Targetability of the neurovascular unit in inflammatory diseases of the central nervous system.

The blood-brain barrier (BBB) is a selectively permeable barrier separating the periphery from the central nervous system (CNS). The BBB restricts the flow of most material into and out of the CNS, including many drugs that could be used as potent therapies. BBB permeability is modulated by several cells that are collectively called the neurovascular unit (NVU). The NVU consists of specialized CNS endothelial cells (ECs), pericytes, astrocytes, microglia, and neurons. CNS ECs maintain a complex "seal" via tight junctions, forming the BBB; breakdown of these tight junctions leads to BBB disruption. Pericytes control the vascular flow within capillaries and help maintain the basal lamina. Astrocytes control much of the flow of material that has moved beyond the CNS EC layer and can form a secondary barrier under inflammatory conditions. Microglia survey the border of the NVU for noxious material. Neuronal activity also plays a role in the maintenance of the BBB. Since astrocytes, pericytes, microglia, and neurons are all able to modulate the permeability of the BBB, understating the complex contributions of each member of the NVU will potentially uncover novel and effective methods for delivery of neurotherapies to the CNS.

Immunity impacts cognitive deficits across neurological disorders.

Cognitive deficits are a common comorbidity with neurological disorders and normal aging. Inflammation is associated with multiple diseases including classical neurodegenerative dementias such as Alzheimer's disease (AD) and autoimmune disorders such as multiple sclerosis (MS), in which over half of all patients experience some form of cognitive deficits. Other degenerative diseases of the central nervous system (CNS) including frontotemporal lobe dementia (FTLD), and Parkinson's disease (PD) as well as traumatic brain injury (TBI) and psychological disorders like major depressive disorder (MDD), and even normal aging all have cytokine-associated reductions in cognitive function. Thus, there is likely commonality between these secondary cognitive deficits and inflammation. Neurological disorders are increasingly associated with substantial neuroinflammation, in which CNS-resident cells secrete cytokines and chemokines such as tumor necrosis factor (TNF)α and interleukins (ILs) including IL-1ß and IL-6. CNS-resident cells also respond to a wide variety of cytokines and chemokines, which can have both direct effects on neurons by changing the expression of ion channels and perturbing electrical properties, as well as indirect effects through glia-glia and immune-glia cross-talk. There is significant overlap in these cytokine and chemokine expression profiles across diseases, with TNFα and IL-6 strongly associated with cognitive deficits in multiple disorders. Here, we review the involvement of various cytokines and chemokines in AD, MS, FTLD, PD, TBI, MDD, and normal aging in the absence of dementia. We propose that the neuropsychiatric phenotypes observed in these disorders may be at least partially attributable to a dysregulation of immunity resulting in pathological cytokine and chemokine expression from both CNS-resident and non-resident cells.

Is the mental health of older adults receiving care from their children related to their children's dual burden of caregiving and work stress? A linked lives perspective.

OBJECTIVES: Mental health problems are a major concern in the older population in Sweden, as is the growing number of older adults aging alone in their homes and in need of informal care. Using a linked lives perspective, this study explored if older parents' mental health is related to their children's dual burden of informal caregiving and job strain. METHODS: Data from a nationally representative Swedish survey, SWEOLD, were used. Mental health problems in older age (mean age 88) were measured with self-reported 'mild' or 'severe' anxiety and depressive symptoms. A primary caregiving adult child was linked to each older parent, and this child's occupation was matched with a job exposure matrix to assess job strain. Logistic regression analyses were conducted with an analytic sample of 334. RESULTS: After adjusting for covariates, caregiving children's lower job control and greater job strain were each associated with mental health problems in their older parents (OR 2.52, p = 0.008 and OR 2.56, p = 0.044, respectively). No association was found between caregiving children's job demands and their older parents' mental health (OR 1.08, p = 0.799). CONCLUSION: In line with the linked lives perspective, results highlight that the work-life balance of informal caregiving adult children may play a role in their older parent's mental health.

COVID-19 Symptoms and Deaths among Healthcare Workers, United States.

