Gender Differences in the Protective Role of Grandparenting in Dementia Risk.

OBJECTIVES: This study provides one of the first national longitudinal studies of the association between caring for grandchildren (i.e., grandparenting) and the risk of dementia in the United States, with a focus on gender-specific variations. METHODS: We estimated discrete-time event history models, drawing upon data from the Health and Retirement Study (2000-2016). The analytic sample included 10,217 community-dwelling White and Black grandparents aged 52 years and older at baseline. RESULTS: Noncoresident grandparenting was associated with a lower risk of dementia for both women and men compared to grandparents who did not take care of grandchildren. However, the cognitive advantage showed different patterns based on gender and the combination of care intensity and family structure. Grandmothers had a lower risk of dementia than noncaregiving grandmothers when providing a light level of noncoresident grandparenting, whereas grandfathers who provided intensive noncoresident grandparenting had a reduced risk of dementia compared to their noncaregiving counterparts. Grandparenting experiences within multigenerational households and skipped-generation households were not associated with dementia risk. DISCUSSION: Intergenerational caregiving plays a pivotal role in shaping cognitive health during later life; however, the impact is nuanced, depending on factors such as gender, care intensity, and family structure.

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.

Characteristics and Predictors of Sleep Among Spousal Care Dyads Living With Chronic Conditions.

OBJECTIVES: Poor sleep is common among older adults with chronic health conditions and their spousal caregivers. However, dyadic sleep patterns among spouses are underexplored within the literature. This study examines dyadic sleep characteristics and associated contextual factors among spousal care dyads. METHODS: Participants included 462 older adult spousal care dyads from the 2015 National Health and Aging Trends Study and National Study of Caregiving (mean ages of care recipients/caregivers = 79 and 76 years, respectively; 22% of dyads were living with dementia). Self-reported sleep included frequency of (a) trouble falling back asleep among dyads, (b) care-related sleep disturbances among caregivers, and (c) trouble initiating sleep among care recipients. Predictors included between-dyad characteristics such as whether respondents had dementia, care burden and support, relationship quality, neighborhood cohesion, and within-dyad characteristics such as demographics, depression, and positive affect. We conducted multilevel dyadic analysis and actor-partner interdependence modeling. RESULTS: Sleep was correlated more among dyads living with dementia than those with other chronic conditions. Care dyads had poorer sleep if caregivers reported higher care burden; however, better relationship quality marginally ameliorated the association. Depressive symptoms had a partner effect on poorer sleep among care dyads, whereas positive emotions and older age only had an actor effect on better sleep for care recipients and spousal caregivers. Neighborhood cohesion, care support, and other demographic characteristics were not associated with dyadic sleep outcomes. DISCUSSION: Addressing both care recipient- and caregiver-related factors may improve sleep health for both members of the care dyad living with chronic conditions.

Multiscale dimensions of county-level disparities in opioid use disorder rates among older Medicare beneficiaries.

Background: Opioid use disorder (OUD) among older adults (age ≥ 65) is a growing yet underexplored public health concern and previous research has mainly assumed that the spatial process underlying geographic patterns of population health outcomes is constant across space. This study is among the first to apply a local modeling perspective to examine the geographic disparity in county-level OUD rates among older Medicare beneficiaries and the spatial non-stationarity in the relationships between determinants and OUD rates. Methods: Data are from a variety of national sources including the Centers for Medicare & Medicaid Services beneficiary-level data from 2020 aggregated to the county-level and county-equivalents, and the 2016-2020 American Community Survey (ACS) 5-year estimates for 3,108 contiguous US counties. We use multiscale geographically weighted regression to investigate three dimensions of spatial process, namely "level of influence" (the percentage of older Medicare beneficiaries affected by a certain determinant), "scalability" (the spatial process of a determinant as global, regional, or local), and "specificity" (the determinant that has the strongest association with the OUD rate). Results: The results indicate great spatial heterogeneity in the distribution of OUD rates. Beneficiaries' characteristics, including the average age, racial/ethnic composition, and the average hierarchical condition categories (HCC) score, play important roles in shaping OUD rates as they are identified as primary influencers (impacting more than 50% of the population) and the most dominant determinants in US counties. Moreover, the percentage of non-Hispanic white beneficiaries, average number of mental health conditions, and the average HCC score demonstrate spatial non-stationarity in their associations with the OUD rates, suggesting that these variables are more important in some counties than others. Conclusions: Our findings highlight the importance of a local perspective in addressing the geographic disparity in OUD rates among older adults. Interventions that aim to reduce OUD rates in US counties may adopt a place-based approach, which could consider the local needs and differential scales of spatial process.

