More Evidence Anticholinergic Meds Boost Dementia Risk

Megan Brooks

May 01, 2018

Antidepressants, drugs for Parkinson's disease, and urologic medications that have definite anticholinergic activity increase the risk of developing dementia up to 20 years after exposure, according to a large study from the United Kingdom.

"Many people use anticholinergic drugs at some point in their lives, and many are prescribed to manage chronic conditions leading to potentially long exposures.... Clinicians should continue to be vigilant with respect to the use of anticholinergic drugs, and should consider the risk of long term cognitive effects, as well as short term effects, associated with specific drug classes when performing their risk-benefit analysis," George Savva, PhD, University of East Anglia, Norwich, United Kingdom, and colleagues write.

The study was published online April 25 in the BMJ.

"Appreciable Risk"

It is well known that anticholinergic medications affect cognition. Guidelines indicate that they are to be avoided in frail, elderly patients. Prolonged exposure to anticholinergics has been linked to long-term cognitive decline and dementia. However, it has been unclear whether the increased risk is specific to the anticholinergic action itself or to the underlying conditions for which they were prescribed.

To investigate, Savva and colleagues conducted a nested case-control study within the UK Clinical Practice Research Datalink, which includes records from 674 practices across the United Kingdom. They used multiple conditional logistic regression to evaluate patients newly diagnosed with dementia between April 2006 and July 2015 and to compare their prescriptions for anticholinergic drugs 4 to 20 years before a diagnosis of dementia with that of a matched control group of patients without dementia.

During the drug exposure period, 14,453 (35.5%) case patients and 86,403 (30.4%) control patients were prescribed at least one drug with definite anticholinergic activity (anticholinergic cognitive burden [ACB] score of 3); 1429 (3.5%) case patients and 7909 (2.8%) control patients were prescribed drugs with an ACB score of 2; most patients (89.4% of case patients and 87.1% of control patients) were prescribed a drug with an ACB score of 1 (possibly anticholinergic).

The analysis showed a "positive and significant" association between any anticholinergic with an ACB score of 1, 2, or 3 and incident dementia, with corresponding adjusted odds ratios (aORs) of 1.10 (95% confidence interval [CI], 1.06 - 1.15), 1.10 (95% CI, 1.03 - 1.16), and 1.11 (95% CI, 1.08 - 1.14). A dose-response effect was evident for drugs with definite anticholinergic activity (ACB 2 and 3).

With respect to drug class, antidepressants, urologic drugs, and antiparkinson medications with definite anticholinergic activity (ACB score of 3) were associated with the development of dementia. The associations persisted 15 to 20 years after exposure. Gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia.

Table. Risk for Dementia With ACB Score of 3 by Drug Class

ACB Score of 3 aOR at Start of Exposure aOR at End of Exposure (95% CI)
Antidepressant 1.13 (1.10 - 1.16) 1.11 (1.08 - 1.14)
Antiparkinson 1.45 (1.25 - 1.68) 1.29 (1.11 - 1.50)
Urologic 1.23 (1.18 - 1.28) 1.18 (1.13 - 1.23)


These associations are "moderate, but given the high incidence of dementia they reflect an appreciable risk to patients," Savva and colleagues note in their article.

Their findings are in line with a US cohort study of more than 3400 elderly adults that found a strong link between anticholinergic drug use and increased risk for dementia, as reported by Medscape Medical News.

The precise mechanisms behind the link between anticholinergic drugs and dementia are not clear, but neuropathologic studies in humans and mice suggest that these medications have a bearing neurodegenerative pathologies, the authors point out.

For example, a recent neuroimaging study found that use of anticholinergic drugs (compared with nonuse) in cognitively normal older adults correlated with increased brain atrophy and hypometabolism, as well as poorer memory, executive function, and increased risk for cognitive decline, as reported by Medscape Medical News.

The study was funded by the Alzheimer's Society. Dr Savva has disclosed no relevant financial relationships. The original article contains a complete list of the other authors' relevant financial relationships.

BMJ. Published online April 25, 2018. Full text


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