The impact of climate change on the mental health of the ageing population: a systematic review

Human ageing involves several physiological impairments—in particular, a decrease in sensorimotor function and changes in the nervous system reduce muscle strength, power, balance, and functional capacity performance. Preventive strategies are essential to ensure the quality of life of the elderly. High-speed resistance training (HSRT) may be an effective approach to muscle power development in this population, with significant short-term effects on neural adaptations and muscle power production. Therefore, the present study intends to analyze and systematize the studies focused on HSRT interventions and their effects on health outcomes in independent older adults. Four electronic databases (PubMed, Web of Science, EBSCO, and Scielo) were used for the purposes of searching randomized controlled trials that measured at least one key outcome measure focusing on velocity-based training and health outcomes in older adults on 7 March 2022 and identified 1950 studies. At the end of the process, fourteen studies were included in this systematic review and ten studies were included in the quantitative analysis. The main results showed that HSRT interventions would improve health measures, mostly cognitive function (large effects, p = 0.001, SMD = 0.94), neuromuscular function (moderate effects, p = 0.003, SMD = 0.70), and physical function (moderate effects, p = 0.04, SMD = 0.55 and p = 0.009, SMD = −0.59). Additionally, the results suggested that interventions with ten weeks or more, performed three times a week, provide significant improvements in neuromuscular function. In this sense, HSRT is effective for improving overall health outcomes in older adults. Future studies should include proper follow-ups (e.g., minimum six months) to assess the durability of HSRT intervention effects on all health-related variables.

Loss of muscle mass and strength are associated with long-term adverse health outcomes in older adults. Urine creatinine concentrations (Ucr; mg/dl) are a measure of muscle tissue mass and turnover. This study assessed the associations of a spot Ucr level with muscle mass and with risk of hospitalization, mortality, and diabetes mellitus in older adults. We examined 3424 participants from the Cardiovascular Health Study who provided spot urine samples in 1996-1997 and who were followed through June 2015. All participants underwent baseline measurement of grip strength. In a sub-cohort, 1331 participants underwent dual energy X-ray absorptiometry (DEXA) scans, from which lean muscle mass was derived. Participants were followed for a median of 10 years for hospitalizations and mortality, and 9 years for diabetes mellitus. In linear regression analysis, a one standard deviation higher Ucr concentration (64.6mg/dl) was associated with greater grip strength (kg force) β=0.44 [0.16, 0.72]; p=0.002) and higher lean muscle mass (kg) (β=0.43 [0.08, 0.78]; p=0.02). In Cox regression analyses, each standard deviation greater Ucr concentration was associated with lower rates of hospitalizations (0.94 [95% confidence interval, 0.90, 0.98]; p < 0.001) and lower mortality risk (0.92 [0.88, 0.97]; p < 0.001), while a one standard deviation increase in muscle mass derived from DEXA had no such significant association. Ucr levels were not associated with incident diabetes mellitus risk (0.97 [0.85, 1.11]; p=0.65). A higher spot Ucr concentration was favorably associated with muscle mass and strength and with health outcomes in older community-living adults. The ease of obtaining a spot Ucr makes it an attractive analyte to use for gauging the health of older adults.

