Search

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).)

Objective: To investigate the prevalence and mortality of dementia and assess the impact of geriatric syndromes (GS) on the risk for dementia and death in elderly population in Beijing. Methods: A cross-sectional survey was conducted in the elderly population aged ≥65 years and selected by a multi-stage sampling in Beijing during 2013-2015. Cognitive function was screened using the Chinese Revised Version of the Mini-Mental State Examination (MMSE). Then, neurological examination and psychiatric assessment were performed for those with the MMSE score lower than the cut-off value. The information about GS prevalence was also collected. The study also collected death records for all individuals from baseline until December 31, 2019. Based on the age and gender distribution from Beijing data of the 2010 Six th National Population Census, the dementia prevalence in the study population was directly standardized. Logistic regression analysis was used to evaluate the association of different forms of dementia with GS, and Cox proportional hazards regression model was used to estimate the hazard ratio ( HR ) and 95% CI of death. Results: During 2013-2015, a total of 2 935 individuals completed dementia assessments, of which 167 were diagnosed with dementia. The standardized prevalence of dementia was 5.9% (95% CI : 5.0%-17.4%). The individuals with Alzheimer's disease (AD) and vascular dementia (VaD) accounted for 58.7% and 28.1% of total individuals with dementia, respectively. Aging, lower education level, urinary incontinence, and fall were risk factors for AD, while disability of activity of daily life dependence, hypertension, and stroke were found to be risk factors for VaD. After a median follow-up of 5.44 person-years, 399 deaths were recorded. The 5-year mortality risk was 2.87 (95% CI : 1.92-4.17) times and 4.93 (95% CI : 3.23-7.53) times higher for the elderly individuals with AD and VaD, respectively, compared to non-demented individuals. After adjusting for demographic, GS, and cardiovascular risk factors, the mortality risk in the elderly individuals with AD showed no significant difference compared with non-demented individuals ( HR =1.32, 95% CI : 0.89-1.97), while the mortality risk in those with VaD was 2.46 (95% CI : 1.49-4.05) times higher than that in non-demented individuals. Conclusions: The prevalence of dementia in Beijing increased significantly in the context of population aging, especially the prevalence of AD. The presence of GS increased the risks for AD and VaD, as well as the risk for death. Close attention needs to be paid to GS management in dementia prevention in elderly population.

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.)

Introduction: Dementia, a term for a range of cognitive impairments impacting memory, thinking, and social abilities, represents a formidable challenge to healthcare systems worldwide. Analysing the temporal trends in dementia-related mortality among individuals, identifying the populations at high risk, and guiding the implementation of tailored interventions to address the escalating effects of dementia on public health., Methods: Data from CDC WONDER database was examined from 1999 to 2020 for the four causes of dementia mortality: unspecified dementia (F03), Alzheimer's disease (G30), vascular dementia (F01), and other degenerative diseases of nervous system not elsewhere classified (G31). Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change (APC) were calculated and stratified by geographic region, year, age groups, sex, and race/ethnicity., Results: A total of 4,077,973 reported deaths were related to dementia from 1999 to 2020 in the United States. The greatest proportion of deaths was associated with Alzheimer's disease (45.9%), followed by unspecified dementia (43.8%). Very low proportion of deaths were associated with vascular dementia (4.9%) or other neurodegenerative diseases (5.3%). The AAMR increased in two distinct periods: a steep incline from 1999 to 2010 (APC: 6.95, 95% CI: 6.00-7.90), followed by a modest incline till 2020 (APC: 1.41, 95% CI: 0.80-2.04). Overall, females had a higher AAMR than males. AAMRs were highest among NH Whites patients and lowest in NH Asians or Pacific Islanders. A significant geographical difference was also observed among different US census regions. Nearly equal AAMRs were seen in non-metropolitan areas and metropolitan areas. States with AAMRs in the top 90th percentile included South Carolina, North Carolina, Maine, Tennessee, Georgia, and Alabama while states with AAMRs in the bottom 10th percentile included South Dakota, Florida, Hawaii, New Jersey, District of Columbia, and New York (33.1). Individuals aged above 85 had the highest AAMRs. Most deaths occurred in nursing homes and least in hospice facilities., Conclusion: The dementia related deaths are continuously increasing. Highest AAMRs were observed among the NH White people, females, and in the southern areas of the United States. People aged 85+ were most affected. To stop the rising death rates, targeted interventions and awareness are required for both prevention and treatment of dementia., (© 2024 John Wiley & Sons Ltd.)

