Antiepileptic drug use and mortality among community-dwelling persons with Alzheimer disease.
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ABSTRACT: Objective
To evaluate the risk of death in relation to incident antiepileptic drug (AED) use compared with nonuse in people with Alzheimer disease (AD) through the assessment in terms of duration of use, specific drugs, and main causes of death.Methods
The MEDALZ (Medication Use and Alzheimer Disease) cohort study includes all Finnish persons who received a clinically verified AD diagnosis (n = 70,718) in 2005-2011. Incident AED users were identified with 1-year washout period. For each incident AED user (n = 5,638), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional regression models and inverse probability of treatment weighting (IPTW).Results
Nearly 50% discontinued AEDs within 6 months. Compared with nonusers, AED users had an increased relative risk of death (IPTW hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.12-1.36). This was mainly due to deaths from dementia (IPTW HR, 1.62; 95% CI, 1.42-1.86). There was no difference in cardiovascular and cerebrovascular deaths (IPTW HR, 0.98; 95% CI, 0.67-1.44). The overall mortality was highest during the first 90 days of AED use (IPTW HR, 2.40; 95% CI, 1.91-3.03). Among users of older AEDs, relative risk of death was greater compared to users of newer AEDs (IPTW HR, 1.79; 95% CI, 1.52-2.16).Conclusion
In older vulnerable patients with a cognitive disorder, careful consideration of AED initiation and close adverse events monitoring are needed.
SUBMITTER: Sarycheva T
PROVIDER: S-EPMC7526675 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background People with Alzheimer disease ( AD ) are more predisposed to seizures than older people in general, and use of antiepileptic drugs ( AED s) is more frequent. AED use has been linked to a higher risk of vascular events in the general population; however, it is not evident whether the same risk exists in people with AD . We assessed the risk of stroke associated with incident AED use among people with AD . Methods and Results The MEDALZ (Medication Use and Alzheimer's Disease) cohort includes all Finnish people who received a clinically verified AD diagnosis (N=70718) from 2005 to 2011. People with previous strokes were excluded. For each incident AED user (n=5617) one nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional hazards models and inverse probability of treatment weighting. Compared with nonuse, AED use was associated with an increased risk of stroke (inverse probability of treatment weighting hazard ratio ( HR ), 1.37; 95% confidence interval [CI], 1.07-1.74). The risk was strongest during the first 90 days (adjusted HR , 2.36; 95% CI , 1.25-4.47) of AED use. According to stroke type, the association was with ischemic strokes (inverse probability of treatment weighting HR , 1.34; 95% CI , 1.00-1.79) and hemorrhagic ones (inverse probability of treatment weighting HR , 1.44; 95% CI , 0.86-2.43). The stroke risk of users of older AED s did not differ from that of the users of newer AED s (adjusted HR , 1.04; 95% CI , 0.71-1.53). Conclusions AED use was related to an increased risk of stroke, regardless of AED type. Our results highlight caution in AED use in this vulnerable population.
| S-EPMC6222965 | biostudies-literature
Project description:BACKGROUND:Although antiepileptic drugs (AEDs) have a potential for adverse drug reactions in older populations, little is known about their use in relation to Alzheimer's disease (AD) diagnosis. OBJECTIVES:In this study, we investigated the incidence and prevalence of AED use in relation to AD diagnosis. METHODS:The MEDALZ-study includes all Finnish persons who received clinically verified AD diagnoses (n?=?70,718) during 2005-2011 and a matched comparison cohort without AD (n?=?70,718). AD diagnoses were identified from the Special Reimbursement Register. We used the Prescription Register to identify dispensed AEDs. Incident AED users were identified with a one-year washout period 9-10 years before AD diagnosis, and incidence rates per 100 person-years were calculated for each six-month period from nine years before to five years after AD diagnosis. Prevalence was assessed as proportion using AEDs during each six-month time period for incident use. RESULTS:Persons with AD were more likely to use AEDs during the study period (4.3%) than persons without AD (3.2%). The incidence and prevalence of AED use was higher among persons with AD and increased around the time of AD diagnosis. Epilepsy diagnoses did not explain these differences. Persons with AD were more likely to use older AEDs. CONCLUSION:Our study highlights the need to balance effective symptom control with the possible risks of treatment.