Caring as curing: Grandparenting and depressive symptoms in China.

Research on grandparenting (i.e., caring for grandchildren) and mental health in Asian contexts has been limited, despite the rapid growth of older adults who take care of grandchildren. This study aims to investigate how grandparenting influences depressive symptoms in China. Using the China Health and Retirement Longitudinal Study (2011-2015, N = 4354), we conducted fixed effects regression models to examine the association between various types of grandparenting and depressive symptoms among older adults between the ages of 45 and 80. The results show that for grandparents, providing care to their grandchildren in skipped-generation households (i.e., grandparent-grandchildren families without adult children) is associated with a lower level of depressive symptoms compared to providing no care, after controlling for socioeconomic status, health behaviors, social support, and basic demographic characteristics. Other types of care (i.e., multigenerational household grandparenting, and part-time and full-time noncoresident grandparenting) are not significantly linked to caregiving grandparents' depressive symptoms. Overall, our findings suggest that sociocultural contexts need to be considered in explaining the different mental health implications of grandparenting.

Examining spatial inequality in COVID-19 positivity rates across New York City ZIP codes.

We aim to understand the spatial inequality in Coronavirus disease 2019 (COVID-19) positivity rates across New York City (NYC) ZIP codes. Applying Bayesian spatial negative binomial models to a ZIP-code level dataset (N = 177) as of May 31st, 2020, we find that (1) the racial/ethnic minority groups are associated with COVID-19 positivity rates; (2) the percentages of remote workers are negatively associated with positivity rates, whereas older population and household size show a positive association; and (3) while ZIP codes in the Bronx and Queens have higher COVID-19 positivity rates, the strongest spatial effects are clustered in Brooklyn and Manhattan.

Marital loss and risk of dementia: Do race and gender matter?

Recent studies have found that marital loss through divorce or widowhood is associated with a higher risk of dementia for older adults. However, whether these associations vary by race and gender is less clear. To address this gap, we drew upon longitudinal data from the Health and Retirement Study (2000-2016) to investigate the association between marital loss and dementia risk, separately for non-Hispanic Whites and non-Hispanic Blacks. We further examined gender variations in the link between marital loss and dementia risk within each racial group. Results from discrete-time event history models suggested that widowhood is significantly associated with a higher risk of dementia for both Whites and Blacks, controlling for basic demographic characteristics. However, while divorce is significantly associated with a higher risk of dementia for Blacks, the association is marginally significant (p < 0.1) for Whites. There are few significant gender variations in these associations except for the effect of divorce among Whites. Even after controlling for economic and health-related factors, we found that divorce is associated with a higher risk of dementia among White men but not among White women. Economic resources explain a significant portion of the association between widowhood and dementia risk, more so for Whites than for Blacks. Our findings call for more research into the pathways through which marital loss shapes the risk of dementia across racial and ethnic groups.

Are Older Populations at a Disadvantage? County-Level Analysis of Confirmed COVID-19 Cases in Urban and Rural America.