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.)

Background: Observational studies have suggested associations between amount of coffee consumption and decreased risk of neurodegenerative diseases. However, these studies do not consider differences among coffee types, including sweetened, unsweetened, caffeinated, and decaffeinated varieties., Objectives: This study aims to identify associations between the consumption of various coffee types (sugar-sweetened, artificially sweetened, unsweetened, caffeinated, and decaffeinated) and risks of Alzheimer's disease and related dementias (ADRD) and Parkinson's disease (PD), along with related mortality., Methods: This prospective study included 204,847 participants (44.7% males) from the UK Biobank. Cox proportional hazards models were used to assess the associations of coffee type with neurodegenerative outcome. On the basis of coffee consumption, participants were divided into 5 groups: non-coffee consumers, >0-1 cup/d, ≥1-2 cups/d, ≥2-3 cups/d, and ≥3 cups/d., Results: Over a median follow-up of 9 y, the study documented 1696 cases of ADRD, 1093 cases of PD, and 419 neurodegenerative-related deaths. In the multivariate analysis, compared with non-coffee consumers, those with the highest intake of unsweetened and caffeinated coffee (≥3 cups/d) showed hazard ratios (95% confidence intervals) of 0.75 (0.62, 0.91) for ADRD, 0.71 (0.56, 0.91) for PD, and 0.67 (0.44, 1.01) for neurodegenerative-related death. However, no significant associations were noted in either decaffeinated or sugar/artificially sweetened coffee groups (P > 0.05)., Conclusions: Higher intake of caffeinated coffee, particularly the unsweetened variety, was associated with reduced risks of ADRD and PD. No such associations were observed for sugar-sweetened or artificially sweetened coffee., (Copyright © 2024 American Society for Nutrition. 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.)

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., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Cancer is considered a risk factor for COVID-19 mortality, yet several countries have reported that deaths with a primary code of cancer remained within historic levels during the COVID-19 pandemic. Here, we further elucidate the relationship between cancer mortality and COVID-19 on a population level in the US. We compared pandemic-related mortality patterns from underlying and multiple cause (MC) death data for six types of cancer, diabetes, and Alzheimer's. Any pandemic-related changes in coding practices should be eliminated by study of MC data. Nationally in 2020, MC cancer mortality rose by only 3% over a pre-pandemic baseline, corresponding to ~13,600 excess deaths. Mortality elevation was measurably higher for less deadly cancers (breast, colorectal, and hematological, 2-7%) than cancers with a poor survival rate (lung and pancreatic, 0-1%). In comparison, there was substantial elevation in MC deaths from diabetes (37%) and Alzheimer's (19%). To understand these differences, we simulated the expected excess mortality for each condition using COVID-19 attack rates, life expectancy, population size, and mean age of individuals living with each condition. We find that the observed mortality differences are primarily explained by differences in life expectancy, with the risk of death from deadly cancers outcompeting the risk of death from COVID-19., Competing Interests: CH, CV, LS No competing interests declared

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.)

