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Anticholinergic drugs and risk of dementia: case-control study

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      Abstract

      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.

      Related collections

      Most cited references 42

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      Data Resource Profile: Clinical Practice Research Datalink (CPRD)

      The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9% of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research.
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        Dementia prevention, intervention, and care

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          Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts.

          Medication toxic effects and drug-related problems can have profound medical and safety consequences for older adults and economically affect the health care system. The purpose of this initiative was to revise and update the Beers criteria for potentially inappropriate medication use in adults 65 years and older in the United States. This study used a modified Delphi method, a set of procedures and methods for formulating a group judgment for a subject matter in which precise information is lacking. The criteria reviewed covered 2 types of statements: (1) medications or medication classes that should generally be avoided in persons 65 years or older because they are either ineffective or they pose unnecessarily high risk for older persons and a safer alternative is available and (2) medications that should not be used in older persons known to have specific medical conditions. This study identified 48 individual medications or classes of medications to avoid in older adults and their potential concerns and 20 diseases/conditions and medications to be avoided in older adults with these conditions. Of these potentially inappropriate drugs, 66 were considered by the panel to have adverse outcomes of high severity. This study is an important update of previously established criteria that have been widely used and cited. The application of the Beers criteria and other tools for identifying potentially inappropriate medication use will continue to enable providers to plan interventions for decreasing both drug-related costs and overall costs and thus minimize drug-related problems.
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            Author and article information

            Affiliations
            [1 ]School of Health Sciences, University of East Anglia, Norwich NR4 7TJ, UK
            [2 ]Norwich Medical School, University of East Anglia, Norwich, UK
            [3 ]School of Life and Health Sciences, Aston University, Birmingham, UK
            [4 ]School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK
            [5 ]Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
            [6 ]Department of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, IN, USA
            [7 ]School of Medicine, Indiana University, Indianapolis, IN, USA
            [8 ]Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK
            [9 ]Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK
            [10 ]Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK
            Author notes
            Correspondence to: K Richardson k.richardson@ 123456uea.ac.uk
            Contributors
            Role: research fellow
            Role: professor
            Role: senior lecturer
            Role: professor
            Role: professor
            Role: professor
            Role: professor
            Role: senior research associate
            Role: research fellow
            Role: associate professor
            Role: assistant professor
            Role: professor
            Role: professor
            Role: professor
            Role: professor
            Role: senior lecturer
            Journal
            BMJ
            BMJ
            BMJ-UK
            bmj
            The BMJ
            BMJ Publishing Group Ltd.
            0959-8138
            1756-1833
            2018
            25 April 2018
            : 361
            5915701 rick042315 10.1136/bmj.k1315
            Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

            This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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            Medicine

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