Burden In Older Adults Research Articles

A multivalent RSV vaccine based on the modified vaccinia Ankara vector shows moderate protection against disease caused by RSV in older adults in a phase 3 clinical study

Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV.Adults aged ≥60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022–2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with ≥3 and ≥ 2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post-vaccination respectively, and SAEs for the entire study period.In total, 18,348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9 % (95 % CI: −16.1; 71.9) against RSV-associated LRTD with ≥3 symptoms, 59.0 % (95 % CI: 34.7; 74.3) against LRTD with ≥2 symptoms, and 48.8 % (95 % CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with ≥3 symptoms since the lower bound of the 95 % CI was below 20 %, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified.MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases.Trial Registration:Clinicaltrials.gov Identifier NCT05238025 (Registered February 14, 2022).

Incidence trends, histological subtypes, and topographical distribution of bladder cancer in Iran: a study based on the Iranian National Cancer Registry during 2006-2015.

Bladder cancer (BCa) is a significant public health concern. This study aimed to analyze the incidence trends, histological subtypes, and topographical distribution of BCa in Iran over a decade. This retrospective registry-based study analyzed data on BCa patients diagnosed between March 20, 2006, and March 20, 2015. Following data quality control, age-standardized incidence rates (ASIRs) were calculated for BCa overall, by sex and histological subtype using the new World Health Organization (WHO) standard population. We identified 51,379 BCa cases (81.97% male) with a mean age of 65.10 ± 14.89 years. The overall ASIR was 8.92 per 100,000 (95% CI: 8.84-9.00). While a modest increase in ASIR was observed overall (8.77 in 2006 to 9.64 in 2015) and among males (14.13 in 2006 to 15.95 in 2015) during the study period, males consistently had a significantly higher ASIR compared to females (approximately 4.5:1 ratio). BCa incidence showed a progressive increase across older age groups, particularly those aged 40-44 to 80-84 years. Urothelial cell carcinoma (UCC) was the most prevalent histological type (ASIR: 8.19 to 7.93), followed by adenocarcinoma (AC; ASIR: 0.13 to 0.11). Squamous cell carcinoma (SCC) displayed a decreasing trend (ASIR: 0.11 to 0.06). Both UCC and AC were more frequent in males (approximately 5 and 3 times higher than females, respectively). Malignant neoplasm of the bladder, unspecified, constituted over 95% of BCa topography classifications. This study identified a modest rise in BCa incidence, with male predominance and a higher burden in older adults. Further investigation into potential risk factors contributing to this increase is warranted.

The Association Between Plasma Amyloid-β 42/40 and Percentage of Semantic Intrusion Errors in Mild Cognitive Impairment.

Semantic intrusion errors (SIEs) are both sensitive and specific to PET amyloid-β (Aβ) burden in older adults with amnestic mild cognitive impairment (aMCI). Plasma Aβ biomarkers including the Aβ42/40 ratio using mass spectrometry are expected to become increasingly valuable in clinical settings. Plasma biomarkers are more clinically informative if linked to cognitive deficits that are salient to Alzheimer's disease (AD). This study included 119 older adults enrolled in the 1Florida Alzheimer's Disease Research Center (ADRC), 45 aMCI participants scored below the established Aβ42/40 ratio cut-off of 0.160 using the Quest AD-Detect™ assay indicating Aβ positivity (Aβ+), while 50 aMCI participants scored above this cut-off indicating Aβ negative status (Aβ-). Additionally, 24 cognitively unimpaired (CU) persons scored above the cut-off of 0.160 (Aβ-). The aMCI plasma Aβ+ group evidenced the greatest percentage of SIEs, followed by the aMCI Aβ-. The CU Aβ- group exhibited the lowest percentage of SIEs. After adjustment for global cognitive impairment, aMCI plasma Aβ+ continued to demonstrate greater SIEs on tests tapping the failure to recover from proactive semantic interference (frPSI) as compared to the aMCI Aβ-group. Using pre-established cut-offs for frPSI impairment, 8.3% of CU Aβ- participants evidenced deficits, compared to 37.8% of aMCI Aβ-, and 74.0% of aMCI Aβ+. SIEs reflecting frPSI were associated with aMCI Aβ+ status based on the Aβ42/40 ratio. Results suggest the importance of SIEs as salient cognitive markers that map onto underlying AD pathology in the blood.