We evaluated whether demographics and COVID-19 symptoms predicted COVID-19 deaths among healthcare workers (HCWs) in the United States by comparing COVID-19 deaths in HCWs with 3 control groups (HCW nondeaths, non-HCW deaths, and non-HCW nondeaths) using a case-control design. We obtained patient-level data of 33 variables reported during January 1, 2020-October 12, 2021, in all US states. We used logistic regression analysis while controlling for confounders. We found that persons who were >50 years of age, male, Black, or Asian experienced significantly more deaths than matched controls. In addition, HCWs who died had higher risks for the most severe clinical indicators. We also found that the most indicative symptoms were preexisting medical conditions, shortness of breath, fever, cough, and gastrointestinal symptoms. In summary, minority, male, and older HCWs had greater risk for COVID-19 death. Severe clinical indicators and specific symptoms may predict COVID-19-related deaths among HCWs.

Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study.

BACKGROUND: As effective medication to treat COVID-19 is currently unavailable, preventive remedies may be particularly important. OBJECTIVE: To examine the relationship between serum 25-hydroxy vitamin D (25(OH)D) level and COVID-19 infection, its severity, and its clinical case characteristics. METHODS: This case-control study compared serum 25(OH)D levels and rates of vitamin D deficiency (VDD) between 80 healthy controls and 62 patients diagnosed with COVID-19 and admitted to Guangxi People's Hospital, China, 2/16/2020-3/16/2020. Cases were categorized into asymptomatic, mild/moderate, and severe/critical disease. Logistic regression analysis was conducted to examine the associations between 25(OH)D level, or VDD, and case status/severity of COVID-19 while controlling for demographics and comorbidities. A threshold level of vitamin D for conveying COVID-19 risk was estimated. RESULTS: Severe/critical COVID-19 cases were significantly older and had higher percentages of comorbidity (renal failure) compared to mild cases. The serum 25(OH)D concentration in COVID-19 patient was much lower than that in healthy control. And 25(OH)D level was the lowest in severe/critical cases, compared with mild cases. In further, significantly higher rates of VDD were found in COVID-19 cases (41.9%) compared to healthy controls (11.1%). And VDD was the greatest in severe/critical cases (80%), compared with mild cases (36%). These statistically significant associations remained even after controlling for demographics and comorbidities. A potential threshold of 25(OH)D (41.19 nmol/L) to protect against COVID-19 was identified. CONCLUSION: Elderly and people with comorbidities were susceptible to severe COVID-19 infection. VDD was a risk factor for COVID-19, especially for severe/critical cases. While further confirmation is needed, vitamin D supplementation may have prevention or treatment potential for COVID-19 disease.

Changes in perceived knowledge about childbirth among pregnant women participating in the Senses of Birth intervention in Brazil: a cross-sectional study.

BACKGROUND: Senses of Birth (SoB) is a health education intervention in Brazil that aims to reduce unnecessary cesareans in the country by providing information on reproductive rights, benefits and risks of childbirth, and use of intrapartum evidence-based practices (EBP) which are recommended by the World Health Organization (WHO) to improve childbirth outcomes and satisfaction. This study evaluates the impact of the SoB on pregnant women's perceived knowledge about normal birth (NB), cesarean, and use of EBP. METHODS: 1287 pregnant women answered a structured survey immediately after their visit to the intervention, between March 2015 and March 2016. To estimate the potential impact of the intervention on women's perceived knowledge, and possible associations between sociodemographic characteristics and perceived knowledge, statistical analyses were performed, including paired T-tests, ANOVA, and logistic and linear regressions. RESULTS: The mean score (MS) of perceived knowledge after the intervention was higher than the MS before experiencing the intervention for all three knowledge domains: Normal Birth (MS Before = 3.71 x MS After = 4.49), Cesarean (MS Before = 3.54 x MS After = 4.26) and EBPs (MS Before = 3.14 x MS After = 4.14). The results suggest that perceived knowledge increased more for low-income women (B = 0.206; p < 0.001 for EBP), women without private health insurance (OR 2.47, 95% CI: 1.49-4.09 for NB), with private prenatal care (OR 2.42, 95% CI: 1.59-3.66 for NB), experiencing their first pregnancy (OR 1.92, 95% CI: 1.31-2.82 for EBP; OR 1.37, 95% CI: 1.03-1.84 for NB; OR 1.37, 95% CI: 1.03-1.84 for cesarean), and in their first or second trimester (OR 1.64, 95% CI: 1.13-2.39 for EBP; OR 1.48, 95% CI: 1.11-1.97 for NB; OR 1.85, 95% CI: 1.40-2.41 for cesarean). CONCLUSION: The study showed that participation in the SoB was associated with an increase in perceived knowledge among Brazilian pregnant women. The intervention gains relevance considering the lack of evidence of the impact of non-clinical interventions to reduce unnecessary cesareans in middle and low-income countries.

