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Objective: The study evaluated the effectiveness of the sarcopenia indices neutrophils/lymphocytes, platelets/lymphocytes, AST/ALT, and creatinine (Cr)/ cystatin C (CysC)*100 in predicting mortality in hospitalized patients with Alzheimer's disease (AD) aged 60 years or older., Measurements: This retrospective observational survey was undertaken in a teaching hospital in western China from January 1, 2017, to December 30, 2022. The neutrophil/lymphocyte, platelet/lymphocyte, AST/ALT, and Cr/CysC*100 ratios were used to assess the presence of sarcopenia, with the upper quartiles used as the cutoff value. Information on all-cause mortality was obtained through telephone interviews or electronic medical records between June 1, 2024, and June 20, 2024. Overall survival (OS) represented the time from hospital admission to death/final follow-up. Cox proportional hazards models were applied to determine the relationships between the above parameters and mortality from all causes., Results: The information on 523 patients with AD was retrieved from the electronic medical record system. Of these, 329 were finally enrolled, all of whom were hospitalized and over the age of 60 years. The use of Cr/Cys C*100 as a sarcopenia indicator was found to be effective in predicting mortality (24.39% vs. 13.77% for patients with sarcopenia vs. those without, P = 0.024). However, the application of neutrophils/lymphocytes, platelets/lymphocytes, and AST/ALT as indicators showed no marked differences between the sarcopenia and non-sarcopenia participants. After further logistic regression analysis and correction of possible variables, participants with sarcopenia had an increased risk of death relative to those without (HR = 2.179, 95%CI: 1.175-4.044)., Conclusions and Implications: This study showed that only Cr/CysC*100 was effective in the prediction of mortality in older individuals with AD and sarcopenia and that neutrophils/lymphocytes, platelets/lymphocytes, and AST/ALT were not effective as predictors., Competing Interests: Declarations. Ethical approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and the ethical approval was obtained from the Research Ethics Committee of Zigong Affiliated Hospital, Southwest Medical University (Zigong Mental Health Center), Department of Geriatric (No. 2023008). The Research Ethics Committee of Zigong Affiliated Hospital, Southwest Medical University (Zigong Mental Health Center), Department of Geriatric waived informed consent for this study. All methods comply with relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Sponsor’s role: The sponsors did not participant in the design, methods, data collection, analysis, or in the preparation of this manuscript., (© 2024. The Author(s).)

Objective: To evaluate mortality for Alzheimer's Disease (AD) in Italy over more than three decades (1980-2015) and discuss the possible role of general and specific contributing factors., Methods: Mortality data were extracted by the Italian National Institute of Statistics: crude mortality rates were computed for sex and age, considering the whole country and its five main geographical sub-areas. Rates were standardized in two ways: directly (annual mortality rates AMRs) and indirectly (standardized mortality rates, SMRs). SMRs were then used to evaluate geographical differences; to study mortality trend, AMRs and joinpoint linear regression analysis were used., Results: Considering the entire period and the whole country, mortality rates were similar for females and males and for geographical regions, with the exception of the older age groups where mortality for AD in females slightly prevailed. In these older patients, a steep increase of mortality was seen starting from the current century. The increase in male mortality mirrored the national trend in North-West and Central Italy, but not in North-East, South, and the Islands, where it did not surge until the mid to late 1990s., Conclusions: the general increase of mortality is in line with international data and it reflects the increasing prevalence of the disease, likely due to increasing longevity, and to improvements in diagnostic accuracy. In addition, the accuracy of death certificate compilation could account for both geographical and temporal differences. Currently available drugs for AD do not seem to have an impact on mortality rates., (© 2024. The Author(s).)

