Over-Prescribed Medications, Under-Appreciated Risks: A Review of the Cognitive Effects of Anticholinergic Medications in Older Adults.
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ABSTRACT:
SUBMITTER: Britt DM
PROVIDER: S-EPMC5125613 | biostudies-literature | 2016 May-Jun
REPOSITORIES: biostudies-literature
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Over-Prescribed Medications, Under-Appreciated Risks: A Review of the Cognitive Effects of Anticholinergic Medications in Older Adults.
Britt Daniel M I DM Day Gregory S GS
Missouri medicine 20160501 3
Anticholinergic medications are associated with adverse cognitive effects in cognitively normal and impaired individuals, with a greater magnitude of effect observed in individuals with preexisting cognitive impairment due to Alzheimer disease. ...[more]
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Project description:BackgroundThis study examines the effect of initiating medications with anticholinergic activity on the cognitive functions of older persons.MethodsParticipants were 896 older community-dwelling, Catholic clergy without baseline dementia. Medication data was collected annually. The Anticholinergic Cognitive Burden Scale was utilized to identify use of a medication with probable or definite anticholinergic activity. Participants had at least two annual cognitive evaluations.ResultsOver a mean follow-up of 10 years, the annual rate of global cognitive function decline for never users, prevalent users, and incident users was -0.062 (SE?=?0.005), -0.081(SE?=?0.011), and -0.096 (SE?=?0.007) z-score units/year, respectively. Compared to never users, incident users had a more rapid decline (difference?=?-0.034 z-score units/year, SE?=?0.008, p<0.001) while prevalent users did not have a significantly more rapid decline (p?=?0.1).ConclusionsOlder persons initiating a medication with anticholinergic activity have a steeper annual decline in cognitive functioning than those who are not taking these medications.
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Project description:PurposeAnticholinergic burden (ACB), the cumulative effect of anticholinergic medications, is associated with adverse outcomes in older people but is less studied in middle-aged populations. Numerous scales exist to quantify ACB. The aims of this study were to quantify ACB in a large cohort using the 10 most common anticholinergic scales, to assess the association of each scale with adverse outcomes, and to assess overlap in populations identified by each scale.MethodsWe performed a longitudinal analysis of the UK Biobank community cohort (502,538 participants, baseline age: 37-73 years, median years of follow-up: 6.2). The ACB was calculated at baseline using 10 scales. Baseline data were linked to national mortality register records and hospital episode statistics. The primary outcome was a composite of all-cause mortality and major adverse cardiovascular event (MACE). Secondary outcomes were all-cause mortality, MACE, hospital admission for fall/fracture, and hospital admission with dementia/delirium. Cox proportional hazards models (hazard ratio [HR], 95% CI) quantified associations between ACB scales and outcomes adjusted for age, sex, socioeconomic status, body mass index, smoking status, alcohol use, physical activity, and morbidity count.ResultsAnticholinergic medication use varied from 8% to 17.6% depending on the scale used. For the primary outcome, ACB was significantly associated with all-cause mortality/MACE for each scale. The Anticholinergic Drug Scale was most strongly associated with mortality/MACE (HR = 1.12; 95% CI, 1.11-1.14 per 1-point increase in score). The ACB was significantly associated with all secondary outcomes. The Anticholinergic Effect on Cognition scale was most strongly associated with dementia/delirium (HR = 1.45; 95% CI, 1.3-1.61 per 1-point increase).ConclusionsThe ACB was associated with adverse outcomes in a middle- to older-aged population. Populations identified and effect size differed between scales. Scale choice influenced the population identified as potentially requiring reduction in ACB in clinical practice or intervention trials.
