“Dementia” is defined in DSM-IV-TR as a group of disorders characterized by the development of multiple cognitive deficits (including memory impairment) that are due to the direct physiologic effects of a general medical condition, the persisting effects of a substance, or multiple etiologies (e.g., the combined effects of a metabolic and a degenerative disorder). The disorders constituting the dementias share a common symptom presentation and are identified and classified on the basis of etiology.

The cognitive deficits exhibited in these disorders must be of sufficient severity to interfere with either occupational functioning or the individual’s usual social activities or relationships. In addition, the observed deficits must represent a decline from a higher level of functioning and not be the consequence of a delirium. A delirium can, however, be superimposed on a dementia, and both can be diagnosed if the dementia is observed when the delirium is not in evidence. Dementia is typically chronic and occurs in the presence of a clear sensorium. If clouding of consciousness occurs, the diagnosis of delirium should be considered. Classifications of dementia are considered in Box 17.1.

17.2.1 Prevalence

The prevalence of dementias is not precisely known. Estimates vary depending on the age range of the population studied and whether the individuals sampled were in the general community, acute care facilities, or long-term nursing institutions.

17.2.2 Symptoms

Essential to the diagnosis of dementia is the presence of cognitive deficits that include memory impairment and at least one of the following abnormalities of cognition: aphasia, agnosia, apraxia, or a disturbance in executive function. In addition to defects in memory, patients with dementia often exhibit impairments in language, recognition, object naming, and motor skills. Aphasia is an abnormality of language that often occurs in vascular dementias involving the dominant hemisphere. Because this hemisphere controls verbal, written, and sign language, these individuals may have significant problems interacting with people in their environment. People with dementia and aphasia may exhibit paucity of speech, poor articulation, and a telegraphic pattern of speech (nonfluent, Broca’s aphasia). Despite faulty communication skills, patients with dementia with nonfluent aphasia have normal comprehension and awareness of their language impairment. As a result, such individuals often present with significant depression, anxiety, and frustration.

By contrast, patients with dementia with fluent (Wernicke’s) aphasia may be quite verbose and articulate, but much of the language is nonsensical and rife with such paraphasias as neologisms and clang (rhyming) associations. Whereas nonfluent aphasias are usually associated with discrete lesions, fluent aphasia can result from such diffuse conditions as dementia of the Alzheimer type. More commonly, fluent aphasias occur in conjunction with vascular dementia secondary to a temporal-lobe or parietal-lobe cerebrovascular accident (CVA). Because the demented patients with fluent aphasia have impaired comprehension, they may seem apathetic and unconcerned with their language deficits, if they are in fact aware of them at all. They do not generally display the emotional distress of patients with dementia and nonfluent aphasia.

Patients with dementia may also lose their ability to recognize. Agnosia is a feature of a dominant hemisphere lesion and involves altered perception in which, despite normal sensations, intellect, and language, the patient cannot recognize objects. This is in contrast to aphasia in which the patient with dementia may not be able to name objects, but can recognize them. The type of agnosia depends on the area of the sensory cortex that is involved. Some demented patients with severe visual agnosia cannot name objects presented, match them to samples, or point to objects named by the examiner. Other patients may present with auditory agnosia and be unable to localize or distinguish such sounds as the ringing of a telephone. A minority of demented patients may exhibit astereognosis, the inability to identify an object by palpation.

Demented patients may also lose their ability to carry out selected motor activities despite intact motor abilities, sensory function, and comprehension of the assigned task (apraxia). Affected patients cannot perform such activities as brushing their teeth, chewing food, or waving goodbye when asked to do so.

The two most common forms of apraxia in demented individuals are ideational and gait apraxia. Ideational apraxia is the inability to perform motor activities that require sequential steps and results from a lesion involving both frontal lobes or the complete cerebrum. Gait apraxia, often seen in such conditions as normal-pressure hydrocephalus, is the inability to perform various motions of ambulation. It also results from conditions that diffusely affect the cerebrum.

Impairment of executive function is the inability to think abstractly, plan, initiate, and end complex behavior. On Mental Status Examination (MSE), patients with dementia display problems coping with new tasks. Such activities as subtracting serial sevens may be impaired.

Clearly, aphasia, agnosia, apraxia, and impairment of executive function can seriously impede the demented individual’s ability to interact with his or her environment. An appropriate MSE of the patient with suspected dementia should include screening for the presence of these abnormalities.

Patients with dementia display other identifying features that often prove problematic. Poor insight and poor judgment are common in dementia and often cause individuals to engage in potentially dangerous activities or make unrealistic and grandiose plans for the future. Visual–spatial functioning may be impaired, and if patients have the ability to construct a plan and carry it out, suicide attempts can occur. More common is unintentional self-harm resulting from carelessness, undue familiarity with strangers, and disregard for the accepted rules of conduct.

