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.

The Impact of Coal-Powered Electrical Plants and Coal Ash Impoundments on the Health of Residential Communities.

BACKGROUND In North Carolina, coal-burning power plants remain the major source of electrical production. Coal burning generates coal ash that is stored in landfills and slurry ponds that are often located near residential communities, signifying high potential for environmental contamination and increasing health risks. We reviewed the literature on potential health effects of coal-burning plants to summarize current knowledge on health risks.METHODS We searched English-language publications issued between January 1, 1987, and December 31, 2017, on PubMed and Google Scholar.RESULTS The algorithm of identification, screening, eligibility, and inclusion/exclusion we used provided 113 peer-reviewed publications selected for the review. Over the past 30 years, scientists reported that the people living in close proximity to coal-fired plants had higher rates of all-cause and premature mortality, increased risk of respiratory disease and lung cancer, cardiovascular disease, poorer child health, and higher infant mortality. The elevated health risk was associated with exposure to air pollutants from the power plant emissions and to a spectrum of heavy metals and radioactive isotopes in coal ash.CONCLUSION In North Carolina, further studies are required to profile the severity of the cumulative impacts of multiple air, water, and soil contaminants related to coal-burning power plants and coal ash impoundments on human health and the environment. Prioritized study directions on evaluation of health impacts of coal-burning power plants in North Carolina are suggested.

The Health Impacts of Environmental Policy: The North Carolina Clean Smokestacks Act.

The North Carolina Clean Smokestacks Act and related policies led to substantial decreases of emitted air pollutants from coal-fired power plants. Improved air quality was associated with statewide improvements in respiratory, cardiovascular, and cerebrovascular health in North Carolina. The effectiveness of environmental policies can be monitored for impact on both environmental and health outcomes.

Mortality and Health Outcomes in North Carolina Communities Located in Close Proximity to Hog Concentrated Animal Feeding Operations.

BACKGROUND Life expectancy in southeastern North Carolina communities located in an area with multiple concentrated animal feeding operations (CAFOs) after adjusting for socioeconomic factors remains low. We hypothesized that poor health outcomes in this region may be due to converging demographic, socioeconomic, behavioral, and access-to-care factors and are influenced by the presence of hog CAFOs.METHODS We studied mortality, hospital admissions, and emergency department (ED) usage for health conditions potentially associated with hog CAFOs-anemia, kidney disease, infectious diseases, and low birth weight (LBW)-in North Carolina communities located in zip codes with hog CAFOs (Study group 1), in zip codes with > 215hogs/km2 (Study group 2), and without hog CAFOs (Control group). We compared cause-specific age-adjusted rates, the odds ratios (ORs) of events in multivariable analyses (adjusted for 6 co-factors), and the changes of ORs relative to the distance to hog CAFOs.RESULTS Residents from Study groups 1 and 2 had higher rates of all-cause mortality, infant mortality, mortality of patients with multimorbidity, mortality from anemia, kidney disease, tuberculosis, and septicemia, and higher rates of ED visits and hospital admissions for LBW infants than the residents in the Control group. In zip codes with > 215hogs/km2, mortality ORs were 1.50 for anemia (P < 0.0001), 1.31 for kidney disease (P < 0.0001), 2.30 for septicemia (P < 0.0001), and 2.22 for tuberculosis (P = 0.0061).LIMITATIONS This study included a lack of individual measurements on environmental contaminants, biomarkers of exposures and co-factors, and differences in residential and occupational locations.CONCLUSION North Carolina communities located near hog CAFOs had higher all-cause and infant mortality, mortality due to anemia, kidney disease, tuberculosis, septicemia, and higher hospital admissions/ED visits of LBW infants. Although not establishing causality with exposures from hog CAFOs, our findings support the need for future studies to determine factors that influence these outcomes, as well as the need to improve screening and diagnostic strategies for these diseases in North Carolina communities adjacent to hog CAFOs.

A Systematic Review of Conceptual Frameworks of Medical Complexity and New Model Development.

