scholarly journals 416 - Risk of Mortality Associated with Antipsychotics in Alzheimer's Disease

2020 ◽  
Vol 32 (S1) ◽  
pp. 132-132
Author(s):  
Liliana P. Ferreira ◽  
Núria Santos ◽  
Nuno Fernandes ◽  
Carla Ferreira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Events ◽  
Mortality Risk ◽  
Antipsychotic Treatment ◽  
Serious Adverse Events ◽  
Risk Of Death ◽  
Mesh Terms ◽  
Risk Of Mortality ◽  
Increased Risk

Objectives: Alzheimer's disease (AD) is the most common cause of dementia and it is associated with increased mortality. The use of antipsychotics is common among the elderly, especially in those with dementia. Evidence suggests an increased risk of mortality associated with antipsychotic use. Despite the short-term benefit of antipsychotic treatment to reduce the behavioral and psychological symptoms of dementia, it increases the risk of mortality in patients with AD. Our aim is to discuss the findings from the literature about risk of mortality associated with the use of antipsychotics in AD.Methods: We searched Internet databases indexed at MEDLINE using following MeSH terms: "Antipsychotic Agents" AND "Alzheimer Disease" OR "Dementia" AND "Mortality" and selected articles published in the last 5 years.Results: Antipsychotics are widely used in the pharmacological treatment of agitation and aggression in elderly patients with AD, but their benefit is limited. Serious adverse events associated with antipsychotics include increased risk of death. The risk of mortality is associated with both typical and atypical antipsychotics. Antipsychotic polypharmacy is associated with a higher mortality risk than monotherapy and should be avoided. The mortality risk increases after the first few days of treatment, gradually reducing but continues to increase after two years of treatment. Haloperidol is associated with a higher mortality risk and quetiapine with a lower risk than risperidone.Conclusions: If the use of antipsychotics is considered necessary, the lowest effective dose should be chosen and the duration should be limited because the mortality risk remains high with long-term use. The risk / benefit should be considered when choosing the antipsychotic. Further studies on the efficacy and risk of adverse events with antipsychotics are needed for a better choice of treatment and adequate monitoring with risk reduction.

scholarly journals The Impact of a Long-Term Rivastigmine and Donepezil Treatment on All-Cause Mortality in Patients With Alzheimer’s Disease

2018 ◽  
Vol 33 (6) ◽  
pp. 385-393 ◽  
Author(s):  
Jakub Kazmierski ◽  
Chaido Messini-Zachou ◽  
Mara Gkioka ◽  
Magda Tsolaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cox Regression ◽  
Symptomatic Treatment ◽  
Risk Of Death ◽  
Increased Risk ◽  
Functional Assessments ◽  
The Impact

Cholinesterase inhibitors (ChEIs) are the mainstays of symptomatic treatment of Alzheimer’s disease (AD); however, their efficacy is limited, and their use was associated with deaths in some groups of patients. The aim of the current study was to assess the impact of the long-term use of ChEIs on mortality in patients with AD. This observational, longitudinal study included 1171 adult patients with a diagnosis of AD treated with donepezil or rivastigmine. Each patient was observed for 24 months or until death. The cognitive and functional assessments, the use of ChEIs, memantine, antipsychotics, antidepressants, and anxiolytics were recorded. The total number of deaths at the end of the observational period was 99 (8.45%). The patients who had received rivastigmine treatment were at an increased risk of death in the follow-up period. The higher risk of death in the rivastigmine group remained significant in multivariate Cox regression models.

scholarly journals Potentially inappropriate medication use in older adults with mild-moderate Alzheimer’s disease: prevalence and associations with adverse events

2020 ◽  
Vol 49 (4) ◽  
pp. 580-587
Author(s):  
Claire Murphy ◽  
Adam H Dyer ◽  
Brian Lawlor ◽  
Sean P Kennelly ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Adverse Events ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Inappropriate Medication ◽  
Potentially Inappropriate Medication ◽  
Randomised Control Trial ◽  
Vulnerable Group ◽  
Serious Adverse Events