Advancement in the development of mRNA-based vaccines for respiratory viruses.

Acute respiratory infections are the leading cause of death and illness in children under 5 years old and represent a significant burden in older adults. Primarily caused by viruses infecting the lower respiratory tract, symptoms include cough, congestion, and low-grade fever, potentially leading to bronchiolitis and pneumonia. Messenger ribonucleic acid (mRNA)-based vaccines are biopharmaceutical formulations that employ mRNA molecules to induce specific immune responses, facilitating the expression of viral or bacterial antigens and promoting immunization against infectious diseases. Notably, this technology had significant relevance during the COVID-19 pandemic, as these formulations helped to limit SARS-CoV-2 virus infections, hospitalizations, and deaths. Importantly, mRNA vaccines promise to be implemented as new alternatives for fighting other respiratory viruses, such as influenza, human respiratory syncytial virus, and human metapneumovirus. This review article analyzes mRNA-based vaccines' main contributions, perspectives, challenges, and implications against respiratory viruses.

Comprehensive management of polypharmacy in older patients with diabetes

Background: Diabetes mellitus is a complex group of chronic metabolic conditions. The incidence of frailty, sarcopenia, geriatric syndrome, and multiple chronic conditions is high in older patients with diabetes, who often require multiple medications for optimal glucose control and treatment of associated chronic complications. Unfortunately, polypharmacy is associated with a high risk of adverse outcomes, such as hypoglycemia, drug-drug interactions, and an increased socioeconomic burden in older adults with diabetes.Current Concepts: Elderly patients with diabetes are at a high risk for polypharmacy and consequently, a high risk of adverse drug reactions. Polypharmacy is defined as the cumulative use of five or more medications. Comprehensive management and deprescribing are the most important approaches to reduce polypharmacy. Deprescription refers to reduction in or cessation of inappropriate medications.Discussion and Conclusion: Polypharmacy continues to increase the risk of morbidity and mortality among older adults with diabetes. A comprehensive polypharmacy management and deprescription plan is warranted for significant risk reduction in elderly patients with diabetes.

Epidemiology of Cancer in Older Adults: A Systematic Review.

What are the prevalence, incidence and mortality rates of cancer among individuals aged 60 or older on a national, regional, and global scale? What factors affect differences in cancer survival between older and younger adults? The epidemiological literature on cancer in older adults, particularly in low- and middle-income countries (LMICs) and that focusing on the oldest adults, is expanding. These studies consistently show increasing global cancer incidence rates in older populations. Recent research also highlights a widening survival gap between middle-aged and older adults, with the stage at diagnosis being the primary driver. More research is needed to describe the cancer burden in older adults, especially focusing on the oldest population and LMICs, to better understand global healthcare challenges. Additionally, further exploring patient-related, clinical, and tumour-related factors which drive age-related survival differences could improve cancer outcomes in older adults.

Effect of lipid-lowering therapy on carotid plaque burden in older adults

BackgroundLittle is known about the benefits of lipid-lowering medications in those age ≥ 75 years. We assessed the effect of lipid-lowering medications on progression to severe atherosclerosis in patients age > 75. MethodsData was retrospectively obtained from the Stroke Prevention & Atherosclerosis Research Centre, Canada. Atherosclerosis burden was measured as carotid total plaque area (TPA), a powerful predictor of cardiovascular risk. Survival time free of severe atherosclerosis (SFSA) was defined as the period when TPA remained <1.19 cm2. Kaplan–Meier, multiple Cox proportional hazard and hierarchical mixed-effect models were used to determine the effects of lipid-lowering medications on progression to severe atherosclerosis. ResultsIn total 1404 cases (mean age 81 ± 4 years; women 52%) were included. Those taking lipid-lowering medications were more likely to have a history of diabetes and a higher burden of atherosclerosis at baseline. In Kaplan–Meier analysis, the SFSA was significantly longer in those receiving lipid-lowering therapy. In multivariable-adjusted analyses, those not receiving lipid lowering therapy (irrespective of their vascular disease at baseline) were more likely to have TPA > 1.19 cm2 (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.09,0.71). Similar findings were observed in mixed effects models when plaque progression was defined as any change >0.05 cm2 per year (odds ratio (OR):2.17, 95% CI:1.38,3.57). ConclusionLipid-lowering therapy is effective in controlling the burden of atherosclerosis among older adults with and without vascular disease. The measurement of plaque burden can guide selection and follow-up of those who may benefit from treatment.