OBJECTIVES: This study examines how areas with different older population compositions are affected by Coronavirus Disease 2019 (COVID-19) and whether urban and rural counties face different challenges. METHODS: Applying negative binomial regression to a data set of U.S. counties (N = 3,042), we estimated the relationship between older population ratios and the number of confirmed COVID-19 cases, and how this relationship changes over time in urban and rural counties, respectively. RESULTS: Although low-ratio counties show the highest number of confirmed cases of COVID-19 at the beginning of the pandemic, confirmed cases in high-ratio counties (>25% of the total population is aged 65 and older) increase exponentially with time in urban areas. High-ratio rural counties hit their peak later and recover more slowly compared to low- and medium-ratio rural counties. DISCUSSION: Both urban and rural counties with larger older populations are more vulnerable and their disadvantages in COVID-19 infections are more rapidly exacerbated over time in urban areas. This underscores the importance of early action in those counties for effective intervention and prevention.

Social Relationships in Early Life and Episodic Memory in Mid- and Late Life.

OBJECTIVES: This study examines the longitudinal relationships between retrospective reports of early-life social relationships (i.e., having good friends, parent-child relationship quality, and childhood neighborhood social cohesion) and episodic memory in China. METHODS: We analyzed 2 waves of data (2011 and 2015) from the China Health and Retirement Longitudinal Study. The analytical sample included 9,285 respondents aged 45 and older at baseline. A lagged dependent variable approach was used to estimate the associations between measures of early-life social relationships and episodic memory change at the study's 4-year follow-up. RESULTS: Retrospective reports of better early-life social relationships are significantly associated with higher levels of episodic memory performance in 2015 among middle-aged and older Chinese, controlling for episodic memory in 2011, childhood socioeconomic status, adulthood sociodemographic variables, and the history of stroke. Educational attainment accounts for a significant portion of the associations between early-life social relationships and episodic memory. In contrast, mental health and social engagement in adulthood account for a small part of these associations. DISCUSSION: The findings suggest that positive early-life social relationships are beneficial for episodic memory in mid- and late life, and more research is needed to examine the underlying mechanisms.

Grandparenting and Mortality: How Does Race-Ethnicity Matter?

Little is known about whether and how intergenerational relationships influence older adult mortality. This study examines the association between caring for grandchildren (i.e., grandparenting) and mortality and how the link differs by race-ethnicity. Drawing from the Health and Retirement Study (1998-2014, N = 13,705), I found different racial-ethnic patterns in the effects of grandparenting on mortality risk. White grandparents who provide intensive noncoresident grandparenting (i.e., over 500 hours of babysitting per two years) and multigenerational household grandparenting have a lower risk of mortality compared to noncaregiving grandparents. In contrast, black grandparents have a higher mortality risk than their noncaregiving counterparts when providing intensive noncoresident, multigenerational household, and skipped-generation household (i.e., grandparent-headed family) grandparenting. Caregiving Hispanic grandparents are not significantly different from their noncaregiving counterparts in mortality risk. These findings suggest that important variations in social and cultural contexts for racial-ethnic groups shape the consequences of grandparenting for older adult mortality.

In vitro and in vivo effects of photodynamic therapy on metastatic breast cancer cells pre-treated with zoledronic acid.

BACKGROUND: Photodynamic therapy (PDT), a non-ionizing, minimally invasive drug-light treatment, has recently been shown to successfully ablate tumor within rat vertebrae with concurrent improvements in bone strength and architecture. The bisphosphonate zoledronic acid (zol), a current drug for patients with skeletal metastases, primarily works by inhibiting osteoclast activity, but direct anti-tumor effects have also been reported. However, it is unknown if or how pre-treatment with zol may alter the tumorcidal effect of PDT. The aim of this study was to evaluate the effect of PDT, both in vitro and in vivo, on zol-pretreated cancer cells. MATERIALS AND METHODS: Human metastatic breast cancer cells (MT-1) were cultured in vitro and treated with zol (10µM) for 24h, followed by PDT treatment. Cell viability was assessed by fluorescence microscopy and flow cytometry. In vivo, MT-1 cells were injected (intracardiac) into athymic rats. On day 7, zol (60µg/kg) was administered subcutaneously. On day 14, PDT was applied (1mg/kg verteporfin; 75J; 690nm) to lumbar vertebrae. Histomorphometric assessment of tumor burden was evaluated on day 21. RESULTS: The cell viability measured in vitro after PDT treatment decreased in cells pre-incubated with zol up to 20% compared to treatment with PDT alone. Zol alone had no influence on the MT-1 cell viability. In vivo, all treatments, either alone or combined, had a tumorcidal effect. CONCLUSIONS: Pre-treatment with zol in vivo did not yield a synergistic effect on tumor ablation in contrast to the in vitro results, but neither did it abrogate the positive tumorcidal effect of PDT, so that those therapies may be applied in combination.