Abstract Aim Potentially inappropriate medication (PIM) use is prevalent in older adults and is associated with adverse events, hospitalisation and mortality. We assessed the patterns and associations of PIM use in older adults with mild-to-moderate Alzheimer’s Disease (AD), who may represent a particularly vulnerable group. Design Analysis of data from NILVad, an 18-month Randomised Control Trial of Nilvadapine in mild-to-moderate AD. The v2 STOPP criteria were applied in duplicate to identify PIM use. Associations between PIM use and adverse events/unscheduled healthcare visits in addition to the associations between PIM use and AD progression were evaluated. Setting and Participants 448 older adults with mild-to-moderate AD from 23 centres in nine European countries. Results Of 448 participants (mean age: 72.56 ± 8.19 years), over half (55.8%) were prescribed a PIM with 30.1% being prescribed 2+ PIMs. The most frequent PIMs were (i) long-term benzodiazepines (11.6% N = 52/448), (ii) selective serotonin reuptake inhibitors without appropriate indication (11.1% N = 50/448), and (iii) Proton-Pump Inhibitors (PPIs) without appropriate indication (10.7% N = 48/448). Increasing number of PIMs was associated with a greater risk of adverse events (IRR 1.17, 1.13–1.19, P < 0.001), serious adverse events (IRR 1.27; 1.17–1.37, P < 0.001), unscheduled hospitalisations (IRR 1.16, 1.03–1.30, P = 0.016) and GP visits (IRR 1.22, 1.15–1.28, P < 0.001). PIM use was not associated with dementia progression. Conclusions and Implications PIM use is highly prevalent in mild-to-moderate AD and is associated with adverse events and unscheduled healthcare utilisation. Further attention to de-prescribing in this vulnerable group is warranted.

Predictors of survival with Alzheimer's disease: a community-based study

1995 ◽  
Vol 25 (1) ◽  
pp. 171-177 ◽  
Author(s):  
Carol Jagger ◽  
Michael Clarke ◽  
Andrew Stone
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Institutional Care ◽  
Community Based ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of ◽  
Group A ◽  
Study Population ◽  
Heavy Alcohol Use

SynopsisFactors associated with reduced survival were investigated in elderly people diagnosed as having Alzheimer's disease (AD) and in those free of dementia at diagnosis. The study population comprised 155 people free of dementia and 222 with AD; all were aged 75 years and over and were part of a two-stage prevalence study of dementia during 1988 in Melton Mowbray, Leicestershire. An increased risk of death was found for those with a history of heavy alcohol use, lower cognitive function, a history of heart failure and those in institutional care, these factors acting in the same manner for persons free of dementia and those with AD. For the non-demented group a greater risk of death was found with increasing age and for those with a history of cancer. A greater risk of death was found for males with AD compared to females with the risk increasing over time. The longer survival of women over men may explain the sex differences found in the prevalence of AD without accompanying differences in incidence.

scholarly journals The Alzheimer’s Disease THErapy with NEuroaid II (ATHENE) Study: A Double-Blind Randomized Delayed-Start Trial to Assess the Safety and Efficacy of MLC901 (NeuroAiD™II) as an add-on Treatment to Cholinesterase Inhibitors or Memantine in Patients With Mild to Moderate Alzheimer's Disease

2021 ◽  
Author(s):  
Christopher Chen ◽  
Qingshu Liu ◽  
Rejesh Babu Moorakonda ◽  
Nagaendran Kandiah ◽  
Boon Yeow Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Events ◽  
Cognitive Assessment ◽  
Standard Treatment ◽  
Serious Adverse Events ◽  
Significant Difference ◽  
Early Starters ◽  
Modifying Effect ◽  
Disease Modifying

