Noll L. Campbell

The cognitive impact of anticholinergics:a clinical review

Context: The cognitive side effects of medications with anticholinergic activity have been documented among older adults in a variety of clinical settings. However, there has been no systematic confirmation that acute or chronic prescribing of such medications lead to transient or permanent adverse cognitive outcomes. Objective: Evaluate the existing evidence regarding the effects of anticholinergic medications on cognition in older adults. Data sources: We searched the MEDLINE, OVID, and CINAHL databases from January, 1966 to January, 2008 for eligible studies. Study selection: Studies were included if the anticholinergic activity was systematically measured and correlated with standard measurements of cognitive performance. Studies were excluded if they reported case studies, case series, editorials, and review articles. Data extraction: We extracted the method used to determine anticholinergic activity of medications and its association with cognitive outcomes. Results: Twenty-seven studies met our inclusion criteria. Serum anticholinergic assay was the main method used to determine anticholinergic activity. All but two studies found an association between the anticholinergic activity of medications and either delirium, cognitive impairment or dementia. Conclusions: Medications with anticholinergic activity negatively affect the cognitive performance of older adults. Recognizing the anticholinergic activity of certain medications may represent a potential tool to improve cognition.

Impact of anticholinergics on the aging brain: a review and practical application

Objective: in an effort to enhance medication prescribing for older adults and reduce the burden of cognitive impairment, this paper reviews the literature regarding the negative impact of anticholinergics on cognitive function and provides clinicians with a practical guidance for anticholinergic use in older adults. Methods: a Medline search identified studies evaluating the use of anticholinergics and the relationship between anticholinergics and cognitive impairment. Results: prescribing anticholinergics for older adults leads to acute cognitive impairment and, possibly, chronic cognitive deficits. Assessing anticholinergic burden with a simple scale may represent a useful noninvasive tool to optimize geriatric pharmacotherapy. Conclusion: more studies are needed to validate the Anticholinergic Cognitive Burden scale and establish therapeutic guidelines in the presence of cognitive anticholinergic adverse effects.

Medication Adherence in Older Adults With Cognitive Impairment: A Systematic Evidence-Based Review

BACKGROUND Cognitive impairment challenges the ability to adhere to the complex medication regimens needed to treat multiple medical problems in older adults. OBJECTIVE Our aim was to conduct a systematic evidence-based review to identify barriers to medication adherence in cognitively impaired older adults and interventions aimed at improving medication adherence. METHODS A search of MEDLINE, EMBASE, PsycINFO, GoogleDocs, and CINAHL for articles published between 1966 and February 29, 2012 was performed. Studies included older adults with a diagnosis of cognitive impairment of any degree (mild cognitive impairment or mild, moderate, or severe dementia). To identify barriers to adherence, we reviewed observational studies. To identify relevant interventions, we reviewed clinical trials targeting medication adherence in cognitively impaired older adults. We excluded studies lacking a measure of medication adherence or lacking an assessment of cognitive function, case reports or series, reviews, and those focusing on psychiatric disorders or infectious diseases. Population demographics, baseline cognitive function, medication adherence methods, barriers to adherence, and prospective intervention methodologies were extracted. RESULTS The initial search identified 594 articles. Ten studies met inclusion criteria for barriers to adherence and three met inclusion criteria for interventional studies. Unique barriers to adherence included understanding new directions, living alone, scheduling medication administration into the daily routine, using potentially inappropriate medications, and uncooperative patients. Two studies evaluated reminder systems and showed no benefit in a small group of participants. One study improved adherence through telephone and televideo reminders at each dosing interval. The results of the review are limited by reviewing only published articles, missing barriers or interventions due to lack of subgroup analysis, study selection and extraction completed by 1 reviewer, and articles with at least an abstract published in English. CONCLUSIONS The few studies identified limit the assessment of barriers to medication adherence in the cognitively impaired population. Successful interventions suggest that frequent human communication as reminder systems are more likely to improve adherence than nonhuman reminders.

Impact and recognition of cognitive impairment among hospitalized elders.

BACKGROUND Older adults are predisposed to developing cognitive deficits. This increases their vulnerability for adverse health outcomes when hospitalized. OBJECTIVE To determine the prevalence and impact of cognitive impairment (CI) among hospitalized elders based on recognition by lCD-coding versus screening done on admission. DESIGN Observational cohort study. SETTING Urban public hospital in Indianapolis. PATIENTS 997 patients age 65 and older admitted to medical services between July 2006 and March 2008. MEASUREMENTS Impact of CI in terms of length of stay, survival, quality of care and prescribing practices. Cognition was assessed by the Short Portable Mental Status Questionnaire (SPMSQ). RESULTS 424 patients (43%) were cognitively impaired. Of those 424 patients with CI, 61% had not been recognized by ICD-9 coding. Those unrecognized were younger (mean age 76.1 vs. 79.1, P <0.001); had more comorbidity (mean Charlson index of 2.3 vs.1.9, P = 0.03), had less cognitive deficit (mean SPMSQ 6.3 vs. 3.4, P < 0.001). Among elders with CI, 163 (38%) had at least one day of delirium during their hospital course. Patients with delirium stayed longer in the hospital (9.2 days vs. 5.9, P < 0.001); were more likely to be discharged into institutional settings (75% vs. 31%, P < 0.001) and more likely to receive tethers during their care (89% vs. 69%, P < 0.001), and had higher mortality (9% vs. 4%, P = 0.09). CONCLUSION Cognitive impairment, while common in hospitalized elders, is under-recognized, impacts care, and increases risk for adverse health outcomes.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality: a systematic review

OBJECTIVES to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes. DESIGN electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible. RESULTS forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good. CONCLUSION medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes.