Age and gender differences in the association between body mass index and all-cause mortality among older Japanese.

ABSTRACTObjective: Increasing evidence suggests a reverse J-shaped association between body mass index (BMI) and all-cause mortality among the older population. However, findings from non-Western societies including Japan are still sparse. Furthermore, little evidence regarding variation by age and gender in the BMI-mortality relationship in old age exists. This study aimed to examine age and gender variations in the relationship between BMI and all-cause mortality among older Japanese. Design: Data came from a national representative sample of community-dwelling Japanese aged 60 years and older at baseline (n = 4,869). Participants were followed for up to 25 years. We categorized BMI into seven categories: < 18.5, 18.5-19.9, 20.0-21.4, 21.5-22.9, 23.0-24.9, 25.0-26.9, and ≥ 27.0. Cox proportional hazards models were used to assess the relative mortality risk associated with BMI categories. Results: Lower BMI (< 18.5 and 18.5-19.9) was associated with higher mortality, compared to the mid-normal weight category (BMI: 21.5-22.9), after adjusting for covariates. In contrast, high-normal weight (BMI: 23.0-24.9) and overweight (BMI: 25.0-26.9 and ≥ 27.0) were not associated with mortality. Relative to old-old (aged ≥ 75 years), the higher mortality risk associated with lower BMI (< 20) appeared to be more prominent among young-old (aged 60-74 years). A moderately increased mortality risk associated with low BMI (18.5-19.9) was identified among men but not among women. Conclusion: Among older Japanese, low BMI (< 20.0) was associated with higher mortality, while high BMI (≥ 27.0) was not. The increased mortality risk associated with low BMI is more apparent among young-old and men. These age and gender differences need to be considered in assessing healthy body weight in old age.

Evaluation of CD33 as a genetic risk factor for Alzheimer's disease.

In 2011, genome-wide association studies implicated a polymorphism near CD33 as a genetic risk factor for Alzheimer's disease. This finding sparked interest in this member of the sialic acid-binding immunoglobulin-type lectin family which is linked to innate immunity. Subsequent studies found that CD33 is expressed in microglia in the brain and then investigated the molecular mechanism underlying the CD33 genetic association with Alzheimer's disease. The allele that protects from Alzheimer's disease acts predominately to increase a CD33 isoform lacking exon 2 at the expense of the prototypic, full-length CD33 that contains exon 2. Since this exon encodes the sialic acid ligand-binding domain, the finding that the loss of exon 2 was associated with decreased Alzheimer's disease risk was interpreted as meaning that a decrease in functional CD33 and its associated immune suppression was protective from Alzheimer's disease. However, this interpretation may need to be reconsidered given current findings that a genetic deletion which abrogates CD33 is not associated with Alzheimer's disease risk. Therefore, integrating currently available findings leads us to propose a model wherein the CD33 isoform lacking the ligand-binding domain represents a gain of function variant that reduces Alzheimer's disease risk.

Ethnic differences in all-cause and cardiovascular mortality by physical activity levels among older adults in the US.

AIMS: This study sought to determine whether the association between varying levels of physical activity (PA) and all-cause and cardiovascular mortality differ by race/ethnicity in older adults. METHODS: The sample comprised 2520 women and 2398 men drawn from National Health and Nutrition Examination Survey III (1988-1994) aged ≥ 60 years. We used the metabolic equivalent (MET) of self-reported PA levels to define activity groups (inactive: those who did not report any PA; active: those who reported 3-6 METs for ≥5 times/week or >6 METs, ≥3 times/week; insufficiently active: those meeting neither criteria). Racial/Ethnic differences were modeled using proportional hazard regression (HR) adjusting for age, education, smoking, diabetes, and hypertension. RESULTS: Among those classified as inactive, Non-Hispanic Blacks (NHB) (HR: 0.72, 95% CI: 0.58-0.90) and Mexican Americans (HR: 0.59, 95%CI: 0.45-0.78) had a lower risk of all-cause mortality when compared to non-Hispanic Whites (NHW). Among those classified as insufficiently active, Mexican Americans (HR: 0.63, 95% CI: 0.51-0.77), but not NHB (HR: 0.81, (95% CI: 0.64-1.02) had a lower risk of all-cause mortality when compared to NHWs Similar results were observed for cardiovascular mortality. CONCLUSION: Overall, PA in the elderly (either insufficient or active) is associated with a lower all-cause mortality across all race/ethnic groups as compared to NHW. Further investigation, including studies with larger sample, is needed to address the health consequences of varying degrees of PA in ethnically diverse populations.