e16615 Background: Bladder cancer remains a significant global health burden, particularly in older adults, with its incidence and mortality varying widely across regions. The median age at diagnosis of bladder is 73 years with 80% over the age of 65 in United States. Age of patients can impact management often requiring a multidisciplinary approach. Methods: Incidence rates for individuals aged 70+ across seven superregions (Central, Eastern Europe and Central Asia, High-income countries, North Africa and Middle East, Latin America and Carribean, South Asia, Sub-Saharan Africa, Southeast, East Asia and Oceania) were extracted from the 2021 Global Burden of Disease (GBD) database and analyzed using ARIMA in Stata 18.0 to forecast rates from 2022–2050. Mortality rates were forecasted using the GBD foresight visualization tool. Percentage changes in incidence and mortality compared to 2021 were calculated and analyzed. Results: Bladder cancer incidence rates are projected to increase in North Africa and the Middle East (+6.8% by 2030, +23.0% by 2050), Southeast Asia, East Asia, and Oceania (+5.2% by 2030, +17.0% by 2050), South Asia (+2.0% by 2030, +7.3% by 2050), Latin America and the Caribbean (+1.6% by 2030, +5.2% by 2050), and Sub-Saharan Africa (+1.8% by 2030, +6.5% by 2050). In contrast, High-Income Regions and Central Europe, Eastern Europe, and Central Asia are expected to decline, with High-Income Regions showing the steepest decrease (-10.6% by 2030, -52.0% by 2050). Mortality rates are projected to rise in High-Income Regions (+3.6% by 2030, +18.8% by 2050) andCentral Europe, Eastern Europe, and Central Asia (+3.6% by 2050, despite a -0.9% drop by 2030). Declines by 2030 are anticipated in Latin America and the Caribbean (-2.9%), North Africa and the Middle East (-4.5%), Southeast Asia, East Asia, and Oceania (-3.0%), and Sub-Saharan Africa (-2.9%), though many regions show stabilization or modest increases by 2050, such as South Asia (+7.0%) and Southeast Asia, East Asia, and Oceania (+12.4%). Conclusions: The study underscores the need for greater emphasis on regions in Asia and Africa expected to see an increase in incidence rates. The increase in mortality in many regions call for greater research in geriatric oncology and targeted interventions in older adults. Incidence rate (per 100,000 population) Mortality rates (per 100,000 population) Region 2021 2030 2050 2021 2030 2050 Central Europe, Eastern Europe, and Central Asia 64.99 61.28 57.28 39.78 39.41 41.22 High-income countries 110.38 98.67 53.03 48.40 50.13 57.49 Latin America and Caribbean 29.84 30.31 31.38 22.34 21.69 22.31 North Africa and Middle East 68.04 72.69 83.69 34.90 33.33 35.24 South Asia 18.75 19.14 20.13 15.39 15.26 16.47 Southeast Asia, East Asia and Oceania 40.60 42.71 47.49 24.02 23.30 27.01 Sub-Saharan Africa 26.57 27.06 28.31 23.64 22.96 22.90

As the population is aging, the prevalence of age-related cognitive decline is now the highest in history, with a long-term trend of increase. Many studies have examined whether cognitive training (CT) is an effective intervention for preventing and slowing down the neurodegenerative processes of aging so as to enable independent functioning and active living in older age. In order to summarize the available data, we conducted a systematic literature overview of meta-analyses investigating the efficacy of various CT interventions on cognitive and subjective/functional outcomes in healthy older adults, older adults with mild cognitive impairment, and older adults with subjective memory/cognitive complaints. We searched six databases (Web of Science, Scopus, PsycINFO, MEDLINE, CINAHL, and Cochrane Library) and identified eight eligible meta-analyses. The quality of the included meta-analyses was assessed using the AMSTAR-2 checklist. The confidence ratings were “moderate” for one meta-analysis, “low” for two meta-analyses, and “critically low” for five meta-analyses. Although there is a need for better methodological standards for meta-analyses, the available evidence suggests that CT is an effective intervention for improving both cognitive and subjective/functional outcomes in older adults. Future research should be more oriented toward measures that indicate the practical efficiency of CT and should be more specific regarding the type of CT intervention, so as to elucidate the potentially different underlying mechanisms of their functioning.

