Toxic metals and pediatric clinical immune dysfunction: A systematic review of the epidemiological evidence.

BACKGROUND: Children are at high risk for exposure to toxic metals and are vulnerable to their effects. Significant research has been conducted evaluating the role of these metals on immune dysfunction, characterized by biologic and clinical outcomes. However, there are inconsistencies in these studies. The objective of the present review is to critically evaluate the existing literature on the association between toxic metals (lead, mercury, arsenic, and cadmium) and pediatric immune dysfunction. METHODS: Seven databases (PubMed (NLM), Embase (Elsevier), CINAHL (Ebsco), Web of Science (Clarivate Analytics), ProQuest Public Health Database, and ProQuest Environmental Science Collection) were searched following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in February 2024. Rayaan software identified duplicates and screened by title and abstract in a blinded and independent review process. The remaining full texts were reviewed for content and summarized. Exclusions during the title, abstract, and full-text reviews included: 1) not original research, 2) not epidemiology, 3) did not include toxic metals, 4) did not examine an immune health outcome, or 5) not pediatric (>18 years). This systematic review protocol followed the PRISMA guidelines. Rayaan was used to screen records using title and abstract by two blinded and independent reviewers. This process was repeated for full-text article screening selection. RESULTS: The search criteria produced 7906 search results; 2456 duplicate articles were removed across search engines. In the final review, 79 studies were included which evaluated the association between toxic metals and outcomes indicative of pediatric immune dysregulation. CONCLUSIONS: The existing literature suggests an association between toxic metals and pediatric immune dysregulation. Given the imminent threat of infectious diseases demonstrated by the recent COVID-19 epidemic in addition to increases in allergic disease, understanding how ubiquitous exposure to these metals in early life can impact immune response, infection risk, and vaccine response is imperative.

Social Support and Depression among Stroke Patients: A Topical Review.

Research has shown a protective association between social support and depression, depression among stroke patients, and health impacts of depression. Despite this, not much is known about the effect of social support on depression among stroke patients. This review aims to summarize the current research examining the association between social support and depression among stroke patients. A literature search was performed in PubMed to find original peer-reviewed journal articles from 2016 to 12 March 2023 that examined the association between social support and depression among stroke patients. The search terms were depression and "social support" and stroke, which lead to 172 articles. After abstract review, seven observational studies that studied the target association among stroke patients were selected. One additional study was found using PsycINFO as a complementary source with the same search strategy and criteria. Overall, a negative association was found between social support and depression among stroke patients in eight studies, with more social support leading to lower rates of depression post-stroke. The other study did not find a statistically significant association. Overall, the results of recent studies suggest that social support is negatively associated with depression among stroke patients. In most studies, this association was statistically significant. The findings suggest the importance of improving social support perceived by stroke patients in the prevention of depression after the occurrence of stroke.

Linking Air Pollution Exposure to Blood-Based Metabolic Features in a Community-Based Aging Cohort with and without Dementia.

BACKGROUND: Long-term exposure to air pollution has been associated with changes in levels of metabolites measured in the peripheral blood. However, most research has been conducted in ethnically homogenous, young or middle-aged populations. OBJECTIVE: To study the relationship between the plasma metabolome and long-term exposure to three air pollutants: particulate matter (PM) less than 2.5µm in aerodynamic diameter (PM2.5), PM less than 10µm in aerodynamic diameter (PM10), and nitrogen dioxide (NO2) in an ethnically diverse, older population. METHODS: Plasma metabolomic profiles of 107 participants of the Washington Heights and Inwood Community Aging Project in New York City, collected from 1995-2015, including non-Hispanic white, Caribbean Hispanic, and non-Hispanic Black older adults were used. We estimated the association between each metabolic feature and predicted annual mean exposure to the air pollutants using three approaches: 1) A metabolome wide association study framework; 2) Feature selection using elastic net regression; and 3) A multivariate approach using partial-least squares discriminant analysis. RESULTS: 79 features associated with exposure to PM2.5 but none associated with PM10 or NO2. PM2.5 exposure was associated with altered amino acid metabolism, energy production, and oxidative stress response, pathways also associated with Alzheimer's disease. Three metabolites were associated with PM2.5 exposure through all three approaches: cysteinylglycine disulfide, a diglyceride, and a dicarboxylic acid. The relationship between several features and PM2.5 exposure was modified by diet and metabolic diseases. CONCLUSIONS: These relationships uncover the mechanisms through which PM2.5 exposure can lead to altered metabolic outcomes in an older population.

