This article includes discussion of drug-induced dementia, cytokine dementia, dilantin dementia, valproate-induced dementia, drug-induced cerebral insufficiency, drug-induced organic brain syndrome, pseudodementia, and reversible dementia. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Drug-induced dementias fall under the broad category of pseudodementias, which differentiates them from dementias associated with degenerative neurologic disorders, as well as under the category of reversible dementias, which imply that the manifestations improve following discontinuation of the offending drug. Several drugs can induce dementia, but significant categories are anticholinergic drugs, antiepileptics, antineoplastic drugs, and sedative-hypnotics. Creutzfeldt-Jakob disease, a transmissible spongiform encephalopathy, is also associated with a number of therapeutic agents. This article explores the pathomechanism, diagnosis, and management of drug-induced dementia.
• Drugs, particularly as polypharmacy, are the leading cause of dementia in the elderly.
• Drugs such as anticholinergic agents are more likely to produce dementia.
• Drug-induced dementia has no characteristic features, except in the situations where it is accompanied by other drug-induced symptoms.
• Drugs known to produce dementia should be avoided in persons who have risk factors predisposing them to dementia.
Historical note and terminology
Dementia is defined as a global impairment of higher cortical functions including memory, the capacity to solve problems of everyday living, the performance of learned perceptual motor skills, the correct use of social skills, and the control of emotional reactions in the absence of gross clouding of consciousness.
Mental deterioration due to alcohol has been recognized for at least a century. The term "alcohol dementia" lacks a distinct defined pathology (Victor 1992). The first mention of a therapeutic drug-induced dementia was after the introduction of synthetic anticholinergic drugs for the treatment of Parkinson disease (Porteous and Ross 1956). The pathophysiology of memory loss associated with anticholinergic drugs was strengthened by the emergence of the cholinergic hypothesis of memory and by the demonstration that memory is adversely affected by the injection of scopolamine, but that these adverse effects are reversible by an injection of physostigmine (Drachman and Leavitt 1974). In the early days of levodopa therapy, its use was deemed responsible for dementia in Parkinson disease patients (Barbeau 1971; Wolf and Davis 1973). Dementia is now considered part of the natural progression of the disease rather than an effect of levodopa.
Various terms are used to describe dementia associated with drugs. Patients on long-term phenytoin therapy have been reported to deteriorate intellectually in the absence of any signs of oversedation, a condition termed "Dilantin dementia" (Rosen 1968). Drug-induced dementias fall under the broad category of pseudodementias, which differentiates them from dementias associated with degenerative neurologic disorders, as well as under the category of reversible dementias, which implies that the manifestations improve following discontinuation of the offending drug.
Drug-induced cognitive disturbance is a broad term that refers mostly to delirium. Drug-disease interaction, such as in patients with dementia where a risk of delirium is present, is enhanced due to diminished "cognitive reserve." Dementia is the most severe form of cognitive deficit and is sometimes referred to as brain failure. Cerebral insufficiency is a general term indicating a decline of mental function. It does not specify the cause, but instead the clinical effects, which may be mild, moderate, or severe (dementia). The frequently used term cognitive impairment refers to disturbances of information processing. It covers the acquisition, storage, retrieval, and use of information. Cognitive processes involved in the acquisition of information are linked to consciousness and cognitive disturbances including delirium. Cognitive disorders also include disturbances of memory and intellect as well as behavioral disturbances.
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