INTRODUCTION
Dementia is a common disorder with a prevalence that doubles every 5 years after the age of 60 years, thereby affecting up to 45% of those aged 85 years and older. Dementia is defined as an acquired, persistent, and usually progressive impairment in intellectual function, with compromise in multiple cognitive domains, at least one of which is memory. The deficits must represent a significant decline in function, and must be severe enough to interfere with work or social life for the diagnosis to be formally applied. As the disorder progresses, individuals with dementia often fail to recognize family members, are unable to express themselves clearly and meaningfully, and often undergo dramatic personality changes. Table 30-1 lists some of the more common causes of dementia.
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Despite the high prevalence of dementia, the diagnosis is often missed by clinicians, particularly in the early stages. The primary care practitioner can play an important role in diagnosing and treating dementia. An early diagnosis can offer the opportunity to involve patients in meaningful advance care planning while they are still able to express their preferences clearly. In addition, potentially treatable causes, though rare, are more likely to be partially or fully reversed if diagnosed early. Later in the disease, the practitioner can work with other team members to manage difficult behaviors, ensure that the patient is as comfortable and safe as possible, recognize when referral for specialist care is needed, educate caregivers about the condition, and support caregivers in coping with their situations to the best of their abilities. Furthermore, with several pharmacological treatments available for dementing illnesses, it has become more important for physicians to be proficient in diagnosing specific subtypes of dementia and knowing what therapies may (or may not) be helpful for that syndrome.
TYPES OF DEMENTIA
Alzheimer disease (AD) is the most common form of dementia, accounting for about 60–70% of the cases. The age of onset varies considerably, but most commonly symptoms arise after the age of 70 years. Incidence of the disease increases with age. Women may be at a slightly higher risk of developing the disorder than men. The rare patient with early onset of AD (before the age of 60 years) may have a genetic disorder with an autosomal dominant pattern of inheritance, so a thorough family history is important in these cases.
| Stage | General Change | Specific Change |
|---|---|---|
| Early | Patients show relatively subtle changes in memory, along with declin-ing clarity of thought and ability to perform everyday tasks. These changes may go largely unnoticed by the patient and significant others. Patients typically retain some ability to compensate for the cognitive changes. |
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| Middle | Cognitive deficits become more prominent during this stage and the loss of functioning becomes obvious to others. |
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| Late | In the third, and terminal, stage of the disorder, the patient becomes very inactive, is extremely withdrawn, and loses nearly all ability to engage in purposeful activities. |
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Alzheimer disease usually follows a slow, but progressive and insidious, course (Table 30-2). Life expectancy following the appearance of the disorder ranges from 3 to 15 years, but considerable variation may occur, and survival of up to 20 years has been reported. Memory deficits are prominent in all dementias, but especially so in AD. Typically, short-term episodic memory problems are the first and most obvious manifestation of the disorder. Alzheimer disease affects both the encoding and retrieval of new information to a profound degree, such that these patients do not appear to benefit from cueing and prompting of memory. For example, a patient asked to remember the words “piano,” “carrot,” and “green” may not be helped by hints such as “musical instrument,” “vegetable,” or “color.” Although diagnostic certainty is less than 100% without pathological examination, careful clinical and neuropsychological evaluation results in a reliable diagnosis of the disease in most instances. A computed tomography (CT) or magnetic resonance imaging (MRI) scan often shows cerebral atrophy and hippocampal volume loss; the electroencephalogram (EEG) may show diffuse slowing.
CASE ILLUSTRATION 1
Gertrude is 74 years old. She is brought by her family to a medical clinic for evaluation. Since the death of her husband 2 years ago, Gertrude has become increasingly absentminded, withdrawn, and sedentary. Her family assumed at first that she was grieving and would eventually readjust. Gertrude’s condition, however, has continued to deteriorate. Now she is confused and disoriented and has difficulty recognizing family members. Her general physical examination is normal, but her mental status examination reveals multiple deficits. For example, given three words to remember, she is unable to recall any of them after several minutes. She cannot give the correct month and year and thinks she is in the city where she had lived many years ago. Asked to repeat several sentences, she makes a number of verbal slips. When she is given a geometric design to copy, her drawing is distorted and unrecognizable. Her laboratory examinations are normal, a CT scan of the head shows mild cerebral atrophy, and no other potential explanations for her deficits are found. A diagnosis of AD is eventually made.
In retrospect, her family recalls that Gertrude had been having some mild difficulties in memory and functioning prior to her husband’s death and had been dependent on him for helping her to manage things. Recognition of Gertrude’s emerging dementia had been made more difficult by her grief and possible depression after her husband’s death.