The Effect of Breathy Vocal Quality on Speech Intelligibility and Listening Effort in Background Noise.

Speech perception is challenging under adverse conditions. However, there is limited evidence regarding how multiple adverse conditions affect speech perception. The present study investigated two conditions that are frequently encountered in real-life communication: background noise and breathy vocal quality. The study first examined the effects of background noise and breathiness on speech perception as measured by intelligibility. Secondly, the study tested the hypothesis that both noise and breathiness affect listening effort, as indicated by linear and nonlinear changes in pupil dilation. Low-context sentences were resynthesized to create three levels of breathiness (original, mild-moderate, and severe). The sentences were presented in a fluctuating nonspeech noise with two signal-to-noise ratios (SNRs) of -5 dB (favorable) and -9 dB (adverse) SNR. Speech intelligibility and pupil dilation data were collected from young listeners with normal hearing thresholds. The results demonstrated that a breathy vocal quality presented in noise negatively affected speech intelligibility, with the degree of breathiness playing a critical role. Listening effort, as measured by the magnitude of pupil dilation, showed significant effects with both severe and mild-moderate breathy voices that were independent of noise level. The findings contributed to the literature by demonstrating the impact of vocal quality on the perception of speech in noise. They also highlighted the complex dynamics between overall task demand and processing resources in understanding the combined impact of multiple adverse conditions.

The role of intracranial artery calcification (IAC) in stroke subtype and risk of vascular events.

OBJECTIVE: To test the hypothesis that intracranial arterial calcification (IAC) is associated with intracranial large artery stenosis (ILAS) and a higher risk of vascular events and mortality. METHOD: We leveraged data from two cohorts, the New York-Presbyterian Hospital/Columbia University Irving Medical Center Stroke Registry Study (NYP/CUIMC-SRS) and the Northern Manhattan Study (NOMAS) to test our hypotheses. We measured IAC using CT scans of participants in both cohorts and expressed IAC as present (vs not) and in tertiles. For the CUIMC-SRS, demographic, clinical and ILAS status was collected retrospectively. In NOMAS, we used research brain MRI and MRA to define asymptomatic ILAS and covert brain infarcts(CBI). We built models adjusted for demographics and vascular risk factors for cross-sectional and longitudinal analyses. RESULTS: Cross-sectionally, IAC was associated with ILAS in both cohorts (OR 1.78, 95% CI: 1.16-2.73 for ILAS-related stroke in the NYP/CUIMC-SRS and OR 3.07, 95%CI 1.13-8.35 for ILAS-related covert brain infarcts in NOMAS). In a meta-analysis of both cohorts, IAC in the upper (HR 1.25, 95%CI 1.01-1.55) and middle tertile (HR 1.27, 95%CI 1.01-1.59) was associated with higher mortality compared with participants with no IAC. There were no longitudinal associations between IAC and risk of stroke or other vascular events. CONCLUSION: In these multiethnic populations, IAC is associated with symptomatic and asymptomatic ILAS as well as higher mortality. IAC may be a useful marker of higher mortality, the role of IAC as an imaging marker of risk of stroke is less certain.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

Long-term exposure to ambient particulate matter and stroke etiology: Results from the Women's Health Initiative.