Emotional lability, as seen in pseudobulbar palsy after cerebral injury, can be particularly frustrating for caregivers, as are occasional psychotic features such as delusions and hallucinations. Changes in their environment and daily routine can be particularly distressing for demented patients, and their frustration can be manifested by violent behavior.

17.2.3 Course

The course of a particular dementia is influenced by its etiology. Although historically the dementias have been considered progressive and irreversible, there is, in fact, significant variation in the course of individual dementias. The disorder can be progressive, static, or remitting. In addition to the etiology, factors that influence the course of the dementia include: the time span between the onset and the initiation of prescribed treatment; the degree of reversibility of the particular dementia; the presence of comorbid psychiatric disorders; and the level of psychosocial support.

The earlier distinction between “treatable” and “untreatable” dementias has been replaced by the concepts of “reversible,” “irreversible,” and “arrestable.” Most reversible cases of dementia are associated with shorter duration of symptoms, mild cognitive impairment, and superimposed delirium. Specifically, the dementias caused by drugs, depression, and metabolic disorders are most likely to be reversible. Other conditions such as normal-pressure hydrocephalus, subdural hematoma, and tertiary syphilis are more commonly arrestable.

Although potentially reversible dementias should be aggressively investigated, in reality only 8% of dementias are partially reversible and about 3% fully reversible. There is some evidence to suggest that early treatment of demented patients, particularly those with Alzheimer type, with agents such as donepezil (which acts as an inhibitor of acetylcholinesterase) and galanthamine may slow the rate of progression of the dementia – although some investigators doubt the ability of these agents to slow the rate of progression.

17.2.4 Differential Diagnosis

Memory impairment occurs in a variety of conditions including delirium, amnestic disorders, and depression. In delirium, the onset of altered memory is acute and the pattern typically fluctuates (waxing and waning) with increased proclivity for confusion during the night. Delirium is more likely to feature autonomic hyperactivity and alterations in level of consciousness. In some cases a dementia can have a superimposed delirium.

Patients with major depression often complain of lapses in memory and judgment, poor concentration, and seemingly diminished intellectual capacity. Often these symptoms are mistakenly diagnosed as dementia, especially in elderly populations. A thorough medical history and MSE focusing on symptoms of hopelessness, crying episodes, and unrealistic guilt in conjunction with a family history can be diagnostically beneficial.

The term pseudodementia has been used to denote cognitive impairment secondary to a psychiatric disorder, most commonly depression. In comparison with demented patients, those with depressive pseudodementia exhibit better insight regarding their cognitive dysfunction, are more likely to give “I don’t know” answers and may exhibit neuro-vegetative signs of depression. Pharmacologic treatment of the depression should improve the cognitive dysfunction as well.

An amnestic disorder also presents with a significant memory deficit, but without the other associated features such as aphasia, agnosia, and apraxia. If cognitive impairment occurs only in the context of drug use, substance intoxication or substance withdrawal is the appropriate diagnosis. Although mental retardation implies below-average intellect and subsequent impairment in other areas of function, the onset is before 18 years of age and abnormalities of memory do not always occur. Mental retardation must be considered in the differential diagnosis of dementias of childhood and adolescence along with such disorders as Wilson’s disease (hepatolenticular degeneration), lead intoxication, subacute sclerosing panencephalitis, HIV spectrum disorders, and substance abuse (particularly abuse of inhalants).

Patients with schizophrenia may also exhibit a variety of cognitive abnormalities, but this condition also has an early onset and a distinctive constellation of symptoms, and it does not result from a medical condition or the persisting effects of a substance.

Factitious disorder must be distinguished from dementia. Unlike dementia, this condition presents with inconsistent symptoms that, although similar in some respects, are not totally consistent with those of a dementia. For example, a patient with factitious disorder with psychological symptoms (in this case dementia) might have equal impairment in all phases of memory, while patients with dementia usually have better remote than recent memory.

Dementia must also be distinguished from benign senescence (normal aging). Only when such changes exceed the level of altered function to be expected for the patient’s age is the diagnosis of dementia warranted.

Alzheimer’s disease is the most common cause of dementia, accounting for 55–65% of all cases. The etiology and pathogenesis of Alzheimer’s disease are unknown.

17.3.1 Biological Features

The brains of patients with Alzheimer’s disease contain many senile plaques, neurofibrillary tangles, and Hirano’s bodies. There is degeneration of nerve cells, but the significant atrophy seen on neurodiagnostic examination may be more the result of shrinkage of neurons and loss of dendritic spines than of actual neuronal loss. The atrophy is most apparent in the associational cortex areas, and early on the primary motor and sensory areas are relatively spared. Significant degenerative changes in neurons are seen in the hippocampus, locus ceruleus, and nucleus basalis of Mynert. With advancing disease these changes, in effect, separate the hippocampus from the remainder of the brain. Initially, the parietal and temporal regions are most affected by plaques and tangles, accounting for the memory impairment and syndromes sometimes associated with the parietal lobe and Alzheimer’s disease (some apraxias, hemi-attention, anosognosia, Gerstmann’s syndrome).