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.

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.

The Effects of Midlife Acute and Chronic Stressors on Black-White Differences in Cognitive Decline.

OBJECTIVES: Midlife stressors may be particularly consequential for cognitive performance and disparities in cognitive decline. This study examined Black-White differences in trajectories of cognition among middle-aged adults and the effects of acute and chronic stressors on these trajectories. METHODS: Data come from 4,011 cognitively healthy individuals aged 51-64 (620 Black and 3,391 White) who participated in the 2006-2018 waves of the Health and Retirement Study. Stressors included a count of recent life events and measures of financial strain and everyday discrimination. Global cognition was assessed using a modified version of the Telephone Interview for Cognitive Status. Linear mixed models with random slopes and intercepts assessed change in cognition over time. Race-by-time, race-by-stressor, time-by-stressor, and race-by-stressor-by-time interactions were assessed as were quadratic terms for time and each stressor. RESULTS: After adjusting for sociodemographic, health behaviors, and health-related factors, Black respondents had lower initial cognitive performance scores (b = -1.75, p < .001) but experienced earlier but slower decline in cognitive performance over time (Black × Time2 interaction: b = 0.02, p < .01). Financial strain, discrimination, and recent life events each had distinct associations with cognitive performance but did not influence racial differences in levels of or change in cognition over time. DISCUSSION: Middle-aged Black adults have lower initial cognition levels and experience earlier but less accelerated cognitive decline compared to White middle-aged adults. Midlife acute and chronic stressors influence baseline cognition but do so in different ways. Future research should examine the influence of other stressors on racial differences in cognitive decline at other points in the life course.

Living Alone During Old Age and the Risk of Dementia: Assessing the Cumulative Risk of Living Alone.

OBJECTIVES: This study examines the association between living alone during old age and dementia. Whereas most previous studies on this topic utilize measures of living alone status that were obtained at a single point in time, we compare this typical approach to one that measures long-term exposure to living alone among older adults and assesses whether dementia is more likely to occur within individuals with more accumulated time living alone. METHODS: Data come from the Health and Retirement Study, with a follow-up period of 2000-2018. A total of 18,171 older adults were followed during this period, resulting in 78,490 person-waves analyzed in a series of multi-level logistic models. Contemporaneous living alone was recorded when a respondent's household size was equal to 1 in a given wave. Cumulative living alone was calculated by adding the number of living alone statuses up to a given wave. RESULTS: Contemporaneous living alone was either not associated (male-only subsample), or inversely associated (female-only subsample) with dementia. By contrast, a one-unit (i.e., one wave) increase in cumulative living alone was associated with about a 10% increase in the odds of dementia for both men (odds ratio [OR] = 1.111) and women (OR = 1.088), net of several covariates, including marital status, age, social activities, and social support. DISCUSSION: Living alone during late life is an important risk factor for dementia, but the cognitive effects of solitary living probably do not take hold immediately for most older adults and potentially demonstrate a dose-response relationship.

Neighborhood characteristics and opioid use disorder among older Medicare beneficiaries: An examination of the role of the COVID-19 pandemic.

This study investigates how the associations between residential characteristics and the risk of opioid user disorder (OUD) among older Medicare beneficiaries (age≥65) are altered by the COVID-19 pandemic. Applying matching techniques and multilevel modeling to the Medicare fee-for-service claims data, this study finds that county-level social isolation, concentrated disadvantage, and residential stability are significantly associated with OUD among older adults (N = 1,080,350) and that those living in counties with low levels of social isolation and residential stability experienced a heightened risk of OUD during the pandemic. The results suggest that the COVID-19 pandemic has aggravated the impacts of residential features on OUD.

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.

Identification and Quantitation of Novel ABI3 Isoforms Relative to Alzheimer's Disease Genetics and Neuropathology.