Background: Recent research suggests that selective serotonin reuptake inhibitors (SSRIs) may reduce mortality in COVID-19 patients; however, research into their benefits for elderly Alzheimer's disease (AD) patients remains limited., Objective: To investigate the relationship between SSRIs therapy and the mortality risk after COVID-19 infection in elderly patients with and without AD., Methods: This retrospective cohort study leveraged a large database containing over 100 million electronic health records in the US from the TriNetX platform to compare the hazard rates of mortality after COVID-19 infection in elderly AD patients prescribed SSRIs versus propensity-score matched individuals prescribed other antidepressants. This study was also conducted in separate cohorts of patients without AD to compare the findings., Results: When compared with non-SSRI antidepressants, SSRIs were associated with lower risk for mortality after COVID-19 infection in elderly patients without AD over early, middle, and later stages of the pandemic with HRs of 0.84 (95% CI: 0.75-0.93), 0.86 (95% CI: 0.79-0.93), and 0.77 (95% CI: 0.71-0.33), respectively. When comparing SSRIs with non-SSRI antidepressants for mortality risk following COVID-19 among patients with AD, HRs of 0.95 (95% CI: 0.71-1.27), 0.80 (95% CI: 0.61-1.06), and 0.99 (95% CI: 0.75-1.32), were found respectively., Conclusions: Our findings suggest that the use of SSRIs is significantly associated with reduced mortality risk following COVID-19 in elderly patients without AD compared to other antidepressants. While a lower mortality risk was also observed among AD patients, the association was not statistically significant., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: We examined the burden of Alzheimer's disease and other dementias (ADOD) and attributable factors at the national and provincial levels in China., Methods: Using the Global Burden of Diseases Study 2021, we estimated incidence, prevalence, mortality rate, disability-adjusted life years (DALYs), and the ratio of years lived with disability (YLD) to DALYs for ADOD in China. Estimated annual percentage changes (EAPCs) were used to quantify the temporal trends from 1990 to 2021., Results: In 2021, China experienced the highest ADOD burden among Group of 20 member nations. The EAPCs for age-standardized rates for incidence, age-standardized rates for prevalence, and age-standardized mortality rate were 0.41 (uncertainty intervals [UIs] 0.34-0.49); 0.44 (UI: 0.36-0.52); and -0.19 (UI: -0.23 to -0.15), respectively. Between 1990 and 2021, the number of people with ADOD increased by 322.18% and DALYs associated with ADOD increased by 272.71%; most of these increases were explained by population aging., Discussion: Considering the aging Chinese population, targeted strategies to prevent dementia are urgently needed., Highlights: China experienced the highest dementia burden among Group of 20 member nations. High body mass index, high fasting plasma glucose, and smoking were major risk factors for Alzheimer's disease and other dementias (ADOD) burden. Since 1990, the incidence and prevalence of ADOD increased substantially in China. The mortality rate related to ADOD decreased consistently. Considering the aging Chinese population, targeted strategies are urgently needed., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: In recent years, there has been an increase in suicide rates in Brazil. From 2015 to 2019, a 34% increase in self-inflicted deaths was observed. The aim of this study was to analyse population data to determine whether some subgroups of the population, specifically the elderly population with Alzheimer's disease, are at a greater risk of suicide., Study Design: An analysis of population data was carried out., Methods: Population data from the state of São Paulo, Brazil, were obtained from two platforms: the Brazilian Institute of Geography and Statistics (IBGE); and the Brazilian Ministry of Health (DataSUS). Data were measured and compared in 2010 and 2022 using the two most recent censuses., Results: Between 2010 and 2022, the number of registered deaths of patients with Alzheimer's increased by 21.93%. In addition, there was a 100.37% increase in suicides among the elderly population compared to a 37.78% increase in the general population., Conclusions: In recent years, there has been a notable increase in both suicides among the elderly and mortality rates attributed to Alzheimer's disease within São Paulo state, Brazil. However, it is not possible to conclude that the increase in suicide among the elderly is directly linked to Alzheimer's disease. To determine a correlation between suicide and Alzheimer's disease, further studies are required., Competing Interests: Competing interests The authors declare no conflicts of interest., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is a prevalent neurodegenerative disease characterized by progressive cognitive and functional decline. Nearly all patients with AD develop neuropsychiatric symptoms (NPSs). Agitation is one of the most distressing and challenging NPS. Brexpiprazole is an oral antipsychotic and is the first approved pharmacologic agent in the United States for the treatment of agitation associated with dementia due to AD. Its effect is thought to be from its partial serotonin 5-HT 1A and dopamine D 2 receptor agonist activity and serotonin 5-HT 2A receptor antagonism. Brexpiprazole is a maintenance medication, and it should not be used "as needed" or as a "PRN" treatment for breakthrough agitation. Brexpiprazole is a major substrate of CYP2D6 and CYP3A4. Dose adjustments may be required for drug interactions or impaired renal or hepatic function. Clinical trials found brexpiprazole 2 to 3 mg/d demonstrated significant improvements in agitation, with brexpiprazole showing an approximate 5-point greater reduction on change in the Cohen-Mansfield Agitation Inventory total score at week 12 from baseline compared with placebo. Brexpiprazole is generally well tolerated and safe, and common adverse reactions when used for this indication include dizziness, headaches, insomnia, nasopharyngitis, somnolence, and urinary tract infections. Like other antipsychotics used for agitation in AD, brexpiprazole is associated with higher mortality rates compared with placebo. In a long-term care setting, there are several considerations for its use. Benefits include an oral agent that is well tolerated and clinical data showing statistically significant effects on agitation. However, brexpiprazole has not been studied in head-to-head clinical trials against other antipsychotics, and there are differing opinions if the agitation score reductions translate to a clinically meaningful difference. The approval of brexpiprazole signals favorably for upcoming agents for this indication, including escitalopram and dextromethorphan-bupropion. Both escitalopram and dextromethorphan-bupropion are currently undergoing clinical trials., Competing Interests: Disclosures E.D.C. reports personal fees from Genomadix Inc and a grant to her institution from Alzheon. A.P.P. reports personal fees from Acadia Pharmaceuticals, Athira, BMS, Cognitive Research Corp, Eisai, IQVIA, Lundbeck, Novartis, ONO Pharmaceuticals, WCG, WebMD, and Xenon; and grants to his institution from Alector, Athira, Biogen, Cassava, Eisai, Eli Lilly, Genentech/Roche, Vaccinex, NIA, NIMH, and DOD. He is a member of the Scientific Advisory Board of Alzheon. D.L. and I.M.A. declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Older adults with Alzheimer's disease and related dementias (ADRD) had a high risk of COVID-19-related mortality. Racial and ethnic minorities were disproportionally impacted by the pandemic. The variations in disparities, including racial and ethnic disparities and disparities across communities, in COVID-19-related mortality across the different stages of the COVID-19 pandemic among the ADRD population are unknown. This observational study estimated linear probability models for community-dwelling older adults with ADRD who were diagnosed with COVID-19 in 2020 and 2021 using multiple national data (e.g., Medicare data), accounting for individual and community characteristics. Disparities in 30-day mortality were compared between 2020 and 2021. The socioeconomic disparity in COVID-19-related mortality across communities became insignificant during the later stage of the pandemic, ethnic differences in COVID-19-related mortality decreased but persisted, and racial disparity remained largely unchanged. The study provides insights into interventions to mitigate lingering disparities in health outcomes among the vulnerable population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The prediction of the susceptibility of an individual to a certain disease is an important and timely research area. An established technique is to estimate the risk of an individual with the help of an integrated risk model, that is, a polygenic risk score with added epidemiological covariates. However, integrated risk models do not capture any time dependence, and may provide a point estimate of the relative risk with respect to a reference population. The aim of this work is twofold. First, we explore and advocate the idea of predicting the time-dependent hazard and survival (defined as disease-free time) of an individual for the onset of a disease. This provides a practitioner with a much more differentiated view of absolute survival as a function of time. Second, to compute the time-dependent risk of an individual, we use published methodology to fit a Cox's proportional hazard model to data from a genetic SNP study of time to Alzheimer's disease (AD) onset, using the lasso to incorporate further epidemiological variables such as sex, APOE (apolipoprotein E, a genetic risk factor for AD) status, 10 leading principal components, and selected genomic loci. We apply the lasso for Cox's proportional hazards to a data set of 6792 AD patients (composed of 4102 cases and 2690 controls) and 87 covariates. We demonstrate that fitting a lasso model for Cox's proportional hazards allows one to obtain more accurate survival curves than with state-of-the-art (likelihood-based) methods. Moreover, the methodology allows one to obtain personalized survival curves for a patient, thus giving a much more differentiated view of the expected progression of a disease than the view offered by integrated risk models. The runtime to compute personalized survival curves is under a minute for the entire data set of AD patients, thus enabling it to handle datasets with 60,000-100,000 subjects in less than 1 h., (© 2024 Wiley Periodicals LLC.)

Background: Dementia is estimated that this kind of neurodegenerative disease directly affects 50 million patients worldwide. About 12% to 70% death of dementia disease can be attributed to pneumonia. We aimed to evaluate the pneumonia-related mortality of dementia patients and how the frequency of pneumonia-related death varies according to the data of death (autopsy or death certificate)., Methods: English literatures published from PubMed and Embase databases were extracted. Stata/SE 16.0 software was used for statistical analysis., Results: In the end, a total of 7 studies were finally included in this meta-analysis. The results showed that: (1) The total mortality rate associated with pneumonia was 24.68% (95% confidence interval [CI]: 19.07%, 30.29%); (2) The pneumonia-related mortality rate of dementia patients confirmed by autopsy was 56.14% (95% CI: 32.36%, 79.92%); (3) The pneumonia-related mortality rate of dementia patients confirmed by death certificate was 16.12% (95% CI: 9.98%, 22.26%); (4) The pneumonia-related direct mortality rate of dementia patients was 50.07% (95% CI: 34.85%, 65.30%); (5) The pneumonia-related indirect mortality rate of dementia patients was 12.43% (95% CI: 5.85%, 19.00%); (6) The hospital-reported mortality rate of dementia patients related to pneumonia was 12.66% (95% CI: 6.60%, 18.72%); (7) The mortality rate of dementia patients related to pneumonia was 17.48% (95% CI: 10.60%, 24.38%)., Conclusion: This meta-analysis shows that the pneumonia-related mortality of dementia patients is much higher than the expectation of clinicians. The results of the study greatly warned clinicians to pay close attention to pneumonia cases of senile dementia patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Pharmacological and non-pharmacological interventions are mostly designed for patients with early Alzheimer's disease (AD) dementia. Long-term case management and planning for the remainder of life with disability require an estimation of the survival duration., Methods: This cohort study utilized data from the National Health Insurance Research Database, Taiwan, to identify incident cases of mild-to-moderate AD dementia diagnosed from 2000 to 2002, followed through December 31, 2017. A multivariate Cox proportional hazards regression model was constructed to compare the independent effects of age, sex, and comorbidities on all-cause mortality risk. Cumulative survival rates and survival times were estimated., Results: A total of 5258 incident cases were identified, all treated with cholinesterase inhibitors after diagnosis confirmation by an expert committee. During the 15-year follow-up period, 4331 deaths occurred. The 1-, 3-, 5-, 10-, and 15-year cumulative survival rates were 95, 92, 67, 37, and 18, respectively. The median (95% CI) survival time after diagnosis was 7.69 (7.46-7.90) years overall, 6.37 (6.06-6.65) years in men, and 8.81 (8.49-9.12) years in women. After stratification by age and number of comorbidities, the median survival time ranged from 13.72 (ages 40-64) to 5.29 (ages ≥ 80) years among those without comorbidities. For those with ≥ 3 comorbidities, the median survival times decreased to 6.43 for individuals diagnosed at ages 40-64 and to 2.98 years for those diagnosed at age 80 or older., Conclusions: This nationwide, large, long-term cohort study provided survival rates and durations from diagnosis to death, varying by sex, age group, and presence/number of comorbidities. This information can serve as a foundation for further cost-effectiveness studies on new treatments, and may aid clinicians, patients, and families in shared decision-making and advance personalized care planning for early dementia cases., (© 2024 John Wiley & Sons Ltd.)