Copper accumulation and toxicity in earthworms exposed to CuO nanomaterials: Effects of particle coating and soil ageing.

Engineered nanomaterials (ENMs) may be functionalised with a surface coating to enhance their properties, but the ecotoxicity of the coatings and how hazard changes with ageing in soil is poorly understood. This study determined the toxic effect of CuO ENMs with different chemical coatings on the earthworm (Eisenia fetida) in fresh soil, and then after one year in aged soil. In both experiments, earthworms were exposed for 14 days to the CuO materials at nominal concentrations of 200 and 1000 mg Cu kg-1 dry weight and compared to CuSO4. In the fresh soil experiment, CuO-COOH was found to be the most acutely toxic of the nanomaterials (survival, 20 ±â€¯50%), with tenfold increase of total Cu in the earthworms compared to controls. Sodium pump activity was reduced in most CuO ENM treatments, although not in the CuSO4 control. There was no evidence of glutathione depletion or the induction of superoxide dismutase (SOD) activity in any treatment. Histology showed a mild hypoplasia of mucous cells in the epidermis with some nanomaterials. In the aged soil, the CuO-NH4+ was the most acutely toxic ENM (survival 45 ±â€¯3%) and Cu accumulation was lower in the earthworms than in the fresh soil study. Depletion of tissue Mn and Zn concentrations were seen in earthworms in aged soil, while no significant effects on sodium pump or total glutathione were observed. Overall, the study showed some coating-dependent differences in ENM toxicity to earthworms which also changed after a year of ageing the soil.

Low hazard of silver nanoparticles and silver nitrate to the haematopoietic system of rainbow trout.

Silver nanoparticles (Ag NPs) are known for their antibacterial properties and are used in a growing number of nano-enabled products, with inevitable concerns for releases to the environment. Nanoparticles may also be antigenic and toxic to the haematopoietic system, but the immunotoxic effect of Ag NPs on non-target species such as fishes is poorly understood. This study aimed to assess the effect of Ag NP exposure via the water on the haematopoietic system of rainbow trout, Oncorhynchus mykiss, and to determine whether or not the hazard from Ag NPs was different from that of AgNO3. Fish were exposed for 7 days to a control (dechlorinated Plymouth freshwater), dispersant control, 1µgl-1 Ag as AgNO3 or 100µgl-1 Ag NPs. Animals were sampled on days 0, 4 and 7 for haematology, tissue trace metal concentration, biochemistry for evidence of oxidative stress/inflammation in the spleen and histopathology of the blood cells and spleen. The Ag NP treatment significantly increased the haematocrit, but the haematological changes were within the normal physiological range of the animal. Thrombocytes in spleen prints at day 4, and melanomacrophage deposits at day 7 in the spleen, of Ag NP exposed-fish displayed significant increases compared to all the other treatments within the time point. A dialysis experiment confirmed that dissolution rates were very low and any pathology observed is likely from the NP form rather than dissolved metal released from it. Overall, the data showed subtle differences in the effects of Ag NPs compared to AgNO3 on the haematopoietic system. The lack of pathology in the circulating blood cells and melanomacrophage deposits in the spleen suggests a compensatory physiological effort by the spleen to maintain normal circulating haematology during Ag NP exposure.

A critical evaluation of the fish early-life stage toxicity test for engineered nanomaterials: experimental modifications and recommendations.

