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Data from 12-week placebo-controlled trials have led to mounting concerns about increased mortality in patients with Alzheimer's disease (AD) who are prescribed antipsychotics; however, there are no mortality data from long-term placebo-controlled trials. We aimed to assess whether continued treatment with antipsychotics in people with AD is associated with an increased risk of mortality. Between October, 2001, and December, 2004, patients with AD who resided in care facilities in the UK were enrolled into a randomised, placebo-controlled, parallel, two-group treatment discontinuation trial. Participants were randomly assigned to continue with their antipsychotic treatment (thioridazine, chlorpromazine, haloperidol, trifluoperazine, or risperidone) for 12 months or to switch their medication to an oral placebo. The primary outcome was mortality at 12 months. An additional follow-up telephone assessment was done to establish whether each participant was still alive 24 months after the enrolment of the last participant (range 24–54 months). Causes of death were obtained from death certificates. Analysis was by intention to treat (ITT) and modified intention to treat (mITT). This trial is registered with the Cochrane Central Registry of Controlled Trials/National Research Register, number ISRCTN33368770. 165 patients were randomised (83 to continue antipsychotic treatment and 82 to placebo), of whom 128 (78%) started treatment (64 continued with their treatment and 64 received placebo). There was a reduction in survival in the patients who continued to receive antipsychotics compared with those who received placebo. Cumulative probability of survival during the 12 months was 70% (95% CI 58–80%) in the continue treatment group versus 77% (64–85%) in the placebo group for the mITT population. Kaplan–Meier estimates of mortality for the whole study period showed a significantly increased risk of mortality for patients who were allocated to continue antipsychotic treatment compared with those allocated to placebo (mITT log rank p=0·03; ITT p=0·02). The hazard ratio for the mITT group was 0·58 (95% CI 0·35 to 0·95) and 0·58 (0·36 to 0·92) for the ITT population. The more pronounced differences between groups during periods of follow up longer than 12 months were evident at specific timepoints (24-month survival 46% vs 71%; 36-month survival 30% vs 59%). There is an increased long-term risk of mortality in patients with AD who are prescribed antipsychotic medication; these results further highlight the need to seek less harmful alternatives for the long-term treatment of neuropsychiatric symptoms in these patients. UK Alzheimer's Research Trust.

IntroductionAn important goal of advance care planning (ACP) is ensuring that patients receive care concordant with their preferences. High-quality evidence is needed about the effect of ACP on this and other outcomes.Methods and analysisPlanning Ahead is a randomised controlled trial to test the effectiveness of facilitated ACP in community-dwelling older adults including those with normal cognition and those with Alzheimer’s Disease and Related Dementias (ADRD) who are at high risk of death. The primary aim is to determine the effect of the intervention on discordance between preferences for medical treatments and the treatments received in the year after the intervention. Secondary outcomes include decision-making quality, care at the end of life and cost. Eligible patients have a primary care provider at one of two Midwest health systems, have an approximate 33% mortality risk and do not have a POLST form at baseline. Patients with capacity can invite the person they would choose to be their healthcare decision maker to participate as a study partner. A surrogate decision maker enrols and receives the intervention for patients who lack capacity due to ADRD. The intervention uses the Respecting Choices Advanced Steps (RCAS) model of ACP delivered by a registered nurse and includes identification of the patient’s values and goals, education about ACP and the POLST form and the opportunity to complete a POLST form.Ethics and disseminationThe study is approved by the Indiana University Institutional Review Board. Primary and secondary analyses will be published in peer-reviewed journals. We also plan dissemination through the media. We will construct a deidentified data set that could be available to other researchers. Survey data will be preserved and shared via the NIH-supported National Archive of Computerised Data on Ageing’s (NACDA) Open Ageing Repository (OAR).Trial registration numberNCT04070183.

Background The poor outcome after a hip fracture is not fully understood. The aim of the study was to describe the prevalence of co-morbidities, complications and causes of death and to investigate factors that are able to predict mortality in old people with femoral neck fracture. Methods Data was obtained from a randomized, controlled trial with a 3-year follow-up at Umeå University Hospital, Sweden, which included 199 consecutive patients with femoral neck fracture, aged ≥70 years. The participants were assessed during hospitalization and in their homes 4, 12 and 36 months after surgery. Medical records and death certificates were analysed. Results Multivariate analysis revealed that cancer, dependence in P-ADL (Personal Activities of Daily Living), cardiovascular disease, dementia at baseline or pulmonary emboli or cardiac failure during hospitalization were all independent predictors of 3-year mortality. Seventy-nine out of 199 participants (40 %) died within 3 years. Cardiovascular events (24 %), dementia (23 %), hip-fracture (19 %) and cancer (13 %) were the most common primary causes of death. In total, 136 participants suffered at least one urinary tract infection; 114 suffered 542 falls and 37 sustained 56 new fractures, including 13 hip fractures, during follow-up. Conclusion Old people with femoral neck fracture have multiple co-morbidities and suffer numerous complications. Thus randomized intervention studies should focus on prevention of complications that might be avoidable such as infections, heart diseases, falls and fractures.