Purpose: To study the effects of benign prostatic hyperplasia treatments, namely: alpha-adrenergic receptor blockers, 5-alpha-reductase inhibitors and phosphodiesterase-5 inhibitors on the risk of Parkinson's disease, Alzheimer's disease and mortality., Materials and Methods: All male Medicare enrollees aged 65 or above who were diagnosed with benign prostatic hyperplasia and received one of the study drugs between 2007-2020 were followed-up for the three outcomes. We used Cox regression analysis to assess the relative risk of each of the outcomes for each study drug compared to the most prescribed drug, tamsulosin, while controlling for demographic, socioeconomic and comorbidity factors., Results and Conclusions: The study analyzed 1.1 million patients for a mean follow-up period of 3.1 years from being prescribed one of the study drugs. For all outcomes, patients on tamsulosin were used as the reference for comparison. For mortality, alfuzosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.68-0.78), and doxazosin with 6% risk reduction (HR 0.94, 95%CI 0.91-0.97). For Parkinson's disease, terazosin was associated with 26% risk reduction (HR 0.74, 95%CI 0.66-0.83), and doxazosin with 21% risk reduction (HR 0.79, 95%CI 0.72-0.88). For Alzheimer's disease, terazosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.65-0.82), and doxazosin with 16% risk reduction (HR 0.84, 95%CI 0.76-0.92). Tadalafil was associated with risk reduction (27-40%) in all 3 outcomes. More research is needed to elucidate the underlying mechanisms of these observations. Given the availability of safer alternatives for treating benign prostatic hyperplasia, caution should be exercised when using tamsulosin in elderly patients, especially those with an increased risk of developing neurodegenerative diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Alzheimer's Disease and Related Dementias (ADRD) affect millions of people worldwide, with mortality rates influenced by several risk factors and exhibiting significant heterogeneity across geographical regions. This study aimed to investigate the impact of risk factors on global ADRD mortality patterns from 1990 to 2021, utilizing clustering and modeling techniques. Data on ADRD mortality rates, cardiovascular disease, and diabetes prevalence were obtained for 204 countries from the GBD platform. Additional variables such as HDI, life expectancy, alcohol consumption, and tobacco use prevalence were sourced from the UNDP and WHO. All the data were extracted for men, women, and the overall population. Longitudinal k-means clustering and generalized estimating equations were applied for data analysis. The findings revealed that cardiovascular disease had significant positive effects of 1.84, 3.94, and 4.70 on men, women, and the overall ADRD mortality rates, respectively. Tobacco showed positive effects of 0.92, 0.13, and 0.39, while alcohol consumption had negative effects of - 0.59, - 9.92, and - 2.32, on men, women, and the overall ADRD mortality rates, respectively. The countries were classified into five distinct subgroups. Overall, cardiovascular disease and tobacco use were associated with increased ADRD mortality rates, while moderate alcohol consumption exhibited a protective effect. Notably, tobacco use showed a protective effect in cluster A, as did alcohol consumption in cluster B. The effects of risk factors on ADRD mortality rates varied among the clusters, highlighting the need for further investigation into the underlying causal factors., (© 2024. The Author(s).)

The relation of vitamin C with Alzheimer's disease (AD) is equivocal. The aim of this study was to assess the relation of serum vitamin C levels with AD-related mortality, and to evaluate the threshold beyond which the potential benefits of higher serum concentrations of vitamin C for AD mortality ceases. The cohort consisted of 4504 adults aged ≥60 years enrolled in the National Health and Nutrition Examination Survey who had serum measures of vitamin C and no cognitive impairment at baseline (1988-1994) and were followed-up for mortality until 2019. Vitamin C was assayed from fasting blood samples using isocratic high-performance liquid chromatography. At baseline, the mean age of participants was 70 years, with 42.7% being men. At the end of follow-up (median: 15 years), the AD mortality rate was 2.4 per 1000 person-years. In the Cox regression models, compared to participants in the lowest tertile of serum vitamin C (<0.56 mg/dL), those in the highest tertile (>0.98 mg/dL) had a lower risk of AD mortality (hazard ratio: 0.44, 95% confidence intervals: 0.25-0.77) after adjusting for sociodemographic factors, behavior/lifestyle factors, prevalent health conditions, and dietary vitamin C intake. In dose-response analysis using restricted cubic splines, vitamin C concentrations beyond 2.3 mg/dL were associated with the elevated risk of AD-related mortality. The findings from this national sample of community-dwelling elderly adults suggest that higher levels of serum vitamin C are associated with slower AD disease progression, although levels beyond the normal reference values were associated with a higher risk of AD mortality.

In precision medicine, both predicting the disease susceptibility of an individual and forecasting its disease-free survival are areas of key research. Besides the classical epidemiological predictor variables, data from multiple (omic) platforms are increasingly available. To integrate this wealth of information, we propose new methodology to combine both cooperative learning, a recent approach to leverage the predictive power of several datasets, and polygenic hazard score models. Polygenic hazard score models provide a practitioner with a more differentiated view of the predicted disease-free survival than the one given by merely a point estimate, for instance computed with a polygenic risk score. Our aim is to leverage the advantages of cooperative learning for the computation of polygenic hazard score models via Cox's proportional hazard model, thereby improving the prediction of the disease-free survival. In our experimental study, we apply our methodology to forecast the disease-free survival for Alzheimer's disease (AD) using three layers of data. One layer contains epidemiological variables such as sex, APOE (apolipoprotein E, a genetic risk factor for AD) status and 10 leading principal components. Another layer contains selected genomic loci, and the last layer contains methylation data for selected CpG sites. We demonstrate that the survival curves computed via cooperative learning yield an AUC of around $0.7$, above the state-of-the-art performance of its competitors. Importantly, the proposed methodology returns (1) a linear score that can be easily interpreted (in contrast to machine learning approaches), and (2) a weighting of the predictive power of the involved data layers, allowing for an assessment of the importance of each omic (or other) platform. Similarly to polygenic hazard score models, our methodology also allows one to compute individual survival curves for each patient., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: Data regarding the trends in Alzheimer's disease (AD) mortality in the modern European Union (EU-27) member states are lacking. We assess the sex- and age-specific trends in AD mortality in the EU-27 member states between years 2012 and 2020., Methods: Data on cause-specific deaths and population numbers by sex for each country of the EU-27 were retrieved through publicly available European Statistical Office (EUROSTAT) dataset from 2012 to 2020. AD-related deaths were ascertained when the ICD-10 code G30 was listed as the primary cause of death in the medical death certificate. To calculate annual trends, we assessed the average annual percent change (AAPC) with relative 95% confidence intervals (CIs) using Joinpoint regression., Results: During the study period, 751,493 deaths (1.7%, 233,271 males and 518,222 females) occurred in the EU-27 because of AD. Trends in the proportion of AD-related deaths per 1000 total deaths slightly increased from 16.8% to 17.5% (p for trend <0.001). The age-adjusted mortality rate was higher in women over the entire study period. Joinpoint regression analysis revealed a stagnation in age-adjusted AD-related mortality from 2012 to 2020 among EU-27 Member States (AAMR: -0.1% [95% CI: -1.8-1.79], p = 0.94). Stratification by Country showed relevant regional disparities, especially in the Northern and Eastern EU-27 member states., Conclusions: Over the last decade, the age-adjusted AD-related mortality rate has plateaued in EU-27. Important disparities still exist between Western and Eastern European countries., (© 2024 John Wiley & Sons Ltd.)