PRESENCE OF OPTIMISM AND ANTIDEPRESSANT REMISSION RATES IN LATE-LIFE DEPRESSION

MP16-15 DISPARITIES IN INPATIENT CARE AND OUTCOMES FOR OLDER ADULTS WITH INFECTED STONES

e22574 Background: Prostate cancer is the second most common and fifth deadliest cancer in men worldwide, with incidence and mortality rates influenced by regional and economic factors. In older adults, differing physiological conditions impact treatment efficacy and side effects, requiring careful therapeutic planning. Methods: Incidence rates for individuals over 70 years of age for the seven super regions (Central, Eastern Europe and Central Asia, High-income countries, North Africa and Middle East, Latin America and Caribbean, South Asia, Sub-Saharan Africa, Southeast, East Asia and Oceania) were extracted from the 2021 Global Burden of Disease (GBD) database and analyzed using Autoregressive Integrated Moving Average (ARIMA) in Stata 18.0 to forecast incidence rates from 2022-2050. Mortality rates were extracted and forecasted from GBD foresight visualization tool. The total percentage change in incidence and mortality rates were calculated compared to 2021 and presented for each of the seven regions. Results: Most of the super regions are expected to have an increase in the incidence rate in 2030 and 2050 (Central, Eastern Europe and Central Asia: 2030-4.0%, 2050-29.3%, North Africa and Middle East: 2030-14.8%, 2050-49.1%, South Asia: 2030-16.7%, 2050-46.2%, Sub-Saharan Africa: 2030-5.0%, 2050-20.3%, Southeast, East Asia and Oceania: 2030-14.7%, 2050-46.1%). Only Latin America and Caribbean is expected to have a decrease in the incidence rate in 2030 and 2050: 2030- 2.3%, 2050-4.7%.Mortality rates are expected to increase for most of the seven super regions (Central, Eastern Europe and Central Asia: 2030-0.4%, 2050-5.6%, High-income countries: 2030-7.5%, 2050-28.9%, Latin America and Caribbean: 2030-1.1%, 2050-13.4%, South Asia: 2030-7.2%, 2050-27.4%, Sub-Saharan Africa: 2030-2.2%, 2050-14.2%, Southeast, East Asia and Oceania: 2030-5.6%, 2050-42.2%). Mortality rate in North Africa and Middle East is expected to decrease in 2030-3.9% and then increase in 2050-7.1%. Conclusions: Forecast trends indicate rising prostate cancer incidence in high-income countries, except Latin America and the Caribbean. The highest increase is expected in North Africa and the Middle East. Mortality rates are also projected to rise globally, emphasizing the need for enhanced treatment research for the elderly. Incidence rate per 100,000 population Mortality rate per 100,000 population Super regions 2021 2030 2050 2021 2030 2050 Central Europe, Eastern Europe, and Central Asia 453.2 471.4 585.9 229.7 231.0 243.2 Southeast Asia, East Asia, and Oceania 115.2 132.1 167.9 71.0 74.4 100.9 North Africa and Middle East 271.1 310.8 403.6 128.0 123.4 136.8 Sub-Saharan Africa 360.5 378.2 433.1 355.5 363.2 405.5 South Asia 78.3 90.9 114.3 69.7 74.7 88.8 High-income countries 641.9 646.8 649.3 221. 4 237.9 284.8 Latin America and Caribbean 554.3 541.3 528.1 290.8 293.3 329.9

INTRODUCTION: Hepatocellular carcinoma (HCC) incidence rates are increasing among older adults in the U.S. Age-related disparities in prognosis and treatment receipt have been described in other cancers; however, there are limited data examining outcomes in older adults with HCC. Our study's aim was to evaluate age-related differences in HCC treatment receipt and prognosis. METHODS: We performed a retrospective study of patients diagnosed with HCC between 2008 and 2017 at 2 U.S. hospital systems. Older and younger adults were defined as ≥65 and &lt;65 years old, respectively. Curative therapy was defined as liver transplantation, surgical resection, or local ablation. We used multivariable logistic regression to identify factors associated with curative treatment receipt and Cox proportional hazard models to identify factors associated with overall survival (OS). RESULTS: Of 1110 patients with HCC, 261 (23.5%) were ≥65 and 849 (76.5%) were &lt;65 years old; the cohort was racially/ethnically diverse (33.3% white, 32.4% black, 27.5% Hispanic). A higher proportion of older adults had non-viral cirrhosis compared to younger adults (46.1% vs 21.8%, P &lt; 0.001). A similar proportion of HCC were detected by surveillance in both groups (41.0% vs 40.0%, P = 0.80), but a higher proportion of older adults presented with early stage HCC (BCLC 0/A; 44.8% vs 40.6%, P &lt; 0.001) compared to younger adults; further, a higher proportion of older adults had Child A cirrhosis (61.1% vs 43.4%, P &lt; 0.001) compared to younger adults. Among treated patients (n = 750), older adults were more likely to receive curative therapy (OR 1.71, 95% CI 1.06–2.77) even after adjusting for sex, race, Child Pugh score, BCLC stage and ECOG performance status; there was no significant difference in complete response rates (31.0% vs 28.9%, P = 0.58) between older and younger adults. Among those who received curative therapy, median OS was significantly lower among older compared to younger adults (37.9 vs 57.5 months, P = 0.04) while survival was similar among older and younger adults receiving palliative HCC therapy (12.6 vs 12.2 months, P = 0.46) and best supportive care (1.6 vs 2.4 months, P = 0.05). Older adults had higher mortality than younger adults (HR 1.28, 95%CI 1.05–1.56) after adjusting for sex, race, Child Pugh score, BCLC stage and ECOG performance status. CONCLUSION: Despite being more likely than younger adults to receive curative treatment, older adults with HCC had worse overall survival, independent of BCLC stage or cirrhosis severity.

