HHS Public Access Author manuscript Author Manuscript
Mo Med. Author manuscript; available in PMC 2017 May 01. Published in final edited form as: Mo Med. 2016 ; 113(3): 207–214.
Over-Prescribed Medications, Under-Appreciated Risks: A review of the cognitive effects of anticholinergic medications in older adults Daniel M I Britt1,2 and Gregory S Day, MD, MSc, FRCPC1,3 Daniel M I Britt: [email protected]
Author Manuscript
1Charles 2St.
F and Joanne Knight Alzheimer Disease Research Center
Louis College of Pharmacy, St. Louis, MO
3Washington
University in St. Louis, Department of Neurology, St. Louis, MO
Key words / search terms cognitive impairment; dementia; polypharmacy; anticholinergic medications; Alzheimer disease
Introduction
Author Manuscript
Dementia refers to an acquired syndrome of intra-individual decline in cognitive performance that ultimately interferes with daily functioning. Although the syndromic label of “dementia” may be widely applied, specific etiological diagnoses are reserved for patients meeting well-defined clinicopathological criteria. Of these, Alzheimer disease (AD) represents the most common cause of dementia in individuals over the age of 65,1 most often manifesting with the gradual onset and progression of memory and other cognitive impairment (characterized as AD dementia).2 The prevalence of AD dementia3 is predicted to rise in line with longevity,4 reflecting the strong association between age and AD.5 An estimated 5.1 million Americans over 65 years are currently affected with AD dementia. This number is expected to swell to 5.8 million by 2020,6 plateauing by 2030, at which point all surviving “baby boomers” (persons born between the years 1946 and 1964) will be 65 years or older, and thus at greater risk of AD.3 In the state of Missouri alone, the number of individuals with AD dementia is expected to grow by 20% by 2030,7 with wide-reaching implications for family members, caregivers, support organizations and health systems.1
Author Manuscript
Corresponding Author: Dr. Gregory S Day, Department of Neurology, Washington University in St. Louis, Knight Alzheimer Disease Research Center, 4488 Forest Park Avenue, Suite 101, St. Louis, Missouri; 63108, Telephone: 314.286.2407, Cell: 636.751.1700, [email protected]. Author Contributions: D Britt participated in the conception and design of the study; review of the literature; acquisition, analysis and interpretation of data; and drafting, revising and finalizing the manuscript. GS Day participated in the conception and design of the study; acquisition, analysis and interpretation of data; and drafting, revising and finalizing the manuscript. GS Day had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the review. Author disclosures: D Britt reports no disclosures. GS Day reports no disclosures.
Britt and Day
Page 2
Author Manuscript Author Manuscript
Beyond AD, advancing age is also associated with multiple chronic illnesses, including heart disease, arthritis, diabetes and cancer.8 Aggressive medical management of these conditions and related risk factors is encouraged to reduce long-term morbidity and mortality.9 As a result, elderly individuals are increasingly likely to be prescribed multiple medications for their therapeutic benefits.10, 11 A secondary consequence of this strategy is that risks of medication non-compliance, adverse drug reactions and mortality also increase.12 The potential cognitive adverse effects of medications in older individuals, with and without dementia, is of particular concern, recognizing that acute declines in cognition may further contribute to negative outcomes associated with medication misuse. Of the medications known to associate with cognitive impairment,13 those with anticholinergic properties pose the greatest risk in older individuals because of the broad indications for their use (e.g., treatment of allergic rhinitis, cold and flu symptoms, nausea and vomiting, urinary incontinence and insomnia), the high frequency with which they are encountered in overthe-counter and prescription preparations (eTable 1), and the potential for age-related changes in pharmacokinetics and pharmacodynamics to increase susceptibility to adverse effects. We review the available literature concerning anticholinergic medication use in older adults, with the goals of qualifying their potential adverse cognitive effects and of clarifying strategies for anticholinergic prescribing in this high risk population.
Author Manuscript
We searched PubMED and Google Scholar databases for English-language studies including the terms Alzheimer('s) disease or dementia; AND anticholinergic medication OR serum anticholinergic activity; AND cognitive function, cognition OR cognitive decline. Additional sources were extracted from study references. Studies were reviewed in detail and included in this review if they met the following inclusion criteria: (1) enrolled older participants ≥50 years old; (2) reported exposure to anticholinergic activity or anticholinergic medication; (3) measured cognitive function; and, (4) reported on cognitive outcomes or change in outcomes following exposure to anticholinergic medications. Fifteen publications met these criteria.
Polypharmacy and Alzheimer disease: An Aging Problem
Author Manuscript
Medication use is on the rise in older populations.11, 14 As many as 50% of Americans over 65 years of age are currently prescribed five or more medications 15—meeting even the most conservative definitions of polypharmacy. Individuals with AD dementia are no exception. A cross-sectional study of community-dwelling elders in Chicago found that older individuals with AD dementia on average were prescribed more medications than those without dementia, including medications known to worsen cognitive impairment (4.9±2.6 versus 3.9±2.5; p
Mo Med. Author manuscript; available in PMC 2017 May 01. Published in final edited form as: Mo Med. 2016 ; 113(3): 207–214.
