Approach to the Patient with Memory Impairment
Daniel Tranel
Natalie L. Denburg
Torricia H. Yamada
The term amnesia refers to conditions in which patients lose, partly or completely, the ability to learn new information or to retrieve information acquired previously. Amnesia (also referred to here as memory impairment or memory dysfunction) is common in neurologic diseases that affect the telencephalon or diencephalon and is a defining characteristic and frequently an early manifestation of some of the most frequently encountered neurologic diseases, including Alzheimer’s disease (AD). As such, reports of memory impairment must be taken seriously.
Accurate diagnosis and effective management of memory disorders are important. A considerable clinical challenge is presented, however, by the facts that the most frequent neurologic diseases affect elderly persons and a certain degree of decline in memory is associated with normal aging. Hence, it can be difficult to differentiate reports of memory problems that may be normal manifestations of aging versus a signal of the presence of neurologic disease. Memory problems are common in nonneurologic conditions such as psychiatric disease, and this constitutes another reason for careful diagnosis. Such distinctions often require laboratory testing that can be conducted by neuropsychological assessments.
I. TYPES OF MEMORY AND MEMORY SYSTEMS IN THE BRAIN
There are several fundamental distinctions between different types of memory and the neural systems to which different types of memory are related (Table 4.1).
A. Anterograde and retrograde memory.
1. Anterograde memory refers to the capacity to learn new information—that is, to acquire new facts, skills, and other types of knowledge. It is closely dependent on neural structures in the mesial temporal lobe, especially the hippocampus and interconnected structures, such as the amygdala, the entorhinal and perirhinal cortices, and other parts of the parahippocampal gyrus.
2. Retrograde memory refers to the retrieval of information that was acquired previously—that is, retrieval of facts, skills, and other knowledge learned in the recent or remote past. This type of memory is related to nonmesial sectors of the temporal lobe, including the polar region (Brodmann’s area 38), the inferotemporal region (including Brodmann’s areas 20, 21, and 36), and the occipitotemporal region (including Brodmann’s area 37 and the ventral parts of areas 18 and 19). Autobiographical memory, a special form of retrograde memory that refers to knowledge about one’s own past, is linked primarily to the anterior part of the nonmesial temporal lobes, especially in the right hemisphere.
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TABLE 4.1 Subdivisions of Memory | ||||||||||||||||||
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TABLE 4.2 Hemispheric Specialization of Memory Systems | ||||||||||||||||
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B. Verbal and nonverbal memory.
Knowledge can be divided into that which exists in verbal form, such as words (written or spoken) and names, and that which exists in nonverbal form, such as faces, geographic routes, and complex musical patterns. This distinction is important because memory systems in the two hemispheres of the human brain are specialized differently for verbal and nonverbal material (Table 4.2). Specifically, systems in the left hemisphere are dedicated primarily to verbal material, and systems in the right hemisphere are dedicated primarily to nonverbal material. This arrangement parallels the general arrangement of the human brain, in which the left hemisphere is specialized for language and the right hemisphere for visuospatial processing. This distinction applies to almost all right-handed persons and to approximately two-thirds of left-handed persons. (In the remaining minority of left-handers, the arrangement may be partially or completely reversed.)
C. Declarative and nondeclarative memory.
1. Declarative memory (also known as explicit memory) refers to knowledge that can be “declared” and brought to mind for conscious inspection, such as facts, words, names, and individual faces, which can be retrieved from memory, placed in the “mind’s eye,” and reported. The acquisition of declarative memories is intimately linked to the functioning of the hippocampus and other mesial temporal lobe structures.
2. Nondeclarative memory (also known as implicit memory) refers to various forms of memory that cannot be declared or brought into the mind’s eye. Examples include sensorimotor skill learning, autonomic conditioning, and certain types of habits. Nondeclarative memory requires participation of the neostriatum, cerebellum, and sensorimotor cortices. A remarkable dissociation between declarative and nondeclarative learning and memory has been repeatedly found among patients with amnesia (including those with Korsakoff’s syndrome, bilateral mesial temporal lobe lesions, medial thalamic lesions, and AD). Among such persons, sensorimotor skill learning and memory often are preserved, whereas declarative memory is profoundly impaired.
D. Short-term and long-term memory.
1. The term short-term memory is used to designate a time span of memory that covers from 0 to approximately 45 seconds, a brief period during which a limited amount of information can be held without rehearsal. Also known as primary memory, it does not depend on the hippocampus or other temporal lobe memory systems but is linked closely to cerebral mechanisms required for attention and concentration, such as subcortical frontal structures.
2. The term long-term memory refers to a large expanse of time that covers everything beyond short-term memory. Also known as secondary memory, it can be divided into recent (the past few weeks or months) and remote (years or decades ago). Unlike short-term memory, the capacity of long-term memory is enormous, and information can be retained in long-term memory almost indefinitely. The mesial temporal system, including the hippocampus, is required for the acquisition of knowledge into long-term memory. Other systems in the temporal lobe and elsewhere are required for the consolidation and retrieval of knowledge from long-term memory.
