Anticholinergic medications used to treat depression, urinary incontinence, or Parkinson’s disease increase the risk of dementia, even if the therapy was taken 20 years before diagnosis of cognitive impairment, a study has found.
The study, “Anticholinergic drugs and risk of dementia: case-control study,” was published in The BMJ.
Anticholinergic medications are designed to prevent the activation of nerve cells by the signaling molecule acetylcholine. Depending on the site where the treatment acts, it can be used to prevent several responses such as tremors in Parkinson’s or respiratory reactions. This class of medicines is also widely used to treat depression and gastrointestinal disorders, among others illnesses and conditions.
Their potential to affect cognition has been previously reported, and guidelines suggest avoiding use in frail older people. However, until now, the long-term effects of anticholinergic medications on cognitive function was not fully realized.
Researchers at the University of East Anglia in the U.K. conducted a large-scale, retrospective study to compare the use of anticholinergic medications among 40,770 people who were diagnosed with dementia and 283,933 individuals without cognitive impairment (EUPAS8705).
Patients’ clinical information was collected from the Clinical Practice Research Datalink, which covers more than 11.3 million patients from across 674 primary care practices in the U.K. The study included patients 65 years or older, who had been diagnosed with dementia between April 2006 and July 2015.
Of the five most common anticholinergic therapies used by participants in the study, 29% took amitriptyline (brand names Endep, Lentizol, Saroten, Tryptanol, and Tryptizol), 16% dosulepin (brand name Prothiaden), 8% paroxetine (brand names Paxil and Seroxat), 7% oxybutynin (brand names Ditropan, Lyrinel XL, Lenditro, Driptane, and Uripan), and 7% tolterodine (brand names Detrol and Detrusitol).
The team found that the use of anticholinergic treatments was linked to a 10-11% increased risk of dementia. When they analyzed the data according to drug indication, they found that dementia was more common among patients who had been prescribed antidepressants, anti-Parkinson’s therapies, and urological medications. No association was found with antispasmodic, antipsychotic, antihistamine, or other treatments.
This increased risk was found to persist even if the medications had been prescribed several years before the dementia diagnosis. In fact, patients who had been treated with anti-Parkinson’s therapies 10 to 15 years before diagnosis had a 54% increased risk of having dementia. For antidepressants, the risk was 19% and for urological therapies, 27%, when taken 15 to 20 years before diagnosis.
“These findings make it clear that clinicians need to carefully consider the anticholinergic burden of their patients and weigh other options,” Malaz Boustani, MD, co-author of the study and a researcher at Indiana University Center for Aging Research in the U.S., said in a press release. “Physicians should review all the anticholinergic medications — including over-the-counter drugs — that patients of all ages are taking and determine safe ways to take individuals off anticholinergic medications in the interest of preserving brain health.”
It is still unclear why these medications have such an adverse effect, and additional studies are needed to fully address the risks linked to their use. Still, these findings highlight not only the short-term effects of anticholinergic therapies but also long-term adverse effects on cognitive function.
“With many medicines having some anticholinergic activity, one key focus should be de-prescribing. Clinical staff, patients and carers need to work together collaboratively to limit the potential harm associated with anticholinergics,” said study co-author Ian Maidment, PhD, a senior lecturer in clinical pharmacy at Aston University in the U.K.
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