BackgroundDiscrimination and persecution (henceforth persecution) can affect socioeconomic status (SES) and health. Central and Eastern Europe (CEE) has a history of war and political instability that has contributed to persecution of various groups across generations. We examine its association with memory and health outcomes in older adults across CEE, an area that remains understudied.MethodsWe analyzed data from 21,989 participants (59% female; mean age 67 years) in 11 CEE countries from wave 7 of the Survey of Health, Ageing, and Retirement in Europe. A self-reported index captured intergenerational persecution with four levels: 0) none, 1) parental only, 2) personal only, 3) both. Outcomes were memory (z-score of immediate and delayed recall), cardiovascular disease (CVD, defined by diagnoses), poor or fair self-reported health (SRH), and chronic disease count. We fitted linear or logistic regression models adjusting for age, sex, region, birth cohort, and childhood SES.Results37% of participants reported experiences of persecution (23% parental only; 6% personal only; 8% both). CVD, poor SRH, and chronic disease count showed a dose-response relationship, where both personal and parental exposure were associated with the worst outcomes (OR 1.2, 95% CI 1.15-1.5 for CVD; OR 1.43, 95% CI 1.32-1.67 for poor SRH; β = 0.48, 95% CI 0.42-0.57 for chronic disease count). Experiencing only personal or parental persecution was also linked to worse health, but with a smaller effect. In contrast, experiencing both personal and parental persecution was associated with higher memory scores (β = 0.07 SD, 95% CI 0.03-0.07), while parental only was linked to lower memory scores (β=-0.03 SD, 95% CI -0.06 to -0.001).ConclusionsPersecution, especially when experienced both personally and by one's parents, is associated with poorer physical health and presents complex associations with memory in older adults in CEE.Key messages• Over one-third of older adults in CEE reported persecution, highlighting its widespread reach across the region.• Parental exposure to persecution is linked to worse physical and cognitive health in older adults across CEE, with a dose-response for physical health outcomes.

While the role of diet and nutrition in cognitive health and prevention of dementia in older adults has attracted much attention, the efficacy of different dietary patterns remains uncertain. Previous reviews have mainly focused on the Mediterranean diet, but either omitted other dietary patterns, lacked more recent studies, were based on cross-sectional studies, or combined older and younger populations. We followed PRISMA guidelines, and examined the efficacy of current research from randomized controlled trials and cohort studies on the effects of different dietary patterns. We reviewed the Mediterranean diet, Dietary Approach to Stop Hypertension (DASH) diet, the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diet, Anti-inflammatory diet, Healthy diet recommended by guidelines via dietary index, or Prudent healthy diets generated via statistical approaches, and their impact on cognitive health among older adults. Of 38 studies, the Mediterranean diet was the most investigated with evidence supporting protection against cognitive decline among older adults. Evidence from other dietary patterns such as the MIND, DASH, Anti-inflammatory, and Prudent healthy diets was more limited but showed promising results, especially for those at risk of cardiovascular disease. Overall, this review found positive effects of dietary patterns including the Mediterranean, DASH, MIND, and Anti-inflammatory diets on cognitive health outcomes in older adults. These dietary patterns are plant-based, rich in poly- and mono-unsaturated fatty acids with lower consumption of processed foods. Better understanding of the underlying mechanisms and effectiveness is needed to develop comprehensive and practical dietary recommendations against age-related cognitive decline among older adult.

