Dementia, a clinical syndrome, can be produced by numerous pathological states that affect the brain. These pathological states can be divided into those that appear, on the basis of our present knowledge, to be primary in the brain, such as Alzheimer's disease or Pick's disease, and those which are outside the brain and affect it secondarily, such as the encephalitides or exogenous intoxications. A clinically useful division of dementia-producing pathological states is made into those that are progressive or fixed, such as Alzheimer's disease and hypoxic-ischemic encephalopathy of cardiac arrest, and those that are arrestable or reversible, such as chronic subdural hematoma or myxedema.
Some pathological states, if allowed to run their course, result inevitably in dementia; others may never go on to dementia or may produce only fragments of the dementia syndrome. Frequently, more than one pathological cause is operating to produce the dementia in an individual patient. The commonest example of this is the person with a progressive degenerative dementia who is taking an excess of a psychoactive medication that is having a potentiating effect upon the primary process.
The investigation of the patient is determined by these nosological considerations. The physician initially seeks out those causes of dementia that can be arrested or reversed. They may be found in all the classical categories of disease: intoxicant, infectious, metabolic, nutritional, vascular, neoplastic, genetic, and traumatic.
Intoxications may result from medication or from nonmedication chemicals deliberately or accidentally ingested. Medications capable of producing dementia include the increasingly large number of neuroactive and psychoactive agents, the opiate analgesics, and the adrenocortical steroids. These are the obvious ones; however, even less obvious, frequently used medications may cause or aggravate dementia: anticholinergic preparations such as are used in movement disorders, allergic reactions, or gastrointestinal disorders; drugs used for cardiovascular purposes, such as antihypertensives; and even digitalis and its derivatives. Finally, multiple drugs in combination may have more than an additive effect. Virtually all of the chemicals used in substance abuse from heroin to glue are capable of producing dementia. Other exogenous chemicals include carbon monoxide, carbon disulfide, lead, mercury, and manganese.
Any of these intoxicants, of whatever sort, may have lethal or irreversible consequences, but they are high on the list of the common causes of arrestable or reversible diseases that affect the central nervous system.
Any infection capable of involving the brain is capable of producing a dementing illness. Many cases of dementia are prevented from happening in the first place by the effective treatment of leptomeningitis and encephalitis, whether caused by bacteria, fungi, protozoa, or viruses. Chronic infectious processes, such as can be caused by bacteria (Whipple's disease), protozoa (syphilis), or fungi (cryptococcus), affect the brain in such a way that the process is reversible and arrestable, at least to a degree. Certain chronic viral illnesses, such as human immunodeficiency virus, are known to produce dementia with great frequency, but it is not known whether the agents that retard the process of AIDS will arrest or reverse the changes in the nervous system that lead to dementia. The agents responsible for conditions like Creutzfeldt-Jakob disease and progressive multifocal leukoencephalopathy are so far resistant to any kind of treatment.
Postinfectious encephalomyelitis, such as follows the viral exanthems, infrequently may produce enough damage to leave the patient demented.
Chronic diseases, tumorous or nontumorous, of thyroid, parathyroid, adrenals, and pituitary are subject to easy identification and generally are reversible. Pulmonary disease produces a dementia consequent upon hypoxia or hypercarbia. The encephalopathies of renal failure and hepatic failure respond up to a point to measures directed at underlying causes. The diabetic becomes vulnerable to a multitude of metabolic mechanisms related to the disease or to the treatment. It must be remembered that dehydration is the commonest metabolic abnormality of the older person with or without dementia.
A number of hereditary metabolic diseases often associated with dementia make their appearance for the first time in adult life. Examples are Wilson's disease (hepatolenticular degeneration), metachromatic leukodystrophy, the adrenoleukodystrophies, and the neuronal storage diseases.
Thiamine deficiency produces Wernicke-Korsakoff's encephalopathy, out of which may emerge Korsakoff's dementia. The dementia of Korsakoff's, once established, may undergo a degree of remission, but the pathological changes are irreversible. Thiamine deficiency is a preventable nutritional deficiency seen in the context of alcoholism, pernicious vomiting of pregnancy, depression, or any other condition in which this deficiency occurs. There are different mechanisms by which pernicious anemia can produce dementia; not all of them are reversible. Folate deficiency is potentially reversible if recognized early. Pellagra, uncommon in developed countries but still a major problem in some parts of the world, shows a dramatic response to niacin even when the mental changes have been present for a long time.
Management of the underlying states can arrest and sometimes reverse the dementias of cardiovascular origin. Hypertension, especially severe hypertension, is one of the most frequent causes of dementia. By producing cerebral infarctions, large and small, it is the commonest cause of multi-infarct dementia. Other causes are atherosclerosis and arteriosclerosis without hypertension, vasculitis, and emboli from the heart or elsewhere in the vascular system. Cardiac disease also produces dementia by single or repeated episodes of cerebral ischemia and hypoxia due to acute or intermittent disorders of cardiac function.
Chronic occlusion of extracranial arteries leading to the brain does not result in dementia in the absence of infarctions.
Chronic subdural hematoma may produce a dementia by itself, or it may complicate and add to the effects of other causes. It is not uncommon in dementias of older people, where the mode of presentation is often different from that seen in younger people.
Benign tumors of the brain produce dementia depending on their size and location. Notable are those on the orbital surface of the frontal lobe or on the medial surface of the temporal lobe because they may not be associated with other more familiar signs of cerebral tumor. Obstructive hydrocephalus may produce dementia in such benign lesions as cerebellopontine angle neurofibromas.
Malignant tumors of brain frequently produce dementia. Only rarely is the dementia relieved by palliative treatment.
Normal pressure hydrocephalus produces a dementia associated with gait disturbance and urinary and fecal incontinence. It is a rare but frequently discussed condition. Some patients respond dramatically to shunting of the ventriculosubarachnoid reservoir.
Depression may be so severe that it produces a true cognitive deficit that is reversible with successful treatment. Depression commonly is present with other causes of dementia, especially Alzheimer's disease.
The most frequent of the dementing diseases are not arrestable or reversible. They are, as far as it is known, primay in the brain and are divisible into two groups, those with no important neurological findings other than dementia and those with other prominent neurological signs.
Alzheimer's disease is the classical example of the first category. It is the most common of all the dementing diseases, increasing in frequency in the older age groups. Although not diagnosable in life with total certainty, a high probability in diagnosis can be attained by using the criteria established by the NINCDS-ADRDA Work Group of 1984. Pick's disease is the other condition in this category, but it is far less frequent than Alzheimer's.
The second category includes a multitude of diseases of the nervous system in which dementia may or may not occur. They include diseases of the basal ganglia (Parkinson's, Huntington's), of the cerebellum (cerebellar and spinocerebellar degenerations, olivopontocerebellar degeneration), and of the motor neurone (amyotrophic lateral sclerosis). Some have more complicated anatomical distributions: Parkinson's-amyotrophic lateral sclerosis-dementia complex of Guam, progressive supranuclear palsy, progressive subcortical gliosis, and multiple system atrophy. It must be recognized that this is only a partial listing of these diseases. Taken all together, they do not compare with the very great frequency of Alzheimer's disease.
The history is the most important component of the initial evaluation; it should be obtained from both the family and the patient. Family members most responsible for and most often in contact with the patient should be consulted first, followed by other family members, friends, and neighbors. Community health workers, especially nurses and social workers, can provide important and objective information. Wherever possible, previous medical records should be reviewed.