BACKGROUND: Ambient particulate matter (PM) air pollution is a leading cause of global disability and accounts for an annual 2.9 million deaths globally. PM is established as an important risk factor for cardiovascular disease, however the evidence supporting a link specifically between long-term exposure to ambient PM and incident stroke is less clear. We sought to evaluate the association of long-term exposure to different size fractions of ambient PM with incident stroke (overall and by etiologic subtypes) and cerebrovascular deaths within the Women's Health Initiative, a large prospective study of older women in the US. METHODS: We studied 155,410 postmenopausal women without previous cerebrovascular disease enrolled into the study between 1993 and 1998, with follow-up through 2010. We assessed geocoded participant address-specific concentrations of ambient PM (fine [PM2.5], respirable [PM10] and coarse [PM10-2.5]), as well as nitrogen dioxide [NO2] using spatiotemporal models. We classified hospitalization events into ischemic, hemorrhagic, or other/unclassified stroke. Cerebrovascular mortality was defined as death from any stroke etiology. We used Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for individual and neighborhood-level characteristics. RESULTS: During a median follow-up time of 15 years, participants experienced 4,556 cerebrovascular events. The hazard ratio for all cerebrovascular events was 2.14 (95% CI: 1.87, 2.44) comparing the top versus bottom quartiles of PM2.5. Similarly, there was a statistically significant increase in events comparing the top versus bottom quartiles of PM10 and NO2 (HR: 1.17; 95% CI: 1.03, 1.33 and HR:1.26; 95% CI: 1.12, 1.42). The strength of association did not vary substantially by stroke etiology. There was little evidence of an association between PMcoarse and incident cerebrovascular events. CONCLUSIONS: Long-term exposure to fine (PM2.5) and respirable (PM10) particulate matter as well as NO2 was associated with a significant increase of cerebrovascular events among postmenopausal women. Strength of the associations were consistent by stroke etiology.

Ambient Air Pollution and Stroke: An Updated Review.

Despite recent advances in treatment and prevention, stroke remains a leading cause of morbidity and mortality. There is a critical need to identify novel modifiable risk factors for disease, including environmental agents. A body of evidence has accumulated suggesting that elevated levels of ambient air pollutants may not only trigger cerebrovascular events in susceptible people (short-term exposures) but also increase the risk of future events (long-term average exposures). This review assesses the updated evidence for both short and long-term exposure to ambient air pollution as a risk factor for stroke incidence and outcomes. It discusses the potential pathophysiologic mechanisms and makes recommendations to mitigate exposure on a personal and community level. The evidence indicates that reduction in air pollutant concentrations represent a significant population-level opportunity to reduce risk of cerebrovascular disease.

Interactions between acoustic challenges and processing depth in speech perception as measured by task-evoked pupil response.

Speech perception under adverse conditions is a multistage process involving a dynamic interplay among acoustic, cognitive, and linguistic factors. Nevertheless, prior research has primarily focused on factors within this complex system in isolation. The primary goal of the present study was to examine the interaction between processing depth and the acoustic challenge of noise and its effect on processing effort during speech perception in noise. Two tasks were used to represent different depths of processing. The speech recognition task involved repeating back a sentence after auditory presentation (higher-level processing), while the tiredness judgment task entailed a subjective judgment of whether the speaker sounded tired (lower-level processing). The secondary goal of the study was to investigate whether pupil response to alteration of dynamic pitch cues stems from difficult linguistic processing of speech content in noise or a perceptual novelty effect due to the unnatural pitch contours. Task-evoked peak pupil response from two groups of younger adult participants with typical hearing was measured in two experiments. Both tasks (speech recognition and tiredness judgment) were implemented in both experiments, and stimuli were presented with background noise in Experiment 1 and without noise in Experiment 2. Increased peak pupil dilation was associated with deeper processing (i.e., the speech recognition task), particularly in the presence of background noise. Importantly, there is a non-additive interaction between noise and task, as demonstrated by the heightened peak pupil dilation to noise in the speech recognition task as compared to in the tiredness judgment task. Additionally, peak pupil dilation data suggest dynamic pitch alteration induced an increased perceptual novelty effect rather than reflecting effortful linguistic processing of the speech content in noise. These findings extend current theories of speech perception under adverse conditions by demonstrating that the level of processing effort expended by a listener is influenced by the interaction between acoustic challenges and depth of linguistic processing. The study also provides a foundation for future work to investigate the effects of this complex interaction in clinical populations who experience both hearing and cognitive challenges.