The physician spends some time with family members discussing the nature of Gertrude’s condition and options for future care. She inquires about immediate concerns such as agitation and other behavioral disturbances, none of which is currently present. The physician then refers the family to a social worker specializing in geriatric issues and indicates the availability of groups such as the Family Caregiver Alliance for education and support. She also advises Gertrude not to drive, and, in accordance with the law in her state, notifies the health department of the new diagnosis of dementia. Finally, the physician initiates a trial of donepezil, which is associated with no obvious benefits at 3 months, according to the family. The physician and family elect to continue treatment for another 3 months and reevaluate the treatment at that time.
Dementia with Lewy Bodies (DLB) is reported to be the second most common cause of dementia in autopsy studies, accounting for 15–30% of the cases. It is defined by the presence of cognitive impairment, parkinsonism, prominent (often bizarre) hallucinations or other psychotic symptoms, and fluctuations in alertness, although patients may not have all of these symptoms. Patients with DLB are often intolerant of traditional antipsychotic medications, and their use can induce severe parkinsonism or even death. At least one randomized-controlled trial suggests that cholinesterase inhibitors may be useful in treating the disorder.
Previously known as multi-infarct dementia, vascular dementia is characterized by the development of cognitive impairment in association with single or multiple areas of infarction and/or subcortical ischemia. Not surprisingly, the risk factors for vascular dementia are identical to the risk factors for cerebrovascular disease, including smoking, hypertension, diabetes mellitus, coronary artery disease (CAD), and previous history of stroke. A patchy and inconsistent pattern of deficits may be seen initially, with relative preservation of some cognitive areas. Because vascular dementia can result from insults to a variety of cortical or subcortical areas, the neuropsychological profile of patients with vascular dementia can be quite varied.
Focal neurologic signs are more common in vascular dementia than in AD, and lateralized motor and sensory findings may be seen. CT and MRI scans frequently reveal multiple areas of infarction in the brain, often with diffuse subcortical white matter changes. Later in the course of the disorder, atrophy from loss of brain tissue may be seen.
A number of diagnostic criteria for vascular dementia have been proposed, but none are sensitive or specific enough to rule the diagnosis in or out with certainty. Many elders show diffuse white matter changes on brain imaging, and yet are cognitively intact. Other demented elders, who were thought by their clinicians to have vascular dementia because of cognitive decline following cerebral infarcts, are subsequently found to have Alzheimer’s pathology at autopsy in addition to the known infarcts. Such individuals, with elements of both AD and vascular dementia, are considered to have mixed dementia. In short, current diagnostic instruments and criteria are often inadequate for clinicians confidently to employ or reject the “vascular dementia” label.
Frontotemporal dementias (FTDs) are a group of disorders characterized by personality change (e.g., apathy or socially inappropriate behavior), hyperorality, and cognitive decline especially involving language and executive function. Frontotemporal dementia tends to affect individuals at a younger age than AD, with many persons receiving the diagnosis in their 50s or 60s. Imaging studies may show marked atrophy in frontal and temporal lobes.
Advanced Parkinson disease commonly results in dementia. These patients frequently display mental sluggishness and a general lack of spontaneity. Language functions (compared with those of AD patients) are relatively preserved.
Chronic alcohol abuse can result in serious cognitive deficits if drinking is severe and prolonged, although it is not clear whether the dementing process occurs in the absence of coexisting thiamine deficiency. Severe head trauma can also result in permanent cognitive impairment, which might be viewed as static dementia.
Human immunodeficiency virus (HIV)-1-associated dementia (HAD) is caused by the direct infection of the brain by the HIV-1 virus. It is associated with late-stage AIDS and is generally seen in individuals whose T-cell count has fallen below 200. Features of this form of dementia are summarized in Table 30-3. HIV-1-associated dementia is discussed further in Chapter 36. Creutzfeldt–Jacob disease is a rare infectious cause that should be suspected when a nonelderly person develops a rapidly dementing illness associated with other neurologic deficits such as myoclonus.
