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Medication Profiles of Patients with Cognitive Impairment and High Anticholinergic Burden.

ABSTRACT: BACKGROUND:Drugs with anticholinergic properties are considered potentially inappropriate in patients with cognitive impairment because harms-including delirium, falls, and fractures-may outweigh benefits. OBJECTIVE:To highlight opportunities to improve clinical decision making and care for patients with cognitive impairment and multiple chronic conditions, we identified distinct subgroups of patients with mild cognitive impairment (MCI) and dementia who had high cumulative anticholinergic burden and specific patterns of anticholinergic use. PATIENTS AND METHODS:We conducted a retrospective cohort study in a not-for-profit, integrated delivery system. Participants included community-dwelling adults aged 65 years and older (n = 13,627) with MCI or dementia and at least two other chronic diseases. We calculated the Anticholinergic Cognitive Burden (ACB) score for each participant from pharmacy and electronic health record (EHR) data. Among individuals with a mean 12-month ACB score ? 2, we used agglomerative hierarchical clustering to identify groups or clusters of individuals with similar anticholinergic prescription patterns. RESULTS:Twenty-four percent (3257 participants) had high anticholinergic burden, defined as an ACB score ? 2. Clinically meaningful clusters based upon anchoring medications or drug classes included a cluster of cardiovascular medications (n = 1497; 46%); two clusters of antidepressant medications (n = 633; 20%); and a cluster based on use of bladder antimuscarinics (n = 431; 13%). Several clusters comprised multiple central nervous system (CNS)-active drugs. CONCLUSIONS:Cardiovascular and CNS-active medications comprise a substantial portion of anticholinergic burden in people with cognitive impairment and multiple chronic conditions. Antidepressants were highly prevalent. Clinical profiles elucidated by these clusters of anticholinergic medications can inform targeted approaches to care.

SUBMITTER: Green AR

PROVIDER: S-EPMC5886812 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Medication Profiles of Patients with Cognitive Impairment and High Anticholinergic Burden.

Green Ariel R AR Reifler Liza M LM Boyd Cynthia M CM Weffald Linda A LA Bayliss Elizabeth A EA

Drugs & aging 20180301 3

<h4>Background</h4>Drugs with anticholinergic properties are considered potentially inappropriate in patients with cognitive impairment because harms-including delirium, falls, and fractures-may outweigh benefits.<h4>Objective</h4>To highlight opportunities to improve clinical decision making and care for patients with cognitive impairment and multiple chronic conditions, we identified distinct subgroups of patients with mild cognitive impairment (MCI) and dementia who had high cumulative antich ...[more]

PMID: 29404965

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Project description:We previously found that subjects with amnestic mild cognitive impairment exhibit a pro-inflammatory immune profile in the cerebrospinal fluid similar to multiple sclerosis, a central nervous system autoimmune disease. We therefore hypothesized that early neuroinflammation would reflect increases in brain amyloid burden during amnestic mild cognitive impairment.Cerebrospinal fluid and blood samples were collected from 24 participants with amnestic mild cognitive impairment (12 men, 12 women; 66?±?6 years; 0.5 Clinical Dementia Rating) enrolled in the AETMCI study. Analyses of cerebrospinal fluid and blood included immune profiling by multi-parameter flow cytometry, genotyping for apolipoprotein (APO)?, and quantification of cytokine and immunoglobin levels. Amyloid (A)? deposition was determined by 18F-florbetapir positron emission tomography. Spearman rank order correlations were performed to assess simple linear correlation for parameters including amyloid imaging, central and peripheral immune cell populations, and protein cytokine levels.Soluble A?42 in the cerebrospinal fluid declined as A? deposition increased overall and in the precuneous and posterior cingulate cortices. Lymphocyte profiling revealed a significant decline in T cell populations in the cerebrospinal fluid, specifically CD4+ T cells, as A? deposition in the posterior cingulate cortex increased. In contrast, increased A? burden correlated positively with increased memory B cells in the cerebrospinal fluid, which was exacerbated in APO?4 carriers. For peripheral circulating lymphocytes, only B cell populations decreased with A? deposition in the precuneous cortex, as peripheral T cell populations did not correlate with changes in brain amyloid burden.Elevations in brain A? burden associate with a shift from T cells to memory B cells in the cerebrospinal fluid of subjects with amnestic mild cognitive impairment in this exploratory cohort. These data suggest the presence of cellular adaptive immune responses during A? accumulation, but further study needs to determine whether lymphocyte populations contribute to, or result from, A? dysregulation during memory decline on a larger cohort collected at multiple centers.AETMCI NCT01146717.

