Associations of infections and vaccines with Alzheimer's disease point to a role of compromised immunity rather than specific pathogen in AD.

Introduction: Diverse pathogens (viral, bacterial, fungal) have been associated with Alzheimer's disease (AD) and related traits in various studies. This suggests that compromised immunity, rather than specific microbes, may play a role in AD by increasing an individual's vulnerability to various infections, which could contribute to neurodegeneration. If true, then vaccines that have heterologous effects on immunity, extending beyond protection against the targeted disease, may hold a potential for AD prevention.

Graves disease is associated with increased risk of clinical Alzheimer's disease: evidence from the Medicare system.

Background: Identification of modifiable risk factors for Alzheimer's Disease (AD) onset is an important aspect of controlling the burden imposed by this disease on an increasing number of older U.S. adults.

Associations of infections and vaccines with Alzheimer's disease point to a major role of compromised immunity rather than specific pathogen in AD.

Introduction: Diverse pathogens (viral, bacterial, fungal) have been linked to Alzheimer's disease (AD) indicating a possibility that the culprit may be compromised immunity rather than particular microbe. If true, then vaccines with broad beneficial effects on immunity might be protective against AD.

Methods: We estimated associations of common adult infections, including herpes simplex, zoster (shingles), pneumonia, and recurrent mycoses, as well as vaccinations against shingles and pneumonia, with the risk of AD in a pseudorandomized sample of the Health and Retirement Study.

Graves Disease is Associated with Increased Risk of Clinical Alzheimer's Disease: Evidence from the Medicare System.

Background: Identification of modifiable risk factors for Alzheimer's Disease (AD) onset is an important aspect of controlling the burden imposed by this disease on an increasing number of older U.S. adults.

Vaccination Against Pneumonia May Provide Genotype-Specific Protection Against Alzheimer's Disease.

Vaccine repurposing that considers individual genotype may aid personalized prevention of Alzheimer's disease (AD). In this retrospective cohort study, we used Cardiovascular Health Study data to estimate associations of pneumococcal polysaccharide vaccine and flu shots received between ages 65-75 with AD onset at age 75 or older, taking into account rs6859 polymorphism in NECTIN2 gene (AD risk factor). Pneumococcal vaccine, and total count of vaccinations against pneumonia and flu, were associated with lower odds of AD in carriers of rs6859 A allele, but not in non-carriers.

Differences in Risk of Alzheimer's Disease Following Later-Life Traumatic Brain Injury in Veteran and Civilian Populations.

Objective: To directly compare the effect of incident age 68+ traumatic brain injury (TBI) on the risk of diagnosis of clinical Alzheimer's disease (AD) in the general population of older adults, and between male veterans and nonveterans; to assess how this effect changes with time since TBI.

Setting And Participants: Community-dwelling traditional Medicare beneficiaries 68 years or older from the Health and Retirement Study (HRS).

Design: Fine-Gray models combined with inverse-probability weighting were used to identify associations between incident TBI, post-TBI duration, and TBI treatment intensity, with a diagnosis of clinical AD dementia.

Understanding Alzheimer's disease in the context of aging: Findings from applications of stochastic process models to the Health and Retirement Study.

There is growing literature on applications of biodemographic models, including stochastic process models (SPM), to studying regularities of age dynamics of biological variables in relation to aging and disease development. Alzheimer's disease (AD) is especially good candidate for SPM applications because age is a major risk factor for this heterogeneous complex trait. However, such applications are largely lacking.

Does the Chronic Stress of Everyday Discrimination or Race Itself Better Predict AD Onset Risk?

Using evidence from the Health and Retirement Study, we explore racial disparities in Alzheimer's Disease (AD) onset risk. From a stress process perspective, there is substantial evidence in the literature that everyday discrimination is a chronic strain for Black individuals that acts as a social determinant of illness. However, few studies have examined specific relationships between this social stressor, race, and AD onset risk.

Epidemiology of geographic disparities in heart failure among US older adults: a Medicare-based analysis.

