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. The study included 16 829 older adults followed over the 1991-2015 period. For analyses of veteran-specific risks, 4281 veteran males and 3093 nonveteran males were identified. Analysis of veteran females was unfeasible due to the age structure of the population. Information on occurrence(s) of TBI, and onset of AD and risk-related comorbidities was constructed from individual-level HRS-linked Medicare claim records while demographic and socioeconomic risk factors were based on the survey data. RESULTS: Later-life TBI was strongly associated with increased clinical AD risk in the full sample (pseudo-hazard ratio [HR]: 3.22; 95% confidence interval [CI]: 2.57-4.05) and in veteran/nonveteran males (HR: 5.31; CI: 3.42-7.94), especially those requiring high-intensity/duration care (HR: 1.58; CI: 1.29-1.91). Effect magnitude decreased with time following TBI (HR: 0.72: CI: 0.68-0.80). CONCLUSION: Later-life TBI was strongly associated with increased AD risk, especially in those requiring high-intensity/duration care. Effect magnitude decreased with time following TBI. Univariate analysis showed no differences in AD risk between veterans and nonveterans, while the protective effect associated with veteran status in Fine-Gray models was largely due to differences in demographics, socioeconomics, and morbidity. Future longitudinal studies incorporating diagnostic procedures and documentation quantifying lifetime TBI events are necessary to uncover pathophysiological mediating and/or moderating mechanisms between TBI and AD.

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. METHODS: The study was a secondary data analysis of HF outcomes in older US adults aged 65+, using Center for Disease Control and Prevention sponsored Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and a nationally representative 5% sample of Medicare beneficiaries over 2000-2017. Empiric estimates of death certificate-based mortality from HF as underlying cause of death (CBM-UCD)/multiple cause of death (CBM-MCD); HF incidence-based mortality (IBM); HF incidence, prevalence, and survival were compared between the leading and lagging states. Cox regression was used to investigate the effect of residence in the lagging states on HF incidence and survival. RESULTS: Between 2000 and 2017, HF mortality rates (per 100,000) were higher in the lagging states (CBM-UCD: 188.5-248.6; CBM-MCD: 749.4-965.9; IBM: 2656.0-2978.4) than that in the leading states (CBM-UCD: 79.4-95.6; CBM-MCD: 441.4-574.1; IBM: 1839.5-2138.1). Compared to their leading counterparts, lagging states had higher HF incidence (2.9-3.9% vs. 2.2-2.9%), prevalence (15.6-17.2% vs. 11.3-13.0%), and pre-existing prevalence at age 65 (5.3-7.3% vs. 2.8-4.1%). The most recent rates of one- (77.1% vs. 80.4%), three- (59.0% vs. 60.7%) and five-year (45.8% vs. 49.8%) survival were lower in the lagging states. A greater risk of HF incidence (Adjusted Hazards Ratio, AHR [95%CI]: 1.29 [1.29-1.30]) and death after HF diagnosis (AHR: 1.12 [1.11-1.13]) was observed for populations in the lagging states. The study also observed recent increases in CBMs and HF incidence, and declines in HF prevalence, prevalence at age 65 and survival with a decade-long plateau stage in IBM in both leading and lagging states. CONCLUSION: There are substantial geographic disparities in HF mortality, incidence, prevalence, and survival across the U.S.: HF incidence, prevalence at age 65 (age of Medicare enrollment), and survival of patients with HF contributed most to these disparities. The geographic disparities and the recent increase in incidence and decline in survival underscore the importance of HF prevention strategies.

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. METHODS: Partitioning of prevalence and mortality trends into their components using SEER data for 1973-2013. RESULTS: The prevalence of lung cancer increases for females and decreases for males. In 1998, the former was due to increased incidence (45%-50% of total trend), improved survival (40%-45%), and increased ascertainment at early stages (10%-15%). In males, a rapidly declining incidence rate overpowered the effects of survival and ascertainment resulting in an overall decrease in prevalence over time. Trends in lung cancer mortality are determined by incidence during 1993-2002 with noticeable contribution of survival after 2002. CONCLUSION: Lung cancer incidence was the main driving force behind trends in prevalence and mortality. Improved survival played essential role from 2000 onwards. Trends in stage ascertainment played a small but adverse role. Our results suggest that further improvement in lung cancer mortality can be achieved through advances in early stage ascertainment, especially for males, and that in spite of success in treatment, adenocarcinoma continues to exhibit adverse trends (especially in female incidence) and its role among other histology-specific lung cancers will increase in the near future.