Individual and Joint Effects of Influenza-Like Illness and Vaccinations on Stroke in the Young: A Case-Control Study.

BACKGROUND: Influenza-like illness (ILI) is an acute trigger for stroke, although joint effects of vaccinations and ILI have not yet been explored. METHODS: Data for our case-control study was obtained from MarketScan Commercial Claims and Encounters between 2008 and 2014. Patients 18 to 65 years old who experienced a stroke were matched on age and admission date to a control, defined as patients with head trauma or ankle sprain at an inpatient or emergency department visit. Exposures were ILI in the prior 30 days, and any type of vaccination during the year prior. Our outcome was ischemic and intracerebral hemorrhagic strokes identified using International Classification of Diseases, Ninth Revision (ICD-9) codes. Logistic regression models estimated adjusted odds ratios (aORs) controlling for preventive care visits, diabetes, valvular heart disease, smoking, alcohol abuse, obesity, and hypertension. RESULTS: We identified and matched 24 103 cases 18 to 44 years old and 141 811 45 to 65 years old. Those aged 18 to 44 years had increased stroke risk 30 days after ILI (aOR, 1.68 [95% CI, 1.51-1.86]) and reduced risk with any vaccination in the year prior (aOR, 0.92 [95% CI, 0.87-0.99]). Joint effects indicate that ILI was associated with increased stroke risk among those with (aOR, 1.41 [95% CI, 1.08-1.85]) and without (aOR, 1.73 [95% CI, 1.55-1.94]) vaccinations in the prior year (Pinteraction=0.16). Among those aged 45 to 65 years, adjusted analyses indicate increased stroke risk for those with ILI (aOR, 1.32 [95% CI, 1.26-1.38]), although there was no effect of vaccinations (aOR, 1.00 [95% CI, 0.97-1.02]). Joint effects indicate that ILI was not associated with stroke among those with any vaccination (aOR, 1.07 [95% CI, 0.96-1.18]) but was associated with increased risk among those without vaccinations ([aOR, 1.39 [95% CI, 1.32-1.47]; Pinteraction<0.001). CONCLUSIONS: ILI was associated with increased stroke risk in the young and middle-aged, while vaccinations of any type were associated with decreased risk among the young. Joint effects of ILI and vaccinations indicate vaccinations can reduce the effect of ILI on stroke.

Rural-Urban Differences in Diagnosed Cervical Artery Dissection in New York State.

BACKGROUND: Cervical artery dissection (CeAD) is a leading cause of stroke in young adults. Incidence estimates may be limited by under- or overdiagnosis. OBJECTIVE: We aimed to investigate if CeAD diagnosis would be higher in urban centers compared to rural regions of New York State (NYS). METHODS: For this ecological study, administrative codes were used to identify CeAD discharges in the NYS Statewide Planning and Research Cooperative System (SPARCS) from 2009 to 2014. Rural Urban Commuting Area (RUCA) codes were taken from the US Department of Agriculture and included the classifications metropolitan, micropolitan, small town, and rural. Negative binomial models were used to calculate effect estimates and 95% confidence limits (eß; 95% CL) for the association between RUCA classification and the number of dissections per ZIP code. Models were further adjusted by population. RESULTS: Population information was obtained from the US Census Bureau on 1,797 NYS ZIP codes (70.7% of NYS ZIP codes), 826 of which had at least 1 CeAD-related discharge from 2009 to 2014. Nonrural ZIP codes were more likely to report more CeAD cases relative to rural areas even after adjusting for population (metropolitan effect = eß 5.00; 95% CI: 3.75-6.66; micropolitan effect 3.02; 95% CI: 2.16-4.23; small town effect 2.34; 95% CI: 1.58-3.47). CONCLUSIONS: CeAD diagnosis correlates with population density as defined by rural-urban status. Our results could be due to underdiagnosis in rural areas or overdiagnosis with increasing urbanicity.