Muscle Mitochondrial Bioenergetic Capacities Are Associated With Multimorbidity Burden in Older Adults: The Study of Muscle, Mobility and Aging.

The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity. The Study of Muscle, Mobility and Aging (SOMMA) assessed ex vivo muscle mitochondrial energetics in 764 older adults (mean age = 76.4, 56.5% women, and 85.9% non-Hispanic White) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95% CI]) for the likelihood of greater multimorbidity (4 levels: 0 conditions, N = 332; 1 condition, N = 299; 2 conditions, N = 98; or 3+ conditions, N = 35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions. Lower oxidative phosphorylation supported by fatty acids and/or complex I- and II-linked carbohydrates (eg, Max OXPHOSCI+CII) was associated with a greater multimorbidity index score (POR = 1.32 [1.13, 1.54]) and separately with diabetes mellitus (OR = 1.62 [1.26, 2.09]), depressive symptoms (OR = 1.45 [1.04, 2.00]) and possibly chronic kidney disease (OR = 1.57 [0.98, 2.52]) but not significantly with other conditions (eg, cardiac arrhythmia, chronic obstructive pulmonary disease). Lower muscle mitochondrial bioenergetic capacities were associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and are more strongly related to some conditions than others.

Older adults with reduced cerebrovascular reactivity exhibit high white matter hyperintensity burden

Cerebrovascular reactivity (CVR) deficits may contribute to small vessel disease, such as white matter hyperintensities (WMH). Moreover, apolipoprotein-e4 (APOE4) carriers at genetic risk for Alzheimer’s disease exhibit cerebrovascular dysfunction relative to non-carriers. We examined whether older adults, and APOE4 carriers specifically, with diminished CVR would exhibit higher WMH burden. Independently living older adults (N = 125, mean age = 69.2 years; SD = 7.6; 31.2% male) free of dementia or clinical stroke underwent brain MRI to quantify cerebral perfusion during CVR to hypercapnia and hypocapnia and determine WMH volume. Adjusting for age, sex and intracranial volume, hierarchical regression analysis revealed a significant association between whole brain CVR to hypercapnia and WMH overall [B = −.02, 95% CI (-.04, −.008), p =.003] and in APOE4 carriers [B = −.03, 95% CI (-.06, −.009), p =.009]. Findings suggest deficits in cerebral vasodilatory capacity are associated with WMH burden in older adults and future studies are warranted to further delineate the effect of APOE4 on precipitating WMH.

Neuropsychiatric Profiles and Cerebral Amyloid Burden in Adults without Dementia

Plain Language SummaryThis study examines how patients’ and their caregivers’ report of neuropsychiatric symptoms are associated with amyloid burden, of the primary markers of risk for amyloid burden, in older adults without dementia. Amyloid burden was measured using a PET-CT scan, and neuropsychological symptoms were measured with a self-reported and an informant-reported questionnaire. We found that neuropsychiatric symptoms were associated with amyloid burden in older adults without dementia, and these relationships were stronger in older adults with greater cognitive and functional impairment. In particular, caregivers’ report of anxiety, depression, and irritability and patients’ report of cognitive concerns were associated with greater amyloid burden. Neuropsychiatric symptoms, observed by both the patient and the informant, may be promising first identifiers of the neuropathology associated with Alzheimer’s disease and related dementias. Although neuropsychiatric symptoms have been characterized in persons with dementia, we do not yet have a clear understanding of how neuropsychiatric symptoms appear in non-dementia stages or which instruments may be the most sensitive screening tools for neuropsychiatric symptoms in older adults without dementia. These older adults without dementia may exist in a window of opportunity for behavioral and pharmacologic interventions that may prevent or slow clinical progression.

Modelling the Public Health Burden of Herpes Zoster and the Impact of Adjuvanted Recombinant Zoster Vaccine in Five Selected Countries in Southeast Asia.