Introduction: Alzheimer's Disease (AD) is the leading cause of dementia and a significant public health concern, characterized by high incidence, mortality, and economic burden. This study analyzes the mortality patterns and demographic disparities in Alzheimer's disease-related deaths among the elderly population in the United States from 1999 through 2020., Methods: Alzheimer's disease mortality data for individuals 65 and older were obtained from the CDC WONDER database, utilizing ICD-10 codes G30.0, G30.1, G30.8, and G30.9 for identification. Demographic and regional variables included age, gender, race/ethnicity, place of death, urban- rural status, and geographic region. Crude death rates (CR) and age-adjusted mortality rates (AAMR) per 100,000 individuals were calculated. Joinpoint Regression Program 5.0.2 was used to analyze trends, calculating Annual Percentage Changes (APCs) and Average Annual Percentage Changes (AAPCs)., Results: From 1999 to 2020, 1,852,432 deaths were attributed to AD among individuals aged 65 and older. The AAMR increased from 128.8 in 1999 to 254.3 in 2020, with an AAPC of 2.99% (95% CI = 2.61-3.48). The age-adjusted mortality rate (AAMR) was higher in females (218.5) than in males (163.5). Among racial and ethnic groups, non-Hispanic whites had the highest AAMR, followed by Non-Hispanic Blacks and Hispanics. Regionally, the West reported the highest AAMR, while the Northeast recorded the lowest. Most deaths occurred in nursing homes (57.3%), with a significant portion also occurring at decedents' homes (22.4%)., Conclusion: AD mortality rates in the U.S. have risen significantly, with notable disparities across age, gender, race, and geographic regions. These findings highlight the need for targeted interventions and research to address the growing burden of AD, particularly among the most affected demographic groups., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Relationships of fish-shellfish consumption, cognitive health and mortality from Alzheimer's disease (AD) among US adults aged 60 years and older have not been adequately studied., Objectives: To determine the relationship of fish-shellfish consumption, cognitive health and mortality from AD in US adults aged 60 years and older., Design, Setting and Participants: The data of this cross-sectional study of US adults aged 60 years and older were from the National Nutrition and Health Examination Survey (NHANES) datasets. Frequency of fish-shellfish consumption, its association with subjective cognitive decline (SCD) and AD mortality of these participants between 1999 and 2018 and cognitive assessment scores between 2011 and 2014 were analyzed., Measurements and Results: US adults aged 60 years and older consumed fish-shellfish 1.2 times/week and had a blood Hg of 1.63 ug/L on average between 1999 and 2018. Participants aged 60 years and older in the highest quartile of fish-shellfish consumption (~3 times/week) had significantly higher cognitive assessment scores than those in the lowest quartile (rare or no fish-shellfish consumption). Adults in the highest quartile of fish-shellfish consumption had a 30% lower risk (odds ratio 0.7, 95%CI 0.57-0.87) of SCD, and 44% lower risk (hazard ratio 0.56, 95%CI 0.35-0.9) of AD mortality than those in the lowest quartile., Conclusion: Increased fish-shellfish consumption was associated with improved scores of cognitive assessment and reduced risks of SCD and AD mortality., Competing Interests: The author has no conflicts of interest to disclose regarding the publication of this paper. There is no external funding source for the project. The results were not presented at any conferences and were not made public in any manner.

Dementia is on the rise in the world population and has been defined by the World Health Organization as a global public health priority. In Italy, according to demographic projections, in 2051 there will be 280 elderly people for every 100 young people, with an increase in all age-related chronic diseases, including dementia. Currently the total number of patients with dementia is estimated to be over 1 million (mainly with Alzheimer's disease (AD) and Parkinson's disease (PD)). In-depth studies of the etiology and physiology of dementia are complicated due to the complexity of these diseases and their long duration. In this work we present a dataset on mortality rates (in the form of Standardized Mortality Ratios, SMR) for AD e PD in Italy at provincial level over a period of 8 years (2012-2019). Access to long-term, spatially detailed and ready-to-use data could favor both health monitoring and the research of new treatments and new drugs as well as innovative methodologies for early diagnosis of dementia., (© 2023. Springer Nature Limited.)

Purpose: The number of American Indian and Alaska Native (AI/AN) people living with dementia is expected to increase 5-fold by 2060. Social determinants of health may explain disparities in the incidence of Alzheimer disease (AD) but remain largely overlooked., Methods: We examined the time trend of AD mortality rates and associations of the percentage of AI/ANs, density of primary care physicians and neurologists, area deprivation index, rurality, and Indian Health Service region with AD mortality in 646 purchased/referred care delivery area counties., Results: AD mortality rates significantly increased over time. Counties with higher concentrations of AI/AN people had lower AD mortality. More deprived counties had 34% higher AD mortality compared with less deprived counties. AD mortality was 20% lower in nonmetro counties than in metro counties., Conclusions: Findings have implications for prioritizing areas where more resources for AD care, education, or outreach are needed., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Prognosis-related information regarding dementia needs to be updated, as changes in medical and long-term care environments for patients with dementia in recent decades may be improving the prognosis of the disease., Objective: We aimed to investigate the mortality, cause of death, and prognostic factors by types of dementia in a Japanese clinic-based cohort., Methods: The National Center for Geriatrics and Gerontology-Life Stories of People with Dementia consists of clinical records and prognostic data of patients who visited the Memory Clinic in Japan. Patients who attended the clinic between July 2010 and September 2018, or their close relatives, were asked about death information via a postal survey. A cohort of 3,229 patients (mean age, 76.9; female, 1,953) was classified into six groups: normal cognition (NC), mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia, dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration. A Cox proportional hazards model was employed to compare the mortality of each type of dementia, MCI, and NC., Results: Patients with all types of dementia and MCI had higher mortality rates than those with NC (hazard risks: 2.61-5.20). The most common cause of death was pneumonia, followed by cancer. In the MCI, AD, and DLB groups, older age, male sex, and low cognitive function were common prognostic factors but not presence of apolipoprotein E ɛ4 allele., Conclusion: Our findings suggest important differences in the mortality risk and cause of death among patients with dementia, which will be useful in advanced care planning and policymaking.

Background: Growing evidence suggests that critical periods in early life may contribute to one's risk of Alzheimer's disease and related dementias (ADRD) in later life. In this paper we explore the role that exposure to infant mortality plays in later life ADRD., Objective: To determine if exposure to early life infant mortality is associated with later mortality from ADRD. Also, we explore how these associations differ by sex and age group, along with the role of state of birth and competing risks of death., Methods: We use a sample of over 400,000 individuals aged 50 and above with the NIH-AARP Diet and Health Study with mortality follow-up, allowing us to examine how early life infant mortality rates along with other risk factors play in one's individual mortality risk., Results: We show that infant mortality rates are associated with death from ADRD among those under 65 years of age, but not those over 65 at baseline interview. Moreover, when factoring in competing risks of death, the associations are relatively unchanged., Conclusion: These results suggest that those exposed to worse adverse conditions during critical periods increase their likelihood of death from ADRD earlier than average, due to that exposure increasing their susceptibility to develop illness later on in life.