Relationship between Residential Segregation, Later-Life Cognition, and Incident Dementia across Race/Ethnicity.

Systemic racism leads to racial/ethnic residential segregation, which can result in health inequities. We examined if the associations between residential segregation and later-life cognition and dementia differed based on segregation measure and by participant race/ethnicity. Tests of memory (n = 4616), language (n = 4333), visuospatial abilities (n = 4557), and incident dementia (n = 4556) were analyzed in older residents of Northern Manhattan, New York (mean age: 75.7 years). Segregation was measured at the block group-level using three indices: dissimilarity, isolation, and interaction. We fit multilevel linear or Cox proportional hazards models and included a race/ethnicity × segregation term to test for differential associations, adjusting for socioeconomic and health factors. Living in block groups with higher proportions of minoritized people was associated with -0.05 SD lower language scores. Living in block groups with higher potential contact between racial/ethnic groups was associated with 0.06-0.1 SD higher language scores. The findings were less pronounced for other cognitive domains and for incident dementia. Non-Hispanic Black adults were most likely to experience negative effects of neighborhood segregation on cognition (language and memory) and dementia. All indices partly capture downstream effects of structural racism (i.e., unequal distributions of wealth/resources) on cognition. Therefore, desegregation and equitable access to resources have the potential to improve later-life cognitive health.

Risk of stroke and myocardial infarction after influenza-like illness in New York State.

BACKGROUND: Influenza may be associated with increased stroke and myocardial infarction (MI) risk. We hypothesized that risk of stroke and MI after influenza-like illness (ILI) would be higher in patients in New York State. We additionally assessed whether this relationship differed across a series of sociodemographic factors. METHODS: A case-crossover analysis of the 2012-2014 New York Statewide Planning and Research Cooperative System (SPARCS) was used to estimate odds of ischemic stroke and MI after ILI. Each patient's case window (the time period preceding event) was compared to their control windows (same dates from the previous 2 years) in conditional logistic regression models used to estimate odds ratios and 95% confidence intervals (OR, 95% CI). We varied the case windows from 15 to 365 days preceding event as compared to control windows constructed using the same dates from the previous 2 years. Analyses were stratified by sex, race, and urban-rural status based on residential zip code. RESULTS: A total of 33,742 patients were identified as having ischemic stroke and 53,094 had MI. ILI events in the 15 days prior were associated with a 39% increase in odds of ischemic stroke (95% CI 1.09-1.77), increasing to an almost 70% increase in odds when looking at ILI events over the last year (95% CI 1.56, 1.83). In contrast, the effect of ILI hospitalization on MI was strongest in the 15 days prior (OR = 1.24, 95% CI 1.06-1.44). The risk of ischemic stroke after ILI was higher among individuals living in rural areas in the 90 days prior to stroke and among men in the year prior to event. In contrast, the association between ILI and MI varied only across race with whites having significantly higher ILI associated MI. CONCLUSION: This study highlights risk period differences for acute cardiovascular events after ILI, indicating possible differences in mechanism behind the risk of stroke after ILI compared to the risk of MI. High risk populations for stroke after ILI include men and people living in rural areas, while whites are at high risk for MI after ILI. Future studies are needed to identify ways to mitigate these risks.

Association Between Hurricane Sandy and Emergency Department Visits in New York City by Age and Cause.