Elucidating the actions of genetic polymorphisms associated with the risk of Alzheimer's disease (AD) may provide novel insights into underlying mechanisms. Two polymorphisms have implicated ABI3 as a modulator of AD risk. Here, we sought to identify ABI3 isoforms expressed in human AD and non-AD brain, quantify the more abundant isoforms as a function of AD genetics and neuropathology, and provide an initial in vitro characterization of the proteins produced by these novel isoforms. We report that ABI3 expression is increased with AD neuropathology but not associated with AD genetics. Single-cell RNAseq of APP/PS1 mice showed that Abi3 is primarily expressed by microglia, including disease-associated microglia. In human brain, several novel ABI3 isoforms were identified, including isoforms with partial or complete loss of exon 6. Expression of these isoforms correlated tightly with total ABI3 expression but were not influenced by AD genetics. Lastly, we performed an initial characterization of these isoforms in transfected cells and found that, while full-length ABI3 was expressed in a dispersed punctate fashion within the cytosol, isoforms lacking most or all of exon six tended to form extensive protein aggregates. In summary, ABI3 expression is restricted to microglia, is increased with Alzheimer's neuropathology, and includes several isoforms that display a variable tendency to aggregate when expressed in vitro.

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.

Exogenous Short Chain Fatty Acid Effects in APP/PS1 Mice.

Elucidating the impact of the gut microbiome on Alzheimer's Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and amyloid burden as assessed by histochemistry and MSD ELISA. We report that SCFA treatment increased alpha-diversity and impacted the gut microbiome profile by increasing, in part, the relative abundance of several bacteria that typically produce SCFAs. However, SCFA treatment did not significantly affect behavior. Similarly, SCFAs did not affect cortical or hippocampal astrocyte activation observed in the APP/PS1 mice. Lastly, although robust levels of soluble and insoluble amyloid were present in the APP/PS1 mice, SCFA treatment had no effect on these indices. Overall, our findings are that SCFA treatment modifies the microbiome in a fashion that may increase further SCFA production. However, SCFA treatment did not alter behavior, astrocyte activation, nor amyloid neuropathology in APP/PS1 mice maintained with a conventional microbiome.

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.

An Alternatively Spliced TREM2 Isoform Lacking the Ligand Binding Domain is Expressed in Human Brain.

BACKGROUND: Genetic variants in TREM2 are strongly associated with Alzheimer's disease (AD) risk but alternative splicing in TREM2 transcripts has not been comprehensively described. OBJECTIVE: Recognizing that alternative splice variants can result in reduced gene expression and/or altered function, we sought to fully characterize splice variation in TREM2. METHODS: Human anterior cingulate autopsy tissue from 61 donors was used for end-point and quantitative PCR and western blotting to identify and quantify novel TREM2 isoforms. RESULTS: In addition to previously described transcripts lacking exon 3 or exon 4, or retaining part of intron 3, we identified novel isoforms lacking exon 2, along with isoforms lacking multiple exons. Isoforms lacking exon 2 were predominant at approximately 10% of TREM2 mRNA in the brain. Expression of TREM2 and frequency of exon 2 skipping did not differ between AD samples and non-AD controls (p = 0.1268 and p = 0.4909, respectively). Further, these novel splice isoforms were also observed across multiple tissues with similar frequency (range 5.3 -13.0%). We found that the exon 2 skipped isoform D2-TREM2 is translated to protein and localizes similarly to full-length TREM2 protein, that both proteins are primarily retained in the Golgi complex, and that D2-TREM2 is expressed in AD and non-AD brain. CONCLUSION: Since the TREM2 ligand binding domain is encoded by exon 2, and skipping this exon retains reading frame while conserving localization, we hypothesize that D2-TREM2 acts as an inhibitor of TREM2 and targeting TREM2 splicing may be a novel therapeutic pathway for AD.

County social isolation and opioid use disorder among older adults: A longitudinal analysis of Medicare data, 2013-2018.