BACKGROUND: Patient complexity is often operationalized by counting multiple chronic conditions (MCC) without considering contextual factors that can affect patient risk for adverse outcomes. OBJECTIVE: Our objective was to develop a conceptual model of complexity addressing gaps identified in a review of published conceptual models. DATA SOURCES: We searched for English-language MEDLINE papers published between 1 January 2004 and 16 January 2014. Two reviewers independently evaluated abstracts and all authors contributed to the development of the conceptual model in an iterative process. RESULTS: From 1606 identified abstracts, six conceptual models were selected. One additional model was identified through reference review. Each model had strengths, but several constructs were not fully considered: 1) contextual factors; 2) dynamics of complexity; 3) patients' preferences; 4) acute health shocks; and 5) resilience. Our Cycle of Complexity model illustrates relationships between acute shocks and medical events, healthcare access and utilization, workload and capacity, and patient preferences in the context of interpersonal, organizational, and community factors. CONCLUSIONS/IMPLICATIONS: This model may inform studies on the etiology of and changes in complexity, the relationship between complexity and patient outcomes, and intervention development to improve modifiable elements of complex patients.

Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions.

An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-ß, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression.

A review of the health impacts of barium from natural and anthropogenic exposure.

There is an increasing public awareness of the relatively new and expanded industrial barium uses which are potential sources of human exposure (e.g., a shale gas development that causes an increased awareness of environmental exposures to barium). However, absorption of barium in exposed humans and a full spectrum of its health effects, especially among chronically exposed to moderate and low doses of barium populations, remain unclear. We suggest a systematic literature review (from 1875 to 2014) on environmental distribution of barium, its bioaccumulation, and potential and proven health impacts (in animal models and humans) to provide the information that can be used for optimization of future experimental and epidemiological studies and developing of mitigative and preventive strategies to minimize negative health effects in exposed populations. The potential health effects of barium exposure are largely based on animal studies, while epidemiological data for humans, specifically for chronic low-level exposures, are sparse. The reported health effects include cardiovascular and kidney diseases, metabolic, neurological, and mental disorders. Age, race, dietary patterns, behavioral risks (e.g., smoking), use of medications (those that interfere with absorbed barium in human organism), and specific physiological status (e.g., pregnancy) can modify barium effects on human health. Identifying, evaluating, and predicting the health effects of chronic low-level and moderate-level barium exposures in humans is challenging: Future research is needed to develop an understanding of barium bioaccumulation in order to mitigate its potential health impacts in various exposured populations. Further, while occupationally exposed at-risk populations exist, it is also important to identify potentially vulnerable subgroups among non-occupationally exposed populations (e.g., elderly, pregnant women, children) who are at higher risk of barium exposure from drinking water and food.

Time trends of incidence of age-associated diseases in the US elderly population: Medicare-based analysis.

OBJECTIVES: time trends of age-adjusted incidence rates of 19 ageing-related diseases were evaluated for 1992-2005 period with the National Long Term Care Survey and the Surveillance, Epidemiology and End RESULTS Registry data both linked to Medicare data (NLTCS-Medicare and SEER-Medicare, respectively). METHODS: the rates were calculated using individual medical histories (34,077 individuals from NLTCS-Medicare and 199,418 from SEER-Medicare) reconstructed using information on diagnoses coded in Medicare data, dates of medical services/procedures and Medicare enrolment/disenrolment. RESULTS: increases of incidence rates were dramatic for renal disease [the average annual percent change (APC) is 8.56%, 95% CI = 7.62, 9.50%], goiter (APC = 6.67%, 95% CI = 5, 90, 7, 44%), melanoma (APC = 6.15%, 95% CI = 4.31, 8.02%) and Alzheimer's disease (APC = 3.96%, 95% CI = 2.67, 5.26%), and less prominent for diabetes and lung cancer. Decreases of incidence rates were remarkable for angina pectoris (APC = -6.17%, 95% CI = -6.96, -5.38%); chronic obstructive pulmonary disease (APC = -5.14%, 95% CI = -6.78,-3.47%), and ulcer (APC = -5.82%, 95% CI = -6.77,-4.86%) and less dramatic for carcinomas of colon and prostate, stroke, hip fracture and asthma. Incidence rates of female breast carcinoma, myocardial infarction, Parkinson's disease and rheumatoid arthritis were almost stable. For most diseases, an excellent agreement was observed for incidence rates between NLTCS-Medicare and SEER-Medicare. A sensitivity analysis proved the stability of the evaluated time trends. CONCLUSION: time trends of the incidence of diseases common in the US elderly population were evaluated. The results show dramatic increase in incidence rates of melanoma, goiter, chronic renal and Alzheimer's disease in 1992-2005. Besides specifying widely recognised time trends on age-associated diseases, new information was obtained for trends of asthma, ulcer and goiter among the older adults in the USA.