Herpes zoster (HZ) can cause substantial patient morbidity and lead to large healthcare costs. However, the disease burden of HZ in Southeast Asia may be underestimated. This study aimed to estimate the public health burden of HZ and the impact of vaccinating adults aged ≥ 50years old in five Southeast Asian countries (Indonesia, Malaysia, Philippines, Thailand, and Vietnam), with adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination. For each country, we adapted a static multicohort Markov model developed with a 1-year cycle length and lifetime horizon. Demographics were obtained from the World Health Organization, HZ incidence from a worldwide meta-regression reporting Asian-specific values, proportions of postherpetic neuralgia (PHN) and non-PHN complications from local/regional studies, and vaccine efficacy from a long-term follow-up trial. First-dose coverage and second-dose compliance were assumed to be 30% and 70%, respectively. A one-way deterministic sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness and uncertainty of inputs for each country. Without RZV, it was estimated that there would be a total of approximately 10million HZ cases, 2.1million PHN cases, and 1.4million non-PHN complications in individuals aged ≥ 50years included in the model. Introducing RZV under 30% coverage could avoid approximately 2.2million (22%) HZ cases, almost 500,000 (21%) PHN cases, and around 300,000 (22%) non-PHN complications. OWSA showed that first-dose coverage and initial HZ incidence had the largest impact on the estimated number of HZ cases avoided. The number needed to vaccinate ranged from 15 to 21 to prevent one case of HZ and from 68 to 104 to prevent one case of PHN across each country. This study demonstrated that there is substantial HZ disease burden in older adults for the five selected countries in Southeast Asia, negatively impacting national healthcare systems. Introducing RZV could potentially reduce this burden. A graphical abstract is available with this article.

Prevalence and association of HIV and tuberculosis status in older adults in South Africa: an urgent need to escalate the scientific and political attention to aging and health.

This study examined the prevalence and sociodemographic factors among older adults with HIV and TB status in South Africa. This data was cross-sectional and obtained from the 2019 General Household Surveys in South Africa. Adults 50 years and over with reported HIV and TB status were included (N = 9,180,047). We reported statistical analyses of the descriptive, Chi-square and Fisher's exact tests, and binary logistic regression. The study has found a prevalence rate of HIV to be 5.3% and TB to be 2.9% among older adults aged 50 years and above in South Africa. However, the study found HIV and TB to be highest among older adults residing in Gauteng, KwaZulu-Natal and Eastern Cape provinces. For HIV status, the female gender [AOR = 0.80*, CI 95% = 0.80-0.80] and secondary education [AOR = 0.57, CI 95% = 0.56-0.58] have lower odds of association among older adults with HIV. Regarding TB status, primary education [AOR = 1.08*, CI 95% = 1.06-1.10] and diabetes [AOR = 1.87*, CI 95% = 1.82-1.91] have lower likelihoods of associations among older adults with TB. There is an urgent need to escalate scientific and political attention to address the HIV/TB burden in older adults and, public health policymakers need to take cognizance of the interdependence of inequality, mobility, and behavioural modification among this high-risk population.

Administrative burden in older adults: A look at SNAP

AbstractAn extensive literature has shown that the rules that govern access to social safety net programs create undue administrative burdens for citizens in accessing the programs. In this paper, we contribute to this literature by describing the experience of older adults with one US social safety net program, the Supplemental Nutrition Assistance Program. Our study gathered data from a total of 267 older adults through interviews and focus groups. Many of our respondents had recently experienced several financial, health, and life crises which affected their ability to seek information, memorize important details, and plan adequately. The main finding of the study is that older adults often experience multiple challenges whose effects tend to amplify each other, affecting their decision‐making abilities. The findings suggest that policies that simplify eligibility processes, reduce the amount of paperwork, and minimize the number of client‐caseworker encounters, have the potential to facilitate greater program access.

Safety and Immunogenicity of an mRNA-Based RSV Vaccine Including a 12-Month Booster in a Phase 1 Clinical Trial in Healthy Older Adults.