The magnitude, timing, and etiology of morbidity associated with tropical cyclones remains incompletely quantified. We examined the relative change in cause-specific emergency department (ED) visits among residents of New York City during and after Hurricane Sandy, a tropical cyclone that affected the northeastern United States in October 2012. We used quasi-Poisson constrained distributed lag models to compare the number of ED visits on and after Hurricane Sandy with all other days, 2005-2014, adjusting for temporal trends. Among residents aged ≥65 years, Hurricane Sandy was associated with a higher rate of ED visits due to injuries and poisoning (relative risk (RR) = 1.19, 95% confidence interval (CI): 1.10, 1.28), respiratory disease (RR = 1.35, 95% CI: 1.21, 1.49), cardiovascular disease (RR = 1.10, 95% CI: 1.02, 1.19), renal disease (RR = 1.44, 95% CI: 1.22, 1.72), and skin and soft tissue infections (RR = 1.20, 95% CI: 1.03, 1.39) in the first week following the storm. Among adults aged 18-64 years, Hurricane Sandy was associated with a higher rate of ED visits for renal disease (RR = 2.15, 95% CI: 1.79, 2.59). Among those aged 0-17 years, the storm was associated with lower rates of ED visits for up to 3 weeks. These results suggest that tropical cyclones might result in increased health-care utilization due to a wide range of causes, particularly among older adults.

Differences in healthcare visit frequency and type one year prior to stroke among young versus middle-aged adults.

BACKGROUND: The incidence and prevalence of stroke among the young are increasing in the US. Data on healthcare utilization prior to stroke is limited. We hypothesized those < 45 years were less likely than those 45-65 years old to utilize healthcare in the 1 year prior to stroke. METHODS: Patients 18-65 years old who had a stroke between 2008 and 2013 in MarketScan Commercial Claims and Encounters Databases were included. We used descriptive statistics and logistic regression to examine healthcare utilization and risk factors between age groups 18-44 and 45-65 years. Healthcare utilization was categorized by visit type (no visits, inpatient visits only, emergency department visits only, outpatient patient visits only, or a combination of inpatient, outpatient or emergency department visits) during the year prior to stroke hospitalization. RESULTS: Of those 18-44 years old, 14.1% had no visits in the year prior to stroke compared to 11.2% of individuals aged 45-65 [OR = 1.30 (95% CI 1.25,1.35)]. Patients 18-44 years old had higher odds of having preventive care procedures associated with an outpatient visit and lower odds of having cardiovascular procedures compared to patients aged 45-65 years. Of stroke patients aged 18-45 and 45-65 years, 16.8 and 13.2% respectively had no known risk for stroke. CONCLUSIONS: Patients aged 45-65 were less commonly seeking preventive care and appeared to be seeking care to manage existing conditions more than patients aged 18-44 years. However, as greater than 10% of both age groups had no prior risk, further exploration of potential risk factors is needed.

Influenza-Like Illness is Associated with Increased Short-Term Risk of Cervical Artery Dissection.

INTRODUCTION: Non-traumatic Cervical Artery Dissection (CeAD) is a leading cause of ischemic stroke in the young. Influenza-like illnesses (ILI) trigger ischemic strokes. We hypothesized that influenza and ILI are associated with CeAD. METHODS: In a case-crossover study within the New York State (NYS) Department of Health Statewide Planning and Research Cooperative System (2006-2014), we used ICD-9 codes to exclude major trauma and to define CeAD, influenza, and the Centers for Disease Control defined ILI. We estimated the association of ILI and influenza with CeAD by comparing their prevalence in intervals immediately prior (0-30,0-90,0-180, and 0-365 days) to CeAD (case period) to their prevalence exactly one and two years earlier (control periods). Conditional logistic regression models generated odds ratios and 95% confidence intervals (OR, 95% CI). Models were adjusted for NYS estimates of influenza prevalence rates. RESULTS: Our sample included 3,610 cases of CeAD (mean age 52±16 years, 54.7% male, 6.2% Hispanic, 9.9% Black, 68.7% White). During case periods, 7.3% had one or more ILI. ILI was more likely within 90 days of CeAD compared to the same time interval one and two years before (0-15 days: adjusted OR 1.88, 95%CI 1.20-2.94; 0-30 days: adjusted OR 1.74, 95%CI 1.22-2.46; 0-90 days: adjusted OR 1.35, 95%CI 1.00-1.81). Influenza trended with CeAD (adjusted OR 1.86, 95%CI 0.37-9.24), but these results were not statistically significant, due to limited instances of confirmed influenza. CONCLUSIONS: ILI may increase risk of CeAD for 15 days, and possibly up to three months.