Optogenetic and chemogenetic manipulation of seizure threshold in mice.

Here, we present a protocol using optogenetics or chemogenetics to assess the neuronal circuits contributing to seizure initiation. Both approaches allow for targeted control of neuronal populations in vivo and can be combined with experimental manipulations to acutely induce seizures in rodent models. We describe how to (1) introduce and (2) activate optogenetic or chemogenetic actuators while (3) inducing seizures via hyperthermia in a mouse model of epilepsy. This protocol can be adapted for use in other induced seizure models. For complete details on the use and execution of this protocol, please refer to Mattis et al. (2022).1.

Expanding the scope of health disparities research in Alzheimer's disease and related dementias: Recommendations from the "Leveraging Existing Data and Analytic Methods for Health Disparities Research Related to Aging and Alzheimer's Disease and Related Dementias" Workshop Series.

Topics discussed at the "Leveraging Existing Data and Analytic Methods for Health Disparities Research Related to Aging and Alzheimer's Disease and Related Dementias" workshop, held by Duke University and the Alzheimer's Association with support from the National Institute on Aging, are summarized.  Ways in which existing data resources paired with innovative applications of both novel and well-known methodologies can be used to identify the effects of multi-level societal, community, and individual determinants of race/ethnicity, sex, and geography-related health disparities in Alzheimer's disease and related dementia are proposed.  Current literature on the population analyses of these health disparities is summarized with a focus on identifying existing gaps in knowledge, and ways to mitigate these gaps using data/method combinations are discussed at the workshop.  Substantive and methodological directions of future research capable of advancing health disparities research related to aging are formulated.

The Construction of a Multidomain Risk Model of Alzheimer's Disease and Related Dementias.

BACKGROUND: Alzheimer's disease (AD) and related dementia (ADRD) risk is affected by multiple dependent risk factors; however, there is no consensus about their relative impact in the development of these disorders. OBJECTIVE: To rank the effects of potentially dependent risk factors and identify an optimal parsimonious set of measures for predicting AD/ADRD risk from a larger pool of potentially correlated predictors. METHODS: We used diagnosis record, survey, and genetic data from the Health and Retirement Study to assess the relative predictive strength of AD/ADRD risk factors spanning several domains: comorbidities, demographics/socioeconomics, health-related behavior, genetics, and environmental exposure. A modified stepwise-AIC-best-subset blanket algorithm was then used to select an optimal set of predictors. RESULTS: The final predictive model was reduced to 10 features for AD and 19 for ADRD; concordance statistics were about 0.85 for one-year and 0.70 for ten-year follow-up. Depression, arterial hypertension, traumatic brain injury, cerebrovascular diseases, and the APOE4 proxy SNP rs769449 had the strongest individual associations with AD/ADRD risk. AD/ADRD risk-related co-morbidities provide predictive power on par with key genetic vulnerabilities. CONCLUSION: Results confirm the consensus that circulatory diseases are the main comorbidities associated with AD/ADRD risk and show that clinical diagnosis records outperform comparable self-reported measures in predicting AD/ADRD risk. Model construction algorithms combined with modern data allows researchers to conserve power (especially in the study of disparities where disadvantaged groups are often grossly underrepresented) while accounting for a high proportion of AD/ADRD-risk-related population heterogeneity stemming from multiple domains.

The antioxidant function of the p53 tumor suppressor.

It is widely accepted that the p53 tumor suppressor restricts abnormal cells by induction of growth arrest or by triggering apoptosis. Here we show that, in addition, p53 protects the genome from oxidation by reactive oxygen species (ROS), a major cause of DNA damage and genetic instability. In the absence of severe stresses, relatively low levels of p53 are sufficient for upregulation of several genes with antioxidant products, which is associated with a decrease in intracellular ROS. Downregulation of p53 results in excessive oxidation of DNA, increased mutation rate and karyotype instability, which are prevented by incubation with the antioxidant N-acetylcysteine (NAC). Dietary supplementation with NAC prevented frequent lymphomas characteristic of Trp53-knockout mice, and slowed the growth of lung cancer xenografts deficient in p53. Our results provide a new paradigm for a nonrestrictive tumor suppressor function of p53 and highlight the potential importance of antioxidants in the prophylaxis and treatment of cancer.

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.