Background: Residential care/assisted living (RC/AL) is an increasingly common place of end-of-life care for persons with Alzheimer's disease and related dementia (ADRD), who have unique care needs as their health declines. Approximately 22% of RC/ALs provide specialized memory care (memory-care RC/AL). Understanding how end-of-life outcomes differ by memory care among residents with ADRD could facilitate aging/dying in place for this population. The objective of this paper is to examine if end-of-life outcomes (i.e., mortality, hospice use, and number of days receiving hospice in the last month of life) differ between residents with ADRD who moved to memory-care RC/AL, compared with residents with ADRD who moved to RC/AL without memory care (general RC/AL)., Methods: Prospective cohort of 15,152 fee-for-service Medicare beneficiaries with ADRD who moved to large RC/AL (> = 25 beds) between 2016 and 2018. We used inverse probability treatment weighting to account for observable differences between memory-care and general RC/AL residents. Two-part models estimated the difference by memory care in the number of days receiving hospice care in the last months of life among RC/AL decedents., Results: The unadjusted mortality rates were 13.4% in general RC/AL and 15.8% in memory-care RC/AL with an adjusted difference of 1.3 percentage points higher mortality among memory-care RC/AL residents (p = 0.04). Hospice use was 8% and 10.6% among general and memory-care RC/AL residents, respectively, with an adjusted difference of 1.4 percentage points (p = 0.01) higher in memory care. Two-part models showed that decedents in memory-care RC/AL spent about 1.4 more days receiving hospice care in the last month of life (p = 0.02)., Conclusion: We find a higher mortality rate and higher rate of hospice use among memory-care RC/AL residents. These findings suggest that memory care may attract residents closer to the end of life and/or promote hospice use at the end of life., (© 2024 The American Geriatrics Society.)

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.)

Background: Sarcopenia contributes to increased hospitalizations, cognitive impairment, falls, and all-cause mortality. Current diagnostic methods, like body Magnetic Resonance Imaging and dual-energy X-ray absorptiometry, are costly and impractical. Notably, there is no standardized approach for assessing sarcopenia in dementia clinics. We studied the association of temporal muscle thickness (TMT) with key prognostic factors in people with Alzheimer's disease (AD) and Lewy body dementia (DLB)., Methods: We utilized data from the DemVest, a longitudinal cohort study, and included participants clinically diagnosed with mild AD or DLB. TMT was measured using baseline MRI scans. The main outcome measures were cognition, functional performance, malnutrition, and mortality. Various demographic and clinical factors were considered as potential confounders., Results: The AD sample was mainly composed by females(76.9%), age 75.5(SD 6.95). The DLB sample was mostly composed by men(63.6%), age 75.8(SD 6.85). At baseline TMT showed significant association with cognitive performance in the DLB group (Est.=0.593, p-value=0.049). The longitudinal analysis revealed significant associations between TMT and functional decline in DLB (Est.=-0.123, p-value 0.007) and increased mortality in the whole sample(HR=0.815, p-value 0.002), the AD group (HR=0.834 p-value=0.031), and the DLB group (HR=0.767 p-value=0.019) respectively. These associations remained significant after adjusting for confounders., Conclusions: The TMT measurement was associated with mortality in both dementia groups as well as with cognition and function in DLB. TMT emerges as a cost-efficient measure of muscle mass indicating clinical relevance and utility in healthcare settings. Implementing TMT assessment could improve patient care and aid in identifying individuals at risk of adverse outcomes in mild dementia., Competing Interests: The authors have no conflicts of interest to declare. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.

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.

Sleep disturbances may promote the development and advancement of Alzheimer's disease. Our purpose was to determine if sleep disturbances were associated with earlier mortality while accounting for cognition. The National Alzheimer's Coordinating Center database was used to evaluate mortality risk conferred by sleep, and the Montreal Cognitive Assessment score determined cognitive status. Demographics, sleep disturbances, cognitive status, and comorbid/other neuropsychiatric conditions were examined as predictors of survival time via Cox regression. The sample (N = 31,110) had a median age [interquartile range] of 72 [66, 79] years, MoCA score of 23 [16, 26], and survival time of 106.0 months [104.0,108.0]; 10,278 (33%) died during follow-up; 21% (n = 6461) experienced sleep disturbances. Sleep disturbances impacted survival time depending on cognition, with the greatest effect in transition from normal to cognitive impairment ( P < .001). Findings support that sleep disturbances negatively impact survival time, and the impact of sleep disturbances on survival time is interrelated with cognition., 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.

