Definition of Drug-Induced Cognitive Impairment in the Elderly

Donna M. Lisi, PharmD, BCPS, BCPP, CGP, FASCP


June 14, 2000

In This Article


According to DSM-IV, multiple cognitive deficits that occur with dementia only in the context of substance use are diagnosed as "Substance Intoxication" or "Substance Withdrawal." If the dementia results from the persisting effects of a substance (ie, a drug of abuse, a medication, or toxic exposure), "Substance-Induced Persisting Dementia" is diagnosed. Other causes of dementia (eg, "Dementia Due to a General Medical Condition") should always be considered, even in a person with substance dependence.[3]

The essential feature of dementia is the development of multiple cognitive deficits that include memory impairment and at least 1 of the following cognitive disturbances: aphasia, apraxia, agnosia, or a disturbance in executive functioning. The cognitive deficits must be sufficiently severe to cause impairment in occupational or social functioning and must represent a decline from a previously higher level of functioning.[3]

Dementia is a chronic, insidious, progressive, and often permanent form of cognitive impairment that includes impaired thinking, memory, and learning abilities and difficulties in daily functioning, problem solving, and emotional control (Table 1).[5] Dementia occurs at age 60 in about 1% of the population; however, this increases to greater than 30% by age 85.[18] Starr and Whalley[19] make the following distinction: "Drug-induced dementias reversed by withdrawal of the offending drug are probably best thought of within the spectrum of delirious states, while dementias that are drug-related and persist when the drug is withdrawn are, de facto, drug induced." However, as they point out, a satisfactory definition of drug-induced dementia is lacking.

Drug-induced dementia may be a cause of cognitive impairment in about 12% of patients with a suspected dementia. In the elderly, this is distinguished from age-related cognitive impairment, where the decline in mental function is considered a part of the normal aging process. The relative odds of a drug-induced dementia increase as the number of medications consumed rises. The relative odds range from 1.0 with the use of 0-1 drugs to 9.3 with the use of 4-5 medicines.[18,20] Medication side effects accounted for 5% of reversible dementias in patients aged 60 or older in one study.[21] The prevalence of drug-induced dementia in the general population is unknown.[1]

Drugs may impair cognition indirectly by metabolic effects, such as hypoglycemia, by alterations of immunologic factors within the CNS, and by actions that interfere with synaptic transmission. Classes of drugs most often associated with the development of drug-induced dementia include benzodiazepines, antihypertensives, and anticholinergic agents.[19]

DSM-IV also recognizes research criteria for "Mild Neurocognitive Disorder." This condition is defined by the presence of 2 or more of the following impairments in cognitive functioning, usually lasting for a period of at least 2 weeks: memory impairment as identified by a reduced ability to learn or recall information; disturbance in executive functioning (ie, planning, organizing, sequencing, abstracting); disturbance in attention or speed of information processing; impairment in perceptual-motor abilities; and impairment in language (ie, comprehension, word finding). However, this condition should not be considered if a patient meets the criteria for "Substance-Related Disorder," including medication-related side effects. "Substance-Related Disorders" include disorders related to the taking of drugs of abuse (including alcohol), the side effects of a medication, and a toxic exposure. Medications that cause substance-related disorders include, but are not limited to, anesthetics and analgesics, anticholinergic agents, anticonvulsants, antihistamines, antihypertensive and cardiovascular medications, antimicrobial medications, antiparkinsonian medications, chemotherapeutic agents, corticosteroids, gastrointestinal medications, muscle relaxants, nonsteroidal anti-inflammatory medications, other over-the-counter medications, antidepressant medications, and disulfiram. Within this classification is "Substance Intoxication." This diagnosis requires the development of a reversible substance-specific syndrome caused by the recent ingestion or exposure of a substance and requires that the clinically significant maladaptive behavioral or psychological changes associated with the intoxication (eg, belligerence, mood lability, cognitive impairment, impaired judgment, impaired social or occupational functioning) are attributable to the direct physiologic effects of the substance on the CNS. In "Substance-Induced Persisting Amnestic Disorder," memory disturbance must not occur exclusively during the course of a delirium or a dementia, and it must persist beyond the usual duration of substance intoxication or withdrawal.[3]

Delirium may be superimposed on dementia. Approximately 22% of ambulatory demented elderly have concomitant delirium.[22] For any patient with a diagnosis of dementia who suddenly develops a change in mental status, delirium should be ruled out. The manifestation of delirium in a patient with dementia may be atypical. Even in demented patients, cognitive function may temporarily improve if an offending agent is removed. Delirium and dementia may be 2 places along a spectrum ie, if delirium is not reversed, it may evolve into dementia. Further, depression may mimic either dementia or the early stages of delirium.


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