Background: Alzheimer's disease (AD) is the most common form of dementia. Its neurodegenerative nature and the lack of a curative treatment result in a substantial burden for healthcare systems and society. This study aimed to analyze the hospital incidence and mortality of AD in Spain and to evaluate patients' use of healthcare resources and direct medical costs., Methods: Admission records of patients with AD treated in hospitals in Spain between 2011 and 2016 were selected from a Spanish hospital discharge database., Results: Records of 7,894 patients with diagnosed AD were analyzed. Hospital incidence was 3.7 per 10,000 persons over the study period, 2.9 and 4.4 for males and females, respectively. In-hospital mortality was 9.5%; both hospital incidence and in-hospital mortality increased over the study period. Mortality was principally associated with acute respiratory failure and other diseases of the respiratory system and heart failure. Annual medical costs of specialized care increased slightly during the study period, with a mean annual cost per patient of €4,969., Conclusions: AD is responsible for an increasing proportion of hospitalizations in Spain and raising medical costs, which highlights the importance of early detection and optimized care.

Objectives: The regions with highest and lowest Alzheimer's disease (AD) mortality across the United States at state/county levels were identified and their contribution to the differences in total mortality rates between these regions was evaluated. The disease, disease group, sex, race/ethnicity, and place-of-death-related inter-region differences that engender the disparity in mortality were quantitatively described. The hypothesis that inter-regional differences in filling out death certificates are a major contributor to differences in AD mortality was tested., Design: Retrospective evaluation of death certificate data., Setting: The United States., Participants: Deceased US residents, 1999-2018., Methods: Region-specific age-adjusted mortality rates and group-specific rate decomposition., Results: The county clusters with the highest and lowest AD mortality rates were in Washington (WA) and New York (NY), respectively, with other notable high-mortality clusters on the border of Tennessee, Georgia, and Alabama as well as in North Dakota and South Dakota. These patterns were stable over the 1999-2018 period. AD had the highest contribution to total mortality difference between WA and NY (156%, higher in WA), in contrast circulatory diseases had a contribution of comparable magnitude (154%) but were higher in NY. Differences in cause-of-death certificate coding, either through coding of non-AD dementias, or other conditions accompanying a potential AD death could not account for differences in AD mortality between NY and WA., Conclusions: Inter-regional differences in filling out death certificates were not a major contributor to variation in AD mortality between the regions with the highest and lowest rates. The respective mitigation of the effects of neural and circulatory diseases and several other high-impact conditions would not negate the disparity in mortality between NY and WA., (© 2021 The American Geriatrics Society.)

Few studies with mixed results have examined the association between chocolate consumption and mortality. We aimed to examine this association in a US population. A population-based cohort of 91891 participants aged 55 to 74 years was identified. Chocolate consumption was assessed via a food frequency questionnaire. Cox regression was used to estimate risk estimates. After an average follow-up of 13.5 years, 19586 all-cause deaths were documented. Compared with no regular chocolate consumption, the maximally adjusted hazard ratios of all-cause mortality were 0.89 [95% confidence interval (CI) 0.84-0.94], 0.84 (95% CI 0.79-0.90), 0.86 (95% CI 0.81-0.93), and 0.87 (95% CI 0.82-0.93) for >0-0.5 servings/week, >0.5-1 serving/week, >1-2 servings/week, and >2 servings/week, respectively ( P trend = 0.009). A somewhat stronger inverse association was observed for mortality from cardiovascular disease and Alzheimer's disease. A nonlinear dose-response pattern was found for all-cause and cardiovascular mortality (all P nonlinearity < 0.01), with the lowest risk observed at chocolate consumption of 0.7 servings/week and 0.6 servings/week, respectively. The favorable associations with all-cause and cardiovascular mortality were found to be more pronounced in never smokers than in current or former smokers (all P interaction < 0.05). In conclusion, chocolate consumption confers reduced risks of mortality from all causes, cardiovascular disease, and Alzheimer's disease in this US population.

Purpose: People with dementia may have indications for aspirin prescription and clinicians are asked to balance the potential risks against benefits. This review examines the evidence for the risk and benefit of long-term aspirin use in people with dementia aged over 65 years, including randomised controlled trials and observational studies., Methods: We searched three databases for research published between 2007 and 2020. Each eligible article was assessed for risk of bias, and confidence in findings was rated using Grading of Recommendations Assessment, Development and Evaluation (GRADE)., Results: Four papers met inclusion criteria: one randomised controlled trial, two cohort studies, and one with pooled data. All looked only at dementia of Alzheimer's type, and none addressed myocardial or cerebral infarction as outcomes. Dementia progression was reported by two studies, with conflicting results. The trial found no significant effect of aspirin on mortality (odds ratio aspirin vs. no aspirin 1.07, 95% confidence interval 0.58-1.97) but found more events of severe bleeding with aspirin (OR aspirin vs. no aspirin 6.9, 1.5-31.2). An excess in intracranial haemorrhage in the aspirin group was judged plausible based on two non-randomised studies., Conclusions: The review findings are limited because studies include only people with Alzheimer's-type dementia and lack confirmatory studies, although an increased risk of bleeding events is recognised. Further research that addresses the benefits and risks of aspirin in more representative groups of people with dementia is needed to guide prescribing decisions.

Objective: Accumulating evidence suggests the possibility that early life exposures may contribute to risk of Alzheimer's Disease (AD). This paper explores geographic disparities in AD mortality based on both state of residence in older age as well as state of birth measures in order to assess the relative importance of these factors., Methods: We use a subset of a large survey, the NIH-AARP Diet and Health Study, of over 150,000 individuals aged 65-70 with 15 years of mortality follow-up, allowing us to study over 1050 cases of AD mortality. We use multi-level logistic regression, where individuals are nested within states of residence and/or states of birth, to assess the contributions of place to AD mortality variation., Results: We show that state of birth explains a modest amount of variation in AD mortality, approximately 4%, which is consistent with life course theories that suggest that early life conditions can produce old age health disparities. However, we also show that nearly all of the variation from state of birth is explained by state of residence in old age., Conclusions: These results suggest that later life factors are potentially more consequential targets for intervention in reducing AD mortality and provide some evidence against the importance of macro-level environmental exposures at birth as a core determinant of later AD., Competing Interests: The authors declare that they have no competing interests.

Objective: To investigate whether cholinesterase inhibitors (ChEIs) are associated with slower cognitive decline in Alzheimer dementia and decreased risk of severe dementia or death., Methods: Patients with Alzheimer dementia from the Swedish Dementia Registry starting on ChEIs within 3 months of the dementia diagnosis were included and compared to nontreated patients with Alzheimer dementia. In a propensity score-matched cohort, the association between ChEI use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores was examined with a mixed model, and severe dementia (MMSE score <10) or death as an outcome was assessed with Cox proportional hazards models., Results: The matched cohort included 11,652 ChEI users and 5,826 nonusers. During an average of 5 years of follow-up, 255 cases developed severe dementia, and 6,055 (35%) died. ChEI use was associated with higher MMSE score at each visit (0.13 MMSE points per year; 95% confidence interval [CI] 0.06-0.20). ChEI users had a 27% lower risk of death (0.73, 95% CI 0.69-0.77) compared with nonusers. Galantamine was associated with lower risk of death (0.71, 95% CI 0.65-0.76) and lower risk of severe dementia (0.69, 95% CI 0.47-1.00) and had the strongest effect on cognitive decline of all the ChEIs (0.18 MMSE points per year, 95% CI 0.07-0.28)., Conclusions: ChEIs are associated with cognitive benefits that are modest but persist over time and with reduced mortality risk, which could be explained partly by their cognitive effects. Galantamine was the only ChEI demonstrating a significant reduction in the risk of developing severe dementia., Classification of Evidence: This study provides Class III evidence that for patients with Alzheimer dementia ChEIs decrease long-term cognitive decline and risk of death and that galantamine decreases the risk of severe dementia., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