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Project description:Patients with psychotic disorders are often treated with numerous medications, many of which have anticholinergic activity. We assessed cognition in relation to the cumulative anticholinergic burden of multiple drugs included in treatment regimens of participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study.Clinically stable participants with schizophrenia (n=206), schizoaffective disorder (n=131), and psychotic bipolar disorder (n=146) were examined. Anticholinergic properties of all scheduled drugs were quantified using the Anticholinergic Drug Scale (ADS). ADS scores were summed across individual drugs to create a total ADS burden score for each participant and examined in relation to the Brief Assessment of Cognition in Schizophrenia (BACS).Anticholinergic burden aggregated across all medications was inversely related to cognitive performance starting at ADS scores of 4 in participants with schizophrenia. Those with ADS scores ?4 had lower composite BACS scores compared to those with ADS<4 (p=0.004). Among BACS subtests, Verbal Memory was the most adversely affected by high anticholinergic burden. Despite similar anticholinergic burden scores across groups, a significant threshold effect of anticholinergic burden was not detected in schizoaffective or psychotic bipolar disorder.We identified an adverse effect threshold of anticholinergic burden on cognition in clinically stable participants with schizophrenia. This relationship was not identified in affective psychoses. Examination of other medications, doses, and clinical measures did not account for these findings. Patients with schizophrenia may have increased cognitive susceptibility to anticholinergic medications and the aggregate effects of one's medication regimen may be important to consider in clinical practice.
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Project description:Introduction: Prescribing cascade refers to use of a medication to treat a drug-related adverse event. Prescribing cascades increase medication use, cost, and risk of adverse events. Objective: Our objective was to use administrative health data to identify whether use of medications from the anticholinergic cognitive burden scale was associated with proton pump inhibitor (PPI) prescribing consistent with a prescribing cascade in older adults with dementia. Method: The cohort was comprised of Nova Scotia Seniors' Pharmacare beneficiaries identified to have dementia and medication dispensation data recorded between 1 April 2010, or cohort entry and 31 March 2015. Anticholinergic medications from the anticholinergic cognitive burden scale (ACB) were abstracted. A look back period of 365 days identified if a PPI had been dispensed preceding anticholinergic dispensation. PPI initiation within 30, 60, 90, or 180 days of the anticholinergic medication was assessed. Demographic description of those dispensed anticholinergic medications or PPIs were reported. Risk factors for the prescribing cascade were investigated with logistic regression and Cox proportional hazards modelling including a sex-stratified analysis. Results: We identified 28,952 Nova Scotia Seniors' Pharmacare beneficiaries with dementia and prescription dispensation data. Anticholinergic medications were frequently dispensed with 63.4% of the cohort dispensed at least one prescription for an anticholinergic medication. The prescribing cascade defined as up to 180-days between anticholinergic medication inititation and PPI dispensation, occurred in 1,845 Nova Scotia Seniors' Pharmacare beneficiaries with dementia (incidence 6.4%). Multivariate regression showed those experiencing the prescribing cascade after initiating any anticholinergic were younger (OR 0.98, 95%CI [0.97-0.98]), less likely to live in an urban location (OR 0.82, 95%CI [0.74-0.91]), or to be men (OR 0.74, 95%CI [0.67-0.82]). Cox regression demonstrated an increased risk of starting a PPI within 180 days when initiating any medication from the ACB (HR 1.38, 95%CI [1.29-1.58]). Discussion: Regression modelling suggested that anticholinergic medications increased the risk of PPI dispensation consistent with a prescribing cascade in the cohort. The identification of the prescribing cascade in this population of older Nova Scotia Seniors' Pharmacare Program beneficiaries with dementia using administrative health data highlights how routinely collected health data can be used to identify prescribing cascades.