There are concerns that regulatory toxicity tests are not fit for purpose for engineered nanomaterials (ENMs) or need modifications. The aim of the current study was to evaluate the OECD 210 fish, early-life stage toxicity test for use with TiO2 ENMs, Ag ENMs, and MWCNT. Both TiO2 ENMS (≤160 mg l(-1)) and MWCNT (≤10 mg l(-1)) showed limited acute toxicity, whilst Ag ENMs were acutely toxic to zebrafish, though less so than AgNO3 (6-day LC50 values of 58.6 and 5.0 µg l(-1), respectively). Evidence of delayed hatching, decreased body length and increased muscle width in the tail was seen in fish exposed to Ag ENMs. Oedema (swollen yolk sacs) was also seen in fish from both Ag treatments with, for example, mean yolk sac volumes of 17, 35 and 39 µm(3) for the control, 100 µg l(-1) Ag ENMs and 5 µg l(-1) AgNO3 treatments, respectively. Among the problems with the standard test guidelines was the inability to maintain the test solutions within ±20 % of nominal concentrations. Pronounced settling of the ENMs in some beakers also made it clear the fish were not being exposed to nominal concentrations. To overcome this, the exposure apparatus was modified with the addition of an exposure chamber that ensured mixing without damaging the delicate embryos/larvae. This allowed more homogeneous ENM exposures, signified by improved measured concentrations in the beakers (up to 85.7 and 88.1 % of the nominal concentrations from 10 mg l(-1) TiO2 and 50 µg l(-1) Ag ENM exposures, respectively) and reduced variance between measurements compared to the original method. The recommendations include: that the test is conducted using exposure chambers, the use of quantitative measurements for assessing hatching and morphometrics, and where there is increased sensitivity of larvae over embryos to conduct a shorter, larvae-only toxicity test with the ENMs.

Screening, brief intervention, and referral to treatment for adolescents: Attitudes, perceptions, and practice of New York school-based health center providers.

BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) has been endorsed by the American Academy of Pediatrics as an evidence-based strategy to address risky substance use among adolescents in primary care. However, less than half of pediatricians even screen adolescents for substance use. The purpose of this study was to identify variation in SBIRT practice and explore how program directors' and clinicians' attitudes and perceptions of effectiveness, role responsibility, and self-efficacy impact SBIRT adoption, implementation, and practice in school-based health centers (SBHCs). METHODS: All 162 New York State SBHC program directors and clinicians serving middle and high school students were surveyed between May and June of 2013 (40% response rate). RESULTS: Only 22% of participants reported practicing the SBIRT model. Of the individual SBIRT model components, using a standardized tool to screen students for risky substance use, referring students with substance use problems to specialty treatment, and assessing students' readiness to change were practiced least frequently. Less than 30% of participants felt they could be effective at helping students reduce substance use, 63% did not believe it was their role to use a standardized screening tool, and 20-30% did not feel confident performing specific aspects of intervention and management. Each of these factors was correlated with SBIRT practice frequency (P < .05). CONCLUSIONS: Findings from this study identify an important gap between an evidence-based SBIRT model and its adoption into practice within SBHCs, indicating a need for dissemination strategies targeting role responsibility, self-efficacy, and clinicians' perceptions of SBIRT effectiveness.

Trajectories of Body Mass Index and Their Associations With Mortality Among Older Japanese: Do They Differ From Those of Western Populations?

Few studies have focused on the relationship between the trajectories of long-term changes in body mass index (BMI; weight (kg)/height (m)(2)) and all-cause mortality in old age, particularly in non-Western populations. We evaluated this association by applying group-based mixture models to data derived from the National Survey of the Japanese Elderly, which included 4,869 adults aged 60 or more years, with up to 7 repeated observations between 1987 and 2006. Four distinct BMI trajectories were identified: "low-normal weight, decreasing" (baseline BMI = 18.7; 23.8% of sample); "mid-normal weight, decreasing" (baseline BMI = 21.9; 44.6% of sample); "high-normal weight, decreasing" (baseline BMI = 24.8; 26.5% of sample); and "overweight, stable" (baseline BMI = 28.7; 5.2% of sample). Survival analysis with an average follow-up of 13.8 years showed that trajectories of higher BMI were associated with lower mortality. In particular, relative to those with a mid-normal weight, decreasing BMI trajectory, those with an overweight, stable BMI trajectory had the lowest mortality, and those with a low-normal, decreasing BMI trajectory had the highest mortality. In sharp contrast with prior observations from Western populations, BMI changes lie primarily within the normal-weight range, and virtually no older Japanese are obese. The association between BMI trajectories and mortality varies according to the distribution of BMI within the population.