This article describes the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on caregivers and society. The Special Report discusses the challenges of providing equitable health care for people with dementia in the United States. An estimated 6.2 million Americans age 65 and older are living with Alzheimer's dementia today. This number could grow to 13.8 million by 2060 barring the development of medical breakthroughs to prevent, slow or cure AD. Official death certificates recorded 121,499 deaths from AD in 2019, the latest year for which data are available, making Alzheimer's the sixth-leading cause of death in the United States and the fifth-leading cause of death among Americans age 65 and older. Between 2000 and 2019, deaths from stroke, heart disease and HIV decreased, whereas reported deaths from AD increased more than 145%. This trajectory of deaths from AD was likely exacerbated in 2020 by the COVID-19 pandemic. More than 11 million family members and other unpaid caregivers provided an estimated 15.3 billion hours of care to people with Alzheimer's or other dementias in 2020. These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver. Unpaid dementia caregiving was valued at $256.7 billion in 2020. Its costs, however, extend to family caregivers' increased risk for emotional distress and negative mental and physical health outcomes - costs that have been aggravated by COVID-19. Average per-person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are more than three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 23 times as great. Total payments in 2021 for health care, long-term care and hospice services for people age 65 and older with dementia are estimated to be $355 billion. Despite years of efforts to make health care more equitable in the United States, racial and ethnic disparities remain - both in terms of health disparities, which involve differences in the burden of illness, and health care disparities, which involve differences in the ability to use health care services. Blacks, Hispanics, Asian Americans and Native Americans continue to have a higher burden of illness and lower access to health care compared with Whites. Such disparities, which have become more apparent during COVID-19, extend to dementia care. Surveys commissioned by the Alzheimer's Association recently shed new light on the role of discrimination in dementia care, the varying levels of trust between racial and ethnic groups in medical research, and the differences between groups in their levels of concern about and awareness of Alzheimer's disease. These findings emphasize the need to increase racial and ethnic diversity in both the dementia care workforce and in Alzheimer's clinical trials., (© 2021 the Alzheimer's Association.)

Background: Cognitive profiles characterized by primarily language or visuospatial deficits have been documented in individuals meeting diagnostic criteria for probable Alzheimer's disease (AD), but their association with progression rate or overall survival is not well described., Objective: To compare time from diagnosis to severe disease stage and death in probable AD patients classified into three groups based on neuropsychological test performance: marked verbal impairment (Verb-PI) with relatively preserved visuospatial function, marked visuospatial impairment with preserved verbal function (Vis-PI), and balanced verbal and visuospatial impairments (Bal-PI)., Methods: This prospective cohort study included 540 probable AD patients attending an academic memory clinic who were enrolled from 1995-2013 and followed annually. Eligible individuals had a Mini-Mental State Exam (MMSE) score ≥10 at baseline, and at least one annual follow up visit. We used Cox proportional hazards modeling to analyze the association of cognitive profiles with time to decline in MMSE and CDR Global Score., Results: Sixty-one (11.3%) individuals had a Verb-PI profile, 86 (16%) had a Vis-PI profile, and 393 (72.8%) a Bal-PI profile. MMSE decline to <10 was faster in Verb-PI than Vis-PI (HR 2.004, 95%CI, 1.062-3.780; p = 0.032). Progression to CDR-GS = 3 was faster in Verb-PI individuals compared to Bal-PI (HR 1.604, 95%CI, 1.022-2.515; p = 0.040) or Vis-PI (HR 2.388, 95%CI, 1.330-4.288; p = 0.004) individuals. Baseline cognitive profile did not affect mortality., Conclusion: A recognition of different AD profiles may help to personalize care by providing a better understanding of pathogenesis and expected progression.

Background: The increasing prevalence of Alzheimer's disease (AD), along with the associated burden on healthcare systems, presents a substantial public health challenge., Objective: This study aimed to investigate trends in AD mortality and the relevant burden across the United States (U.S.) from 1999 to 2018 and to predict mortality trends between 2019 and 2023., Methods: Data on AD-related deaths between 1999 and 2018 were collected from the WONDER database administered by the U.S. Centers for Disease Control and Prevention (CDC). The Joinpoint Regression Program was used to analyze mortality trends due to AD. Years of life lost (YLL) were calculated to explore the burden of AD deaths. An autoregressive integrated moving average (ARIMA) model was employed to forecast mortality trends from 2019 to 2023., Results: Over a recent 20-year period, the number of AD deaths in the U.S. increased from 44,536 (31,145 females and 13,391 males) to 122,019 (84,062 females and 37,957 males). The overall age-adjusted mortality rate increased from 16.5/100,000 in 1999 to 30.5/100,000 in 2018. AD mortality is projected to reach 42.40/100000 within the year 2023. Overall, AD resulted in 322,773.00 YLL (2.33 per 1000 population) in 1999 and 658,501.87 YLL (3.68 per 1000 population) in 2018., Conclusion: Our findings demonstrate an increase in AD mortality in the U.S. from 1999 to 2018 as well as a rapid increase from 2019 to 2023. The high burden of AD deaths emphasizes the need for targeted prevention, early diagnosis, and hierarchical management.

Background: Alzheimer's Disease (AD) is a neurodegenerative brain disease in the elderly. Recent studies have revealed the heterogeneous nature of AD. Mild Cognitive Impairment (MCI) is the prodromal stage of AD., Objectives: In this study, we identified subtypes of MCI based on genetic polymorphism and gene expression., Methods: We utilized the two types of omics data, namely genetic polymorphism and gene expression profiling, derived from 125 MCI patients' peripheral blood samples from the ADNI-1 dataset. Similarity network fusion (SNF) algorithm was implemented to cluster MCI patient subtypes. And 185 MCI patients in ADNI-2 were utilized to evaluate the effectiveness of this method. Two MCI subtypes were identified by implementing the SNF algorithm., Results: We used Kaplan-Meier analysis and log-rank testing for the conversion from MCI to AD between two subtypes, and p-value is 4.58×10-3. In addition, we compared patients among two MCI subtypes by the following factors: the changes in Alzheimer's Disease cognitive scales and MRI image; significantly enriched pathways based on differentially expressed genes. This study proved that MCI is a heterogeneous disease by concluding that AD development in two MCI subtypes is significantly different., Conclusions: MCI patients with different molecular characteristics have different risks converting to AD. In addition to evaluating statistics, genetic polymorphism and gene expression profiling from MCI patients' peripheral blood are non-invasiveness and cost-effectiveness markers to identify MCI subtypes for clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Early diagnosis of Alzheimer's disease (AD) provides an opportunity for early intervention. Cognitive testing has proven to be a reliable way to identify individuals who may be at risk of AD. The Telephone Assessment for Cognitive Screening (TICS) is proficient in screening for cognitive impairment. However, its ability to identify those at risk of developing AD pathology is unknown., Objective: We aim to investigate associations between TICS scores, collected over a period of 13 years, and the cognitive status of participants at death. We also examine relationships between TICS scores and neuropathological indices of AD (CERAD score, Thal phase, and Braak stage)., Methods: Between 2004 and 2017, participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age underwent cognitive assessment using TICS. Scores from four time points were available for analysis. Cognitive impairment and AD pathology at death was evaluated in 101 participants., Results: TICS scores at time points 2, 3, and 4 were significantly lower in those cognitively impaired at death compared to those considered cognitively normal. There were significant negative correlations between TICS scores and CERAD score and Braak stage at time points 2 and 4. No correlations between Thal phase and TICS were found., Conclusion: Findings indicate that TICS could be used not only to screen for cognitive impairment, but also to identify individuals at risk of developing AD pathology, many years before any overt symptoms occur. Once identified, 'at risk' individuals could be targeted for early interventions which could attenuate the progression of the disease.

