DEMENTIA

The term dementia describes a decline of previously acquired intellectual, or cognitive, skills. Memory loss is the primary symptom of dementia, but other cognitive symptoms exist as well. A diagnosis of dementia requires an impairment in memory and at least one other cognitive domain (American Psychiatric Association, 1994). This can include an impairment in comprehending or expressing language, sustaining attention, orientation (knowing where one is and the date and time), visual perception, visual construction, or executive (planning and organizing) skills. In addition to cognitive deficits, dementia is often associated with behavioral and/or psychiatric changes such as poor judgment (for example, spending money recklessly or dressing inappropriately), delusions (false beliefs), or hallucinations (seeing, feeling, or hearing things that are not actually there). Disinhibition, exemplified by the use of inappropriate language (i.e., swearing), the telling of off-color jokes, or acting overly familiar with others, can also occur. Mood symptoms, such as depression, apathy, or increased irritability, can accompany dementia as well.

Dementia is not a disease, but a syndrome that has many causes, including head injury, vitamin deficiency, hydrocephalus, epilepsy, depression, medication effects, and toxic exposure. In addition, there are a number of diseases that can cause dementia. These include Alzheimer's disease, vascular disease, HIV infection, multiple sclerosis, Parkinson's disease, Huntington's disease, Lewy body disease, and others. Depending on the cause of dementia, its onset may be gradual or sudden, and its course may be progressive, stable, or reversible.

Pathophysiology of Dementia

The pathology associated with dementia varies, depending on the cause of dementia. The term neurodegenerative is used to describe dementia caused by diseases that lead to the progressive death of nerve cells (neurons) in the brain. Some diseases are associated with the development of abnormalities within or around neurons that interfere with communication between brain cells and/or cause cell death. For example, the amyloid plaques (insoluble deposits of a type of protein found between neurons) and neurofibrillary tangles (abnormal collections of twisted threads found within neurons) associated with Alzheimer's disease (AD) are found primarily in the cerebral cortex (outer covering of the brain), hippocampus, and entorhinal cortex. Parkinson's disease, in contrast, is associated with Lewy bodies (accumulations of neurofilamentous material located within neurons) in the substantia nigra and locus ceruleus (Kish, Shannak, and Horneykiewicz, 1988). Pick bodies (a common neuropathological finding in frontotemporal dementia) are concentrated primarily in the frontal and/or temporal cortex of the brain (McKhann et al., 2001).

Cerebrovascular disease causes dementia by disrupting blood flow to brain cells and is not considered to be neurodegenerative. If blood vessels in the brain are blocked (e.g., by cholesterol), blood flow is constricted. Such an event, called ischemia, results in oxygen deprivation, which can cause neuron death. Vascular dementia is the term used to refer to dementia caused by multiple vascular accidents, such as small strokes (in which case it is sometimes referred to as multiinfarct dementia), or a single stroke. Whether numerous small vessel changes can cause dementia is unclear, but with sufficient accumulation these changes have been associated with significant cognitive changes (Boone et al., 1992). There are, of course, many other mechanisms leading to death of brain tissue and dementia, but these examples explain some of the ways dementia can be caused.

Dementia, Delirium, Senility, or Mental Retardation?

Dementia is diagnosed only in the absence of delirium. Like dementia, delirium is associated with memory loss, but it is also associated with disorientation, confusion, and alterations in consciousness that fluctuate throughout the day. Unlike dementia, delirium typically begins suddenly and is usually the result of a treatable cause such as illness or the effects of medications.

Dementia and advancing age often co-occur because the biggest risk factor for the development of dementia is advancing age. Dementia is not, however, an inevitable consequence of aging. The term senility has been incorrectly applied to memory impairment that accompanies old age. Senility actually refers only to the age of onset of dementia; the term senile dementia is sometimes used to refer to dementia that occurs after age sixty-five. The term presenile dementia, in contrast, signifies dementia whose onset is prior to age sixty-five.

Mental retardation differs from dementia in that it describes intellectual and adaptive functioning that has developed subnormally. Thus, functioning has not declined from a previously higher level, as is the case with dementia. It is possible, however, for someone with mental retardation to acquire dementia. The most common example of this occurs in people with Down's syndrome, most of whom will develop AD by the time they are in their fifties (Mann, 1993).

Memory Functioning in Dementia

Due to similarities in the clinical presentation of patients with disorders affecting primarily subcortical structures, which differs from that observed in dementia caused by cortical damage, the terms cortical dementia and subcortical dementia are often used. A cortical pattern of cognitive deficits is characterized by an inability to perform purposeful motor movements (apraxia), language disturbance (aphasia), memory impairment (amnesia), and difficulty with object recognition (agnosia). The most common disease causing cortical dementia is AD. Subcortical dementia, in contrast, has many more causes, such as Huntington's disease (HD) or Parkinson's disease (PD), and is characterized by slowed mentation (bradyphrenia), forgetfulness, motor abnormalities, impaired planning and judgment (so-called "executive" dysfunction), and mood changes such as depression or apathy (Cummings and Benson, 1984). Memory performance also differs between cortical and subcortical dementia (see Table 1).

Short-Term Memory

Short-term, or working, memory refers to information that is stored for only a few seconds, such as when one repeats a list of numbers immediately after hearing them. This skill does not reliably differentiate patients with cortical from those with subcortical dementia, as both have been shown to perform as well as normal control subjects in repeating digits forwards, and deficits in their ability to repeat digits in reverse order (Calderon et al., 2001; Redondo Verge, Brown, and Chacon Pena., 2001). Patients with Lewy body dementia, however, are impaired on both portions of this task (Calderon et al., 2001).