| S-EPMC6226301 | biostudies-other
Project description:BackgroundAntiepileptic drugs (AEDs) have sedative properties which may lead to an increased risk of pneumonia.ObjectivesTo investigate whether incident AED use is associated with an increased risk of pneumonia among community-dwelling persons with Alzheimer's disease (AD). In addition, we determined the risk according to duration of AED use and specific AEDs.MethodsPersons with AD were identified from the MEDALZ dataset which includes all community-dwelling persons who received a clinically verified diagnosis of AD during 2005-2011 in Finland (N=70,718). New AED users were identified with one-year washout period. A matched cohort (1 : 1, N=5,769, matching criteria age, gender, and time since AD diagnoses) of nonusers was formed. Data from nationwide registers included dispensed medications which were modelled with PRE2DUP method, hospitalizations, and causes of death. The association between AED use and hospital admission or death due to pneumonia was analyzed with Cox proportional hazard models.ResultsAED use was associated with an increased risk of pneumonia (adjusted HR 1.92, 95% CI 1.63-2.26; incidence rate per 100 person-years 12.58, 95% CI 12.49-12.66 during AED use and 6.41, 95% CI 6.37-6.45 during nonuse). The highest risk was observed during the first month of use (aHR 3.59, 95% CI 2.29-5.61) and the risk remained elevated until two years of use. Of specific drug substances, phenytoin, carbamazepine, valproic acid, and pregabalin were associated with an increased risk.ConclusionAntiepileptic drug use may increase the risk of pneumonia which is concerning as persons with AD have elevated risk of pneumonia.
| S-EPMC6484268 | biostudies-literature
Project description:People with dementia are at high risk for falls. However, little is known of the features causing falls in Alzheimer disease (AD). Our aim was to investigate how participants with AD fall.In the FINALEX (Finnish Alzheimer Disease Exercise Trial) study, participants' (n = 194) falls were followed up for 1 year by diaries kept by their spouses.The most common reason for falls (n = 355) was stumbling (n = 61). Of the falls, 123 led to injuries, 50 to emergency department visits, and 13 to fractures. The participants without falls (n = 103) were younger and had milder dementia than those with 1 (n = 34) or ≥2 falls (n = 57). Participants with a Mini Mental State Examination score of around 10 points were most prone to fall. In adjusted regression models, good nutritional status, good physical functioning, and use of antihypertensive medication (incident rate ratio [IRR] 0.68, 95% confidence interval [CI] 0.54-0.85) protected against falls, whereas fall history (IRR 2.71, 95% CI 2.13-3.44), osteoarthritis, diabetes mellitus, chronic obstructive pulmonary disease, higher number of drugs, drugs with anticholinergic properties, psychotropics, and opioids (IRR 4.27, 95% CI 2.92-6.24) were risk factors for falls.Our study provides a detailed account on how and why people with AD fall, suggesting several risk and protective factors.
| S-EPMC5498949 | biostudies-other
Project description:BACKGROUND: In the many descriptive studies on prescribed psychotropic drug use by community-dwelling older persons, several sociodemographic and other factors associated with drug use receive inconsistent support. METHOD: Empirical reports with data on at least benzodiazepine or antidepressant drug use in samples of older persons published between 1990 and 2001 (n = 32) were identified from major databases and analyzed to determine which factors are most frequently associated with psychotropic drug use in multivariate analyses. Methodological aspects were also examined. RESULTS: Most reports used probability samples of users and non-users and employed cross-sectional designs. Among variables considered in 5 or more reports, race, proximity to health centers, medical consultations, sleep complaints, and health perception were virtually always associated to drug use. Gender, mental health, and physical health status were associated in about two-thirds of reports. Associations with age, marital status, medication coverage, socioeconomic status, and social support were usually not observed. CONCLUSIONS: The large variety of methods to operationalize drug use, mental health status, and social support probably affected the magnitude of observed relationships. Employing longitudinal designs and distinguishing short-term from long-term use, focusing on samples of drug users exclusively, defining drug use and drug classes more uniformly, and utilizing measures of psychological well-being rather than only of distress, might clarify the nature of observed associations and the direction of causality. Few studies tested specific hypotheses. Most studies focused on individual characteristics of respondents, neglecting the potential contribution of health care professionals to the phenomenon of psychotropic drug use among seniors.