Background: There are prominent geographic disparities in the life expectancy (LE) of older US adults between the states with the highest (leading states) and lowest (lagging states) LE and their causes remain poorly understood. Heart failure (HF) has been proposed as a major contributor to these disparities. This study aims to investigate geographic disparities in HF outcomes between the leading and lagging states.

Vulnerability to Hypertension Is a Major Determinant of Racial Disparities in Alzheimer's Disease Risk.

Background: Higher incidence levels of Alzheimer's disease (AD) in Black Americans are well documented. However, quantitative explanations of this disparity in terms of risk-factor diseases acting through well-defined pathways are lacking.

Methods: We applied a Blinder-Oaxaca-based algorithm modified for censored data to a 5% random sample of Medicare beneficiaries age 65+ to explain Black/White disparities in AD risk in terms of differences in exposure and vulnerability to morbidity profiles based on 10 major AD-risk-related diseases.

Extended anesthesia exposure for abdominal and pelvic procedures in older adults with colorectal cancer: Associations with chart dementia diagnoses.

Background: We hypothesized that cumulative anesthesia exposure over the course of routine treatment of colorectal cancer in older adults can increase long-term risk of Alzheimer's disease (AD), Alzheimer's disease-related dementias (ADRD), and other chronic neurocognitive disorders (CND).

Methods: We conducted a SEER-Medicare-based retrospective cohort study of 84,770 individuals age 65 years and older diagnosed with colorectal cancer between 1998 and 2007 using a proportional hazards model with inverse probability weighted estimators. The primary exploratory variable was a time-variant measure of cumulative anesthesia exposure for abdominal and pelvic procedures, updated continuously.

Genome-wide analysis of genetic predisposition to common polygenic cancers.

Lung, breast, prostate, and colorectal cancers are among the most common and fatal malignancies worldwide. They are mainly caused by multifactorial mechanisms and are genetically heterogeneous. We investigated the genetic architecture of these cancers through genome-wide association, pathway-based, and summary-based transcriptome-/methylome-wide association analyses using three independent cohorts.

Roles of interacting stress-related genes in lifespan regulation: insights for translating experimental findings to humans.

Aim: Experimental studies provided numerous evidence that caloric/dietary restriction may improve health and increase the lifespan of laboratory animals, and that the interplay among molecules that sense cellular stress signals and those regulating cell survival can play a crucial role in cell response to nutritional stressors. However, it is unclear whether the interplay among corresponding genes also plays a role in human health and lifespan.

Methods: Literature about roles of cellular stressors have been reviewed, such as amino acid deprivation, and the integrated stress response (ISR) pathway in health and aging.

Epidemiology of Geographic Disparities of Myocardial Infarction Among Older Adults in the United States: Analysis of 2000-2017 Medicare Data.

There are substantial geographic disparities in the life expectancy (LE) across the U.S. with myocardial infarction (MI) contributing significantly to the differences between the states with highest (leading) and lowest (lagging) LE.

Interactions Between Genes From Aging Pathways May Influence Human Lifespan and Improve Animal to Human Translation.

A major goal of aging research is identifying genetic targets that could be used to slow or reverse aging - changes in the body and extend limits of human lifespan. However, majority of genes that showed the anti-aging and pro-survival effects in animal models were not replicated in humans, with few exceptions. Potential reasons for this lack of translation include a highly conditional character of genetic influence on lifespan, and its heterogeneity, meaning that better survival may be result of not only activity of individual genes, but also gene-environment and gene-gene interactions, among other factors.

Analysis of Time Trends in Alzheimer's Disease and Related Dementias Using Partitioning Approach.

Background: Understanding the dynamics of epidemiologic trends in Alzheimer's disease (AD) and related dementias (ADRD) and their epidemiologic causes is vital to providing important insights into reducing the burden associated with these conditions.

Objective: To model the time trends in age-adjusted AD/ADRD prevalence and incidence-based mortality (IBM), and identify the main causes of the changes in these measures over time in terms of interpretable epidemiologic quantities.