This study aims to fill three knowledge gaps: (1) unclear role of ecological factors in shaping older adults' risk of opioid use disorder (OUD), (2) a lack of longitudinal perspective in OUD research among older adults, and (3) underexplored racial/ethnic differences in the determinants of OUD in older populations. This study estimates the effects of county-level social isolation, concentrated disadvantage, and income inequality on older adults' risk of OUD using longitudinal data analysis. We merged the 2013-2018 Medicare population (aged 65+) data to the American Community Survey 5-year county-level estimates to create a person-year dataset (N = 47,291,217 person-years) and used conditional logit fixed-effects modeling to test whether changes in individual- and county-level covariates alter older adults' risk of OUD. Moreover, we conducted race/ethnicity-specific models to compare how these associations vary across racial/ethnic groups. At the county-level, a one-unit increase in social isolation (mean = -0.197, SD = 0.511) increased the risk of OUD by 5.5 percent (OR = 1.055; 95% CI = [1.018, 1.094]) and a one-percentage-point increase in the working population employed in primary industry decreases the risk of OUD by 1 percent (OR = 0.990; 95% CI = [0.985, 0.996]). At the individual-level, increases in the Medicare Hierarchical Condition Categories risk score, physical comorbidity, and mental comorbidity all elevate the risk of OUD. The relationship between county-level social isolation and OUD is driven by non-Hispanic whites, while Hispanic beneficiaries are less sensitive to the changes in county-level factors than any other racial ethnic groups. Between 2013 and 2018, US older adults' risk of OUD was associated with both ecological and individual factors, which carries implications for intervention. Further research is needed to understand why associations of individual factors with OUD are comparable across racial/ethnic groups, but county-level social isolation is only associated with OUD among non-Hispanic white beneficiaries.

Older adults' physical activity-related social control and social support in the context of personal norms.

This study investigated whether perceived physical activity norms moderated the effects of physical activity-related social interactions on intentions to engage in physical activity among community-residing older adults (N = 217). Structural equation modeling tested whether two types of social support and social control interacted with personal norms in predicting intentions to be active. Emotional and informational support were associated with higher intentions, and negative social control was associated with lower intentions to engage in activity. Each of these effects was more prominent in the context of weak personal norms, suggesting future research and interventions should consider joint effects of support and norms.

Isolation and identification of leukocyte populations in intracranial blood collected during mechanical thrombectomy.

Using standard techniques during mechanical thrombectomy, the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (NCT03153683) isolates intracranial arterial blood distal to the thrombus and proximal systemic blood in the carotid artery. We augmented the current protocol to study leukocyte subpopulations both distal and proximal to the thrombus during human stroke (n = 16 patients), and from patients with cerebrovascular disease (CVD) undergoing angiography for unrelated conditions (e.g. carotid artery stenosis; n = 12 patients). We isolated leukocytes for flow cytometry from small volume (<1 mL) intracranial blood and systemic blood (5-10 mL) to identify adaptive and innate leukocyte populations, in addition to platelets and endothelial cells (ECs). Intracranial blood exhibited significant increases in T cell representation and decreases in myeloid/macrophage representation compared to within-patient carotid artery samples. CD4+ T cells and classical dendritic cells were significantly lower than CVD controls and correlated to within-patient edema volume and last known normal. This novel protocol successfully isolates leukocytes from small volume intracranial blood samples of stroke patients at time of mechanical thrombectomy and can be used to confirm preclinical results, as well as identify novel targets for immunotherapies.

Medical views on the death by crucifixion of Jesus Christ.

The death of Jesus Christ remains a pivotal moment in world history and a symbol of love, mercy, and courage across the globe. Yet for centuries, the manner of Jesus' death has remained a subject of controversy in academic and medical circles. Forensic pathologists and clinicians have argued for several hypotheses concerning Jesus' death, including pulmonary embolism, cardiac rupture, suspension trauma, asphyxiation, fatal stab wound, and shock. This article surveys a broad range of medical and other specialist views regarding Jesus' experience on the cross, concluding that asphyxiation or asphyxiation-dominant theories have emerged as the consensus position regarding the cause of Jesus' death. Two features of this article are significant. First, it provides a rich resource of different medical opinions regarding the effects of Jesus' crucifixion. Second, and more importantly, the survey results show that, perhaps less similar to crucifixion in general, there is a growing consensus regarding Jesus' cause of death by medical professionals. A table maps these results, summarizing for those in the medical field as well as historians and theologians what medical professionals consider to be the cause of Jesus' death.

Pseudogene-Mediated Gene Conversion After CRISPR-Cas9 Editing Demonstrated by Partial CD33 Conversion with SIGLEC22P.