Lifecourse socioeconomic position and 16 year body mass index trajectories: differences by race and sex.

OBJECTIVE: The aim of this study is to evaluate the association between lifecourse socioeconomic position (SEP) and changes in body mass index (BMI), and assess disparities in these associations across racial/ethnic groups. METHODS: With longitudinal data from 4 waves of the Americans' Changing Lives Study (1986-2002), we employed mixed-effects modeling to estimate BMI trajectories for 1174 Blacks and 2323 White adults. We also estimated associations between these trajectories and lifecourse SEP variables, including father's education, perceived childhood SEP, own education, income, wealth, and financial security. RESULTS: Blacks had higher baseline BMIs, and steeper increases in BMI, compared to Whites. Childhood SEP, as measured by high father's education, was associated with lower baseline BMI among Whites. High education was associated with a lower baseline BMI within both race and sex categories. Income had contrasting effects among men and women. Higher income was associated with higher BMI only among males. Associations between indicators of SEP and BMI trajectories were only found for Whites. CONCLUSIONS: Our study demonstrates that lifecourse SEP may influence adult BMI differently within different racial and sex groups.

A novel PSMB8 isoform associated with multiple sclerosis lesions induces P-body formation.

Introduction: Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Current therapies primarily target the inflammatory component of the disease and are highly effective in early stages of MS while limited therapies have an effect in the more chronic progressive stages of MS where resident glia have a larger role. MS lesions tend to be inflammatory even after the initial peripheral immune cell invasion has subsided and this inflammation is known to cause alternative splicing events. Methods: We used qPCR of normal-appearing white matter and white matter lesions from postmortem MS tissue, in vitro studies, and immunostaining in MS tissue to investigate the alternative splicing of one gene known to be important during recovery in an animal model of MS, PSMB8. Results: We found a novel, intron-retained isoform which has not been annotated, upregulated specifically in MS patient white matter lesions. We found that this novel isoform activates the nonsense-mediated decay pathway in primary human astrocytes, the most populous glial cell in the CNS, and is then degraded. Overexpression of this isoform in astrocytes leads to an increased number of processing bodies in vitro, the primary site of mRNA decay. Finally, we demonstrated that MS white matter lesions have a higher burden of processing bodies compared to normal-appearing white matter, predominantly in GFAP-positive astrocytes. Discussion: The increase in alternative splicing of the PSMB8 gene, the stress that this alternative splicing causes, and the observation that processing bodies are increased in white matter lesions suggests that the lesion microenvironment may lead to increased alternative splicing of many genes. This alternative splicing may blunt the protective or reparative responses of resident glia in and around white matter lesions in MS patients.

A novel PSMB8 isoform associated with multiple sclerosis lesions induces P-body formation.

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Current therapies primarily target the inflammatory component of the disease and are highly effective in early stages of MS while limited therapies have an effect in the more chronic progressive stages of MS where resident glia have a larger role. MS lesions tend to be inflammatory even after the initial peripheral immune cell invasion has subsided and this inflammation is known to cause alternative splicing events. We used qPCR of normal-appearing white matter and white matter lesions from postmortem MS tissue, in vitro studies, and immunostaining in MS tissue to investigate the alternative splicing of one gene known to be important during recovery in an animal model of MS, PSMB8. We found a novel, intron-retained isoform which has not been annotated, upregulated specifically in MS patient white matter lesions. We found that this novel isoform activates the nonsense-mediated decay pathway in primary human astrocytes, the most populous glial cell in the CNS, and is then degraded. Overexpression of this isoform in astrocytes leads to an increased number of processing bodies in vitro, the primary site of mRNA decay. Finally, we demonstrated that MS white matter lesions have a higher burden of processing bodies compared to normal-appearing white matter, predominantly in GFAP-positive astrocytes. The increase in alternative splicing of the PSMB8 gene, the stress that this alternative splicing causes, and the observation that processing bodies are increased in white matter lesions suggests that the lesion microenvironment may lead to increased alternative splicing of many genes. This alternative splicing may blunt the protective or reparative responses of resident glia in and around white matter lesions in MS patients.