Over-Prescribed Medications, Under-Appreciated Risks: A review of the cognitive effects of anticholinergic medications in older adults Daniel M I Britt1,2 and Gregory S Day, MD, MSc, FRCPC1,3 Daniel M I Britt: [email protected]
Author Manuscript
1Charles 2St.
F and Joanne Knight Alzheimer Disease Research Center
Louis College of Pharmacy, St. Louis, MO
3Washington
University in St. Louis, Department of Neurology, St. Louis, MO
Key words / search terms cognitive impairment; dementia; polypharmacy; anticholinergic medications; Alzheimer disease
Introduction
Author Manuscript
Dementia refers to an acquired syndrome of intra-individual decline in cognitive performance that ultimately interferes with daily functioning. Although the syndromic label of “dementia” may be widely applied, specific etiological diagnoses are reserved for patients meeting well-defined clinicopathological criteria. Of these, Alzheimer disease (AD) represents the most common cause of dementia in individuals over the age of 65,1 most often manifesting with the gradual onset and progression of memory and other cognitive impairment (characterized as AD dementia).2 The prevalence of AD dementia3 is predicted to rise in line with longevity,4 reflecting the strong association between age and AD.5 An estimated 5.1 million Americans over 65 years are currently affected with AD dementia. This number is expected to swell to 5.8 million by 2020,6 plateauing by 2030, at which point all surviving “baby boomers” (persons born between the years 1946 and 1964) will be 65 years or older, and thus at greater risk of AD.3 In the state of Missouri alone, the number of individuals with AD dementia is expected to grow by 20% by 2030,7 with wide-reaching implications for family members, caregivers, support organizations and health systems.1
Author Manuscript
Corresponding Author: Dr. Gregory S Day, Department of Neurology, Washington University in St. Louis, Knight Alzheimer Disease Research Center, 4488 Forest Park Avenue, Suite 101, St. Louis, Missouri; 63108, Telephone: 314.286.2407, Cell: 636.751.1700, [email protected]. Author Contributions: D Britt participated in the conception and design of the study; review of the literature; acquisition, analysis and interpretation of data; and drafting, revising and finalizing the manuscript. GS Day participated in the conception and design of the study; acquisition, analysis and interpretation of data; and drafting, revising and finalizing the manuscript. GS Day had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the review. Author disclosures: D Britt reports no disclosures. GS Day reports no disclosures.
Britt and Day
Page 2
Author Manuscript Author Manuscript
Beyond AD, advancing age is also associated with multiple chronic illnesses, including heart disease, arthritis, diabetes and cancer.8 Aggressive medical management of these conditions and related risk factors is encouraged to reduce long-term morbidity and mortality.9 As a result, elderly individuals are increasingly likely to be prescribed multiple medications for their therapeutic benefits.10, 11 A secondary consequence of this strategy is that risks of medication non-compliance, adverse drug reactions and mortality also increase.12 The potential cognitive adverse effects of medications in older individuals, with and without dementia, is of particular concern, recognizing that acute declines in cognition may further contribute to negative outcomes associated with medication misuse. Of the medications known to associate with cognitive impairment,13 those with anticholinergic properties pose the greatest risk in older individuals because of the broad indications for their use (e.g., treatment of allergic rhinitis, cold and flu symptoms, nausea and vomiting, urinary incontinence and insomnia), the high frequency with which they are encountered in overthe-counter and prescription preparations (eTable 1), and the potential for age-related changes in pharmacokinetics and pharmacodynamics to increase susceptibility to adverse effects. We review the available literature concerning anticholinergic medication use in older adults, with the goals of qualifying their potential adverse cognitive effects and of clarifying strategies for anticholinergic prescribing in this high risk population.
Author Manuscript
We searched PubMED and Google Scholar databases for English-language studies including the terms Alzheimer('s) disease or dementia; AND anticholinergic medication OR serum anticholinergic activity; AND cognitive function, cognition OR cognitive decline. Additional sources were extracted from study references. Studies were reviewed in detail and included in this review if they met the following inclusion criteria: (1) enrolled older participants ≥50 years old; (2) reported exposure to anticholinergic activity or anticholinergic medication; (3) measured cognitive function; and, (4) reported on cognitive outcomes or change in outcomes following exposure to anticholinergic medications. Fifteen publications met these criteria.
Polypharmacy and Alzheimer disease: An Aging Problem
Author Manuscript
Medication use is on the rise in older populations.11, 14 As many as 50% of Americans over 65 years of age are currently prescribed five or more medications 15—meeting even the most conservative definitions of polypharmacy. Individuals with AD dementia are no exception. A cross-sectional study of community-dwelling elders in Chicago found that older individuals with AD dementia on average were prescribed more medications than those without dementia, including medications known to worsen cognitive impairment (4.9±2.6 versus 3.9±2.5; p