Sequence and domain arrangements influence mechanical properties of elastin-like polymeric elastomers.

Elastin is the polymeric, extracellular matrix protein that provides properties of extensibility and elastic recoil to large arteries, lung parenchyma, and other tissues. Elastin assembles by crosslinking through lysine residues of its monomeric precursor, tropoelastin. Tropoelastin, as well as polypeptides based on tropoelastin sequences, undergo a process of self-assembly that aligns lysine residues for crosslinking. As a result, both the full-length monomer as well as elastin-like polypeptides (ELPs) can be made into biomaterials whose properties resemble those of native polymeric elastin. Using both full-length human tropoelastin (hTE) as well as ELPs, we and others have previously reported on the influence of sequence and domain arrangements on self-assembly properties. Here we investigate the role of domain sequence and organization on the tensile mechanical properties of crosslinked biomaterials fabricated from ELP variants. In general, substitutions in ELPs involving similiar domain types (hydrophobic or crosslinking) had little effect on mechanical properties. However, modifications altering either the structure or the characteristic sequence style of these domains had significant effects on such properties. In addition, using a series of deletion and replacement constructs for full-length hTE, we provide new insights into the role of conserved domains of tropoelastin in determining mechanical properties.

Non-destructive evaluation of the effects of combined bisphosphonate and photodynamic therapy on bone strain in metastatic vertebrae using image registration.

Skeletal metastases most frequently affect the vertebral column and may lead to severe consequences including fracture. Clinical management of skeletal metastases often utilizes a multimodal treatment approach, including bisphosphonates (BPs). Previous work has demonstrated the synergistic potential of photodynamic therapy (PDT) in combination with BP in treating osteolytic disease through structural, histologic, and destructive mechanical testing analyses. Recent work has developed and validated image-based methods that may be used to non-destructively determine mechanical stability in whole bones, and enable their use for additional (i.e. histologic) analysis. In this work we use an intensity-based 3D image registration technique to compare the strain patterns throughout untreated control and BP + PDT treated rnu/rnu rat spinal motion segments with osteolytic metastases. It was hypothesized that the combination treatment will reduce average and maximum strain values and restore the pattern of strain to that of healthy vertebrae. Mean, median, and 90th percentile strains in the control group were significantly higher than the treatment group. High strain areas in both groups were observed around the endplates; in the control group, large areas of high strains were also observed around the lesions and adjacent to the dorsal wall. Absence of high strains adjacent to the dorsal wall (similar to healthy vertebrae) may correspond to a reduced risk of burst fracture following BP + PDT therapy. This study demonstrates the application of non-destructive image analysis to quantify the positive mechanical effects of combined BP + PDT treatment in the metastatic spine.

Methylglyoxal-modified collagen promotes myofibroblast differentiation.

Fibrosis is a frequent complication of diabetes mellitus in many organs and tissues but the mechanism of how diabetes-induced glycation of extracellular matrix proteins impacts the formation of fibrotic lesions is not defined. As fibrosis is mediated by myofibroblasts, we investigated the effect of collagen glycation on the conversion of human cardiac fibroblasts to myofibroblasts. Collagen glycation was modeled by the glucose metabolite, methylglyoxal (MGO). Cells cultured on MGO-treated collagen exhibited increased activity of the α-smooth muscle actin promoter and enhanced expression of α-smooth muscle actin, ED-A fibronectin and cadherin, which are markers for myofibroblasts. In cells remodeling floating or stress-relaxed collagen gels, MGO treatment promoted more contraction (p<0.025) than vehicle controls, which was MGO dose-dependent. Transwell assays showed that cell migration was increased by MGO-treated collagen (p<0.025). In shear-force detachment assays, cells on MGO-treated collagen were less adherent than untreated collagen, and the formation of high affinity, ß1 integrin-dependent adhesions was inhibited. MGO-collagen-induced expression of SMA was dependent on TGF-ß but not on Rho kinase. We conclude that collagen glycation augments the formation and migration of myofibroblasts, critical processes in the development of fibrosis in diabetes.

