Definition of Drug-Induced Cognitive Impairment in the Elderly

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


June 14, 2000

In This Article

Risk Factors for Drug-Induced Cognitive Impairment

Major risk factors that have been identified as predisposing to delirium include a diagnosis of dementia or other neuropsychological disorders, advanced age, and sepsis. Other predisposing factors include hypoalbuminemia, hospitalization, postoperative status, myocardial infarction, congestive heart failure, acute blood loss, stroke involving subcortical regions, severe chronic illnesses, total knee arthroplasty, cardiac and noncardiac thoracic surgical procedures, aortic aneurysm surgery, functional impairment, high blood urea nitrogen/serum creatinine ratio (azotemia), proteinuria, lymphocytosis, HIV disease, sensory impairment, untreated pain, fluid and electrolyte imbalances, acid-base disturbances, infection, hypoxia/ hypercarbia, Parkinson's disease, depression, abnormal glucose levels, acute urinary retention, nutritional deficiencies (vitamin B12, folate), collagen diseases, blood dyscrasias, constipation/diarrhea, hypo- or hyperthermia, unfamiliar environment/ isolation, sleep deprivation, malignancies, alcohol or substance abuse, psychosocial factors or acute stress, disorders caused by hypersensitivity, injury by physical agents, male gender, fracture present on admission, family history of mental illness, history of serious brain trauma, and, of course, medications (eg, anticholinergic agents, psychotropic drugs).[2,5,6,8,10,11,13,15,17,22,24,25] Often, multiple causes and risk factors for the development of cognitive impairment are present.

It is not known what causes delirium; however, among the theories proposed are: a reduction of cerebral oxidative metabolism; CNS dopamine and endorphin hyperfunction; brain acetylcholine-dopamine-serotonin-glutamate imbalances; increased CNS cortisol activity; damaged neuronal enzyme systems; decreased synthesis and function of neurotransmitters, namely acetylcholine; increased central noradrenergic activity; dysfunction of beta-endorphinergic neurons; disturbances of the normal ionic passage through excitable membranes; gross changes in the electrolyte and water content, osmolality, and pH of the internal milieu; presence of false neurotransmitters; impaired synthesis of macromolecules needed for renewal of the structural and functional integrity of neurons; mismatch of metabolic supply and demand; involvement of cytokines; and neuronal loss.[5,7] These proposed mechanisms point to a number of ways in which drugs may be involved in inducing delirium by affecting the function, supply, or use of substrates of CNS neurotransmitters or neuropeptides. Cerebrospinal fluid (CSF) somatostatin-like immunoreactivity and CSF beta endorphin-like immunoreactivity were found to be lower in delirious vs nondelirious patients, and these changes persisted even 1 year after the initiating event.[8,24,25]

In the elderly, polypharmacy may predispose patients to developing drug-induced delirium. However, there is a lack of data on this subject, because reports citing multiple causative agents are often not published. In the late 1970s, Summers[26] tried to estimate the risk of developing drug-induced delirium based on the propensity of a drug either to have anticholinergic effects OR to be associated with the onset of altered mental status AND its daily effective dose. The relative risk of developing delirium when 3 or more medications are added during the hospital course may increase 3-fold.[27]


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