Effect of Prior Anti-VEGF Injections on the Risk of Retained Lens Fragments and Endophthalmitis after Cataract Surgery in the Elderly.

PURPOSE: To investigate the effect of prior intravitreal anti-vascular endothelial growth factor (VEGF) injections on surgical and postoperative complication rates associated with cataract surgery in a nationally representative longitudinal sample of elderly persons. DESIGN: Retrospective, longitudinal cohort analysis. PARTICIPANTS: A total of 203 643 Medicare beneficiaries who underwent cataract surgery from January 1, 2009, to December 31, 2013. METHODS: By using the 5% sample of Medicare claims data, the study assessed risks of 3 adverse outcomes after receipt of cataract surgery for beneficiaries with a history of intravitreal injections. Risks of these outcomes in beneficiaries with a history of intravitreal injections relative to those without were calculated using the Cox proportional hazard model. MAIN OUTCOME MEASURES: The primary outcome was the risk of subsequent removal of retained lens fragments (RLFs) within 28 days after cataract surgery. Secondary outcomes were a new diagnosis of acute (<40 days) or delayed-onset (40+ days) endophthalmitis and risk of a new primary open-angle glaucoma (POAG) diagnosis within 365 days after cataract surgery. RESULTS: Prior intravitreal anti-VEGF injections were associated with a significantly increased risk of subsequent RLF removal within 28 days after cataract surgery (hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.19-4.30). Prior injections were also associated with increased risk of both acute (HR, 2.29; 95% CI, 1.001-5.22) and delayed-onset endophthalmitis (HR, 3.65; 95% CI, 1.65-8.05). Prior injections were not a significant indicator of increased risk of a new POAG diagnosis. CONCLUSIONS: A history of intravitreal injections may be a risk factor for cataract surgery-related intraoperative complications and endophthalmitis. Given the frequency of intravitreal injections and cataract surgery, increased preoperative assessment, additional intraoperative caution, and postoperative vigilance are recommended in patients with a history of intravitreal injections undergoing cataract extraction.

Introducing Anti-Vascular Endothelial Growth Factor Therapies for AMD Did Not Raise Risk of Myocardial Infarction, Stroke, and Death.

PURPOSE: To assess the effect of availability of anti-vascular endothelial growth factor (VEGF) therapy on mortality and hospitalizations for acute myocardial infarction (AMI) and stroke over a 5-year follow-up period in United States Medicare beneficiaries newly diagnosed with exudative age-related macular degeneration (AMD) in 2006 compared with control groups consisting of beneficiaries (1) newly diagnosed with exudative AMD at a time when anti-VEGF therapy was not possible and (2) newly diagnosed with nonexudative AMD. DESIGN: Retrospective cohort study. PARTICIPANTS: Beneficiaries newly diagnosed with exudative and nonexudative AMD in 2000 and 2006 selected from a random longitudinal sample of Medicare 5% claims and enrollment files. METHODS: Beneficiaries with a first diagnosis of exudative AMD in 2006 were the treatment group; beneficiaries newly diagnosed with exudative AMD in 2000 or nonexudative AMD in 2000 or 2006 were control groups. To deal with potential selection bias, we designed an intent-to-treat study, which controlled for nonadherence to prescribed regimens. The treatment group consisted of patients with clinically appropriate characteristics to receive anti-VEGF injections given that the therapy is available, bypassing the need to monitor whether treatment was actually received. Control groups consisted of patients with clinically appropriate characteristics but first diagnosed at a time when the therapy was unavailable (2000) and similar patients but for whom the therapy was not clinically indicated (2000, 2006). We used a Cox proportional hazard model. MAIN OUTCOME MEASURES: All-cause mortality and hospitalization for AMI and stroke during follow-up. RESULTS: No statistically significant changes in probabilities of death and hospitalizations for AMI and stroke within a 5-year follow-up period were identified in exudative AMD beneficiaries newly diagnosed in 2006, the beginning of widespread anti-VEGF use, compared with 2000. As an alternative to our main analysis, which excluded beneficiaries from nonexudative AMD group who received anti-VEGF therapies during follow-up, we performed a sensitivity analysis with this group of individuals reincluded (11% of beneficiaries newly diagnosed with nonexudative AMD in 2006). Results were similar. CONCLUSIONS: Introduction of anti-VEGF agents in 2006 for treating exudative AMD has not posed a threat of increased risk of AMI, stroke, or all-cause mortality.

