Co-morbidity and drug treatment in Alzheimer's disease. A cross sectional study of participants in the dementia study in northern Norway.
ABSTRACT: BACKGROUND: Inappropriate medical treatment of co-morbidities in Alzheimer's disease (AD) is an increasing concern in geriatric medicine. The objective of this study was to compare current drug use related to co-morbidity between individuals with a recent diagnosis of AD and a cognitively healthy control group in a population based clinical trial in Northern Norway. METHODS: SETTING: Nine rural municipalities with 70,000 inhabitants in Northern Norway. PARTICIPANTS: PARTICIPANTS with and without AD recruited in general practice and by population based screening.187 participants with a recent diagnosis of AD were recruited among community dwellers. Of 791 respondents without cognitive symptoms, 500 were randomly selected and invited to further clinical and cognitive testing. The final control group consisted of 200 cognitively healthy individuals from the same municipalities. Demographic characteristics, data on medical history and current medication were included, and a physical and cognitive examination was performed. The statistical analyses were carried out by independent sample t-test, chi-square, ANCOVA and logistic regression. RESULTS: A co-morbidity score was significantly higher in AD participants compared to controls. The mean number of drugs was higher for AD participants compared to controls (5.1±3.6 and 2.9±2.4 respectively, p<0.001 age and gender adjusted), also when adjusted for co-morbidity. AD participants used significantly more anticholinergic, sedative and antidepressant drugs. For nursing home residents with AD the mean number of drugs was significantly higher compared to AD participants living at home (6.9±3.9 and 4.5±3.3, respectively, p<0.001). CONCLUSIONS: AD participants were treated with a significantly higher number of drugs as compared to cognitively healthy controls, even after adjustment for co-morbidity. An inappropriate use of anticholinergic and sedative drugs was identified, especially among nursing home residents with AD. The drug burden and the increased risk of adverse reactions among individuals suffering from AD need more attention from prescribing doctors.
Project description:BACKGROUND: Evidence is lacking about outcomes associated with the cumulative use of anticholinergic and sedative drugs in people with Alzheimer's disease (AD). This retrospective cohort study investigated the relationship between cumulative exposure to anticholinergic and sedative drugs and hospitalization and mortality in people with and without AD in Finland. METHODS: Community-dwelling people aged 65 years and over, with AD on December 31(st) 2005 (n?=?16,603) and individually matched (n?=?16,603) comparison persons (age, sex, region of residence) were identified by the Social Insurance Institution of Finland. Drug utilization data were extracted from the Finnish National Prescription Register. Exposure to anticholinergic and sedative drugs was defined using the Drug Burden Index (DBI). Hospitalization and mortality data were extracted from national registers. Cox and zero-inflated negative binomial analyses were used to investigate the relationship between DBI and hospitalization and mortality over a one-year follow-up. RESULTS: In total, 5.8% of people with AD and 3.7% without AD died during 2006. For every unit increase in DBI, the adjusted hazard ratio for mortality was 1.21 (95% confidence intervals [CI]: 1.09-1.33) among people with AD, and 1.37 (95%CI: 1.20-1.56) among people without AD. Overall, 44.3% of people with AD and 33.4% without AD were hospitalized. When using no DBI exposure as the reference group, the adjusted incidence rate ratio for length of hospital stay among high DBI group (?1) in people with AD was 1.15 (95%CI: 1.05-1.26) and 1.63 (95%CI: 1.41-1.88) in people without AD. CONCLUSION: There is a dose-response relationship between cumulative anticholinergic and sedative drug use and hospitalization and mortality in people with and without AD.