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.

The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of "remaining" heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.

Transcription of mammalian messenger RNAs by a nuclear RNA polymerase of mitochondrial origin.

Transcription of eukaryotic genes is performed by three nuclear RNA polymerases, of which RNA polymerase II is thought to be solely responsible for the synthesis of messenger RNAs. Here we show that transcription of some mRNAs in humans and rodents is mediated by a previously unknown single-polypeptide nuclear RNA polymerase (spRNAP-IV). spRNAP-IV is expressed from an alternative transcript of the mitochondrial RNA polymerase gene (POLRMT). The spRNAP-IV lacks 262 amino-terminal amino acids of mitochondrial RNA polymerase, including the mitochondrial-targeting signal, and localizes to the nucleus. Transcription by spRNAP-IV is resistant to the RNA polymease II inhibitor alpha-amanitin but is sensitive to short interfering RNA specific for the POLRMT gene. The promoters for spRNAP-IV differ substantially from those used by RNA polymerase II, do not respond to transcriptional enhancers and contain a common functional sequence motif.

Homeostatic functions of the p53 tumor suppressor: regulation of energy metabolism and antioxidant defense.

The p53 tumor suppressor plays pivotal role in the organism by supervising strict compliance of individual cells to needs of the whole organisms. It has been widely accepted that p53 acts in response to stresses and abnormalities in cell physiology by mobilizing the repair processes or by removing the diseased cells through initiating the cell death programs. Recent studies, however, indicate that even under normal physiological conditions certain activities of p53 participate in homeostatic regulation of metabolic processes and that these activities are important for prevention of cancer. These novel functions of p53 help to align metabolic processes with the proliferation and energy status, to maintain optimal mode of glucose metabolism and to boost the energy efficient mitochondrial respiration in response to ATP deficiency. Additional activities of p53 in non-stressed cells tune up the antioxidant defense mechanisms reducing the probability of mutations caused by DNA oxidation under conditions of daily stresses. The deficiency in the p53-mediated regulation of glycolysis and mitochondrial respiration greatly accounts for the deficient respiration of the predominance of aerobic glycolysis in cancer cells (the Warburg effect), while the deficiency in the p53-modulated antioxidant defense mechanisms contributes to mutagenesis and additionally boosts the carcinogenesis process.

Exposure to low-dose ambient fine particulate matter PM2.5 and Alzheimer's disease, non-Alzheimer's dementia, and Parkinson's disease in North Carolina.

Alzheimer's disease (AD), non-AD dementia, and Parkinson's disease (PD) are increasingly common in older adults, yet all risk factors for their onset are not fully understood. Consequently, environmental exposures, including air pollution, have been hypothesized to contribute to the etiology of neurodegeneration. Because persistently elevated rates of AD mortality in the southern Piedmont area of North Carolina (NC) have been documented, we studied mortality and hospital admissions for AD, non-AD dementia, and PD in residential populations aged 65+ with long-term exposures to elevated levels of ambient air particulate matter 2.5 (PM2.5) exceeding the World Health Organization (WHO) air quality standards (≥10µg/m3). Health data were obtained from the State Center for Health Statistics and the Healthcare Cost and Utilization Project. PM2.5 levels were obtained from the MODIS/MISR and SeaWiFS datafiles. Residents in the Study group of elevated air particulate matter (87 zip codes with PM2.5≥10µg/m3) were compared to the residents in the Control group with low levels of air particulate matter (81 zip codes with PM2.5≤7.61µg/m3), and were found to have higher age-adjusted rates of mortality and hospital admissions for AD, non-AD dementia, and PD, including a most pronounced increase in AD mortality (323/100,000 vs. 257/100,000, respectively). After adjustment for multiple co-factors, the risk of death (odds ratio, or OR) from AD in the Study group (OR = 1.35, 95%CI[1.24-1.48]) was significantly higher than ORs of non-AD dementia or PD (OR = 0.97, 95%CI[0.90-1.04] and OR = 1.13, 95%CI[0.92-1.31]). The OR of hospital admissions was significantly increased only for AD as a primary case of hospitalization (OR = 1.54, 95%CI[1.31-1.82]). Conclusion: NC residents aged 65+ with long-term exposures to ambient PM2.5 levels exceeding the WHO standard had significantly increased risks of death and hospital admissions for AD. The effects for non-AD dementia and PD were less pronounced.

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.