Abstract BackgroundPreclinical and clinical studies indicate a role for MLC901 (NeuroAiDTMII) in Alzheimer’s Disease (AD). We investigated its safety and efficacy as add-on therapy to standard treatment and evaluated a disease modifying effect in mild to moderate AD.MethodsMild-moderate probable AD patients by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n=125) were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months during which all patients received MLC901, in a delayed-start design. The primary outcome measure was serious adverse events at 6 months, secondary outcomes included the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) and other cognitive assessment scales.ResultsThere was no significant difference in the risk of serious adverse events between early and delayed starters at month (M) 6 (22.6% vs. 27.0%, risk difference = -4.4%, 90% CI -16.9 to 8.3%). Furthermore, there was no significant difference in the risk of adverse events, including the occurrence of stroke or vascular events, between early and delayed starters throughout the 12-month study period. The early-starters differed significantly on ADAS-Cog from the delayed-starters at M9 (mean difference -3.36, 95% CI -5.64 to -1.09) and M12 (mean difference -2.35, 95% CI -5.45 to 0.74). Other cognitive assessment scales showed trends in favor of MLC901.ConclusionsMLC901 is a safe adjunct to standard treatment for mild-moderate AD. There is no indication that the risk of any adverse events, including vascular, is increased with MLC901 in the study population. The cognitive outcomes provide support for a disease-modifying effect of MLC901 which requires confirmation in further studies. Clinical trial registration: ClinicalTrials.gov, NCT03038035. https://clinicaltrials.gov/ct2/show/NCT03038035

scholarly journals Length of Hospital Stay for Hip Fracture and 30-Day Mortality in People With Alzheimer’s Disease: A Cohort Study in Finland

2020 ◽  
Vol 75 (11) ◽  
pp. 2184-2192
Author(s):  
Piia Lavikainen ◽  
Marjaana Koponen ◽  
Heidi Taipale ◽  
Antti Tanskanen ◽  
Jari Tiihonen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hospital Stay ◽  
Older Persons ◽  
Length Of Hospital Stay ◽  
Inpatient Rehabilitation ◽  
Risk Of Death ◽  
Increased Risk ◽  
Hospital Stays ◽  
Worse Prognosis

Abstract Background Persons with Alzheimer’s disease (AD) are at higher risk of hip fractures (HFs) than general older population and have worse prognosis after HF. Hospital stays after HF have shortened along time. We investigated the association between length of hospital stay after HF and mortality after discharge among persons with AD. Method The MEDALZ cohort includes all Finnish community dwellers who received clinically verified AD diagnosis in 2005–2011 (N = 70 718). Patients who experienced first HF after AD diagnosis in 2005‒2015 (n = 6999) were selected. Length of hospital stay for HF was measured as a sum of the consecutive days spent in hospital after HF until discharge. Outcome was defined as death within 30 days after hospital discharge. Results Mean of overall length of hospital stay after a HF decreased from 52.6 (SD 62.9) days in 2005 to 19.6 (SD 23.1) days in 2015. Shortest treatment decile (1‒4 days) had the highest risk of death within 30 days after discharge (adjusted hazard ratio [aHR] 2.76; 95% confidence interval [CI] 1.66–4.60) in addition to second (5‒6 days; aHR 2.52; 95% CI 1.50–4.23) and third (7‒10 days; aHR 2.22; 95% CI 1.34–3.69) deciles when compared to the sixth decile of length of stays (21‒26 days). Conclusions Among persons with AD, shorter length of hospital stay after HF was associated with an increased risk of death after discharge. After acute HF treatment, inpatient rehabilitation or proper care and services in home need to be organized to older persons with AD.