Project description:INTRODUCTION:We examined how long-term anticholinergic (AC) drug use beginning at midlife affects risk of Alzheimer's disease (AD) and rates of brain atrophy in cognitively normal older adults. METHODS:We followed 723 individuals (mean baseline age 52.3 years; mean follow-up interval 20.1 years) in the Baltimore Longitudinal Study of Aging. The AC drug exposure was defined using the Anticholinergic Cognitive Burden Scale: Nonusers (n = 404), as well as participants exposed to medications with AC activity but without known clinically relevant negative cognitive effects (i.e., "possible AC users"; n = 185) and those exposed to AC drugs with established and clinically relevant negative cognitive effects (i.e., "definite AC users"; n = 134). The neuroimaging sample included 93 participants who remained cognitively normal through follow-up and underwent serial magnetic resonance imaging (n = 93, 724 brain scans, mean follow-up interval 8.2 years, and baseline age 68.6 years). RESULTS:Possible AC users, but not definite AC users, showed increased risk of incident AD compared with nonusers (hazard ratio, 1.63; 95% confidence interval, 1.02-2.61; P = .04) and greater rates of atrophy in total cortical gray matter volume compared with nonusers (? = -0.74, P = .018). Faster rates of brain atrophy were also observed among possible AC users in the right posterior cingulate, as well as right middle frontal and left superior temporal gyri. Data on frequency and duration of medication use were available in only approximately half of the sample. Among these participants, definite AC users had both shorter duration and lower frequency of medication use relative to possible AC users. DISCUSSION:Long-term exposure to medications with mild AC activity during midlife is associated with increased risk of AD and accelerated brain atrophy.
Project description:<h4>Purpose</h4>The Drug Burden Index (DBI) is a non-invasive method to quantify patients' anticholinergic and sedative drug burden from their prescriptions. This systematic review aimed to summarise the evidence on the associations between the DBI and clinical outcomes and methodological quality of studies.<h4>Methods</h4>A search in PubMed and Embase (search terms: 'drug', 'burden', and 'index') was performed and experts were contacted. We excluded publications that did not report empirical results or clinical outcomes. Methodological quality was assessed using the Newcastle-Ottawa Scale. Potential omissions of relevant clinical outcomes and populations were studied.<h4>Results</h4>Of the 2998 identified publications, 21 were eligible. Overall, methodological quality of studies was good. In all but one study, adjustment was made for prevalent co-morbidity. The DBI was examined in diverse older individuals, i.e. both males and females from different settings and countries. However, no studies were conducted in other relevant patient groups, e.g. psychiatric patients. Exposure to anticholinergic and sedative drugs was thoroughly ascertained, though the specific calculation of the DBI differed across studies. Outcomes were assessed from medical records, record linkage or validated objective tests or questionnaires. Many studies found associations between the DBI and outcomes including hospitalisation, physical and cognitive function. Cognitive function and quality of life were understudied and the number and scope of longitudinal studies was limited.<h4>Conclusions</h4>An accumulating body of evidence supports the validity of the DBI. Longitudinal studies of cognitive function and quality of life and in other patient groups, e.g. psychiatric patients, are warranted.
Project description:INTRODUCTION:Targeted deprescribing of anticholinergic and sedative medicines can lead to positive health outcomes in older people; as they have been associated with cognitive and physical functioning decline. This study will examine whether the proposed intervention is feasible at reducing the prescription of anticholinergic and sedative medicines in older people. METHODS AND ANALYSIS:The Standard Protocol Items: Recommendations for Interventional trials (SPIRIT checklist) was used to develop and report the protocol. Single group (precomparison and postcomparison) feasibility study design. STUDY POPULATION:3 residential care homes have been recruited. INTERVENTION:This will involve a New Zealand registered pharmacist using peer-reviewed deprescribing guidelines, to recommend to general practitioners (GPs), sedative and anticholinergic medicines that can be deprescribed. The cumulative use of anticholinergic and sedative medicines for each participant will be quantified, using the Drug Burden Index (DBI). OUTCOMES:The primary outcome will be the change in the participants' DBI total and DBI PRN 3 and 6?months after implementing the deprescribing intervention. Secondary outcomes will include the number of recommendations taken up by the GP, participants' cognitive functioning, depression, quality of life, activities of daily living and number of falls. DATA COLLECTION POINTS:Participants' demographic and clinical data will be collected at the time of enrolment, along with the DBI. Outcome measures will be collected at the time of enrolment, 3 and 6?months' postenrolment. ETHICS AND DISSEMINATION:Ethics approval has been granted by the Human Disability and Ethics Committee. Ethical approval number (16/NTA/61). TRIAL REGISTRATION NUMBER:Pre-results; ACTRN12616000721404.