Long-Term Memory

Long-term, or secondary, memory refers to memory for information that must be recalled after some period of time, such as after few minutes or after many years. Semantic memory, a type of long-term memory relating to meanings of words and their relationships, is typically impaired in patients with cortical dementia. Perhaps the most impressive example of this deficit is observed in patients with fronto-temporal dementia (FTD), who can have very severe language impairment, such as word-finding difficulty, inability to appreciate syntax, and/or impaired language comprehension, with relative sparing of other cognitive abilities (Mesulam, 2000). The word-finding difficulty observed in AD is also an example of the impaired semantic memory seen among patients with cortical dementia. Semantic memory is not typically impaired in patients with subcortical dementia.

Another type of long-term memory, episodic memory, concerns memory for events. Patients with AD are typically severely impaired in their ability to recall recent events, but are much better able to recall events that occurred many years ago (Dorrego et al., 1999). Patients with HD, however, have been found to exhibit a "flat" gradient of remote memory, with equal impairment for all previous years (Albert, Butters, and Brandt, 1981). Whether this is the case for patients with other types of subcortical dementia (e.g., PD) has not been consistently shown (Fama et al., 2000).

Long-term memory has been further divided into explicit and implicit memory. Explicit memory (sometimes used interchangeably with the term declarative memory) is typically more severely impaired in cortical than subcortical dementia. Both types of dementia cause an impairment in this ability to recall information (e.g. a list of words, a story, or simple line drawings) that was presented earlier. Provided with cues, however, such as the category from which the words belong, or a recognition (e.g., multiple choice or yes/no) paradigm, the performance of those with cortical dementia is not improved. Patients with subcortical dementia, however, benefit from cues, and might even perform as well as normal healthy adults. This difference is thought to demonstrate that cortical dementia causes an inability to encode new information, whereas subcortical dementia causes a deficit in retrieving information. Tests of implicit (or procedural) memory (memory that occurs without conscious awareness, such as the learning of motor movements) elicit the opposite pattern. That is, subcortical dementia produces impairment on tests of implicit memory, such as a mirror-tracing task, whereas patients with cortical dementia improve as much as normal healthy adults with practice, even if they have no recollection of having performed the task previously (Butters, Heindel, and Salmon, 1990).

Recent Developments in Dementia Research

New Drug Treatments

In 1996, the Food and Drug Administration approved the first drug (tacrine) to treat the memory impairment that results from AD. The drug works by increasing the amount of a particular chemical, called a neurotransmitter, in the brain. This neurotransmitter, called acetylcholine, is related to memory functioning, and is depleted in the brains of people with AD. Since approval of the first drug to treat AD, three new drugs with similar mechanisms of action have also been approved. Another development in clinical trials research for memory disorders has been the investigation of over-the-counter herbs such as Ginkgo biloba and the antioxidant vitamin E.

Refining Diagnostic Criteria for Types of Dementia

Because dementia-causing disorders can be difficult to diagnose during life, and because of new developments in neuropathological techniques, criteria for dementing disorders are evolving. To achieve consistency, experts in these disorders meet to establish a consensus regarding the features that distinguish a particular disorder from others. From 1984 to 1999, fourteen consensus guidelines concerning dementing disorders were published (Beck et al., 2000). Examples of these include Lewy body dementia (McKeith et al., 1997) and FTD (McKhann et al., 2001).

Mild Cognitive Impairment

Sometimes patients do not meet criteria for dementia because they have a mild impairment in memory but in no other cognitive domain, and their everyday functioning is not impaired. Scientists have introduced the term mild cognitive impairment (MCI) to describe this syndrome, and in 2001 consensus criteria for MCI were published (Petersen et al., 2001). This disorder has received a great deal of attention because, in many cases, it is considered to be a harbinger of AD (Morris et al., 2001). Because of the availability of new drug treatments for the memory impairment caused by AD, there is a great deal of interest in diagnosing this disease before it has progressed to dementia.

Conclusion

Burgeoning interest in dementia research in the late twentieth century has led to better understanding of its neuropathological underpinnings, treatments for its memory impairments, and refinements in the diagnostic criteria for the disorders causing it. The importance of early diagnosis of neurodegenerative disorders has led to an increasing efforts to identify very mild, objective memory problems. Thus, characterization of memory functioning continues to be an essential aspect for the diagnosis of dementia syndromes.

See also:ALZHEIMER'S DISEASE: BEHAVIORAL ASPECTS; ALZHEIMER'S DISEASE: HUMAN DISEASE AND THE GENETICALLY ENGINEERED ANIMAL MODELS; COGNITIVE ENHANCERS; PHARMACOLOGICAL TREATMENT OF MEMORY DEFICITS

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Redondo Verge, L., Brown, R. G., and Chacon Pena, J. R. (2001). Executive dysfunction in Huntington's disease. Reviews in Neurology 32, 923-929.

JasonBrandt

Ralph H. B.Benedict

Revised byCynthia A.Munro

See also:APLYSIA: DEVELOPMENT OF PROCESSES UNDERLYING LEARNING; CHILDREN, DEVELOPMENT OF MEMORY IN; EARLY EXPERIENCE AND MEMORY; LANGUAGE LEARNING; SCHOOL LEARNING