Abstract P017: Serum N-Carboxymethyl-Lysine and Risk of Mortality in Older Adults

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Mary Lou Biggs ◽  
David Benkeser ◽  
Joachim Ix ◽  
Jorge Kizer ◽  
Luc Djousse ◽  
...  
Keyword(s):  
Renal Failure ◽  
Mortality Risk ◽  
Community Dwelling ◽  
Cardiovascular Health Study ◽  
Risk Of Death ◽  
Risk Of Mortality ◽  
Organ Systems ◽  
Increased Risk ◽  
Carboxymethyl Lysine ◽  
The Mean

Advanced glycation end products (AGEs) are compounds formed by the non-enzymatic glycation of proteins, lipids, and nucleic acids, and are thought to play a role in the pathogenesis of diseases across multiple organ systems. Carboxymethyl-lysine (CML) is a dominant AGE found in tissue proteins and in the circulation, and a commonly used AGE biomarker. Only a few epidemiological studies have evaluated the association between circulating CML and mortality risk, and none have evaluated the association between CML and cause-specific non-CVD mortality. We measured CML by ELISA on serum specimens collected from 3,373 Cardiovascular Health Study participants in 1996. Participants were followed for death through 2010, and cause of death was classified using death certificates, medical records, and proxy interview. We used Cox regression to estimate the relative risk of total and cause-specific mortality associated with circulating CML, adjusting for confounders (Models 1 & 2) and estimated glomerular filtration rate (eGFR) as a potential mediator (Model 3). We tested whether sex or diabetes modified the association between CML and mortality. The mean age among participants was 78 years and 60% were women. The mean CML level among participants was 629 ng/mL. Over median follow-up of 10 years, 2,322 deaths occurred (73.4 per 1,000 person-years). After adjustment for confounders (Models 1 & 2), CML was associated with an increased risk of death from CVD, dementia, infection, fracture/trauma, and renal failure (Table). Aside from renal failure, adjustment for eGFR attenuated the HR estimates modestly. There was no evidence for effect modification of the association of CML and all-cause mortality risk by sex or diabetes. In a cohort of community-dwelling older individuals, elevated circulating CML was associated with increased risk of mortality from cardiovascular causes, dementia, infection, fracture/trauma, and renal failure. A portion of the increased risk may be mediated through decreased renal function.

scholarly journals Phase II (NAVIGATE-AD study) Results of LY3202626 Effects on Patients with Mild Alzheimer’s Disease Dementia

2021 ◽  
pp. 1-16
Author(s):  
Albert C. Lo ◽  
Cynthia Duggan Evans ◽  
Michele Mancini ◽  
Hong Wang ◽  
Sergey Shcherbinin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Events ◽  
Functional Decline ◽  
Neurofibrillary Tangle ◽  
Amyloid Β ◽  
System Organ Class ◽  
Serious Adverse Events ◽  
Study Results ◽  
Significant Difference

Background: LY3202626 is a small molecule inhibitor of β-site amyloid precursor protein cleaving enzyme (BACE)1 shown to reduce amyloid-β (Aβ)1–40 and Aβ1–42 concentrations in plasma and cerebrospinal fluid developed for the treatment of Alzheimer’s disease (AD). Objective: To assess the change from baseline in flortaucipir positron emission tomography (PET) after treatment with LY3202626 compared with placebo in patients with mild. Methods: Patients received daily 3 mg or 12 mg doses of LY3202626 or placebo for 52 weeks. The primary outcome was assessment of cerebral neurofibrillary tangle load by flortaucipir PET. The study was terminated early following an interim analysis due to a low probability of identifying a statistically significant slowing of cognitive and/or functional decline. Results: A total of 316 patients were randomized and 47 completed the study. There was no statistically significant difference between placebo and either dose of LY3202626 from baseline to 52 weeks, or in annualized change for flortaucipir PET. There was no clinically meaningful difference between placebo and LY3202626 doses on efficacy measures of cognition and function. No deaths or serious adverse events considered related to LY3202626 were reported. A statistically significant increase in treatment-emergent adverse events in the psychiatric disorders system organ class was reported for both LY3202626 doses compared to placebo. Conclusion: LY3202626 tested at doses generating 70–90% BACE inhibition was generally well tolerated in this study. LY3202626 treatment did not result in a clinically significant change in cerebral tau burden as measured by flortaucipir nor in change of functional or cognitive decline compared to placebo.