An mRNA-based respiratory syncytial virus (RSV) vaccine, mRNA-1345, is under clinical investigation to address RSV disease burden in older adults. Based on a randomized, observer-blind, placebo-controlled design, this phase 1 dose-ranging study evaluated the safety, reactogenicity, and immunogenicity of mRNA-1345 in adults aged 65 to 79 years. Participants were randomized to receive 1 dose of mRNA-1345 (12.5, 25, 50, 100, or 200 µg) or placebo and matched mRNA-1345 booster or placebo at 12 months. Overall, 298 participants received the first injection and 247 received the 12-month booster injection. mRNA-1345 was generally well tolerated after both injections, with the most frequently reported solicited adverse reactions being injection site pain, fatigue, headache, arthralgia, and myalgia. Reactogenicity was higher after the booster injection but with severity, time to onset, and duration similar to the first injection. A single mRNA-1345 injection boosted RSV-A and RSV-B neutralizing antibody titers and prefusion F binding antibody (preF bAb) concentrations at 1 month (geometric mean fold rises: RSV-A, 10.2-16.5; RSV-B, 5.3-12.5; preF bAb, 7.2-12.1). RSV antibody levels remained above baseline through 12 months, indicating immune persistence. A 12-month booster injection also increased RSV-A and RSV-B neutralizing antibody titers and preF bAb concentrations; titers after booster injection were numerically lower than those after the first dose, with overlapping 95% CIs. mRNA-1345 was well tolerated and immunogenic following a single injection and a 12-month booster. NCT04528719 (ClinicalTrials.gov).

Abstract WP122: Statins May Increase White Matter Hyperintensity Burden in Older Adults: A Systematic Review and Meta-Analysis

Introduction: White matter hyperintensities (WMH) are a hallmark radiographic finding of cerebral microangiopathy. Longitudinal studies have shown varying effects of statins on accrual of WMH over time. We aimed to understand the impact of statins on WMH volume over time through a systematic review and meta-analysis. Methods: We performed a systematic review using standard search and risk of bias assessment practices. We included statin-exposed and statin-naive adults with longitudinal brain MRIs with computer-generated WMH volumetric analyses. The primary outcome was change in WMH volume (mL). Allowing for curvilinear change, a mixed-effects model was applied to capture the dynamic change over time. Model forecasts were used to visualize results, comparing changes over time among younger cohorts (60 years) and older cohorts (75 years) based on the the cohort mean age standard deviation. A p value ≤ 0.05 was considered significant. Results: We identified 6 studies enrolling 1911 participants from China, Europe, and North America (2 studies each); mean age 67.5 (± 7.5). The maximal study duration was 60-months. All studies had a least some degree of bias. Control groups had steady increase in WMH volume over time, Figures. The younger statin-exposed cohort developed statistically less WMH after 40 months of use. Older statin exposed patients had an increase in WMH volume compared with naïve patients which remained over the study duration. Conclusion: The impact of statins on WMH volume may be age dependent whereby older patients may have an accelerated accumulation. Further studies are warranted to confirm this data and investigate underlying mechanisms leading to this finding.

Disentangling drug contributions: anticholinergic burden in older adults linked to individual medications: a cross-sectional population-based study