Causes of the change in the rates of mortality and severe complications of diabetes mellitus: 1992-2012.

OBJECTIVE: To quantify the causes of the changes in the rates of mortality and select severe complications of diabetes mellitus, type 2 (T2D) among the elderly between 1992 and 2012. RESEARCH DESIGN: A retrospective cohort study design based on Medicare 5% administrative claims data from 1992 to 2012 was used. Traditional fee-for-service Medicare beneficiaries, age 65 and older, diagnosed with T2D and living in the United States between 1992 and 2012 were included in the study. Blinder-Oaxaca decomposition was used to quantify the potential causes of the change in the rates of death, congestive heart failure and/or acute myocardial infarction, stroke, amputation of lower extremity and end-stage renal disease between 1992 and 2012. RESULTS: The number of beneficiaries in the analysis sample diagnosed with T2D increased from 152,191 in 1992 to 289,443 in 2012. Over the same time period, rates of mortality decreased by 1.2, congestive heart failure and/or acute myocardial infarction by 2.6, stroke by 1.6, amputation by 0.6 while rates of end-stage renal disease increased by 1.5 percentage points. Improvements in the management of precursor conditions and utilization of recommended healthcare services, not population composition, were the primary causes of the change. CONCLUSIONS: With the exception of end-stage renal disease, outcomes among Medicare beneficiaries diagnosed with T2D improved. Analysis suggests that persons diagnosed with T2D are living longer with fewer severe complications. Much of the improvement in outcomes likely reflects more regular contact with health professionals and better management of care.

Effect of diabetes mellitus on giant cell arteritis.

BACKGROUND: To determine if Type 2 diabetes mellitus (DM) is protective against giant cell arteritis (GCA) and to estimate the incidence of GCA diagnosis from Medicare claims. METHODS: Medicare 5% claims files from 1991 to 2011 were used to identify beneficiaries diagnosed with DM, but not GCA, within a 3-year ascertainment period. Propensity score matching was used to define a control group of nondiabetics with comparable demographic covariates. Competing risk regression was then used to assess the impact of DM diagnosis on GCA diagnosis. To allow for a 3-year ascertainment period, the analysis sample was limited to beneficiaries older than 68 years at baseline. RESULTS: A total of 151,041 beneficiaries diagnosed with DM were matched to an equal number of controls. Mean study follow-up was 67.75 months. GCA was diagnosed among 1116 beneficiaries with DM (0.73%) vs 465 (0.30%) controls. The risk of receiving a GCA diagnosis among patients with DM was increased by 100% (subhazard ratio, 2.00; 95% confidence interval, 1.78-2.25). The annual incidence of GCA diagnosis among claims for US Medicare beneficiaries older than 68 years old was 93 in 100,000. CONCLUSIONS: A DM diagnosis is not protective against a GCA diagnosis in the Medicare population. Our data suggest that a DM diagnosis increases the risk of GCA diagnosis within 5.7 years for Medicare beneficiaries older than 68 years.

Gaps in receipt of regular eye examinations among medicare beneficiaries diagnosed with diabetes or chronic eye diseases.