E. Working memory
refers to a short time during which the brain can hold several pieces of information actively and perform operations on them. It is akin to short-term memory but implies a somewhat longer duration (several minutes) and more focus on the operational features of the mental process rather than simply the acquisition of information. It can be thought of as “online” processing and operating on knowledge that is being held in activated form.
Working memory depends on the integrity of the frontal lobes. More specifically, recent functional imaging studies have linked working memory to the dorsolateral prefrontal sector of the frontal lobes. A laterality effect also has been noted wherein verbal working memory tasks depend on the left dorsolateral prefrontal sector, whereas spatial tasks depend on the right dorsolateral prefrontal sector.
II. CLINICAL MANIFESTATIONS
Several frequent neurologic conditions damage memory-related neural systems and lead to various profiles and severities of amnesia (Table 4.3).
A. Degenerative diseases.
1. Cortical dementia.
a. AD is characterized by two principal features—the neurofibrillary tangle and the neuritic plaque. Early in the course of the disease, the entorhinal cortex, which is a pivotal way station for input to and from the hippocampus, is disrupted by neurofibrillary tangles in cortical layers II and IV. The perforant pathway, which is the main route for entry into the hippocampal formation, is gradually and massively demyelinated. The hippocampus eventually is almost deafferentated from cortical input. AD also breaks down the efferent linkage of the hippocampus back to the cerebral cortex through destruction of the subiculum and entorhinal cortex. The hallmark behavioral sign of this destruction is amnesia—specifically, an anterograde (learning) defect that covers declarative knowledge but largely spares nondeclarative learning and retrieval. Early in the course of the disease, retrograde memory is relatively spared, but as the pathologic process extends to nonmesial temporal sectors, a defect in the retrograde compartment (retrieval impairment) appears and gradually worsens.
b. Pick’s disease, characterized by Pick bodies (cells containing degraded protein material), is an uncommon form of cortical dementia that often shows a striking predilection for one lobe of the brain, producing a state of circumscribed lobar atrophy. The disease often is concentrated in the frontal lobes, in which case personality alterations as well as compromised judgment and problem solving, rather than amnesia, are the prominent manifestations. However, the disease can affect one or the other temporal lobe and produce signs of a material-specific amnesia.
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TABLE 4.3 Causes of and Conditions Associated with Amnesia | |||||||||||
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c. Frontal lobe dementia is another form of cortical dementia. It involves focal atrophy of the frontal lobes, which causes personality changes and other signs of executive dysfunction. This condition is similar to Pick’s disease, except there is no predominance of Pick bodies.
d. Frontotemporal dementia is characterized by symmetric atrophy of the frontal and temporal lobes. The earliest and most prominent cognitive symptoms involve personality and behavioral changes. Although reports of memory problems are common in frontotemporal dementia, they are never the sole or dominating feature. Severe amnesia is considered an exclusionary criterion. Memory functioning is described as selective (e.g., “she remembers what she wants to remember”). Knowledge regarding orientation and current autobiographical events remains largely preserved.
2. Subcortical dementia.
a. Parkinson’s disease is focused in subcortical structures and influences memory in a manner different from cortical forms of dementia such as AD and Pick’s disease. Disorders of nondeclarative memory (e.g., acquisition and retrieval of motor skills) are more prominent, and there may be minimal or no impairment in learning of declarative material. Patients with Parkinson’s disease often have more problems in recall of newly acquired knowledge than in storage. When cuing strategies are provided, the patients have normal levels of retention.
b. Huntington’s disease is also concentrated in subcortical structures and amnesia of patients with Huntington’s disease resembles that of patients with Parkinson’s disease. In particular, there is disproportionate involvement of nondeclarative memory. Patients with Huntington’s disease also tend to have disruption of working memory.
c. Progressive supranuclear palsy is another primarily subcortical disease process that frequently produces problems with memory. In general, however, the associated amnesia is considerably less severe than that of AD. Laboratory assessment often shows relatively mild defects in learning and retrieval despite the patient’s reports of forgetfulness.
3. Other degenerative conditions.
a. Dementia related to Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) is notable for varying degrees of memory impairment, with severity being roughly proportional to disease progression. Early in the course, memory defects may be the sole signs of cognitive dysfunction. The problems center on the acquisition of new material, particularly material of the declarative type. Memory defects in this disease appear to be attributable mainly to defective attention, concentration, and overall efficiency of cognitive functioning rather than to focal dysfunction of memory-related neural systems. Various investigators have found that the rate of percentage of CD4 lymphocyte cell loss is associated with and may represent a risk factor for cognitive dysfunction among persons with HIV/AIDS.
b. Multiple sclerosis (MS) patients have varying degrees of amnesia, although the severity can wax and wane considerably in concert with other neurologic symptoms. Many patients with MS have no memory defects during some periods of the disease. When present, the memory impairment most commonly manifests as defective recall of newly learned information. Encoding and working memory are normal or near-normal. Patients with MS often benefit from cuing. The amnesia of MS usually affects declarative material of both verbal and nonverbal types; defects in nondeclarative memory are rare.
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