Project description:Prescribing of medications with anticholinergic properties in older nursing home residents is relatively common, despite an association with an increased risk for falls, delirium, and other outcomes. Few studies have investigated what factors influence different levels of prescribing of these agents.The primary objective was to identify factors associated with low- and high-level anticholinergic burden in nursing home residents. A secondary objective was to examine in detail the contribution of different medications to low versus high burden to aid in determining which drugs to target in interventions.This was a retrospective, cross-sectional analysis of a national sample of 2009-2010 Medicare Part A and B claims, Part D prescription drug events, and Minimum Data Set (MDS) v2.0 assessments. The cohort included 4730 Medicare beneficiaries aged ? 65 years with continuous Medicare Parts A, B, and D enrollment, admitted for non-skilled stays of ? 14 days between 1 January 2010 and 30 September 2010. Anticholinergic burden was defined using the Anticholinergic Cognitive Burden (ACB) scale. Medication scores were summed at the patient level and categorized as high (score ? 3), low (score 1-2), or none. Baseline predisposing factors (age, sex, race/ethnicity), enabling factors (prior year hospitalization, emergency department, primary care, specialist visits; region; Medicaid/low-income subsidy), and medical need factors (dementia severity, anti-dementia medication, Charlson co-morbidity index [CCI], select comorbidities) were evaluated for association with anticholinergic burden using multinomial logistic regression.Overall, 29.6% of subjects had a high anticholinergic burden and 35.2% had a low burden. High burden was most often (72%) due to one highly anticholinergic medication rather than a cumulative effect. In adjusted analyses, factors associated with increased risk of both low and high anticholinergic burden included comorbidity, antidementia medication, depression, hypertension, and prior year hospitalization. Older age was associated with decreased odds of high anticholinergic burden. Urinary incontinence and prior year specialist visit were associated with increased odds of high anticholinergic burden. Severe and nonsevere dementia were associated with decreased odds of low burden but increased odds of high burden.Almost two-thirds of nursing home patients have some degree of anticholinergic burden. Several medical need variables are significantly associated with increased risk for low and high anticholinergic burden. Interventions should be developed to optimize prescribing for residents at increased risk of receiving medications with anticholinergic properties. Future study is needed to evaluate the difference in the risk of adverse outcomes associated with various levels of anticholinergic burden.
Project description:<h4>Purpose</h4>The Drug Burden Index (DBI) is a tool to quantify the anticholinergic and sedative load of drugs. Establishing functional correlates of the DBI could optimize drug prescribing in patients with dementia. In this cross-sectional study, we determined the relationship between DBI and cognitive and physical functions in a sample of patients with dementia.<h4>Methods</h4>Using performance-based tests, we measured physical and cognitive functions in 140 nursing home patients aged over 70 with all-cause dementia. We also determined anticholinergic DBI (AChDBI) and sedative DBI (SDBI) separately and in combination as total drug burden (TDB).<h4>Results</h4>Nearly one half of patients (48%) used at least one DBI-contributing drug. In 33% of the patients, drug burden was moderate (0 < TDB < 1) whereas in 15%, drug burden was high (TDB ??1). Multivariate models yielded no associations between TDB, AChDBI, and SDBI, and physical or cognitive function (all p >?0.05).<h4>Conclusions</h4>A lack of association between drug burden and physical or cognitive function in this sample of patients with dementia could imply that drug prescribing is more optimal for patients with dementia compared with healthy older populations. However, such an interpretation of the data warrants scrutiny as several dementia-related factors may confound the results of the study.
Project description:The Drug Burden Index (DBI) tool quantifies individual exposure to anticholinergic and sedative medications. The DBI has been internationally validated against adverse health outcomes in older people. DBI exposure has not been reported in the Irish older population. This study aimed to: (1) develop a list of drugs with clinically significant anticholinergic and/or sedative effects (DBI medications) relevant to Ireland; (2) examine, using the DBI formula, the prevalence of exposure to DBI medications in Irish older people and (3) explore patient factors associated DBI exposure.A cross-sectional national pharmacy claims database study.Community setting using the General Medical Services (GMS) scheme pharmacy claims database maintained by the Health Service Executive Primary Care Reimbursement Services.Irish older individuals (aged ?65 years) enrolled in the GMS scheme and dispensed at least one prescription item in 2016 (n=428?516).Prevalence of exposure to DBI medications and patient factors associated with DBI exposure.282?874 (66%) of the GMS population aged ?65 years were exposed to at least one DBI medication in 2016. Prevalence of exposure to DBI medications was significantly higher in females than males (females 71.6% vs males 58.7%, adjusted OR 1.65, 95%?CI 1.63 to 1.68). Prevalence of DBI exposure increased progressively with the number of chronic drugs used, rising from 42.7% of those prescribed 0-4 chronic drugs to 95.4% of those on ?12?chronic drugs (adjusted OR 27.8, 95%?CI 26.7 to 29.0). The most frequently used DBI medications were codeine/paracetamol combination products (20.1% of patients), tramadol (11.5%), zopiclone (9.5%), zolpidem (8.5%), pregabalin (7.9%) and alprazolam (7.8%).The majority of older people in Ireland are exposed to medications with anticholinergic and/or sedative effects, particularly females and those with multiple comorbidities. The high use of low-dose codeine/paracetamol combination products, Z-drugs and benzodiazepines, suggests there are opportunities for deprescribing.