scholarly journals Loneliness, health and mortality

2017 ◽  
Vol 28 (2) ◽  
pp. 234-239 ◽  
Author(s):  
J. Henriksen ◽  
E. R. Larsen ◽  
C. Mattisson ◽  
N. W. Andersson
Keyword(s):  
Mortality Risk ◽  
Structured Interviews ◽  
Community Based ◽  
Risk Of Death ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Relative Risk Of Death ◽  
The Relationship ◽  
Health And Mortality

Aims.Literature suggests an association between loneliness and mortality for both males and females. Yet, the linkage of loneliness to mortality is not thoroughly examined, and need to be replicated with a long follow-up time. This study assessed the association between loneliness and mortality, including associations to gender, in 1363 adult swedes.Methods.This community-based prospective cohort study from the Swedish Lundby Study included 1363 individuals of whom 296 individuals (21.7%) were identified as lonely with use of semi-structured interviews in 1997. The cohort was followed until 2011 and survival analyses were used to estimate the relative risk of death.Results.Death occurred with an incidence rate of 2.63 per 100 person-years and 2.09 per 100 person-years for lonely and non-lonely individuals, respectively. In crude analysis, loneliness was associated with a significant increased mortality risk of 27% compared with non-lonely individuals [hazard ratio (HR) 1.27; 95% CI 1.01–1.60]. Unadjusted, lonely females had a significant increased risk (HR 1.76; 95% CI 1.31–2.34) and adjusted insignificant increased mortality risk of 27% (HR 1.27; 95% CI 0.92–1.74), compared with non-lonely females. Lonely males were found to have an adjusted significant decreased risk of mortality (HR 0.50; 95% CI 0.32–0.80), compared with non-lonely males.Conclusions.Findings suggest an association between loneliness and increased risk of mortality and that gender differences may exist, which have not been previously reported. If replicated, our results indicate that loneliness may have differential physical implications in some subgroups. Future studies are needed to further investigate the influence of gender on the relationship.

scholarly journals Enough with the madness: a systematic review and meta-analysis of hydroxychloroquine for COVID-19

2021 ◽  
Vol 13 (2) ◽  
pp. 186-220
Author(s):  
André Santos ◽  
◽  
Érica Gonçalves ◽  
Ananda Oliveira ◽  
Douglas Lima ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Standard Of Care ◽  
P Value ◽  
Serious Adverse Events ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference

Objective: Because of preliminary results from in vitro studies, hydroxychloroquine (HCQ) and chloroquine (CQ) have been proposed as possible treatments for COVID-19, but the clinical evidence is discordant. This study aims to evaluate the safety and efficacy of CQ and HCQ for the treatment of COVID-19. Methods: A systematic review with meta-analysis was performed. An electronic search was conducted in four databases for randomized controlled trials that compared HCQ or CQ with standard-of-care. A complementary search was performed. A quantitative synthesis of clinical outcomes was performed using the inverse variance method adjusting for a random-effects model. Results: In total, 16 studies were included. The meta-analysis found no significant difference between intervention and control groups in terms of mortality at the most extended follow-up (RR = 1.09, CI95% = 0.99-1.19, p-value = 0.08), patients with negative PCR results (RR = 0.99, CI95% = 0.89-1.10, p-value = 0.86), or serious adverse events (RR = 2.21, CI95% = 0.89-5.47, p-value = 0.09). HCQ was associated with an increased risk of adverse events (RR = 2.28, CI95% = 1.36-2.83, p-value < 0.01). The quality of evidence varied from very low to high. Conclusion: There is no evidence that HCQ reduces the risk of death or improves cure rates in patients with COVID-19, but it might be associated with an increased risk of adverse events

Increased risk of mortality in Alzheimer's disease patients with higher education? A replication study

Neurology ◽  
1997 ◽  
Vol 49 (3) ◽  
pp. 798-802 ◽  
Author(s):  
M. I. Geerlings ◽  
D.J. H. Deeg ◽  
B. Schmand ◽  
J. Lindeboom ◽  
C. Jonker
Keyword(s):  
Higher Education ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Replication Study ◽  
Risk Of Mortality ◽  
Increased Risk
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