Seasonality of Influenza-Like-Illness and Acute Cardiovascular Events Are Related Regardless of Vaccine Effectiveness.

Background Influenza has been identified as a trigger for stroke and myocardial infarction (MI) with prior studies demonstrating that influenza vaccination may decrease risk of stroke and MI. Methods and Results We used data from the New York Department of Health Statewide Planning and Research Cooperative System to evaluate whether annual variability in influenza vaccination effectiveness (VE) would be associated with cardiovascular events. Daily and monthly counts of outpatient and inpatient visits for influenza-like illness (ILI), stroke, and MI were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes; VE data for each year are publicly available. We identified pertinent lags between ILI, stroke, and MI using prewhitening cross-correlation functions and applied them to autoregressive integrated moving average time series regression models. Time series forecasting systems assessed correlations among ILI, stroke, and MI, and the effect of VE on these relationships. Cross-correlation functions indicated stroke events increased 1 month after increases in ILI rates; MIs increased immediately. Accounting for seasonality and lag, peaks in ILI rates were significantly related to peaks in stroke (P=0.04) and MI (P=0.01). Time forecasting analyses indicated no relationship between VE and cardiovascular events. Conclusions We identified that seasonality of cardiovascular events may be associated with seasonality in ILI, though VE did not modify this relationship.

Long-term exposure to air pollution and trajectories of cognitive decline among older adults.

OBJECTIVE: To evaluate the association between long-term exposure to ambient air pollution and cognitive decline in older adults residing in an urban area. METHODS: Data for this study were obtained from 2 prospective cohorts of residents in the northern Manhattan area of New York City: the Washington Heights-Inwood Community Aging Project (WHICAP) and the Northern Manhattan Study (NOMAS). Participants of both cohorts received in-depth neuropsychological testing at enrollment and during follow-up. In each cohort, we used inverse probability weighted linear mixed models to evaluate the cross-sectional and longitudinal associations between markers of average residential ambient air pollution (nitrogen dioxide [NO2], fine particulate matter [PM2.5], and respirable particulate matter [PM10]) levels in the year prior to enrollment and measures of global and domain-specific cognition, adjusting for sociodemographic factors, temporal trends, and censoring. RESULTS: Among 5,330 participants in WHICAP, an increase in NO2 was associated with a 0.22 SD lower global cognitive score at enrollment (95% confidence interval [CI], -0.30, -0.14) and 0.06 SD (95% CI, -0.08, -0.04) more rapid decline in cognitive scores between visits. Results were similar for PM2.5 and PM10 and across functional cognitive domains. We found no evidence of an association between pollution and cognitive function in NOMAS. CONCLUSION: WHICAP participants living in areas with higher levels of ambient air pollutants have lower cognitive scores at enrollment and more rapid rates of cognitive decline over time. In NOMAS, a smaller cohort with fewer repeat measurements, we found no statistically significant associations. These results add to the evidence regarding the adverse effect of air pollution on cognitive aging and brain health.

Association Between Blood Pressure and Later-Life Cognition Among Black and White Individuals.

