, focal neurologic signs, regressive reflexes, movement disorders) before referring them for psychiatric care.

Evaluation of the Demented Patient

After having decided that a person is demented, certain features of the history and examination help determine the subsequent evaluation. The following questions are helpful to keep in mind:

  1. Do the mental changes themselves localize the lesions(s)? The important diagnostic points were reviewed earlier in this chapter and in Chapter 2.
  2. Are there associated focal neurologic deficits such as hemiparesis, visual field defects, or sensory changes to suggest focal brain injury?
  3. Are there neurologic deficits suggestive of systems degeneration, for example, chorea, parkinsonism, or cerebellar abnormalities? These might suggest a particular type of degenerative disease (such as Huntington disease, parkinsonism, or spinocerebellar degeneration), or less often, a metabolic problem (such as Wilson's disease or chronic hepatic encephalopathy).
  4. Is there evidence of increased intracranial pressure?
  5. Is confusion or inattention a major part of the picture? Certain findings on the neurologic examination strongly suggest a metabolic deficit. A prominent confusional state is one. Multifocal myoclonus and asterixis are other findings often associated with metabolic encephalopathy.
  6. Are there associated symptoms or signs indicative of a systemic disease, such as a thyroid disorder, Cushing's disease, collagen vascular disease, malignancy, or infection?
  7. Is the patient taking medications that can affect mentation (e.g., antihypertensives, sedatives, neuroleptics, antidepressants, anti-convulsants, etc.)?
  8. Is the course acute or chronic? Most (but not all) irreversible degenerative diseases are chronic. As mentioned, although the chance of finding a reversible etiology are less with the chronic dementias, remediable causes are found in enough patients to merit a complete evaluation.
  9. Are there major fluctuations in performance? While patients with the progressive dementing disorders do have their ups and downs, marked fluctuations in performance suggest the presence of an encephalopathy and increase the chances of finding some treatable factor that will improve performance.

The answers to these general questions determine the sort of evaluation required. If the examination indicates a focal brain lesion, the evaluation should aim to document the lesion (e.g., tumor, stroke, subdural hematoma) and to determine its nature (computerized tomography, magnetic resonance imaging, and if necessary, arteriography). If the examination suggests a metabolic problem (confusion without focal neurologic signs), an intensive search for metabolic derangements should be made before looking for focal lesions or bilateral degenerative disease. This evaluation includes numerous blood studies and a lumbar puncture (to exclude subarachnoid hemorrhage or infection). In the patient in whom there is no obvious clue to the nature of the underlying disease, the screening evaluation outlined in Table 16-2 as indicated. Most of the treatable causes of dementia (listed in Table 16-3) would be excluded on the basis of this evaluation combined with a careful history and physical examination.

Following this evaluation, treatable causes of dementia should have been ruled out; however, there are still a large number of persons for whom a diagnosis has not been made. The vast majority of such patients will have degenerative disease, the most common by far being Alzheimer disease.

Normal-Pressure Hydrocephalus

Although there is little question that this entity exists, its exact pathogenesis is disputed, and there is no agreement about how to select patients for treatment. The entity consists of progressive hydrocephalus, with normal CSF pressure (as determined by lumbar puncture), producing gait disorder, and urinary incontinence and, usually later, dementia. The gait disorder is usually a broad-based gait with a tendency to fall backward. These patients tend to slide their feet along the floor (sometimes described as "robotic", "glue-footed", or "magnetic") rather than picking them up and going through the normal heel-to-toe gait cycle (gait apraxia). The incontinence is also usually somewhat unusual in that it results in the loss of large volumes of urine without any warning. Reducing the hydrocephalus with ventriculoatrial or ventriculoperitoneal shunts improves the clinical picture. However, since this procedure has significant morbidity in the elderly, selection of patients for this procedure is problematic.

About half of patients with NPH have a history of subarachnoid hemorrhage, trauma or meningeal infection. In these cases, presumably blood or proteinaceous fluid has blocked the normal flow of CSF. In the rest of cases, no such predisposition is historically apparent. The normal CSF pressure is difficult to explain. In some patients, the CSF pressure fluctuates; although a single lumbar puncture may show normal pressure, 24-hour monitoring demonstrates abnormally high-pressures some of the time, or persistently high normal pressures. According to Poiseuille's Law, pressure should actually be low in patients with large ventricles. Therefore, it is possible that the pressure it too high for the size of the ventricles.