Although many factors have been associated with mobility among older adults, there is paucity of research that explores the complexity of factors that influence mobility. This review aims to synthesise the available evidence for factors comprising the cognitive, psychological, and social mobility determinants and their associations with mobility self-reported and performance-based outcomes in older adults (60 years). We followed Arksey and O'Malley's five stages of a scoping review and searched PubMed, EMBASE, PsychINFO, Web of Science, AgeLine, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature and Sociological Abstract databases. Reviewers in pairs independently conducted title, abstract, full-text screening and data extraction. We reported associations by analyses rather than articles because articles reported multiple associations for factors and several mobility outcomes. Associations were categorised as significantly positive, negative, or not significant. We included 183 peer-reviewed articles published in 27 countries, most of which were cross-sectional studies and conducted among community-dwelling older adults. The 183 articles reported 630 analyses, of which 381 (60.5%) were significantly associated with mobility outcomes in the expected direction. For example, older adults with higher cognitive functioning such as better executive functioning had better mobility outcomes (e.g., faster gait speed), and those with poor psychological outcomes, such as depressive symptoms, or social outcomes such as reduced social network, had poorer mobility outcomes (e.g., slower gait speed) compared to their counterparts. Studies exploring the association between cognitive factors, personality (a psychological factor) and self-reported mobility outcomes (e.g., walking for transportation or driving), and social factors and performance-based mobility outcomes in older adults are limited. Understanding the additive relationships between cognitive, psychological, and social factors highlights the complexity of older adults' mobility across different forms of mobility, including independence, use of assistive devices, transportation, and driving.

To quantify the effects of melatonin on total sleep time and global cognition, and to examine secondary outcomes (sleep efficiency, circadian markers, neuropsychiatric symptoms, depression, activities of daily living) in older adults with cognitive impairment. Systematic review and meta-analysis of randomised controlled trials (PROSPERO CRD42024539227). PubMed, PsycINFO (via EBSCOhost), CINAHL Plus, Cochrane Library, Web of Science, to October 2024. Randomised controlled trials (RCTs) comparing melatonin versus placebo in adults ≥65years with mild cognitive impairment or dementia. Two reviewers extracted data; risk of bias was assessed by RoB 2. Random-effects models estimated Hedges' g and mean differences (MD), with Benjamini-Hochberg false discovery rate (FDR) correction for multiple outcomes. Heterogeneity assessed via I2; publication bias via Egger's test. Ten RCTs (n = 516) were included. Melatonin increased total sleep time by MD +12.4min (95% CI 8.1-16.7; P < .001; I2= 72%; g = 0.42) and improved Mini-Mental State Examination scores by MD +1.8 points (95% CI 0.9-2.7; P = .002; I2= 65%; g = 0.47). Neuropsychiatric symptoms decreased (g = -0.23; 95% CI -0.44 to -0.03; P = .02). Effects on sleep efficiency, circadian markers, depression and activities of daily living were small and nonsignificant. Melatonin yields modest improvements in sleep duration and cognition that approach clinically important thresholds but fall short of definitive efficacy. Larger, rigorously designed RCTs with harmonised outcomes and pre-specified primary endpoints are needed to confirm these findings.

The Physical Activity Guidelines for Americans (Guidelines) advises older adults to be as active as possible. Yet, despite the well documented benefits of physical activity just 12.8% of those ages 65 and older meet the Guidelines. To address this, the U.S. Department of Health and Human Services (HHS) developed a Midcourse Report focused on effective strategies to improve older adult physical activity behaviors. The first step in this process was a systematic literature review. A literature review team was contracted to examine the evidence on key settings and effective behavioral intervention strategies, as well as effective policy, systems, and environmental (PSE) approaches, to improve physical activity among older adults. The PSE search employed an equity-centered framework adapted to researching PSE approaches for improving physical activity outcomes in older adults. Sixteen thousand eight hundred and eighty-three titles and abstracts were screened, and 734 full articles were reviewed for inclusion. Of those, 64 original research articles were included for the final review to answer two questions, one (plus 5 sub-questions) focused on Settings/Strategies literature (45 studies) and one (plus 2 sub-questions) focused on PSE literature (19 studies). The literature review process identified key settings and evidence-based strategies to support older adults in becoming more physically active, and provides a foundation for the Physical Activity Guidelines for Americans Midcourse Report: Implementation Strategies for Older Adults. More research is needed to address how factors related to equity and psychosocial constructs influence physical activity behaviors among older adults.