| S-EPMC514897 | biostudies-other
Project description:BackgroundHip fractures are common among persons with Alzheimer's disease (AD), but problems in pain assessment may lead to insufficient analgesia after hospitalization.ObjectiveWe investigated the prevalence of opioid use in the 6 months after discharge from hospital care due to hip fracture among community-dwellers with and without AD.Setting and methodThe Medication use and Alzheimer's disease (MEDALZ) cohort was used for this study, consisting of all community-dwelling persons newly diagnosed with AD during 2005-2011 in Finland and their comparison persons without AD matched on age, sex, and region of residence at the time of AD diagnosis. Data were collected from nationwide healthcare registers.Main outcome measuresWe investigated opioid use versus non-use in persons with and without AD in the 6 months after discharge from hospital care due to hip fracture.ResultsAltogether 2342 persons with AD and 1615 persons without AD, discharged to community settings within ≤ 120 days after a hip fracture, were included. A higher percentage of persons with AD used opioids compared to those without AD, 39.5% [95% confidence interval (CI) 37.5-41.5] versus 31.2% (95% CI 28.9-33.5). Persons with AD used more frequently strong opioids during the first 3 months and buprenorphine during the 6-month period, and used weak opioids less frequently after the first month after discharge compared to those without AD.ConclusionsFrequent opioid use after hospital care due to hip fracture may indicate increased attention to pain among persons with AD. Nevertheless, the benefits and harms of opioid use should be evaluated regularly in community-dwelling older persons.
| S-EPMC7044157 | biostudies-literature
Project description:Clinical decision-making for statin treatment in older patients with coronary artery disease (CAD) is under debate, particularly in community-dwelling frail patients at high risk of death. In this retrospective observational study on 2,597 community-dwelling patients aged ?65 years with a previous hospitalization for CAD, we estimated mortality risk assessed with the Multidimensional Prognostic Index (MPI), based on the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA), used to determine accessibility to homecare services/nursing home admission in 2005 to 2013 in the Padua Health District, Veneto, Italy. Participants were categorized as having mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) baseline mortality risk, and propensity score-adjusted hazard ratios (HRs) of 3-year mortality rate were calculated according to statin treatment in these subgroups. Greater MPI-SVaMA scores were associated with lower rates of statin treatment and higher 3-year mortality rate (MPI-SVaMA-1 = 23.4%; MPI-SVaMA-2 = 39.1%; MPI-SVaMA-3 = 76.2%). After adjusting for propensity score quintiles, statin treatment was associated with lower 3-year mortality risk irrespective of MPI-SVaMA group (HRs [95% confidence intervals] 0.45 [0.37 to 0.55], 0.44 [0.36 to 0.53], and 0.28 [0.21 to 0.39] in MPI-SVaMA-1, -2, and -3 groups, respectively [interaction test p = 0.202]). Subgroup analyses showed that statin treatment was also beneficial irrespective of age (HRs [95% confidence intervals] 0.38 [0.27 to 0.53], 0.45 [0.38 to 0.54], and 0.44 [0.37 to 0.54] in 65 to 74, 75 to 84, and ?85 year age groups, respectively [interaction test p = 0.597]). In conclusion, in community-dwelling frail older patients with CAD, statin treatment was significantly associated with reduced 3-year mortality rate irrespective of age and multidimensional impairment, although the frailest patients were less likely to be treated with statins.