To make the diagnosis, the examiner should be able to document the presence of hydrocephalus, the absence of severe cortical atrophy, and inadequate reabsorption of spinal fluid. Computerized tomography (CT) or magnetic resonance imaging (MRI), will adequately assess ventricular size and cortical atrophy. Two tests are available to assess CSF flow: cisternography and the CSF infusion test. These are described in Chapter 11. Withdrawing 40-50 cc of spinal fluid has been shown to acutely and temporarily improve gait and continence in some patients with NPH. Such a finding would confirm the diagnosis and predict a positive response to a permanent shunt. However, these tests are not terribly sensitive and, therefore, there are no absolute guidelines are available for patient selection. The appearance of the patient (i.e., a typical picture of gait apraxia, incontinence and mild dementia), the tempo of the illness, the history of predisposing causes, and the results of these tests must all be considered and weighed against the possible complications of shunting (infection, embolization, shunt failure, subdural hematoma, and effusion).

Multi-infarct dementia

Approximately 20% of patients with dementia will ultimately be shown to have multi-infarct dementia, the result of multifocal small artery occlusive disease. A history of acute episodes of focal dysfunction superimposed on progressive dementia in a person with appropriate risk factors for vascular disease (hypertension, smoking history, diabetes mellitus, hyperlipidemia, obesity, etc.) and the presence of focal dysfunction(s) on examination are strong support for the diagnosis. Magnetic resonance imaging (MRI) will show the typical bilateral multifocal small areas of attenuation deep in the hemispheres. Treatment consists of attending to the risk factors when possible. Anticoagulation with antiplatelet agents such as aspirin may be useful prophylaxis. The use of antithrombic agents (such as Coumadin) has not been proven effective outside of the setting of cardioembolism and may be too risky in a demented patient (due to increased chance of falling and hemorrhage). In the special case of the quite rare cerebral vasculitis, treatment may be able to arrest the underlying condition. Of course, preventing more strokes does not result in resolution of the dementia (although there may be some improvement due to compensation).

Alcohol

Surprisingly, chronic alcoholism and its associated nutritional deficiencies, plus a probable direct toxic effect of alcohol upon neurons, is an often overlooked cause of dementia in our society. Chronic alcoholics, of whom there are approximately ten to eleven million in the United States, show deficits in frontal lobe function when carefully tested. This is in the absence of significant blood alcohol levels which, when present, markedly amplify the defects. This is a preventable and treatable dysfunction, although reversibility of the chronic state is likely to only be partial. The end stage Wernicke-Korsakoff Syndrome (see Table 16-3) or, for that matter, acute alcoholic cerebellar degeneration are only partially and inadequately reversible in most cases.

Reference

Questions

Define the following terms:

dementia, Alzheimer disease, amnesia, Creutzfeldt-Jacob disease, Huntington's disease, transcortical aphasia, dysinhibition, paratonia, gait apraxia, palmomental reflex, grasp reflex.
Dementia is a diffuse loss of cortical function.
Alzheimer disease is a cortical degenerative condition characterized by senile (amyloid) plaques and neurofibrillary tangles mostly affecting the temporal and parietal lobes.
Amnesia is a loss of memory.
Creutzfeldt-Jacob disease is an infectious condition due to prion proteins. It is characterized by subacute dementia, often accompanied by startle myoclonus, ataxia and cortical blindness.
Huntington's disease is an autosomal dominant hereditary disease characterized by choreoathetosis, behavioral symptoms and dementia.
Transcortical aphasia is a form of aphasia often seen in Alzheimer's disease in which repetition is spared but the ability to name objects presented to the patient (confrontational naming) is impaired.
Dysinhibition is a loss of normal inhibition of certain behavioral responses or reflexes.
Paratonia (gegenhalten) is an involuntary, irregular resistance to passive movements. It is a soft sign of cerebral cortical dysfunction.
Gait apraxia is an inability to generate the normal patterns of gait. The gait becomes simple with sliding the feet along the floor, and is described as "robotic" or "glue-footed." There may ultimately be retropulsion.
Palmomental reflex this is a primitive reflex in which scratching the palm results in wrinkling of the chin on that side. It is a soft sign of cerebral cortical dysfunction.
Grasp reflex is a primitive reflex (present in very young children) in which the fingers involuntarily flex when the palm is stroked, It is a sign of frontal cortical dysfunction.