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.)

Objective: Evidence of spatial disparity in dementia mortality in China has been found to have higher dementia mortality in eastern and rural China. Regional factors of physical and social features may be influencing this spatial disparity. However, the extent of spatial difference in dementia mortality across small regional localities is unclear. This study aims to investigate the geographic variations in mortality and risk of all dementia subtypes and identify the effect of the associated environmental risk factors., Methods: We used surveillance data on death reports from Alzheimer's disease and other forms of dementia in Zhejiang province from 2015 to 2019. We estimated the relative risk of dementia mortality using a Bayesian spatial model. We mapped predicted relative risk to visualize the risk of death from different types of dementia and to identify risk factors associated with dementia., Results: Thirty thousand three hundred and ninety-eight deaths attributable to dementia as the underlying or related cause (multiple causes) were reported during 2015-2019. Counties and districts in the southeast and west of Zhejiang province had significantly higher standardized mortality ratios than others. Counties and districts with a smaller proportion of residents aged 60 years or older, poorer economic status, insufficient health resources, and worse pollution had a higher risk of deaths due to dementia., Conclusion: Higher risks of dementia mortality were found in counties and districts with poorer economic status, insufficient health resources, and worse pollution in Zhejiang. Our study adds new evidence on the association between socioeconomic and environmental factors and the mortality risk due to dementia., 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., (Copyright © 2023 Heng, Liu, Li, Lin and Zhou.)

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.

Studies performed in the field of oxidative medicine and cellular longevity frequently focus on the association between biomarkers of cellular and molecular mechanisms of oxidative stress as well as of aging, immune function, and vascular biology with specific time to event data, such as mortality and organ failure. Indeed, time-to-event analysis is one of the most important methodologies used in clinical and epidemiological research to address etiological and prognostic hypotheses. Survival data require adequate methods of analyses. Among these, the Kaplan-Meier analysis is the most used one in both observational and interventional studies. In this paper, we describe the mathematical background of this technique and the concept of censoring (right censoring, interval censoring, and left censoring) and report some examples demonstrating how to construct a Kaplan-Meier survival curve and how to apply this method to provide an answer to specific research questions., Competing Interests: No conflict of interest is related to this manuscript., (Copyright © 2021 Graziella D'Arrigo et al.)

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.

BAP31 is a ubiquitously expressed integral membrane protein of the endoplasmic reticulum. BAP31 is involved in various biological and molecular processes, including protein transport, viral processing, apoptosis signaling, MHC 1 antigen processing and presentation, mitochondria and ER calcium regulation, and proteasomal protein degradation. We employed a BAP31 interaction search using STRING and inBioMap™ protein-protein interaction networks, and the Metabolic Atlas, which revealed molecular and metabolic interactors involved in various pathways essential for cell growth, cell survival, and disease development. BAP31, as a chaperone and resident protein of the ER, was reported in the development of some central nervous system disorders and metabolic diseases about AD, ALS, and Liver disease. In addition, BAP31 is overexpressed in many cancers. Furthermore, research around BAP31 involvement in cancer has taken up a shape, focusing on its roles in cancer cell survival, disease prognosis, and targeted treatment. Here, we address published data on the Biological roles of BAP31 in both health and disease. We present an analytical description of BAP31 expression and functional implication in some human cancers and the impact of its expression and regulation while it models as a potential target in cancer therapy. Besides, a profound understanding of BAP31 is insightful of the gap between cancer development and neurodegeneration, thus generating novel ideas surrounding the link between the two different cell phenomena.

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.