| S-EPMC6121726 | biostudies-literature
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.
| S-EPMC5651434 | biostudies-literature
Project description:BACKGROUND: Glomerular filtration rate (GFR) decline with age increases the risk of inappropriate dosing of drugs. We investigated the determinants and the mortality associated with the use of drugs that are contraindicated or require dose adjustment according to kidney function among the community-dwelling elderly. METHODS: The Three-City population-based study included 8701 participants ?65 years from 1999 to 2001. Exposure to the risk of inappropriate drug dosage was defined as reported use of either a contraindicated drug or one requiring dose adjustment according to the individual baseline glomerular filtration rate estimated (eGFR) with the Modification of Diet in Renal disease study equation. Six-year mortality was analysed using Cox models adjusted for several sociodemographic, biologic and clinical risk factors. RESULTS: The overall percentage of exposure to the risk of inappropriate drug use was 13.3% (contraindication, 0.8%): it was 52.5% (4.5%) in those with an eGFR of 30-59 and 96% (48%) in those <30 mL/min/1.73 m(2). Antihypertensive agents, fibrates and psycholeptics accounted for most of the drugs with dosing recommendations and antidiabetic agents and antihistamines for those contraindicated. Individuals at risk were more likely to be men, older, and under treatment for hypertension or hypercholesterolemia. Exposure to either risk was independently related to higher all-cause mortality (hazard ratio 1.4, 95% confidence interval 1.0-1.9) in participants with eGFR <60 mL/min/1.73 m(2). CONCLUSIONS: Contraindicated drug prescription was uncommon but >10% of the population took drugs requiring renal dosing adjustments. Regular monitoring of eGFR may prevent excess mortality associated with inappropriate drug prescription in the elderly.
| S-EPMC3907357 | biostudies-literature
Project description:Antidepressant use has been associated with an increased risk of falling, but no studies have been conducted on whether antidepressant use is associated with an increased risk of head injuries which often result from falling among older persons. The objective of this study was to investigate the risk of head and brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer's disease.A matched cohort study was conducted by comparing new antidepressant users (n = 10,910) with two matched nonusers (n = 21,820) in the MEDALZ study cohort. The MEDALZ cohort includes all community-dwelling persons newly diagnosed with Alzheimer's disease between 2005 and 2011 in Finland. Incident antidepressant users were identified based on register-based dispensing data from the Prescription register with a 1-year washout period for antidepressant use. Nonusers were matched with users based on age, gender, and time since Alzheimer's disease diagnosis. The outcome events were defined as any head injuries and traumatic brain injuries based on diagnoses in Hospital Discharge and Causes of Death registers. Propensity score adjusted Cox proportional hazard models were utilized. Sensitivity analyses with case-crossover design were conducted. All registers are linkable with unique personal identification numbers assigned for each resident.Antidepressant use was associated with an increased risk of head injuries (age-adjusted event rate per 100 person-years 2.98 (95% confidence interval (CI) 2.49-3.06) during use and 2.43 (95% CI 2.06-2.35) during nonuse, adjusted hazard ratio (HR) 1.35, 95% CI 1.20-1.52) and traumatic brain injuries (age-adjusted event rate per 100 person-years 1.33 (95% CI 1.13-1.53) during use and 1.10 (95% CI 1.00-1.20) during nonuse, adjusted HR 1.26, 95% CI 1.06-1.50). The risk was highest during the first 30 days of use (HR 1.71, 95% CI 1.10-2.66 for head injuries; HR 2.06, 95% CI 1.12-3.82 for traumatic brain injuries) and remained at an elevated level for head injuries for over 2 years of use. In case-crossover analyses, antidepressant use was consistently associated with a higher risk of head injuries.Antidepressant use was associated with an increased risk of the most severe outcomes, head and brain injuries, in persons with Alzheimer's disease. Antidepressant use should be carefully considered and the association confirmed in future studies.
| S-EPMC5540546 | biostudies-other