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Common Class of Drugs Linked to Dementia, Even When Taken 20 Years Before Diagnosis

Summary: Researchers have identified a link between anticholinergic medications, including antidepressants and incontinence drugs, and an increased risk of developing dementia later in life.

Source: Regenstrief Institute.

The largest and most detailed study of the long-term impact of anticholinergic drugs, a class of drugs commonly prescribed in the United States and United Kingdom as antidepressants and incontinence medications, has found that their use is associated with increased risk of dementia, even when taken 20 years before diagnosis of cognitive impairment.

An international research team from the US, UK and Ireland analyzed more than 27 million prescriptions as recorded in the medical records of 40,770 patients over age 65 diagnosed with dementia compared to the records of 283,933 older adults without dementia.

The researchers found greater incidence of dementia among patients prescribed anticholinergic antidepressants, anticholinergic bladder medications and anticholinergic Parkinson’s disease medications than among older adults who were not prescribed these drugs.

Dementia increased with greater exposure to anticholinergic medications.

“Anticholinergic Medication and Risk of Dementia: Case-control Study” is published in BMJ (formerly the British Medical Journal) an international peer-reviewed medical journal.

“Anticholinergics, medications that block acetylcholine, a nervous system neurotransmitter, have previously been implicated as a potential cause of cognitive impairment,” said Regenstrief Institute and Indiana University Center for Aging Research investigator Noll Campbell, PharmD, MS, a co-author of the new BMJ study. “This study is large enough to evaluate the long-term effect and determine that harm may be experienced years before a diagnosis of dementia is made.” Dr. Campbell is also an assistant professor of pharmacy practice at Purdue University College of Pharmacy.

“These findings make it clear that clinicians need to carefully consider the anticholinergic burden of their patients and weigh other options,” said study co-author Malaz Boustani, M.D., MPH, a Regenstrief Institute and IU Center for Aging Research investigator. Dr. Boustani is the founder of the Indiana Clinical and Translational Science Institute’s IU Center for Health Innovation and Implementation Science and the Richard M. Fairbanks Professor of Aging Research at IU School of Medicine.

“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,” Dr. Boustani said.

The study, which was led by the University of East Anglia and funded by the Alzheimer’s Society, both in the UK, utilized data from the Clinical Practice Research Datalink which includes anonymized diagnosis, referral and prescription records for more than 11 million patients from 674 primary care practices across the UK. The data is broadly representative of the UK population in terms of age, sex and ethnicity.

“This research is really important because there are an estimated 350 million people affected globally by depression. Bladder conditions requiring treatment are estimated to affect over 13 percent of men and 30 percent of women in the UK and US,” said study lead researcher George Savva, PhD, visiting researcher at University of East Anglia’s School of Health Sciences.

pill bottle

The researchers found greater incidence of dementia among patients prescribed anticholinergic antidepressants, anticholinergic bladder medications and anticholinergic Parkinson’s disease medications than among older adults who were not prescribed these drugs. NeuroscienceNews.com image is in the public domain.

“We don’t know exactly how anticholinergics might cause dementia,” said study co-author Chris Fox, MD, professor of clinical psychiatry at UEA’s Norwich Medical School and a consultant psychiatrist. “Further research is needed to understand possible reasons for this link. In the meantime, I strongly advise patients with any concerns to continue taking their medicines until they have consulted their doctor or pharmacist.”

Study co-author Ian Maidment, PhD, senior lecturer in clinical pharmacy at Aston University in the UK, said: “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.”

About this neuroscience research article

In addition to Regenstrief Institute, IU, Purdue, University of East Anglia and Aston University investigators, collaborators included researchers from the University of Aberdeen, the Royal College of Surgeons in Ireland, Newcastle University, and the University of Cambridge.

Funding: The Alzheimer’s Society funded this study.

Source: Cindy Fox Aisen – Regenstrief Institute
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “Anticholinergic Medication and Risk of Dementia: Case-control Study” by Kathryn Richardson, Chris Fox, Ian Maidment, Nicholas Steel, Yoon K Loke, Antony Arthur, Phyo K Myint, Carlota M Grossi, Katharina Mattishent, Kathleen Bennett, Noll L Campbell, Malaz Boustani, Louise Robinson, Carol Brayne, Fiona E Matthews, and George M Savva in The BMJ. Published April 25 2018.
doi:10.1136/bmj.k1315

Cite This NeuroscienceNews.com Article
Regenstrief Institute “Common Class of Drugs Linked to Dementia, Even When Taken 20 Years Before Diagnosis.” NeuroscienceNews. NeuroscienceNews, 26 April 2018.
<http://neurosciencenews.com/dementia-anticholinergics-8884/>.
Regenstrief Institute (2018, April 26). Common Class of Drugs Linked to Dementia, Even When Taken 20 Years Before Diagnosis. NeuroscienceNews. Retrieved April 26, 2018 from http://neurosciencenews.com/dementia-anticholinergics-8884/
Regenstrief Institute “Common Class of Drugs Linked to Dementia, Even When Taken 20 Years Before Diagnosis.” http://neurosciencenews.com/dementia-anticholinergics-8884/ (accessed April 26, 2018).

Abstract

Anticholinergic Medication and Risk of Dementia: Case-control Study

Objectives To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia.

Design Case-control study.

Setting General practices in the UK contributing to the Clinical Practice Research Datalink.

Participants 40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia.

Interventions Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia.

Main outcome measures Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates.

Results 14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis.

Conclusions A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure.

Trial registration Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.

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