Although gene editing workflows typically consider the possibility of off-target editing, pseudogene-directed homology repair has not, to our knowledge, been reported previously. Here, we employed a CRISPR-Cas9 strategy for targeted excision of exon 2 in CD33 in U937 human monocyte cell line. Candidate clonal cell lines were screened by using a clinically relevant antibody known to label the IgV domain encoded by exon 2 (P67.6, gemtuzumab). In addition to the anticipated deletion of exon 2, we also found unexpected P67.6-negative cell lines, which had apparently retained CD33 exon 2. Sequencing revealed that these lines underwent gene conversion from the nearby SIGLEC22P pseudogene during homology repair that resulted in three missense mutations relative to CD33. Ectopic expression studies confirmed that the P67.6 epitope is dependent upon these amino acids. In summation, we report that pseudogene-directed homology repair can lead to aberrant CRISPR gene editing.

Analysis of Genetic Variants Associated with Levels of Immune Modulating Proteins for Impact on Alzheimer's Disease Risk Reveal a Potential Role for SIGLEC14.

Genome-wide association studies (GWAS) have identified immune-related genes as risk factors for Alzheimer's disease (AD), including TREM2 and CD33, frequently passing a stringent false-discovery rate. These genes either encode or signal through immunomodulatory tyrosine-phosphorylated inhibitory motifs (ITIMs) or activation motifs (ITAMs) and govern processes critical to AD pathology, such as inflammation and amyloid phagocytosis. To investigate whether additional ITIM and ITAM-containing family members may contribute to AD risk and be overlooked due to the stringent multiple testing in GWAS, we combined protein quantitative trait loci (pQTL) data from a recent plasma proteomics study with AD associations in a recent GWAS. We found that pQTLs for genes encoding ITIM/ITAM family members were more frequently associated with AD than those for non-ITIM/ITAM genes. Further testing of one family member, SIGLEC14 which encodes an ITAM, uncovered substantial copy number variations, identified an SNP as a proxy for gene deletion, and found that gene expression correlates significantly with gene deletion. We also found that SIGLEC14 deletion increases the expression of SIGLEC5, an ITIM. We conclude that many genes in this ITIM/ITAM family likely impact AD risk, and that complex genetics including copy number variation, opposing function of encoded proteins, and coupled gene expression may mask these AD risk associations at the genome-wide level.

Trends in Opioid Use Disorder Among Older Adults: Analyzing Medicare Data, 2013-2018.

INTRODUCTION: Opioid use disorder has grown rapidly over the years and is a public health crisis in the U.S. Although opioid use disorder is widely studied, relatively little is known about it among older adults. The goal of this study is to gain a better understanding of opioid use disorder among older Medicare beneficiaries over time and across several sociodemographic dimensions. METHODS: Data from the 2013-2018 Centers for Medicare & Medicaid Services Master Beneficiary Summary Files were analyzed in 2020 to examine the trends in opioid use disorder prevalence among Fee-for-Service Medicare beneficiaries aged ≥65 years. Utilizing the overarching opioid use disorder flag, trends in opioid use disorder prevalence were examined for the following sociodemographic dimensions: age, sex, race/ethnicity, and dual eligibility status (i.e., enrolled in both Medicare and Medicaid owing to low income). Chi-square tests were used to compare opioid use disorder prevalence across groups. RESULTS: Since 2013, estimated rates of opioid use disorder among older adults have increased by >3-fold overall in the U.S. Estimated opioid use disorder is more prevalent among the young-old (i.e., ages 65-69 years) beneficiaries than among other older adults, and dually eligible beneficiaries have consistently shared a heavier burden of opioid use disorder than Medicare-only beneficiaries. Regarding race/ethnicity, Blacks and American Indians/Alaskan Natives are more vulnerable to opioid use disorder than other groups. CONCLUSIONS: The descriptive trends between 2013 and 2018 indicate that estimated opioid use disorder prevalence has increased greatly over the study period in all sociodemographic subgroups of older adults, highlighting an urgent challenge for public health professionals and gerontologists.