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A number of medical conditions can result in cognitive impairment. These may be treatable, but full or partial reversal of dementia is relatively rare, even with appropriate treatment. However, because dementia is such a devastating diagnosis, assessing the patient for these conditions is an important part of the dementia workup. Fully or partially reversible dementia syndromes are usually the result of depression, medication, or a toxic or metabolic disorder. The most common types of primary and secondary treatable syndromes are listed in Table 30-4.
| Hydrocephalus | Chronic subdural hematoma |
| Metabolic disorders: hypercalcemia, hyper- and hypoglycemia, hyper- and hyponatremia, hyperuricemia | CNS infection (meningitis, encephalitis, abscess) |
| Myxedema | Medication side effects or toxicity |
| Hepatic encephalopathy | Vitamin deficiencies: B12′ thiamine, niacin |
| Depression | Delirium |
| Status epilepticus | CNS malignancy |
Persons suspected of having dementia are encountered in a number of medical settings. For example, a patient who presents to the emergency department with confusion, disorientation, and hallucinations should be evaluated for delirium (e.g., from infection, metabolic derangement, or use of or withdrawal from medications or recreational substances) and psychotic disorders. An older adult with a history of recent bereavement, withdrawal, and increased forgetfulness may indeed be demented, or may be suffering from cognitive deficits related to major depression. Other problems that initially may be confused with dementia include sensory deficits (severe visual or hearing impairment), aphasia, developmental disability, and low levels of literacy or education.
As people age, some degree of decline in cognitive functioning is common. The presence of mild memory impairment among older adults has been reported to occur among a very wide range (11–96%) of participants in various research studies. Normal aging often brings minor word-finding difficulties, slowed memory retrieval, and some changes in the speed and efficiency of thought. These changes, however, typically do not cause significant problems in everyday functioning or produce confusion or disorientation, which are signs of impaired cognition (see Chapter 14).
Mild cognitive impairment (MCI) is an increasingly recognized condition in which a patient complains of memory problems, demonstrates mild deficits (most commonly in short-term memory) on formal testing, but does not meet criteria for dementia. Dementia will develop in roughly 10% of people with MCI each year. Amnestic MCI, in which the deficit is primarily episodic memory, is more likely to progress to AD than nonamnestic MCI, which may be more pathophysiologically heterogeneous. At the time of this writing, no medication intended for the treatment of MCI has been approved by the FDA. Acetylcholinesterase inhibitors have shown mixed results in clinical trials. Any potentially reversible conditions, including depression, hearing loss, or B12 deficiency, should be addressed in patients with MCI. They also should be advised to complete advance care planning and followed with serial clinical evaluation at least every 6 months.
Research suggests that AD pathophysiology begins many years and possibly decades prior to the clinical expression of the disease. In an attempt to identify a preclinical phase of AD and to improve the accuracy of the diagnosis of AD and MCI, several working groups have suggested new guidelines and diagnostic criteria. Many of these incorporate biomarker measures (either from neuroimaging or cerebrospinal fluid) as these may provide direct evidence of the underlying pathophysiology associated with AD. How these new guidelines will be incorporated into clinical practice is uncertain. In particular, the concept of a preclinical phase of AD will require much greater research and public health policy guidelines.
CASE ILLUSTRATION 2
George is an 80-year-old man who is admitted through the emergency department with a fracture of the femoral neck. He undergoes an open reduction and internal fixation. On the second postoperative day, he develops agitation, pulls out his IV, and is restrained. Physical examination reveals an elderly man who is inattentive, moaning, and seeming to drift in and out of the conversation. The consultant notes that the patient was given 50 mg of diphenhydramine as a “sleeper” the night before, and he now appears to have a distended bladder. Placement of a Foley catheter, around-the-clock treatment with opioids, low-dose haloperidol, and having family members at his bedside, all seem to help calm him down. Over the next 3 days, he receives no further diphenhydramine, his pain improves, his catheter is removed, and his mental status clears somewhat, but not to his baseline level.
The family says that George had very mild dementia, but seemed to be functioning well at home prior to his hip fracture. Following hospital discharge, he goes to a nursing home for short-term rehabilitation, but he never seems to regain his former level of cognition or functioning. He lives in a nursing home for the remaining years of his life. He dies of apparent aspiration pneumonia after a period of progressive functional and cognitive decline.
Delirium is a state of cognitive impairment that is acute in onset and associated with fluctuations in mental status and behavior, inattention, disorganized thinking, and an altered level of consciousness. Because dementia is a significant risk factor for delirium, the two syndromes are closely linked (Table 30-5). It is not uncommon for delirious patients to be incorrectly labeled as demented by an inpatient team with no prior knowledge of the patient. Optimized communication between inpatient and outpatient teams, good baseline mental status testing on elderly outpatients, and/or collateral information from family and friends, can often be critical in trying to determine how likely it is that the delirious patient will “clear” enough to be able to live independently following hospital discharge. Unfortunately, some patients, like George, never return to their prior level of functioning following an episode of delirium.
| Delirium | Dementia |
|---|---|
| • Rapid onset; short duration | • Insidious onset; progressive deterioration |
| • May show heightened autonomic arousal | • No impairment in autonomic arousal |
| • Clouded consciousness or gross confusion | • Alertness retained in early stages |