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Project description: Not available
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Project description:Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder, characterized by age inappropriate and impairing levels of inattention and/or hyperactivity/impulsivity. Pharmacotherapy is an important part of the ADHD multimodal treatment. The extent to which ADHD is pharmacologically over or under treated worldwide is controversial. We aimed to estimate the pooled worldwide rate of ADHD pharmacological treatment in individuals with and without the disorder.We will include published or unpublished studies reporting the rates of ADHD pharmacological treatment in participants with and without ADHD of any age group. Population-based, cohort, or follow-up studies, as well as data from insurance health system and third-party reimbursements will be eligible. Searches will be performed in a large number of electronic databases, including Medline, Embase, CINAHL, Cochrane, PsycINFO, Web of Science, and Scopus. The primary outcome will be the prevalence of ADHD pharmacological treatment in individuals with ADHD and without ADHD. Two independent reviewers will perform the screening, and data extraction process. Study quality/bias will be assessed with the Newcastle-Ottawa scale by 2 independent reviewers. To test the robustness of the findings, we will perform a series of sensitivity and meta-regression analysis. Analyses will be performed with R and STATA software.No IRB approval will be necessary. The results of this systematic review and meta-analysis will be presented at international conferences and published in peer-reviewed journals.PROSPERO 2018 CRD42018085233.
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Project description:ObjectiveTo determine the cognitive consequences of anticholinergic medications (aCH) in cognitively normal older adults as well as interactive effects of genetic and CSF Alzheimer disease (AD) risk factors.MethodsA total of 688 cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative were evaluated (mean age 73.5 years, 49.6% female). Cox regression examined risk of progression to mild cognitive impairment (MCI) over a 10-year period and linear mixed effects models examined 3-year rates of decline in memory, executive function, and language as a function of aCH. Interactions with APOE ε4 genotype and CSF biomarker evidence of AD pathology were also assessed.ResultsaCH+ participants had increased risk of progression to MCI (hazard ratio [HR] 1.47, p = 0.02), and there was a significant aCH × AD risk interaction such that aCH+/ε4+ individuals showed greater than 2-fold increased risk (HR 2.69, p < 0.001) for incident MCI relative to aCH-/ε4-), while aCH+/CSF+) individuals demonstrated greater than 4-fold (HR 4.89, p < 0.001) increased risk relative to aCH-/CSF-. Linear mixed effects models revealed that aCH predicted a steeper slope of decline in memory (t = -2.35, p = 0.02) and language (t = -2.35, p = 0.02), with effects exacerbated in individuals with AD risk factors.ConclusionsaCH increased risk of incident MCI and cognitive decline, and effects were significantly enhanced among individuals with genetic risk factors and CSF-based AD pathophysiologic markers. Findings underscore the adverse impact of aCH medications on cognition and the need for deprescribing trials, particularly among individuals with elevated risk for AD.
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Project description:BackgroundMedications with potent anticholinergic properties have well-documented adverse effects. A high cumulative anticholinergic burden may arise from the concurrent use of multiple medications with weaker anticholinergic effects. We sought to identify patterns of high anticholinergic burden and associated patient characteristics.MethodsWe identified patients aged ≥ 65 who filled ≥ 1 medication with anticholinergic adverse effects in 2019 and had a cumulative Anticholinergic Burden score (ACB) ≥ 4 (i.e., high anticholinergic burden) in a large US health insurer. We classified patients based on how they attained high burden, as follows: 1) only filling strong or moderate anticholinergic medications (i.e., ACB = 2 or 3, "moderate/strong"), 2) only filling lightly anticholinergic medications (i.e., ACB = 1, "light/possible"), and 3) filling any combination ("mix"). We used multinomial logistic regression to assess the association between measured patient characteristics and membership in the three anticholinergic burden classifications, using the moderate/strong group as the referent.ResultsIn total, 83,286 eligible patients with high anticholinergic burden were identified (mean age: 74.3 years (SD:7.1), 72.9% female). Of these, 4.5% filled only strong/moderate anticholinergics, 4.3% filled only light/possible anticholinergics, and the rest filled a mix (91.2%). Within patients in the mixed group, 64.3% of medication fills were for light/possible anticholinergics, while 35.7% were for moderate/strong anticholinergics. Compared with patients in the moderate/strong anticholinergics group, patients filling only light/possible anticholinergics were more likely to be older (adjusted Odds Ratio [aOR] per 1-unit of age: 1.06, 95%CI: 1.05-1.07), less likely to be female (aOR: 0.56, 95%CI: 0.50-0.62 vs. male), more likely to have comorbidities (e.g., heart failure aOR: 3.18, 95%CI: 2.70-3.74 or depression aOR: 1.20, 95%CI: 1.09-1.33 vs. no comorbidity), and visited fewer physicians (aOR per 1-unit of change: 0.98, 95%CI: 0.97-0.98). Patients in the mixed group were older (aOR per 1-unit of age: 1.02, 95%CI: 1.02-1.03) and less likely to be female (aOR: 0.89, 95%CI: 0.82-0.97 vs. male) compared with those filling moderate/strong anticholinergics.ConclusionMost older adults accumulated high anticholinergic burden through a combination of light/possible and moderate/strong anticholinergics rather than moderate/strong anticholinergics, with light/possible anticholinergics being the major drivers of overall anticholinergic burden. These insights may inform interventions to improve prescribing in older adults.