OBJECTIVE: To examine a wide range of factors associated with regular eye examination receipt among elderly individuals diagnosed with glaucoma, age-related macular degeneration, or diabetes mellitus (DM). DESIGN: Retrospective analysis of Medicare claims linked to survey data from the Health and Retirement Study (HRS). PARTICIPANTS: The sample consisted of 2151 Medicare beneficiaries who responded to the HRS. METHODS: Medicare beneficiaries with ≥ 1 of the 3 study diagnoses were identified by diagnosis codes and merged with survey information. The same individuals were followed for 5 years divided into four 15-month periods. Predictors of the number of periods with an eye examination evaluated were beneficiary demographic characteristics, income, health, cognitive and physical function, health behaviors, subjective beliefs about longevity, the length of the individual's financial planning horizon, supplemental health insurance coverage, eye disease diagnoses, and low vision/blindness at baseline. We performed logit analysis of the number of 15-month periods in which beneficiaries received an eye examination. MAIN OUTCOME MEASURES: The primary outcome measure was the number of 15-month periods with an eye examination. RESULTS: One third of beneficiaries with the study's chronic diseases saw an eye care provider in all 4 follow-up periods despite having Medicare. One quarter only obtained an eye examination at most during 1 of the four 15-month follow-up periods. Among the 3 groups of patients studied, utilization was particularly low for persons with diagnosed DM and no eye complications. Age, marriage, education, and a higher score on the Charlson index were associated with more periods with an eye examination. Male gender, being limited in instrumental activities of daily living at baseline, distance to the nearest ophthalmologist, and low cognitive function were associated with a reduction in frequency of eye examinations. CONCLUSIONS: Rates of eye examinations for elderly persons with DM or frequently occurring eye diseases, especially for DM, remain far below recommended levels in a nationally representative sample of persons with health insurance coverage. Several factors, including limited physical and cognitive function and greater distance to an ophthalmologist, but not health insurance coverage, account for variation in regular use.

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. METHODS: We evaluated the associations of common adult infections (herpes simplex, zoster (shingles), pneumonia, and recurrent mycoses), and vaccinations against shingles and pneumonia, with the risks of AD and other dementias in a pseudorandomized sample of the Health and Retirement Study (HRS). RESULTS: Shingles, pneumonia and mycoses, diagnosed between ages 65 and 75, were all associated with significantly increased risk of AD later in life, by 16 %-42 %. Pneumococcal and shingles vaccines administered between ages 65-75 were both associated with a significantly lower risk of AD, by 15 %-21 %. These effects became less pronounced when AD was combined with other dementias. DISCUSSION: Our findings suggest that both the pneumococcal polysaccharide vaccine and the live attenuated zoster vaccine can offer significant protection against AD. It remains to be determined if non-live shingles vaccine has a similar beneficial effect on AD. This study also found significant associations of various infections with the risk of AD, but not with the risks of other dementias. This indicates that vulnerability to infections may play a more significant role in AD than in other types of dementia, which warrants further investigation.

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. This paper starts filling this gap and applies SPM to data on onset of AD and longitudinal trajectories of body mass index (BMI) constructed from the Health and Retirement Study surveys and Medicare-linked data. We found that APOE e4 carriers are less robust to deviations of trajectories of BMI from the optimal levels compared to non-carriers. We also observed age-related decline in adaptive response (resilience) related to deviations of BMI from optimal levels as well as APOE- and age-dependence in other components related to variability of BMI around the mean allostatic values and accumulation of allostatic load. SPM applications thus allow revealing novel connections between age, genetic factors and longitudinal trajectories of risk factors in the context of AD and aging creating new opportunities for understanding AD development, forecasting trends in AD incidence and prevalence in populations, and studying disparities in those.

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. RESULTS: Shingles, pneumonia, and mycoses diagnosed between ages 65-75, were all associated with higher risk of AD later in life, by 16%-42%. Pneumococcal and shingles vaccines received between ages 65-75 both lowered the risk of AD, by 15%-21%. DISCUSSION: Our results support the idea that the connection between AD and infections involves compromised immunity rather than specific pathogen. We discuss mechanisms by which the declining immune surveillance may promote AD, and the role of biological aging in it. Repurposing of vaccines with broad beneficial effects on immunity could be a reasonable approach to AD prevention. Pneumococcal and zoster vaccines are promising candidates for such repurposing.