INTRODUCTION COVID‐19 had devastating impacts worldwide. However, most research examining the impact of dementia on COVID‐19 outcomes has been conducted in Europe and Asia and has not examined dementia subtypes. METHODS A retrospective analysis of electronic health record data from 21 US health‐care systems examined relationships of all‐cause dementia, Alzheimer's disease (AD), and vascular dementia with in‐hospital mortality, intensive care unit (ICU) admission, and hospital stay duration. RESULTS All‐cause dementia, but not AD or vascular dementia independently, was associated with increased mortality risk, the inclusion of discharge to hospice as a mortality equivalent increased risk for mortality for all‐cause dementia, and AD and vascular dementia. Patients with all‐cause dementia and AD were less likely to be admitted to the ICU than patients without. Patients with any form of dementia had longer hospital stays than patients without. DISCUSSION Dementia was associated with increased mortality or hospice discharge, decreased ICU admissions, and longer hospital stays. Highlights Only all‐cause dementia was associated with increased mortality risk. This risk was lower than what has been published in previous research. Combining mortality and hospice discharge increased risk for all dementia subtypes. All‐cause and Alzheimer's disease (AD) dementia were associated with decreased intensive care unit admissions. All‐cause, vascular, and AD dementia were associated with longer hospital stays.

Objective To investigate the effect on survival of treatment with memantine in patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Methods 75 patients with DLB and PDD were included in a prospective double-blinded randomised placebo-controlled trial (RCT) of memantine, of whom long-term follow-up was available for 42. Treatment response was recorded 24 weeks from baseline and measured by Clinical Global Impression of Change (CGIC). The participants were grouped as responders (CGIC 1–3) or non-responders (CGIC 4–7). The 24-week RCT was followed by open-label treatment and survival was recorded at 36 months. Results After 36-month follow-up, patients in the memantine group had a longer length of survival compared with patients in the placebo group (log rank x²=4.02, p=0.045). Within the active treatment group, survival analysis 36 months from baseline showed that the memantine responders, based on CGIC, had higher rates of survival compared with the non-responders (log rank x²=6.595, p=0.010). Similar results were not seen in the placebo group. Conclusions Early treatment with memantine and a positive clinical response to memantine predicted longer survival in patients with DLB and PDD. This suggests a possible disease-modifying effect and also has implications for health economic analysis. However, owing to the small study sample, our results should merely be considered as generating a hypothesis which needs to be evaluated in larger studies. Trial registration number ISRCTN89624516.

ABSTRACTObjectivesThe aim of this study was to investigate survival time and life-expectancy in people with young-onset dementia (YOD) and to examine the relationship with age, sex, dementia subtype and comorbidity. Design, Setting and ParticipantsSurvival was examined in 198 participants in the Needs in Young-onset Dementia study, including participants with Alzheimer’s dementia (AD), vascular dementia (VaD) and frontotemporal dementia (FTD). MeasuresThe primary outcomes were survival time after symptom onset and after date of diagnosis. Cox proportional hazards models were used to explore the relationship between survival and age, sex, dementia subtype and comorbidity. Additionally, the impact on remaining life expectancy was explored. ResultsDuring the six-year follow-up, 77 of the participants died (38.9%), 78 participants survived (39.4%) and 43 were lost to follow-up (21.7%). The mean survival time after symptom onset and diagnosis was 209 months (95% CI 185-233) and 120 months (95% CI 110-130) respectively. Participants with AD had a statistically significant shorter survival compared with VaD participants, both regarding survival after symptom onset (p = 0.047) as well as regarding survival after diagnosis (p = 0.049). Younger age at symptom onset or at diagnosis was associated with longer survival times. The remaining life expectancy, after diagnosis, was reduced with 51% for males and 59% for females compared to the life expectancy of the general population in the same age groups. Conclusion/ImplicationsIt is important to consider the dementia subtype when persons with YOD and their families are informed about the prognosis of survival. Our study suggests longer survival times compared to other studies on YOD, and survival is prolonged compared to studies on LOD. Younger age at symptom onset or at diagnosis was positively related to survival but diagnosis at younger ages, nevertheless, still diminishes life expectancy dramatically.