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Project description:BackgroundAge-associated decline in central cholinergic activity makes older adults susceptible to the harmful effects of anticholinergic (AC) medications; however, there is an inadequate understanding of the association and possible effects of AC drugs on cognition. This cross-sectional study examines the associations of AC medications on cognition among older adults with questionable cognitive impairment (QCI).MethodsFor this cross-sectional study, we used a multicenter database of community-dwelling older adults (N = 7351) aged 60+ years with QCI, from September 2005 to March 2014, as the baseline data. The Anticholinergic Drug Scale was used to categorize AC drug load into no, low, or moderate/high groups. Individuals with a Clinical Dementia Rating-Sum of Boxes score between 0.5 and 2.5 were identified as having QCI, while cognitive performance was evaluated using the Neuropsychological Test Battery. The mean z-scores of neuropsychological tests were grouped into a global cognition score.ResultsParticipants who took AC medications were older, largely female, and had a higher prevalence of incontinence than those without AC exposure. Global cognition was significantly greater in the moderate/high-AC group than the no-AC group (-0.23 ± 0.53 vs. -0.32 ± 0.53). Multivariable linear regression showed that the global cognition score among the low- and moderate/high-AC groups, compared with the no-AC group, was 0.064 higher (p = 0.006 and p = 0.12, respectively).ConclusionsThis cross-sectional study indicates that older adults with QCI who were exposed to AC medications might have higher global cognitive scores than those without AC exposure. The observed associations indicate that older adults might experience some beneficial cognitive effects from AC drugs, possibly due to the therapeutic effects of these medications in controlling comorbidities, thus outweighing their adverse effects on cognition.
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Project description:Objectives: Many medications have cognitive impairment, memory loss, amnesia, or dementia as side effects ("cognitive side effects" hereafter), but little is known about trends in the prevalence of these medications or their implications for population-level cognitive impairment. Method: We use data from the National Health and Nutrition Examination Survey (1999-2016) to describe trends in the use of medications with cognitive side effects among adults aged 60+ (N = 16,937) and their implications for cognitive functioning (measured using word learning and recall, animal fluency, and digit symbol substitution assessments). Results: Between 1999 to 2000 and 2015 to 2016, the prevalence of older adults taking one, two, and at least three medications with cognitive side effects increased by 10.2%, 57.3%, and 298.7%, respectively. Compared to non-users, respondents who simultaneously used three or more medications with cognitive side effects scored 0.22 to 0.27 standard deviations lower in word learning and recall (p = .02), digit symbol substitution (p < .01), and the average standardized score of the three assessments (p < .001). Limitation: Dosage of medications associated with cognitive side effects was not measured. Discussion: Concurrent use of medications with cognitive side effects among older adults has increased dramatically over the past two decades. The use of such medications is associated with cognitive impairment and may explain for disparities in cognitive function across subgroups. These findings highlight the need for cognitive screenings among patients who consume medications with cognitive side effects. They also highlight the synergic effects of polypharmacy and potential drug-drug interactions that result in cognitive deficits.
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