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. We conclude that pneumococcal polysaccharide vaccine is a promising candidate for genotype-tailored AD prevention.

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. RESULTS: The primary contribution to racial disparities in AD risk comes from morbidity profiles that included hypertension with about 1/5th of their contribution due to differences in prevalence (exposure effect) and 4/5ths to differences in the effects of the morbidity profile on AD risk (vulnerability effect). In total, disease-related effects explained a higher proportion of AD incidence in Black Americans than in their White counterparts. CONCLUSIONS: Disease-related causes may represent some of the most straightforward targets for targeted interventions aimed at the reduction of racial disparities in health among US older adults. Hypertension is a manageable and potentially preventable condition responsible for the majority of the Black/White differences in AD risk, making mitigation of the role of this disease in engendering higher AD incidence in Black Americans a prominent concern.

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. RESULTS: Our primary outcomes, AD and ADRD, occurred in 6005/84,770 (7.1%) and 14,414/83,444 (17.3%) individuals respectively. No statistically significant association was found between cumulative anesthesia exposure and AD (hazard ratio [HR], 0.993; 95% CI, 0.973-1.013). However, it was moderately associated with the risk of ADRD (HR, 1.016; 95% CI, 1.004-1.029) and some secondary outcomes including most notably: cerebral degeneration (HR, 1.048; 95% CI, 1.033-1.063), hepatic encephalopathy (HR, 1.133; 95% CI, 1.101-1.167), encephalopathy-not elsewhere classified (HR,1.095; 95% CI: 1.076-1.115), and incident/perioperative delirium (HR, 1.022; 95% CI, 1.012-1.032). Furthermore, we observed an association between perioperative delirium and increased risk of AD (HR, 2.05; 95% CI, 1.92-2.09). CONCLUSION: Cumulative anesthesia exposure for abdominal and pelvic procedures was not associated with increased risk of AD directly and had a small but statistically significant association with ADRD and a number of other CNDs. Cumulative anesthesia exposure was also associated with perioperative delirium, which had an independent adverse association with AD risk.

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. Our genome-wide association analyses identified the associations of 33 single-nucleotide polymorphisms (SNPs) at P < 5E - 06, of which 32 SNPs were not previously reported and did not have proxy variants within their ± 1 Mb flanking regions. Moreover, other polymorphisms mapped to their closest genes were not previously associated with the same cancers at P < 5E - 06. Our pathway enrichment analyses revealed associations of 32 pathways; mainly related to the immune system, DNA replication/transcription, and chromosomal organization; with the studied cancers. Also, 60 probes were associated with these cancers in our transcriptome-wide and methylome-wide analyses. The ± 1 Mb flanking regions of most probes had not attained P < 5E - 06 in genome-wide association studies. The genes corresponding to the significant probes can be considered as potential targets for further functional studies. Two genes (i.e., CDC14A and PMEL) demonstrated stronger evidence of associations with lung cancer as they had significant probes in both transcriptome-wide and methylome-wide association analyses. The novel cancer-associated SNPs and genes identified here would advance our understanding of the genetic heterogeneity of the common cancers.

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. Using Cox Proportional Hazard Models, we examined racial differences in exposure and vulnerability to everyday discrimination. Findings suggest that everyday discrimination predicts AD onset risk, and Black individuals experience more frequent exposure to everyday discrimination as a chronic strain. However, contrary to the stress process model, Black respondents were not more vulnerable to the effect of everyday discrimination on AD onset risk. Racial bias from medical professionals during the diagnostic process and mortality selection bias may explain this effect. Overall, the results of this study provide further evidence that discrimination is a key factor in predicting AD while also considering that many racial minorities with high rates of this type of social stress may not receive an unbiased diagnosis and/or survive to late life to develop AD.