Project description:ObjectivesThe aims of our study were to examine the anticholinergic drug use and to assess the association between anticholinergic burden and cognitive function in the multimorbid elderly patients of the MultiCare cohort.SettingMultiCare was conducted as a longitudinal cohort study in primary care, located in eight different study centres in Germany.Participants3189 patients (59.3% female).Primary and secondary outcome measuresBaseline data were used for the following analyses. Drugs were classified according to the well-established anticholinergic drug scale (ADS) and the recently published German anticholinergic burden (German ACB). Cognitive function was measured using a letter digit substitution test (LDST) and a mixed-effect multivariate linear regression was performed to calculate the influence of anticholinergic burden on the cognitive function.ResultsPatients used 1764 anticholinergic drugs according to ADS and 2750 anticholinergics according to the German ACB score (prevalence 38.4% and 53.7%, respectively). The mean ADS score was 0.8 (±1.3), and the mean German ACB score was 1.2 (±1.6) per patient. The most common ADS anticholinergic was furosemide (5.8%) and the most common ACB anticholinergic was metformin (13.7%). The majority of the identified anticholinergics were drugs with low anticholinergic potential: 80.2% (ADS) and 73.4% (ACB), respectively. An increasing ADS and German ACB score was associated with reduced cognitive function according to the LDST (-0.26; p=0.008 and -0.24; p=0.003, respectively).ConclusionMultimorbid elderly patients are in a high risk for using anticholinergic drugs according to ADS and German ACB score. We especially need to gain greater awareness for the contribution of drugs with low anticholinergic potential from the cardiovascular system. As anticholinergic drug use is associated with reduced cognitive function in multimorbid elderly patients, the importance of rational prescribing and also deprescribing needs to be further evaluated.Trial registration numberISRCTN89818205.

Project description:The complexity of medication therapy in older adults with multiple comorbidities often leads to inappropriate prescribing. Drugs with anticholinergic properties are of particular interest because many are not recognized for this property; their use may lead to increased anticholinergic burden resulting in significant health risks, as well as negatively impacting cognition. Medication therapy management (MTM) interventions showed promise in addressing inappropriate medication use, but the effectiveness of targeted multidisciplinary team interventions addressing anticholinergic medications in older populations is yet to be determined.We conducted an 8-week, parallel-arm, randomized trial to evaluate whether a targeted patient-centered pharmacist-physician team MTM intervention ("targeted MTM intervention") reduced the use of inappropriate anticholinergic medications in older patients enrolled in a longitudinal cohort at University of Kentucky's Alzheimer's Disease Center. Study outcomes included changes in the medication appropriateness index (MAI) targeting anticholinergic medications and in the anticholinergic drug scale (ADS) score from baseline to the end of study.Between October 1, 2014 and September 30, 2015 we enrolled and randomized 50 participants taking at least one medication with anticholinergic properties. Of these, 35 (70%) were women, 45 (90%) were white, and 33 (66%) were cognitively intact (clinical dementia rating [CDR]?=?0); mean age was 77.7?±?6.6 years. At baseline, the mean MAI was 12.6?±?6.3; 25 (50%) of the participants used two or more anticholinergics, and the mean ADS score was 2.8?±?1.6. After randomization, although no statistically significant difference was noted between groups, we identified a potentially meaningful imbalance as the intervention group had more participants with intact cognition, and thus included CDR in all of the analyses. The targeted MTM intervention resulted in statistically significant CDR adjusted differences between groups with regard to improved MAI (change score of 3.6 (1.1) for the MTM group as compared with 1.0 (0.9) for the control group, p?=?0.04) and ADS (change score of 1.0 (0.3) for the MTM group as compared with 0.2 (0.3) for the control group, p?=?0.03).Our targeted MTM intervention resulted in improvement in anticholinergic medication appropriateness and reduced the use of inappropriate anticholinergic medications in older patients. Our results show promise in an area of great importance to ensure optimum outcomes for medications used in older adults.ClinicalTrials.gov NCT02172612 . Registered 20 June 2014.

Dataset Information

Medication Profiles of Patients with Cognitive Impairment and High Anticholinergic Burden.

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Medication Profiles of Patients with Cognitive Impairment and High Anticholinergic Burden.

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