16-1. What is a good working definition of dementia?

Answer 16-1. Dementia is defined as diffuse loss of cortical functions. By definition, there must be more than one cognitive function lost.

16-2. How can you test for the presence of dementia?

Answer 16-2. Testing involves various neuropsychological measures that define the loss of more than one type of cortical functions (not just memory, for example).

16-3. Are there any physical exam findings in dementia?

Answer 16-3. There may be some "soft" physical findings of frontal lobe damage (grasp reflex, gait apraxia, palmomental reflex, snout reflex, suck reflex) or diffuse cortical loss (paratonia, problems with upgaze).

16-4. What are the two basic types of dementia?

Answer 16-4. Dementia may be due to diffuse loss of cortical neurons (so-called "cortical dementia") or damage to subcortical structures ("subcortical dementia") that project to the cerebral cortex.

16-5. What is the most common cause of dementia?

Answer 16-5. The most common cause is Alzheimer's disease. It is very common, reaching about 40-50% of the population by age 85.

16-6. What is the second most common cause of dementia?

Answer 16-6. Multi-infarct dementia is the second most common cause of dementia.

16-7. What is the pathology of Alzheimer disease?

Answer 16-7. Neurofibrillary tangles and senile plaques, usually most prominent in the temporal lobes (and hippocampi) and parietal lobes.

16-8. What language problems are found in Alzheimer's disease?

Answer 16-8. Patients often have transcortical dysphasia (can repeat complex phrases but trouble with naming objects).

16-9. What are the characteristics of multi-infarct dementia?

Answer 16-9. There is usually stepwise deterioration in function (with strokes) and there may be specific areas of damage such as aphasia, hemianopsia, etc.

16-10. What are the characteristics of Creutzfeldt-Jacob disease?

Answer 16-10. Creutzfeldt-Jacob disease (akin to Bovine Spongiform Encephalopathy - mad cow disease) is rapidly progressive over months. It is due to a prion protein. There are symptoms of dementia with ataxia early on. Other signs may include amyotrophy and cortical blindness. Later on there are severe myoclonic jerks (often produced by startle).

16-11. What diagnostic tests are there for Creutzfeldt-Jacob disease?

Answer 16-11. The only definitive diagnosis is brain biopsy although recently it is possible to measure prion proteins in spinal fluid. The EEG may be helpful (regular, 1 per second triphasic waves).

16-12. What is Huntington's disease?

Answer 16-12. Huntington's disease is an autosomal dominant hereditary disease due to expansion of CAG repeats. Progressive symptoms may arise at any age (most common in middle age). The symptoms include the triad of choreoathetosis, behavioral symptoms and dementia. Movements and behaviors may improve slightly with neuroleptics (dopamine blockers), but there is definitive therapy.

16-13. What is normal pressure hydrocephalus (NPH)?

Answer 16-13. Normal pressure hydrocephalus (NPH) presents with gait disorder (ataxia), incontinence, and dementia, progressive over months. Dementia is usually the last symptoms to develop. The gait is apraxic (glue-footed, magnetic, robotic).

16-14. How can you diagnose normal pressure hydrocephalus (NPH)?

Answer 16-14. History and physical exam are paramount. There is a normal LP opening pressure. Imaging shows panventriculomegaly on CT or MR scan without prominent cortical atrophy. CSF drainage procedure (15-30 cc) followed by improved gait and bladder control is the best predictor of good response to therapy (shunting of CSF). The condition may be idiopathic or it may result from sequellae of bacterial meningitis, subarachnoid hemorrhage. Ventricular or lumbar shunt may help (50% improve; 40% morbidity).

16-15. What are some treatable causes of diffuse cortical dysfunction (dementia)?

Answer 16-15. Most common treatable causes include depression ("pseudodementia"), thyroid dysfunction, metabolic encephalopathy secondary to medications, hypoxia, nutritional deprivation, or dehydration (electrolyte and fluid imbalances). Rarely, it may be caused by: B12, thiamine or folic acid deficiency, anemia, subdural hematoma (usually bilateral), tumor, hyperlipidemia, chronic meningitis (cryptococcal, syphilitic), demyelinating disease, normal pressure hydrocephaly.
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