BackgroundMedications with potent anticholinergic properties have well-documented adverse effects. A high cumulative anticholinergic burden may arise from the concurrent use of multiple medications with weaker anticholinergic effects. We sought to identify patterns of high anticholinergic burden and associated patient characteristics.MethodsWe identified patients aged ≥ 65 who filled ≥ 1 medication with anticholinergic adverse effects in 2019 and had a cumulative Anticholinergic Burden score (ACB) ≥ 4 (i.e., high anticholinergic burden) in a large US health insurer. We classified patients based on how they attained high burden, as follows: 1) only filling strong or moderate anticholinergic medications (i.e., ACB = 2 or 3, “moderate/strong”), 2) only filling lightly anticholinergic medications (i.e., ACB = 1, “light/possible”), and 3) filling any combination (“mix”). We used multinomial logistic regression to assess the association between measured patient characteristics and membership in the three anticholinergic burden classifications, using the moderate/strong group as the referent.ResultsIn total, 83,286 eligible patients with high anticholinergic burden were identified (mean age: 74.3 years (SD:7.1), 72.9% female). Of these, 4.5% filled only strong/moderate anticholinergics, 4.3% filled only light/possible anticholinergics, and the rest filled a mix (91.2%). Within patients in the mixed group, 64.3% of medication fills were for light/possible anticholinergics, while 35.7% were for moderate/strong anticholinergics. Compared with patients in the moderate/strong anticholinergics group, patients filling only light/possible anticholinergics were more likely to be older (adjusted Odds Ratio [aOR] per 1-unit of age: 1.06, 95%CI: 1.05–1.07), less likely to be female (aOR: 0.56, 95%CI: 0.50–0.62 vs. male), more likely to have comorbidities (e.g., heart failure aOR: 3.18, 95%CI: 2.70–3.74 or depression aOR: 1.20, 95%CI: 1.09–1.33 vs. no comorbidity), and visited fewer physicians (aOR per 1-unit of change: 0.98, 95%CI: 0.97–0.98). Patients in the mixed group were older (aOR per 1-unit of age: 1.02, 95%CI: 1.02–1.03) and less likely to be female (aOR: 0.89, 95%CI: 0.82–0.97 vs. male) compared with those filling moderate/strong anticholinergics.ConclusionMost older adults accumulated high anticholinergic burden through a combination of light/possible and moderate/strong anticholinergics rather than moderate/strong anticholinergics, with light/possible anticholinergics being the major drivers of overall anticholinergic burden. These insights may inform interventions to improve prescribing in older adults.

Concomitant Administration of Ad26.RSV.preF/RSV preF Protein Vaccine and High-Dose Influenza Vaccine in Adults 65 Years and Older: A Noninferiority Trial.

Since influenza and respiratory syncytial virus (RSV) carry significant burden in older adults with overlapping seasonality, vaccines for both pathogens would ideally be coadministered in this population. Here we evaluate the immunogenicity and safety of concomitant administration of Ad26.RSV.preF/RSV preF protein and high-dose seasonal influenza vaccine (Fluzone-HD) in adults ≥65 years old. Participants were randomized 1:1 to the Coadministration or Control group. The Coadministration group received concomitant Ad26.RSV.preF/RSV preF protein and Fluzone-HD on day 1 and placebo on day 29, while the Control group received Fluzone-HD and placebo on day 1 and Ad26.RSV.preF/RSV preF protein on day 29. Influenza hemagglutination-inhibiting and RSV preF-binding antibody titers were measured postvaccination and tested for noninferiority between both groups. Safety data were collected throughout the study and analyzed descriptively. Coadministered Ad26.RSV.preF/RSV preF protein and Fluzone-HD vaccines induced noninferior immune responses compared to each vaccine administered alone. Seroconversion and seroprotection rates against influenza were similar between groups. Both vaccines remained well tolerated upon concomitant administration. Coadministration of Ad26.RSV.preF/RSV preF protein and Fluzone-HD showed an acceptable safety profile and did not hamper the immunogenicity of either vaccine, thus supporting that both vaccines can be concomitantly administered in adults ≥65 years old.

POLYPHARMACY AND THE SYMPTOM EXPERIENCE OF OLDER ADULTS WITH AND WITHOUT ALZHEIMER’S DISEASE AND RELATED DEMENTIAS

Abstract Older adults, including those living with Alzheimer’s disease and related dementias (ADRD), experience polypharmacy (PPY) (&amp;gt;5 medications daily) due to multiple chronic conditions. High symptom burden in older adults with ADRD and multimorbidity is well known. However, there is a gap in knowledge regarding symptoms experienced by older adults with and without ADRD who experience PPY. To address this gap, we conducted a longitudinal case-control observational study utilizing Rounds 6 to 9 (2016 to 2019) of the National Health and Aging Trends Study (NHATS) datasets. PPY was categorized by the number of medications from Round 6. We categorized individuals into four groups based on presence of ADRD and/or PPY (PPY and ADRD, PPY only, ADRD only, no PPY/ADRD) (N=2052). We identified symptoms associated with PPY (hopelessness, anxiety, general pain, stomach pain, breathing problems, weight loss, balance problems, fatigue, insomnia) in each group over each time point. Among those with ADRD (11.8%), over half experienced PPY (52.3%). Older adults with PPY and ADRD experienced a mean of 4.85 symptoms over all time points compared to 3.52 (ADRD only), 2.79 (no PPY/ADRD) and 3.93 (PPY only) (p=&amp;lt;0.001). Symptom frequencies in the PPY and ADRD group remained higher than all other groups across all four time points. Understanding the impact of medications on older adult’s quality life is a goal of the 4Ms framework. Future research will examine the symptoms associated with PPY and ADRD, physical function and health outcomes to inform medication management for older adults with dementia.