Given the association between periodontal disease (PdD) and Alzheimer's disease (AD), we examined correlations between states' age-adjusted AD mortality rates, AD prevalence, subjective cognitive decline (SCD) prevalence, and oral health data. Data sources include the Centers for Disease Control and Prevention, scientific literature, and oral health rankings formulated by WalletHub.com and Toothbrush.org. Pearson (r) or Spearman (r s ) correlation coefficients were generated and evaluated. AD mortality rates correlate with dental visits (r = - 0.50, p = 0.0003), partial (r = 0.39, p = 0.005) or total (r = 0.44, p = 0.001) edentulism, WalletHub.com (r s  = 0.30, p = 0.03) and Toothbrush.org (r s  = 0.35, p = 0.01) rankings. AD prevalence correlates with dental visits (r = - 0.30, p = 0.03), partial (r = 0.55, p = 0.00003) or total (r = 0.46, p = 0.0009) edentulism, prevalence of any (r = 0.38, p = 0.006) or severe-stage (r = 0.46, p = 0.0009) PdD, and WalletHub.com (r s  = 0.38, p = 0.006) rankings. SCD prevalence in adults aged ≥ 45 years correlates with dental visits (r = - 0.69, p < 0.00001), partial (r = 0.33, p = 0.02) or total (r = 0.37, p = 0.008) edentulism, prevalence of any (r = 0.53, p = 0.0001) or severe-stage (r = 0.57, p = 0.00002) PdD, WalletHub.com (r s  = 0.53, p = 0.00008) and Toothbrush.org (r s  = 0.60, p < 0.00001) rankings. State metrics indicative of compromised oral health correlate with AD mortality rates, AD prevalence and SCD prevalence.

Data collected from clinical trials and cohort studies, such as dementia studies, are often high-dimensional, censored, heterogeneous and contain missing information, presenting challenges to traditional statistical analysis. There is an urgent need for methods that can overcome these challenges to model this complex data. At present there is no cure for dementia and no treatment that can successfully change the course of the disease. Machine learning models that can predict the time until a patient develops dementia are important tools in helping understand dementia risks and can give more accurate results than traditional statistical methods when modelling high-dimensional, heterogeneous, clinical data. This work compares the performance and stability of ten machine learning algorithms, combined with eight feature selection methods, capable of performing survival analysis of high-dimensional, heterogeneous, clinical data. We developed models that predict survival to dementia using baseline data from two different studies. The Sydney Memory and Ageing Study (MAS) is a longitudinal cohort study of 1037 participants, aged 70-90 years, that aims to determine the effects of ageing on cognition. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal study aimed at identifying biomarkers for the early detection and tracking of Alzheimer's disease. Using the concordance index as a measure of performance, our models achieve maximum performance values of 0.82 for MAS and 0.93 For ADNI.

Although the ε2 allele of apolipoprotein E ( APOE2 ) benefits longevity, its mechanism is not understood. The protective effects of the APOE 2 on Alzheimer's disease (AD) risk, particularly through their effects on amyloid or tau accumulation, may confound APOE2 effects on longevity. Herein, we showed that the association between APOE2 and longer lifespan persisted irrespective of AD status, including its neuropathology, by analyzing clinical datasets as well as animal models. Notably, APOE2 was associated with preserved activity during aging, which also associated with lifespan. In animal models, distinct apoE isoform levels, where APOE2 has the highest, were correlated with activity levels, while some forms of cholesterol and triglycerides were associated with apoE and activity levels. These results indicate that APOE2 can contribute to longevity independent of AD. Preserved activity would be an early-observable feature of APOE2 -mediated longevity, where higher levels of apoE2 and its-associated lipid metabolism might be involved., Competing Interests: MS, TK, MT, AK, MS, YF, JZ, XH, PS, GR, JF, MH, GB No competing interests declared, (© 2020, Shinohara et al.)

Background: Impaired recovery of blood pressure (BP) after standing has been shown to be related to cognitive function and mortality in people without dementia, but its role in people with Alzheimer's disease (AD) is unknown. The aim of this study was to investigate the association of the orthostatic BP response with cognitive decline and mortality in AD., Methods: In this post hoc analysis of a randomized controlled trial (Nilvad), we measured the beat-to-beat response of BP upon active standing in mild-to-moderate AD. This included the initial drop (nadir within 40 seconds) and recovery after 1 minute, both expressed relative to resting values. We examined the relationship between a small or large initial drop (median split) and unimpaired (≥100%) or impaired recovery (<100%) with 1.5-year change in Alzheimer's Disease Assessment-cognitive subscale (ADAS-cog) scores and all-cause mortality., Results: We included 55 participants (age 73.1 ± 6.2 years). Impaired BP recovery was associated with higher increases in ADAS-cog scores (systolic: β [95% confidence interval] = 5.6 [0.4-10.8], p = .035; diastolic: 7.6 [2.3-13.0], p = .006). During a median follow-up time of 49 months, 20 participants died. Impaired BP recovery was associated with increased mortality (systolic: HR [95% confidence interval] = 2.9 [1.1-7.8], p = .039; diastolic: HR [95% confidence interval] = 5.5 [1.9-16.1], p = .002). The initial BP drop was not associated with any outcome. Results were adjusted for age, sex, and intervention group., Conclusions: Failure to fully recover BP after 1 minute of standing is associated with cognitive decline and mortality in AD. As such, BP recovery can be regarded as an easily obtained marker of progression rate of AD., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Introduction: Small observational studies with short-term follow-up suggest that cancer patients are at reduced risk of Alzheimer's disease (AD) compared to the general population., Methods: A nationwide cohort study using Danish population-based health registries (1980-2013) with cancer patients (n = 949,309) to identify incident diagnoses of AD. We computed absolute reductions in risk attributed to cancer and standardized incidence rate ratios (SIRs) accounting for survival time, comparing the observed to expected number of AD cases., Results: During up to 34 years of follow-up of cancer survivors, the attributable risk reduction was 1.3 per 10,000 person-years, SIR = 0.94 (95% confidence interval 0.92-0.96). SIRs were similar after stratification by sex, age, and cancer stage, and approached that of the general population for those surviving >10 years., Discussion: Inverse associations between cancer and AD were small and diminished over time. Incidence rates in cancer survivors approached those of the general population, suggesting limited association between cancer and AD risk., (© 2020 the Alzheimer's Association.)

Background: Alzheimer's disease (AD) is the fifth-leading cause of death in people more than 65 years old. Acupuncture therapy has been traditionally used to treat various kinds of health problems including AD. This protocol aims to summarize the available evidence from current systematic reviews (SRs) for the efficacy of acupuncture therapy for AD., Methods: Seven databases will be searched: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chongqing VIP (CQVIP), and Chinese Biomedical Literature Database (CBM). SRs/meta-analyses (MAs) of acupuncture therapy for AD which were reported in Chinese or English will be included. Study selection, data extraction, and assessment of the study quality will be performed independently by 2 or more reviewers. And the methodological quality, report quality and evidence quality will be evaluated by Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool, Preferred Reporting Items for Systematic Reviews and Meta Analyses Statement (PRISMA) checklist and Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, respectively., Results: The article in this overview will be submitted for publication in a peer-reviewed journal., Conclusion: We expect to compile evidence from multiple systematic reviews of acupuncture therapy in AD patients in an accessible and useful document.Registration number: INPLASY202040035.