Effects of photodynamic therapy on the structural integrity of vertebral bone.

STUDY DESIGN: This study investigates the effects of photodynamic therapy (PDT) on the structural integrity of vertebral bone in healthy rats. OBJECTIVE: To determine the short-term (1 week) and intermediate term (6 weeks) effects of a single PDT treatment on the mechanical and structural properties of vertebral bone. SUMMARY OF BACKGROUND DATA: Spinal metastasis develops in up to one-third of all cancer patients, compromising the mechanical integrity of the spine and thereby increasing the risk of pathologic fractures and spinal cord damage. PDT has recently been adapted to ablate metastatic tumors in the spine in preclinical animal models. However, little is known about the effects of PDT on the structural integrity of vertebral bone. METHODS: A single PDT treatment was administered to healthy Wistar rats at photosensitizer and light doses known to be effective in athymic rats bearing human breast cancer metastases. At both 1 and 6 weeks posttreatment, changes in trabecular architecture, global stiffness and strength of vertebrae were quantified using micro-CT stereological analysis and axial compression testing. RESULTS: At 6 weeks, there was a significant increase in bone volume fraction (to 55.7 +/- 11.1% vs. 38.5 +/- 6.4%, P < 0.001) and decrease in bone surface area-to-volume ratio (16.9 +/- 5.0/mm vs. 22.8 +/- 4.5/mm, P = 0.001), attributed to trabecular thickening (130 +/- 40 microm vs. 90 +/- 20 microm, P < 0.001). Similar trends were found at 1 week after PDT. There was a significant increase in stiffness from control (306 +/- 123 N/mm) at 1 week (399 +/- 150 N/mm, P = 0.04) and 6 weeks (410 +/- 113 N/mm, P = 0.05) post PDT. There was a positive trend toward increased ultimate stress at 1 week, which became statistically significant at 6 weeks compared with control (39.3 +/- 11.3 MPa vs. 27.5 +/- 9.5 MPa control, P = 0.002). CONCLUSION: Not only may PDT be successful in ablating metastatic tumor tissue in the spine, but the positive effects of PDT on bone found in this study suggest that PDT may also improve vertebral mechanical stability.

Beyond bisphosphonates: photodynamic therapy structurally augments metastatically involved vertebrae and destroys tumor tissue.

Breast cancer patients commonly develop metastases in the spine, which compromises its mechanical stability and can lead to skeletal related events. The current clinical standard of treatment includes the administration of systemic bisphosphonates (BP) to reduce metastatically induced bone destruction. However, response to BPs can vary both within and between patients, which motivates the need for additional treatment options for spinal metastasis. Photodynamic therapy (PDT) has been shown to be effective at treating metastatic lesions secondary to breast cancer in an athymic rat model, and is proposed as a treatment for spinal metastasis. The objective of this study was to determine the effect of PDT, alone or in combination with previously administered systemic BPs, on the structural and mechanical integrity of both healthy and metastatically involved vertebrae. Human breast carcinoma cells (MT-1) were inoculated into athymic rats (day 0). At 14 days, a single PDT treatment was administered, with and without previous BP treatment at day 7. In addition to causing tumor necrosis in metastatically involved vertebrae, PDT significantly reduced bone loss, resulting in strengthening of the vertebrae compared to untreated controls. Combined treatment with BP + PDT further enhanced bone architecture and strength in both metastatically involved and healthy bone. Overall, the ability of PDT to both ablate malignant tissue and improve the structural integrity of vertebral bone motivates its consideration as a local minimally invasive treatment for spinal metastasis secondary to breast cancer.