Importance: Black individuals are more likely than white individuals to develop dementia. Whether higher blood pressure (BP) levels in black individuals explain differences between black and white individuals in dementia risk is uncertain. Objective: To determine whether cumulative BP levels explain racial differences in cognitive decline. Design, Setting, and Participants: Individual participant data from 5 cohorts (January 1971 to December 2017) were pooled from the Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represented a 0.1-SD difference in cognition. The median (interquartile range) follow-up was 12.4 (5.9-21.0) years. Analysis began September 2018. Main Outcomes and Measures: The primary outcome was change in global cognition, and secondary outcomes were change in memory and executive function. Exposures: Race (black vs white). Results: Among 34 349 participants, 19 378 individuals who were free of stroke and dementia and had longitudinal BP, cognitive, and covariate data were included in the analysis. The mean (SD) age at first cognitive assessment was 59.8 (10.4) years and ranged from 5 to 95 years. Of 19 378 individuals, 10 724 (55.3%) were female and 15 526 (80.1%) were white. Compared with white individuals, black individuals had significantly faster declines in global cognition (-0.03 points per year faster [95% CI, -0.05 to -0.01]; P = .004) and memory (-0.08 points per year faster [95% CI, -0.11 to -0.06]; P < .001) but significantly slower declines in executive function (0.09 points per year slower [95% CI, 0.08-0.10]; P < .001). Time-dependent cumulative mean systolic BP level was associated with significantly faster declines in global cognition (-0.018 points per year faster per each 10-mm Hg increase [95% CI, -0.023 to -0.014]; P < .001), memory (-0.028 points per year faster per each 10-mm Hg increase [95% CI, -0.035 to -0.021]; P < .001), and executive function (-0.01 points per year faster per each 10-mm Hg increase [95% CI, -0.014 to -0.007]; P < .001). After adjusting for cumulative mean systolic BP, differences between black and white individuals in cognitive slopes were attenuated for global cognition (-0.01 points per year [95% CI, -0.03 to 0.01]; P = .56) and memory (-0.06 points per year [95% CI, -0.08 to -0.03]; P < .001) but not executive function (0.10 points per year [95% CI, 0.09-0.11]; P < .001). Conclusions and Relevance: These results suggest that black individuals' higher cumulative BP levels may contribute to racial differences in later-life cognitive decline.

Long-term exposure to ambient air pollution, APOE-ε4 status, and cognitive decline in a cohort of older adults in northern Manhattan.

BACKGROUND: There is mounting evidence that long-term exposure to air pollution is related to accelerated cognitive decline in aging populations. Factors that influence individual susceptibility remain largely unknown, but may involve the apolipoprotein E genotype E4 (APOE-ε4) allele. OBJECTIVES: We assessed whether the association between long-term exposure to ambient air pollution and cognitive decline differed by APOE-ε4 status and cognitive risk factors. METHODS: The Washington Heights Inwood Community Aging Project (WHICAP) is a prospective study of aging and dementia. Neuropsychological testing and medical examinations occur every 18-24 months. We used mixed-effects models to evaluate whether the association between markers of ambient air pollution (nitrogen dioxide [NO2]), fine [PM2.5], and coarse [PM10] particulate matter) and the rate of decline in global and domain-specific cognition differed across strata defined by APOE-ε4 genotypes and cognitive risk factors, adjusting for sociodemographic factors and temporal trends. RESULTS: Among 4821 participants with an average of 6 years follow-up, higher concentrations of ambient air pollution were associated with more rapid cognitive decline. This association was more pronounced among APOE-ε4 carriers (p < 0.001). A one interquartile range increase in NO2 was associated with an additional decline of 0.09 standard deviations (SD) (95%CI -0.1, -0.06) in global cognition across biennial visits among APOE-ε4 positive individuals and a 0.07 SD (95%CI -0.09, -0.05) decline among APOE-ε4 negative individuals. Results for PM2.5, PM10 and cognitive domains were similar. The association between air pollutants and rate of cognitive decline also varied across strata of race-ethnicity with the association strongest among White non-Hispanic participants. CONCLUSIONS: These results add to the body of evidence on the adverse impact of ambient air pollution on cognitive aging and brain health and provide new insights into the genetic and behavioral factors that may impact individual susceptibility.