Use of anticholinergics and the risk of cognitive impairment in an African American population

Background: Anticholinergic properties of certain medications often go unrecognized, and are frequently used by the elderly population. Few studies have yet defined the long-term impact of these medications on the incidence of cognitive impairment. Methods: We report a 6-year longitudinal, observational study, evaluating 1,652 community-dwelling African American subjects over the age of 70 years who were enrolled in the Indianapolis-Ibadan Dementia Project between 2001 and 2007 and who had normal cognitive function at baseline. The exposure group included those who reported the baseline use of possible or definite anticholinergics as determined by the Anticholinergic Cognitive Burden scale. Our main outcome measure was the incidence of cognitive impairment, defined as either dementia or cognitive impairment not dementia, or poor performance on a dementia screening instrument during the follow-up period. Results: At baseline, 53% of the population used a possible anticholinergic, and 11% used a definite anticholinergic. After adjusting for age, gender, educational level, and baseline cognitive performance, the number of definite anticholinergics was associated with an increased risk of cognitive impairment (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.07–1.99; p = 0.02), whereas the number of possible anticholinergics at baseline did not increase the risk (OR 0.96, 95% CI 0.85–1.09; p = 0.55). The risk of cognitive impairment among definite anticholinergic users was increased if they were not carriers of the APOE ε4 allele (OR 1.77, 95% CI 1.03–3.05; p = 0.04). Conclusions: Limiting the clinical use of definite anticholinergics may reduce the incidence of cognitive impairment among African Americans.

Long-term anticholinergic use and the aging brain

Older Americans are facing an epidemic of chronic diseases and are thus exposed to anticholinergics (ACs) that might negatively affect their risk of developing mild cognitive impairment (MCI) or dementia.

Delirium in hospitalized patients: Implications of current evidence on clinical practice and future avenues for research—A systematic evidence review

BACKGROUND Despite the significant burden of delirium among hospitalized adults, critical appraisal of systematic data on delirium diagnosis, pathophysiology, treatment, prevention, and outcomes is lacking. PURPOSE To provide evidence-based recommendations for delirium care to practitioners, and identify gaps in delirium research. DATA SOURCES Medline, PubMed, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) information systems from January 1966 to April 2011. STUDY SELECTION All published systematic evidence reviews (SERs) on delirium were evaluated. DATA EXTRACTION Three reviewers independently extracted the data regarding delirium risk factors, diagnosis, prevention, treatment, and outcomes, and critically appraised each SER as good, fair, or poor using the United States Preventive Services Task Force criteria. DATA SYNTHESIS Twenty-two SERs graded as good or fair provided the data. Age, cognitive impairment, depression, anticholinergic drugs, and lorazepam use were associated with an increased risk for developing delirium. The Confusion Assessment Method (CAM) is reliable for delirium diagnosis outside of the intensive care unit. Multicomponent nonpharmacological interventions are effective in reducing delirium incidence in elderly medical patients. Low-dose haloperidol has similar efficacy as atypical antipsychotics for treating delirium. Delirium is associated with poor outcomes independent of age, severity of illness, or dementia. CONCLUSION Delirium is an acute, preventable medical condition with short- and long-term negative effects on a patients cognitive and functional states.

Association between prescribing of anticholinergic medications and incident delirium: a cohort study.

To describe the association between anticholinergic medications and incident delirium in hospitalized older adults with cognitive impairment and to test the hypothesis that anticholinergic medications would increase the risk of incident delirium.

Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: A meta-analysis

Objective To determine the efficacy of cholinesterase inhibitors (ChEIs) in improving the behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer’s disease (AD). Data sources We searched MEDLINE, Cochrane Registry, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1966 to 2007. We limited our search to English Language, full text, published articles and human studies. Data extraction We included randomized, double-blind, placebo-controlled trials evaluating the efficacy of donepezil, rivastigmine, or galantamine in managing BPSD displayed by AD patients. Using the United States Preventive Services Task Force (USPSTF) guidelines, we critically appraised all studies and included only those with an attrition rate of less than 40%, concealed measurement of the outcomes, and intention to treat analysis of the collected data. All data were imputed into pre-defined evidence based tables and were pooled using the Review Manager 4.2.1 software for data synthesis. Results We found 12 studies that met our inclusion criteria but only nine of them provided sufficient data for the meta-analysis. Among patients with mild to severe AD and in comparison to placebo, ChEIs as a class had a beneficial effects on reducing BPSD with a standard mean difference (SMD) of −0.10 (95% confidence interval [CI]; −0.18, −0.01) and a weighted mean difference (WMD) of −1.38 neuropsychiatry inventory point (95% CI; −2.30, −0.46). In studies with mild AD patients, the WMD was −1.92 (95% CI; −3.18, −0.66); and in studies with severe AD patients, the WMD was −0.06 (95% CI; −2.12, +0.57). Conclusion Cholinesterase inhibitors lead to a statistical significant reduction in BPSD among patients with AD, yet the clinical relevance of this effect remains unclear.