Neighborhood Features and Cognitive Function: Moderating Roles of Individual Socioeconomic Status.

INTRODUCTION: There is an interest in exploring the associations between neighborhood characteristics and individual cognitive function; however, little is known about whether these relationships can be modified by individual socioeconomic status, such as educational attainment and income. METHODS: Drawing from the 2010-2018 Health and Retirement Study, this study analyzed 10,621 older respondents (aged 65+) with a total of 33,931 person-waves. These respondents did not have dementia in 2010 and stayed in the same neighborhood throughout the study period. Cognitive function was measured with a 27-point indicator biennially, and neighborhood characteristics (i.e., walkability, concentrated disadvantage, and social isolation) were assessed in 2010. All analyses were performed in 2023. RESULTS: Cognitive function is positively associated with neighborhood walkability and negatively related to concentrated disadvantage, suggesting that exposures to these neighborhood characteristics have long-lasting impacts on cognitive function. Furthermore, individual socioeconomic status modifies the relationship between neighborhood characteristics and cognitive function. Compared with those graduating from college, respondents without a bachelor's degree consistently have lower cognitive function but the educational gap in cognitive function narrows with increases in walkability (b= -0.152, SE=0.092), and widens when neighborhood concentrated disadvantage (b=0.212, SE=0.070) or social isolation (b=0.315, SE=0.125) rises. The income gap in cognitive function shrinks with increases in walkability (b= -0.063, SE=0.027). CONCLUSIONS: The moderating role of socioeconomic status indicates that low-socioeconomic status older adults who also live in disadvantaged neighborhoods face a higher risk of poor cognitive function. Low-education and low-income aging adults may have the most to gain from investments to improve neighborhood characteristics.

Smoking trajectories from midlife to old age and the development of non-life-threatening health problems: a 34-year prospective cohort study.

OBJECTIVE: To examine how trajectories of smoking observed over a 34-year period, were associated with the progression of mobility impairment, musculoskeletal pain, and symptoms of psychological distress from midlife to old age. METHOD: The Swedish Level of Living Survey (LNU) and the Swedish Panel Study of the Oldest Old (SWEOLD) were merged to create a nationally representative longitudinal sample of Swedish adults (aged 30-50 at baseline; n=1060), with four observation periods, from 1968 through 2002. Five discrete smoking trajectory groups were treated as predictors of variation in health trajectories using multilevel regression. RESULTS: At baseline, there were no differences in mobility impairment between smoking trajectory groups. Over time all smokers, particularly persistent and former heavy smokers, exhibited faster increases in mobility problems compared with persistent non-smokers. Additionally, all smoking groups reported more pain symptoms than the non-smokers, at baseline and over time, but most of these differences did not reach statistical significance. Persistent heavy smokers reported elevated levels of psychological distress at baseline and over time. CONCLUSION: Smokers, and even some former smokers, who survive into old age appear to be at increased risk for non-life-threatening conditions that can diminish quality of life and increase demands for services.

Trajectories of social activities from middle age to old age and late-life disability: a 36-year follow-up.

OBJECTIVES: to examine the association between 34-year trajectories of social activity, from middle age to old age and late-life disability. METHODS: data from the Swedish Level of Living Survey (LNU) and the Swedish Panel Study of the Oldest Old (SWEOLD) were used. LNU data from 1968, 1981, 1991 and 2000 were merged with SWEOLD data from 1992, 2002 and 2004 to create a longitudinal data set with five observation periods. Trajectories of social activities covered 1968-2002, and late-life disability was measured in 2004. The sample consisted of 729 individuals aged 33-61 at baseline (1968), who participated in at least four observation periods and who were free from mobility limitations at baseline. Four trajectories of social activity were identified and used as predictors of late-life disability. RESULTS: reporting low/medium levels of social activity from mid-life to old age was the most common trajectory group. Persons reporting continuously low/medium or decreasing levels of social activity had higher odds ratios for late-life disability (OR = 2.33 and OR = 2.15, respectively) compared with those having continuously high levels of activity, even when adjusting for age, sex and mobility limitations, and excluding persons with baseline mobility limitations. CONCLUSIONS: results suggest that the disability risk associated with social activities is related to recent levels of activity, but also that risk may accumulate over time, as indicated by the higher disability risk associated with the continuously low/medium level social activity trajectory.