Methods: Trend decomposition was applied to a 5%sample of Medicare beneficiaries between 1991 and 2017.

Geographic disparities in mortality from Alzheimer's disease and related dementias.

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.

Chemotherapy and the Risk of Alzheimer's Disease in Colorectal Cancer Survivors: Evidence From the Medicare System.

Purpose: Evidence on the nature of the relationship between patients receiving chemotherapy as an essential part of guideline-concordant cancer care and the onset of Alzheimer's Disease (AD) and other adverse cognitive outcomes has been mixed. Biological mechanisms were proposed to support both a potentially beneficial and an adverse role. To explore the relationship between chemotherapy and onset of AD and other neurocognitive disorders (ND) in colorectal cancer survivors.

A medicare-based comparative mortality analysis of active surveillance in older women with DCIS.

Over 97% of individuals diagnosed with ductal carcinoma in situ (DCIS) will choose to receive guideline concordant care (GCC), which was originally designed to treat invasive cancers and is associated with treatment related morbidity. An alternative to GCC is active surveillance (AS) where therapy is delayed until medically necessary. Differences in mortality risk between the two approaches in women age 65+ are analyzed in this study.

Partitioning of time trends in prevalence and mortality of bladder cancer in the United States.

Purpose: The aim of the study was to evaluate the relative contributions of incidence, stage-specific relative survival, and stage ascertainment to changes in bladder cancer (BC) prevalence and incidence-based mortality.

Methods: Partitioning of prevalence and incidence-based mortality trends into their epidemiologic components.

Results: BC prevalence estimated from our model increased but at monotonically decreasing rates until 2007, after which it decreased again.

Outcomes and Costs for Women After Breast Cancer: Preparing for Improved Survivorship of Medicare Beneficiaries.

Purpose: Increasing health care costs, longer life expectancy, improved breast cancer (BC) survival, and higher levels of complex comorbidities have important implications for future Medicare expenditures.

Methods: Data from the SEER program linked to Medicare claims records were used. Women with BC (cases) were categorized into 3 groups on the basis of their year of diagnosis (1998, 2003, or 2008) and were propensity score matched to women without a BC diagnosis (controls).

Longitudinal patterns of cost and utilization of medicare beneficiaries with bladder cancer.

Background: Bladder cancer (BC) is highly prevalent and costly. This study documented cost and use of services for BC care and for other (non-BC) care received over a 15-year follow-up period by a cohort of Medicare beneficiaries diagnosed with BC in 1998.

Methods: Data came from the Surveillance, Epidemiology and End Results Program linked to Medicare claims.

The Cost to Medicare of Bladder Cancer Care.

Background: Bladder cancer care is costly, including cost to Medicare, but the medical cost associated with bladder cancer patients relative to identical persons without bladder cancer is unknown.

Objective: To determine incremental bladder cancer cost to Medicare and the impact of diagnosis stage and bladder cancer survival on cost.

Design, Setting, And Participants: A case-control study was conducted using 1998-2013 Surveillance, Epidemiology and End Results-Medicare data.

Partitioning of time trends in prevalence and mortality of lung cancer.

Background: Time trends of lung cancer prevalence and mortality are the result of three competing processes: changes in the incidence rate, stage-specific survival, and ascertainment at early stages. Improvements in these measures act concordantly to improve disease-related mortality, but push the prevalence rate in opposite directions making a qualitative interpretation difficult. The goal of this paper is to evaluate the relative contributions of these components to changes in lung cancer prevalence and mortality.

Genetic heterogeneity of Alzheimer's disease in subjects with and without hypertension.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder caused by the interplay of multiple genetic and non-genetic factors. Hypertension is one of the AD risk factors that has been linked to underlying pathological changes like senile plaques and neurofibrillary tangles formation as well as hippocampal atrophy. In this study, we investigated the differences in the genetic architecture of AD between hypertensive and non-hypertensive subjects in four independent cohorts.