Bacteremia is an increasingly common cause of hospitalization and mortality in the United States. Annual rates of bacteremia increased from 83 cases per 100,000 persons in 1979 to 240 cases per 100,000 persons in 2000,1 primarily because of disproportionate increases in bacteremia rates in persons aged 65 and older.2 Adults aged 65 and older consistently experience higher morbidity and mortality than individuals younger than 65.3, 4 Whether age remains a linear predictor of poor outcomes in persons aged 65 and older is less clear.2, 5, 6 A study of 1,740 episodes of bacteremia in France found that mortality rates did not differ between adults aged 65 to 75 (young-old), 76 to 85 (old), or 85 and older (old-old) except in the subset of individuals with catheter-related bacteremia, in which the mortality rate was approximately 5% greater in old-old than young-old individuals.5 In contrast, a longitudinal study of bacteremic outcomes in the United States found that bacteremia case-fatality rates increased linearly across age deciles.2 The association between advancing age and negative outcomes in persons with bacteremia will probably not surprise most clinicians. Nevertheless, confirmation of this rather obvious association in the studies cited above begs a more fundamental question. What aspects of aging drive negative outcomes in persons with bacteremia? Although there may be intrinsic aspects of aging, such as immunosenescence7 and increasing frailty due to oxidative stress,8 that influence negative outcomes, it is more likely that age is acting as a proxy for a number of related conditions that directly or indirectly influence outcome (Figure 1). Some have suggested that age-related increases in the frequency and severity of comorbidity are the most likely explanation for the discrepancy in outcomes between older and young adults.2, 6, 9, 10 Most of these studies were small and performed in select populations.6, 9, 10 Moreover, none was designed to enumerate the “residual” effect of age after accounting for age-related increases in comorbidity. Conceptual model of the dimensions of aging that may influence outcomes in persons with bacteremia. The model makes no assumptions about the relative influence of each dimension but does imply that they are all, to some extent, related to one another. In this issue of the Journal of the American Geriatrics Society, Sogaard et al. present the results of a study that examined short-term mortality in a large population-based cohort of individuals with community-acquired bacteremia in Denmark.11 Not surprisingly, the authors found that older age and greater comorbidity were associated with a higher 30-day mortality rate. Thirty-day mortality rates increased from 11% in patients younger than 65 to 21% in patients aged 80 and older. Likewise, the 30-day mortality rate in patients with low comorbidity was 7% but increased to 23% in patients with high comorbidity. Through a number of different analyses, the authors found that age remained an independent predictor of 30-day mortality after accounting for age-related changes in comorbidity. When stratified according to age and comorbidity, 30-day mortality in patients with the lowest comorbidity increased from 7.3% in persons younger than 65 to 16.5% in persons aged 80 and older. Likewise, 30-day mortality in patients with the highest level of comorbidity increased from 18.3% in persons younger than 65 to 27.2% in persons aged 80 and older. If one is to believe that age is an important predictor of bacteremic outcomes, independent of comorbidity, the methods used to measure comorbidity must be carefully scrutinized. Sogaard et al. measured comorbidity using the Charlson Comorbidity Index.12 The Charlson index is the most commonly used measure of comorbidity in clinical and epidemiological trials and has demonstrated predictive validity for mortality in different patient populations.13 It primarily captures information on the number of diseases an individual has but does not capture a large amount of information on the severity of those medical conditions. This has important implications for research in older adults, because aging is associated not only with an increasing number of comorbidities, but also with greater severity of those conditions. We are not aware of studies that have specifically examined whether the predictive validity of the Charlson index is poorer in persons with advanced age, although combining the Charlson index with other measures of comorbidity can significantly improve the predictive validity of models based on it,14 suggesting that it is an imperfect measure. Perhaps even more important, even assuming that it can measure medical conditions with reasonable accuracy in older adults, the Charlson index fails to capture important information on functional status. A number of studies have found that inclusion of functional status measures significantly improves the predictive validity of models based on the Charlson index.15, 16 This suggests that there are features of functional status—including physical and cognitive functioning—that are independent of comorbidity or reflect dimensions of comorbidity not adequately captured by the Charlson index. Future studies on outcomes in aging should seek to identify and incorporate more-rigorous instruments to measure comorbidity if we are to gain greater confidence in their ability to control for this important confounder. These instruments should not only measure the number and severity of medical conditions, but also provide an assessment of functional status.8 The authors of the current study are to be commended for moving beyond simple descriptions of the association between age and bacteremic outcomes. The next step is to more closely examine which aspects of aging, after accounting for comorbidity, influence negative outcomes in older adults with bacteremia. For example, aging is associated with well-described changes in adaptive humoral and cell-mediated immunity,7 as well as abnormal cytokine responses during episodes of septicemia,17 although it is unclear whether these changes are causative risk factors for adverse bacteremic outcomes and, at least for the near future, are not readily amenable to intervention. More likely to be of immediate benefit are interventions that seek to improve the timely initiation of appropriate antimicrobial therapy. Older adults are more likely to present with attenuated or atypical manifestations of infection than younger adults18 and are more likely to develop infection caused by antimicrobial-resistant bacteria.19 In both situations, there is likely to be considerable delay in initiation of antimicrobial therapy with activity against causative microorganisms, which often results in considerable harm to the patient.5, 20, 21 In the current study, rates of inappropriate antimicrobial therapy were greater with older age and greater comorbidity. The authors adjusted for inappropriate antimicrobial therapy in their analyses, although they did not collect information on the time from onset of symptoms to receipt of antimicrobials. As a result, how much the timely initiation of antimicrobial therapy affected the association between aging and bacteremic outcomes was not adequately addressed in the current study. So where do the results of the current study leave us? Despite deficiencies in methods used to measure comorbidity, the current study provides strong evidence that underlying medical conditions do not entirely account for the negative outcomes seen in older adults with bacteremia. The explanation for the “residual” effect of age remains hypothetical and may be due to intrinsic aspects of aging but is more likely due to potentially modifiable determinants of health outcomes such as timely administration of appropriate antimicrobial therapy. More than anything, the current study tells us that it is no longer enough to ask whether but why aging is associated with worse outcomes in persons with bacteremia. Future studies must address this fundamental question head on. Conflict of Interest: None. Author Contributions: Christopher J. Crnich and David R. Zimmerman: preparation of manuscript. Sponsor's Role: Not applicable.

