REFILE-Certain anticholinergics tied to risk of future dementia

Last Updated: 2018-06-05

(Fixes typo in para 7: changes "at four of more" to "and four or more")

By Marilynn Larkin

NEW YORK (Reuters Health) - Antidepressants, urologicals, and antiparkinson's drugs with anti-cholinergic action are associated with an increased risk of future dementia, researchers say.

Dr. Chris Fox and Dr. George Savva of the University of East Anglia in Norwich, UK and colleagues analyzed data from 2006 to 2015 on more than 40,000 patients ages 65-99 diagnosed with dementia and about 284,000 controls without dementia from UK general practices.

Daily doses of anticholinergic drugs prescribed four to 20 years before a dementia diagnosis were coded using the Anticholinergic Cognitive Burden (ACB) scale and grouped by subclass.

As reported online April 25 in BMJ, 14,453 individuals with dementia and 86,403 controls were prescribed at least one anticholinergic drug with an ACB score of 3, meaning definite anticholinergic activity.

The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11, and dementia was associated with an increasing average ACB score.

When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not linked to dementia (nor were antihistamines). However, a "robust" association was seen with antidepressants, urologicals, and antiparkinson drugs.

"The odds ratio associated with four or more years' worth of antidepressant use in this period was 1.29, controlling for health and lifestyle factors including diagnoses of depression," Dr. Savva told Reuters Health. "Similarly, the adjusted association between dementia and four or more years' worth of urologicals was OR=1.24."

"Putting the risk into context," he said by email, "in 2017, the Lancet Commission on Dementia Prevention and Care identified through systematic review nine risk factors for dementia with relative risks estimated at between 1.4 and 1.9. These included smoking (RR=1.6), obesity (RR=1.6), having less than secondary level educational attainment (RR=1.6), and depression itself (RR=1.9) among others."

"Many different medications have an anticholinergic action or side effect," he said, "and (our)study extends previous work first by disaggregating anticholinergics into classes depending on their indication, and by using a longer patient history than had previously been possible."

"Importantly, we cannot rule out residual confounding or reverse causation as an alternative explanation for these results," he said.

The lack of a link with anticholinergic antihistamines or gastrologicals "calls into question whether it is the anticholinergic effect itself driving the association, another action of the medication or another cause," he said.

"Moreover," he noted, "we have not prospectively compared these medications with alternative treatments in specific patient groups, and we have not identified specific patient groups in which the risk is higher or lower."

"We have demonstrated an association which at the individual level is smaller in magnitude than that associated with other common modifiable risk factors . . . and that still has only moderate evidence behind it," he said.

"Any risk we have demonstrated is solely associated with long-term use," he added, "which suggests regular medication review is essential for patients prescribed the classes of medications that we have identified."

Dr. Fox told Reuters Health in an email, "In my view, prescribers need to consider usage of the medicines we have identified . . . in any patient middle-aged upwards and take into account these medicines and other risk factors (e.g., lack of exercise, weight) when deciding on treatments for such conditions."

"There are alternatives," he said, "or the condition (that required) such medicines may no longer require treatment."

Dr. D.P. Devanand, director of geriatric psychiatry at Columbia University Medical Center in New York City, told Reuters Health by phone, "There's a fair amount of information showing that anticholinergic medications worsen cognitive performance, so being alert to that is a good idea because worsening cognitive performance can lead to dementia or just worsening without necessarily leading to a diagnosis of dementia."

"Lowering the anticholinergic burden when possible is something to be considered," he said, "but many of these medicines are given for a specific reason, such as urinary incontinence, and you can't simply stop them even if they're causing some cognitive problems because we have very few alternatives. So there needs to be a balance based on what's happening."

With respect to the study, Dr. Devanand noted that while three classes were more likely to be associated with dementia, two were protective. "When the authors combined all the scores together, there was a small but significant risk, but it's important to recognize that three are going in one direction and two in the other."

"Another important point is that when people say dementia in a database like this, the patients may actually have delirium - a disorientation because of toxic medications - and that is reversible," he noted. "That is a key question, yet the word delirium is not mentioned in the paper. People can get delirium acutely without dementia."

SOURCE: http://bit.ly/2rhEf2e

BMJ 2018.