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

Background: 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. This study aimed to systematically investigate the epidemiology of geographic disparities in MI among older adults. Methods: Data on MI outcomes among adults aged 65+ were derived from the Center for Disease Control and Prevention-sponsored Wide-Ranging Online Data for Epidemiologic Research database and a 5% sample of Medicare Beneficiaries for 2000-2017. Death certificate-based mortality from MI as underlying/multiple cause of death (CBM-UCD/CBM-MCD), incidence-based mortality (IBM), incidence, prevalence, prevalence at age 65, and 1-, 3-, and 5-year survival, and remaining LE at age 65 were estimated and compared between the leading and lagging states. Cox model was used to investigate the effect of residence in the lagging states on MI incidence and survival. Results: Between 2000 and 2017, MI mortality was higher in the lagging than in the leading states (per 100,000, CBM-UCD: 236.7-583.7 vs. 128.2-357.6, CBM-MCD: 322.7-707.7 vs. 182.4-437.7, IBM: 1330.5-1518.9 vs. 1003.3-1197.0). Compared to the leading states, lagging states had higher MI incidence (1.1-2.0% vs. 0.9-1.8%), prevalence (10.2-13.1% vs. 8.3-11.9%), pre-existing prevalence (2.5-5.1% vs. 1.4-3.6%), and lower survival (70.4 vs. 77.2% for 1-year, 63.2 vs. 67.2% for 3-year, and 52.1 vs. 58.7% for 5-year), and lower remaining LE at age 65 among MI patients (years, 8.8-10.9 vs. 9.9-12.8). Cox model results showed that the lagging states had greater risk of MI incidence [Adjusted hazards ratio, AHR (95% Confidence Interval, CI): 1.18 (1.16, 1.19)] and death after MI diagnosis [1.22 (1.21, 1.24)]. Study results also showed alarming declines in survival and remaining LE at age 65 among MI patients. Conclusion: There are substantial geographic disparities in MI outcomes, with lagging states having higher MI mortality, incidence, and prevalence, lower survival and remaining LE at age 65. Disparities in MI mortality in a great extent could be due to between-the-state differences in MI incidence, prevalence at age 65 and survival. Observed declines in survival and remaining LE require an urgent analysis of contributing factors that must be addressed.

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. RESULTS: Prevalence of AD was increasing between 1992 and 2011 and declining thereafter, while IBM increased over the study period with a significant slowdown in its rate of growth from 2011 onwards. For ADRD, prevalence and IBM increased through 2014 prior to taking a downwards turn. The primary determinant responsible for declines in prevalence and IBM was the deceleration in the increase and eventual decrease in incidence rates though changes in relative survival began to affect the overall trends in prevalence/IBM in a noticeable manner after 2008. Other components showed only minor effects. CONCLUSION: The prevalence and IBM of ADRD is expected to continue to decrease. The directions of these trends for AD are not clear because AD incidence, the main contributing component, is decreasing but at a decreasing rate suggesting a possible reversal. Furthermore, emerging treatments may contribute through their effects on survival. Improving ascertainment of AD played an important role in trends of AD/ADRD over the 1991-2009/10 period but this effect has exhausted itself by 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. 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.

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. METHODS: We conducted a retrospective cohort study of 135,834 individuals older than 65 years diagnosed with colorectal cancer between 1998 and 2007, using SEER-Medicare data. A proportional hazards model was used before and after the use of inverse probability weighting to account for populational differences between the chemotherapy and nonchemotherapy groups. Weights were normalized to the total sample size. RESULTS: After inverse probability weighting, chemotherapy was associated with decreased AD risk (hazard ratio [HR]: 0.791; 95% CI: 0.758 to 0.824) and lower risk for the majority of other ND including AD-related diseases (HR: 0.823; CI: 0.802 to 0.844), dementia (permanent mental disorder) (HR: 0.807; CI: 0.782 to 0.832), and dementia (senile) (HR: 0.772; CI: 0.745 to 0.801). The only adverse effect to remain significant was cerebral degeneration (excluding AD) (HR: 1.067; CI: 1.033 to 1.102). The effects for AD remained after treatment was stratified by chemotherapy agent type and remained significant for up to 6 years past diagnosis. CONCLUSION: Chemotherapy use in colorectal cancer survivors demonstrated an association with reduced risk for AD and other ND.