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., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objectives: The current study was designed to investigate the relationship between the soil arsenic (As) concentration and the mortality from Alzheimer's disease (AD) in mainland China., Study Design: Ecological study., Methods: Twenty-two provinces and 3 municipal districts in mainland China were included in this study. The As concentrations in soil in 1990 was obtained from the China State Environmental Protection Bureau; the data on annual mortality of AD from 1991 to 2000 were obtained from the National Death Cause Surveillance Database of China. Using these data, we calculated the spearman correlation coefficient between soil As concentration and AD mortality, and the relative risk (RR) between soil As levels and AD mortality by quartile-dividing study groups., Results: The spearman correlation coefficient between As concentration and AD mortality was 0.552 (p = 0.004), 0.616 (p = 0.001) and 0.622 (p = 0.001) in the A soil As (eluvial horizon), the C soil As (parent material horizon), and the Total soil As (A soil As + C soil As), respectively. When the A soil As concentration was over 9.05 mg/kg, 10.40 mg/kg and 13.10 mg/kg, the relative risk was 0.835 (95 % CI: 0.832, 0.838), 1.969 (95 %CI: 1.955, 1.982), and 2.939 (95 % CI: 2.920, 2.958), respectively; when the C soil As reached 9.45 mg/kg, 11.10 mg/kg and 13.55 mg/kg, the relative risk was 4.349 (95 % CI: 4.303, 4.396), 6.108 (95 % CI: 6.044, 6.172), and 9.125 (95 %CI: 9.033, 9.219), respectively. No correlation was found between lead, cadmium, and mercury concentration in the soil and AD mortality., Conclusion: There was an apparent soil As concentration dependent increase in AD mortality. Results of this study may provide evidence for a possible causal linkage between arsenic exposure and the death risk from AD., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: Smoking is a well-defined modifiable risk factor for dementia. Understanding national temporal trends of dementia deaths due to smoking is critical for prioritizing action for the global prevention of dementia, as well as smoking prevention. We aimed to estimate the patterns and temporal trends of smoking-attributable dementia-related deaths for 195 countries from 1990 to 2017., Methods: Detailed data on dementia deaths attributable to smoking were obtained from the Global Burden of Disease Study 2017. The estimated annual percentage change (EAPC) was used to quantify the temporal trends in the age-standardized mortality rate (ASMR) of dementia attributable to smoking by age, sex, region, and country., Results: In 2017, approximately 2.51 million deaths attributable to dementia occurred globally; among them, 317,747 dementia-related deaths were attributable to smoking. The corresponding ASMR decreased by 31.1% from 6.33 per 100,000 population in 1990 to 4.36 per 100,000 population in 2017, with an EAPC of -1.43 (95% CI -1.48, -1.37). The reduction in the ASMR in women (EAPC = -2.13; 95% CI -2.18, -2.08) was more pronounced than that in men (EAPC = -1.26; 95% CI -1.32, -1.20). Most geographic region have achieved significant declines in ASMRs since 1990; however, Central Asia and 24 countries and territories showed increased trends in ASMRs over the same period., Conclusions: Despite large reductions in the ASMRs of dementia attributable to smoking over the past three decades, the corresponding number of deaths has steadily increased due to population growth and aging. The ASMR trend patterns were heterogeneous across countries, and there were undesirable increases in the dementia ASMR in some countries. Strengthened efforts for tobacco prevention are still needed to reduce the disease burden due to smoking, particularly in countries where the dementia ASMR is increasing., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To evaluate the risk of death from Alzheimer's disease among cancer survivors in a population-based setting. Methods: Within Surveillance, Epidemiology and End Results (SEER)-9 registries, cancer patients who were diagnosed between 1975 and 2016 have been reviewed. Observed/expected ratios for the risk of death from Alzheimer's disease were calculated for the overall group as well as for clinically defined subgroups. "Observed" is the number of observed deaths from Alzheimer's disease in the studied group, while "Expected" is the number of deaths from Alzheimer's disease in a demographically similar group within the US and within the same period. Results: The current study evaluates a total of 3,579,199 cancer patients (diagnosed between 1975 and 2016) within the SEER-9 registries. Among those patients, 25,894 patients (0.72%) have Alzheimer's disease as their cause of death. Among long-term cancer survivors (≥10 years), O/E ratio of death from Alzheimer's disease was 1.13 (1.12-1.15). Death from Alzheimer's disease seems to be particularly associated with older age at time of cancer diagnosis (O/E for patients ≥70 years: 1.29 [95% CI: 1.26-1.31] versus O/E for patients <70 years: 1.01 [95% CI: 0.98-1.03]), American Indian race (O/E for American Indian patients: 1.94 [95% CI: 1.30-2.78] versus O/E for White patients: 1.12 [95% CI: 1.10-1.14]), localized tumor stage (O/E for patients with localized disease stage: 1.13 [95% CI: 1.11-1.15] versus O/E for patients with distant disease stage: 1.04 [95% CI: 0.93-1.15]) and brain tumors (O/E for brain tumors: 2.54 [95% CI: 1.42-4.19]). Conclusion: Long-term cancer survivors (≥10 years) are more likely to die from Alzheimer's disease compared to the US general population. This risk seems to be higher among patients with older age at the time of cancer diagnosis, American Indian race and those with brain tumors.

Introduction: in Italy and Tuscany the resident population aged&gt; 99 reached its all-time high in 2015. Respiratory diseases in men and ischemic heart diseases in women were the leading causes of death for Italian centenarians in 2015. The aim of this study is to describe the mortality of Tuscan centenarians by cause., Materials and Methods: population-based observational study using current health data, extracted from the Tuscan Regional Mortality Register. Main outcome measures are: proportional mortality and annual mortality trend at age &gt;99, age-specific mortality rates (85-89; 90-94; 95-99, &gt;99)., Results: at age &gt;99 ischemic heart diseases, cerebrovascular diseases and respiratory diseases are among the top 5 causes of death as in the less elderly age, the relative frequency of tumors decreases and that of the ill-defined causes increases. If ill-defined and ischemic heart diseases are separated, the first cause of death is cerebrovascular diseases in males and senility in females. In the period 2002-2015 at age &gt;99 all-cause mortality fell on average every year by -0.15% for males and -0.14% for females, mortality due to arteriosclerosis decreases -10% (males) and -12% (females) every year, due to cardiac arrest and other non-specific cardiopathies -5% (males) and -7% (females) and due to cerebrovascular diseases -3% (females). Mortality due to senility increases +6% per year in women., Conclusions: in Tuscany the first cause of death is different by gender (cerebrovascular diseases in males and senility in females) and differs from what has been observed nationally. In the 2000s, mortality from cardiovascular diseases without diagnostic significance decreased in Tuscan centenarians and that from senility increased.

Recently, an asymmetric vascular compromise approach that replicates many aspects of human vascular cognitive impairment (VCI) has been reported. The present study aimed to first investigate on the reproducibility in the disease progression of this newly reported VCI model using wild-type C57BL6/J mice. The second aim was to assess how this approach will affect the disease progression of transgenic Alzheimer's disease (AD) 5XFAD mice subjected to VCI. C57BL6/J and 5XFAD mice were subjected to VCI by placing an ameroid constrictor on the right CCA and a microcoil on the left CCA. Infarcts and hippocampal neuronal loss did not appear predominantly in the right (ameroid side) as expected but randomly in both hemispheres. The mortality rate of C57BL6/J mice was unexpectedly high. Inducing VCI reduced amyloid burden in the hippocampi of 5XFAD mice. Since VCI is known to be complex and complicated, the heterogeneous disease progression observed from this current study shares close resemblance to the clinical manifestation of VCI. This heterogeneity, however, makes it challenging to test novel treatment options using this model. Further study is warranted to tackle the heterogeneous nature of VCI.