Aims/hypothesisThe term prediabetes is used for individuals who have impaired glucose metabolism whose glucose or HbA1c levels are not yet high enough to be diagnosed as diabetes. Prediabetes may already be associated with an increased risk of chronic ‘diabetes-related’ complications. This umbrella review aimed to provide a systematic overview of the available evidence from meta-analyses of prospective observational studies on the associations between prediabetes and incident diabetes-related complications in adults and to evaluate their strength and certainty.MethodsFor this umbrella review, systematic reviews with meta-analyses reporting summary risk estimates for the associations between prediabetes (based on fasting or 2 h postload glucose or on HbA1c) and incidence of diabetes-related complications, comorbidities and mortality risk were included. PubMed, Web of Science, the Cochrane Library and Epistemonikos were searched up to 17 June 2021. Summary risk estimates were recalculated using a random effects model. The certainty of evidence was evaluated by applying the GRADE tool. This study is registered with PROSPERO, CRD42020153227.ResultsNinety-five meta-analyses from 16 publications were identified. In the general population, prediabetes was associated with a 6–101% increased risk for all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, heart failure, atrial fibrillation and chronic kidney disease, as well as total cancer, total liver cancer, hepatocellular carcinoma, breast cancer and all-cause dementia with moderate certainty of evidence. No associations between prediabetes and incident depressive symptoms and cognitive impairment were observed (with low or very low certainty of evidence). The association with all-cause mortality was stronger for prediabetes defined by impaired glucose tolerance than for prediabetes defined by HbA1c.Conclusions/interpretationPrediabetes was positively associated with risk of all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, chronic kidney disease, cancer and dementia. Further high-quality studies, particularly on HbA1c-defined prediabetes and other relevant health outcomes (e. g. neuropathy) are required to support the evidence.

Interventions relieving the burden of caregiving may postpone or prevent patient institutionalization. The objective of this study was to determine whether a family meetings intervention was superior to usual care in postponing nursing home placement of patients with dementia. A randomized multicenter trial was conducted among 192 patients with a clinical diagnosis of dementia living at home at enrolment and their primary family caregiver. Dyads of caregivers and patients were randomized to the family meetings intervention (n = 96) or usual care (n = 96) condition. The intervention consisted of two individual sessions with the primary caregiver and four family counseling sessions that included family members and friends. The primary outcome measure was the time until institutionalization of the patient. Intention-to-treat as well as per protocol analyses were performed. Survival analyses were carried out to evaluate the effectiveness of the intervention. During 18 months follow-up 23 of 96 relatives with dementia of caregivers in the intervention group and 18 of 96 relatives with dementia of caregivers in the usual care group were institutionalized. No significant difference between the intervention and the usual care group was found in time until institutionalization (adjusted hazard ratio (HR) 1.46, 95% confidence interval (CI) 0.78 to 2.74). The per-protocol analysis revealed no significant effect either (adjusted HR 0.57, 95% CI 0.21 to 1.57), although the number of placements among the adherers was relatively low (9.4%). A subgroup effect was found for patients' age, with a significantly higher risk of institutionalization for 'younger' patients in the intervention group compared with the usual care group (adjusted HR = 4.94, 95% CI 1.10 to 22.13). This family meetings intervention for primary caregivers of patients with dementia did not postpone patient institutionalization more than usual care. CONTROLLED-TRIALS.COM ISRCTN90163486.

Background/Aims: Our aims were two-fold: firstly, to investigate the association and interaction between apolipoprotein E (ApoE), lifestyle risk factors and dementia-related mortality and, secondly, to examine if using dementia-related mortality yielded comparable risk estimates for the ApoE genotypes as reported in studies using a clinical dementia diagnosis as the end point. Methods: We used a nested case-control study with 561 cases drawn from dementia deaths in the Cohort of Norway (CONOR) and 584 alive controls. Results: ApoE ε4 carriers were at increased risk of dementia-related mortality compared to noncarriers [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.93-3.13], and ε4 homozygotes were at particularly high risk (OR 7.86, 95% CI 3.80-13.8), while the ε2 type was associated with a lower risk. The highest risk of dementia-related mortality was found among ε4 carriers with more lifestyle risk factors (ε4 carriers who were smokers, hypertensive, physically inactive and diabetics) versus ε4 noncarriers without lifestyle risk factors (OR 15.4, 95% CI 4.37-52.4). The increased risk was additive, not multiplicative. Conclusions: Ensuring a healthy lifestyle is important to be able to prevent dementia in populations at large, but especially for ε4 carriers. Using dementia mortality gives comparable results for the ApoE-dementia association as studies using clinical dementia diagnoses.

The current study aims to examine the risk of suicide in persons diagnosed with dementia during a hospitalization and its relationship to mood disorders. Event-history analysis using time-varying covariates. Population-based record linkage. All individuals aged 50+ living in Denmark (N=2,474,767) during January 1, 1990 through December 31, 2000. Outcome of interest is suicide. Relative risks are calculated based on person-days spent in each stratum. A total of 18,648,875 person-years were observed during the 11-year study period. During this period, 136 persons who previously had been diagnosed with dementia died by suicide. Men and women aged 50-69 years with hospital presentations of dementia have a relative suicide risk of 8.5 (95% confidence interval: 6.3-11.3) and 10.8 (95% confidence interval: 7.4-15.7), respectively. Those who are aged 70 or older with dementia have a threefold higher risk than persons with no dementia. The time shortly after diagnosis is associated with an elevated suicide risk. The risk among persons with dementia remains significant when controlling for mood disorders. As many as 26% of the men and 14% of the women who died by suicide died within the first 3 months after being diagnosed whereas 38% of the men and 41% of the women died more than 3 years after initial dementia diagnosis. Dementia, determined during hospitalization, was associated with an elevated risk of suicide for older adults. Preventive measures should focus on suicidal ideation after initial diagnosis but also acknowledge that suicides can occur well after a dementia diagnosis has been established.