Anticholinergic drugs and dementia in older adults

Regarding the forecasts of an increasing number of dementia cases in Europe and worldwide, the following awareness should receive more public and scientific attention:

"Dementia is one of the most prevalent problems in the elderly. Chronic cognitive impairment due to drug toxicity is particularly important and challenging. This problem is a by-product of the increased use of drugs during the past few decades. The elderly have the largest burden of illness, consume the most drugs, are more sensitive to adverse drug reactions, and are the fastest-growing segment of the industrialized world." (1)

As early as 1987, geriatrician Eric B. Larson and co-authors pointed out the connection between the handling of medication and the development of dementia syndromes or Alzheimer's disease (AD). Several recent medical papers explicitly suggest that dementia behaviour (including forgetfulness, restlessness, or aggressiveness) may be due to an underlying delirium mediated or deepened and made chronic by medication (especially, but not only anticholinergic drugs). (2)

However, this topic is still rarely addressed by the numerous scientific publications on AD.

Drug consumption increases exponentially during the course of the life of an average German up to their 80th year. (3) With advanced age, a dilemma often arises between multimorbidity and vulnerability: the older the patient is, the more medication they take on average, although the elderly are more sensitive to these drugs.

This problem makes it increasingly difficult to recognize dementia as a potential adverse drug reaction. Factors such as excessive demands or lack of time may lead to relatives, caregivers, and doctors accepting the fluent passage from delirium (i.e. acute states of confusion) as a result of medication to a dementia diagnosis: sometimes tacitly, but mostly unknowingly. The often difficult and severe distinction between transient delirium and chronic dementia in clinical practice is tricky. Chronic delirium may be often misunderstood in the elderly as dementia although it results from daily drug consumption. In 2007, for example, the neurologist Oliver Sacks described the case of a supposed Alzheimer's patient and his rheumatism-related ingestion of the steroid prednisone:

"This robust performance on all cognitive fronts, 5 years after he was considered to have Alzheimer’s disease, is inconsistent with such a diagnosis and seems to confirm our impression that his months-long dementia in 2001 was solely a consequence of the steroids he was taking." (4)

Delirium is considered the most common and problematic "adverse drug effect" in the elderly. Regular and simultaneous use of multiple medications increasingly produces such side effects, while people over the age of 65 are often excluded from clinical trials because of their "irregular" drug reactions. However, they are the ones who actually take the medication and are more susceptible to side effects and drug interactions than younger people because of, for example, altered (brain) metabolism and weaker organ performance.

However, people of advanced age are not only vulnerable in the pharmacological sense. They are often also socially vulnerable to a partially questionable invasiveness of medical treatment. Connected to the fundamental question of the increasing importance of dealing with old age in our society, the use of drugs should be fundamentally reconsidered by every single person, whether patient, doctor, or family member. Concerning Gray’s and Hanlon’s editorial: A lot of drugs, e.g. antidepressants, have anticholinergic side effects. Furthermore especially in nursing homes the use of particular anticholinergic drugs is still very common.

In 1999, a study by Moore and colleagues on adverse drug events, delirium, and dementia specifically addressed the problematic anticholinergic effects of many common medicines and implicitly delineated the fine line between delirium and dementia:
"Almost any drug can cause delirium, especially in a vulnerable patient. Impaired cholinergic neurotransmission has been implicated in the pathogenesis of delirium and of Alzheimer’s disease. Anticholinergic medications are important causes of acute and chronic confusional states. Nevertheless, polypharmacy with anticholinergic compounds is common [...]." (5)

1 Larson EB, Kukull WA, Buchner D, Reifler BV. Adverse Drug Reactions Associated with Global Cognitive Impairment in Elderly Persons. Ann Intern Med 1987; 107: 169–73.
2 Fick DM, Agostini JV, Inouye SK. Delirium Superimposed on Dementia: A Systematic Review. J Am Geriatr Soc 2002; 50: 1723–32.
3 Schaufler J, Telschow C (2013). „Arzneimittelverordnungen nach Alter und Geschlecht“. In: Schwabe U, Paffrath D (Eds.) (2013). Arzneiverordnungs-Report 2013. Aktuelle Daten, Kosten, Trends und Kommentare. Berlin/ Heidelberg: Springer Verlag: 967–81.
4 Sacks O, Shulman M. Steroid dementia: A follow-up. Neurology 2007; 68: 622.
5 Moore AR, O'Keeffe ST. Drug-Induced Cognitive Impairment in the Elderly. Drugs Aging 1999; 15 (1): 15–28.

Email: vogt@europa-uni.de