Project description:PURPOSE:To identify the proportion of older adults with a high anticholinergic/sedative load and to identify patient subgroups based on type of central nervous system (CNS)-active medication used. METHODS:A cross-sectional study of a nationwide sample of patients with anticholinergic/sedative medications dispensed by 1779 community pharmacies in the Netherlands (90% of all community pharmacies) in November 2016 was conducted. Patients aged older than 65 years with a high anticholinergic/sedative load defined as having a drug burden index (DBI) greater than 1 were included. Proportion of patients with a high anticholinergic/sedative load was calculated by dividing the number of individuals in our study population by the 2.4 million older patients using medications dispensed from study pharmacies. Patient subgroups based on type of CNS-active medications used were identified with latent class analysis. RESULTS:Overall, 8.7% (209 472 individuals) of older adults using medications had a DBI greater than 1. Latent class analysis identified four patient subgroups (classes) based on the following types of CNS-active medications used: "combined psycholeptic/psychoanaleptic medication" (class 1, 57.9%), "analgesics" (class 2, 17.9%), "antiepileptic medication" (class 3, 17.8%), and "anti-Parkinson medication" (class 4, 6.3%). CONCLUSIONS:A large proportion of older adults in the Netherlands had a high anticholinergic/sedative load. Four distinct subgroups using specific CNS-active medication were identified. Interventions aiming at reducing the overall anticholinergic/sedative load should be tailored to these subgroups.
Project description:OBJECTIVE:To evaluate if a pharmacist-led medication review is effective at reducing the anticholinergic/sedative load, as measured by the Drug Burden Index (DBI). DESIGN:Randomised controlled single blind trial. SETTING:15 community pharmacies in the Northern Netherlands. PARTICIPANTS:157 community-dwelling patients aged ?65 years who used ?5 medicines for ?3 months, including at least one psycholeptic/psychoanaleptic medication and who had a DBI?1. INTERVENTION:A medication review by the community pharmacist in collaboration with the patient's general practitioner and patient. PRIMARY AND SECONDARY OUTCOMES MEASURES:The primary outcome was the proportion of patients whose DBI decreased by at least 0.5. Secondary outcomes were the presence of anticholinergic/sedative side effects, falls, cognitive function, activities of daily living, quality of life, hospital admission and mortality. Data were collected at baseline and 3?months follow-up. RESULTS:Mean participant age was 75.7 (SD, 6.9) years in the intervention arm and 76.6 (SD, 6.7) years in the control arm, the majority were female (respectively 69.3% and 72.0%). Logistic regression analysis showed no difference in the proportion of patients with a?0.5?decrease in DBI between intervention arm (17.3%) and control arm (15.9%), (OR 1.04, CI 0.47 to 2.64, p=0.927). Intervention patients scored higher on the Digit Symbol Substitution Test, measure of cognitive function (OR 2.02, CI 1.11 to 3.67, p=0.021) and reported fewer sedative side effects (OR 0.61, CI 0.40 to 0.94, p=0.024) at follow-up. No significant difference was found for other secondary outcomes. CONCLUSIONS:Pharmacist-led medication review as currently performed in the Netherlands was not effective in reducing the anticholinergic/sedative load, measured with the DBI, within the time frame of 3 months. Preventive strategies, signalling a rising load and taking action before chronic use of anticholinergic/sedative medication is established may be more successful. TRIAL REGISTRATION NUMBER:NCT02317666.