"It's Incapacitated Me in so Many Ways": Older Adults' Lived Experience With Postoperative Symptoms at Home After Major Elective Surgery.

This qualitative study aimed to explore the challenges faced by older adults regarding the postoperative symptom experience after major elective surgery. Although extensively studied in oncology settings, the impact of postoperative symptom burden remains largely underexplored in elective major surgery among older adults. We employed convenience sampling to recruit adults aged 65 years or above undergoing major elective surgery at the University of California, San Francisco. Semistructured interviews regarding the surgical experience were conducted at 1 and 3 months postoperatively. An inductive qualitative approach was used to identify emerging themes. Symptoms revealed by participants during interviews were also captured. Nineteen participants completed a 1-month postoperative interview, and 17 additionally completed a 3-month interview. Three themes emerged: (1) postoperative symptoms significantly impacted valued life activities and psychosocial well-being, (2) participants felt "caught off guard" by the intensity and duration of postoperative symptoms, and (3) participants expressed the need for additional support, resources, and education on symptom management. The most frequently mentioned symptoms were postoperative pain (n=12, 63.1%), gastrointestinal discomfort (n=8, 42.1%), and anxiety/stress (n=8, 42.1%) at 1-month postsurgery compared with pain and depression (both n=6, 35.3%) at 3 months. Study participants were surprised by the negative impact of postoperative symptoms on their psychosocial well-being and ability to engage in valued life activities. Symptom burden is an important patient-reported outcome that should be assessed postoperatively. Interventions to minimize postoperative symptom burden in older adults could optimize quality of life and participation in meaningful activities during surgical recovery.

FC34: Cognitive reserve and depressive burden in older adults: variation according to reserve measurement

Objective:Individual differences in the timing of dementia have been attributed to cognitive reserve (CR), thought to reflect lifelong engagement in stimulating experiences, which provide resilience against brain pathology. In older adults, dementia and depression are closely related, and some studies have linked CR with depression risk in old age. It is unclear if different ways of operationalizing CR exhibit similar association with old-age depression. We examined the association of two measures of CR with depressive burden in older adults: activity-based CR, capturing engagement in stimulating activities using proxy variables, and residual-based CR, indicating residual variance in cognition, not explained by the brain status.Methods:We used data on 354 adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, followed for 15 years. Residual-based reserve was computed from a regression predicting episodic memory with a brain-integrity index incorporating six structural neuroimaging markers (white- matter hyperintensities volume, whole-brain gray matter volume, hippocampal volume, lateral ventricular volume, lacunes, and perivascular spaces), age, and sex. Activity-based reserve incorporated education, work complexity, social network, and leisure activities. Depressive burden was captured over the follow- up with the Montgomery-Åsberg Depression Rating Scale and time until clinically relevant level of symptoms (&gt;6) was modelled using Cox proportional hazard models.Results:Preliminary results indicate that, upon minimal adjustment (age, sex, brain integrity status), top tertiles (ref: bottom tertile) of both activity-based (HR: 0.77; 95% CI: 0.61-0.98) and residual-based CR (HR: 0.62; 95% CI: 0.44-0.98) were associated with a lower risk of depressive burden onset over 15 years. Upon further adjustment for anthropometrics, health behaviors, and chronic disease burden, the association of activity-based CR was attenuated, whereas residual-based CR preserved its effect on depressive burden (HR [fully adjusted model]: 0.59; 95% CI: 0.40-0.88). Next steps include evaluating the ability of reserve measures to attenuate the association of brain integrity with depressive burden using interaction analysis.Conclusion:Preliminary findings suggest that CR may be linked with depression development in older adults, although the association may vary depending on measurement of reserve. Association of activity- based reserve may be attributed to somatic disease pathways.