e16481 Background: Gastric cancer is a malignant disease characterized by the uncontrolled growth of cells in the stomach lining. It is a global health concern with regional variation in incidence and prevalence. This study investigates the regional incidence and prevalence of gastric cancer among adults aged 70 and older from 1990 to 2021, utilizing data from 26 global regions. Methods: Global Burden of Disease (GBD) data for 2021 were analyzed to assess regional incidence and prevalence of gastric cancer among adults aged ≥ 70. The Annual Average Percentage Change (AAPC) was calculated to evaluate trends from 1990 to 2021, with statistical significance determined using p-values. Results: In 2021, East Asia has the highest incidence (273403) followed by Middle SDI (189383) and High-middle SDI (176691). Highest Prevalence numbers were recorded for East Asia (398,000) followed by High SDI (337,000) and High-middle SDI (250,000). With regards to rates per 100,000, Oceania has the lowest incidence (257) as well as prevalence (252) followed by Central Sub-Saharan Africa (I:1142 , P: 1081) and Southern Sub-Saharan Africa (I:1295, P: 1227). The largest increase in AAPC of incidence was exhibited by Western Sub Saharan Africa (-0.24, CI: -0.27 to -0.23), Southern Sub Saharan Africa (-0.29, CI: 0.37 to -0.22), and South Asia (-0.306, CI: -0.422 to -0.158) regions, while South Asia (-0.087, CI: -0.1748 to 0.0308), East Asia (-0.0952, CI: 0.0284 to 0.1606), and Andean Latin America (-0.1696, CI: -0.3498 to -0.0381) showed largest increase in AAPC of prevalence. Western Europe region had the greatest decline in AAPC of incidence (-2.3995, CI: -2.4374 to -2.3691) followed by Central Europe (-2.2010, CI: -2.3007 to -2.1445) and Eastern Europe (-2.1554, CI: -2.212 to -2.0925 ) regions while Central Asia had the greatest decline in AAPC of prevalence (-1.9281, CI: -2.0109 to -1.8522) followed by High Income Asia Pacific (-1.8268, CI: -1.8926 to -1.7913) and Eastern Europe (-1.8103, CI: -1.8631 to -1.7623). All AAPC values were statistically significant (p &lt; 0.000001). Conclusions: The East Asia region exhibited the highest incidence and prevalence, highlighting the vulnerability of these populations, while Central Sub-Saharan Africa bore the least burden. Notably, several regions, particularly in Asia, experienced substantial increases in both incidence and prevalence, emphasizing the need for targeted interventions. Conversely, some regions, such as Europe, showed encouraging declines in prevalence, suggesting that effective prevention and control strategies can be implemented. These findings underscore the importance of tailored approaches to address the evolving burden of Gastric Cancer.