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Abstract Background Little is known regarding outcomes for patients prescribed antibiotics on discharge from the hospital to nursing homes (NHs). We quantified the association between suboptimal antibiotic prescribing and clinical outcomes at discharge to NHs. Methods This was a multicenter, retrospective cohort study of adult (age >18 years) patients prescribed systemic antibiotics on discharge from 9 acute care hospitals in Oregon, Washington, and Wisconsin to a NH from 2016 – 2018. Study data were electronically extracted from hospital and NH electronic health records and supplemented with chart review. Suboptimal antibiotic therapy was determined by an infectious disease pharmacist or physician using clinical information (e.g., antibiotic regimen, indication, and culture results) available at discharge. Outcomes included emergency department (ED) visits, hospital readmissions, or Clostridioides difficile infection (CDI) within 30 days of hospital discharge. Comparison of outcomes between patients with suboptimal and non-suboptimal antibiotic therapy were tested by chi-squared tests. Results Among 280 included patients, mean (SD) age was 76.0 (11.5) years, 35.7% (n=100) were male, and median (IQR) inpatient length of stay was 6 (4-9) days. The most prevalent antibiotic indications were urinary tract infections (n =109, 38.9%), lung indications (n=60, 21.4%), and prophylaxis (n=29, 10.4%). Among 317 antibiotic prescriptions, the most frequently prescribed antibiotic classes were cephalosporins (n=83, 29.6%), fluoroquinolones (n=57, 20.4%), and beta-lactam/beta-lactamase-inhibitors (n=40, 14.3%). Fifty-eight patients (20.7%) were prescribed suboptimal antibiotic therapy on hospital discharge. There were no significant differences in the frequency of 30-day ED visits (14% vs 11%, p=0.76) or hospital readmission (19% vs 18%, p=0.94) between patients prescribed and not prescribed suboptimal antibiotics; however, suboptimal antibiotics were significantly associated with CDI within 30 days of discharge (10% vs 2%, p=0.01). Conclusion Suboptimal antibiotic prescribing on discharge to NHs was associated with increased risk of CDI within 30 days of discharge. This finding may inform interventions to improve antibiotic prescribing on discharge to NHs. Disclosures YoungYoon Ham, PharmD, Gilead: Honoraria Jon P. Furuno, PhD, Merck & Co., Inc: Grant/Research Support

Abstract Background Mycobacterium abscessus complex (MABC) is a difficult-to-treat infection due to antibiotic resistance. Our study aimed to assess omadacycline’s (OMC) clinical and microbiological outcomes for the treatment of pulmonary MABC. Methods A retrospective study was carried out across 12 US medical institutions from 1/2018-4/2023 to examine the clinical outcomes, and tolerability of OMC treatment for pulmonary MABC. Patients aged ≥ 18 years who were treated with OMC for ≥ 3 months were included. The primary outcome was clinical success at 3, 6, and 12 months. The secondary outcomes were sputum culture conversion rate, adverse effects, and clinical success by subspecies and macrolide susceptibility. Results Thirty-five patients were included in this analysis. Most patients were female (74.3%) and Caucasian (74.3%), with a median (IQR) age of 61 years (51–70). Subspeciation was performed for 22 isolates with predominant M. abscessus subspecies (77.3%). Moreover, coinfection with other NTM species was present in 28.6% of cases where Mycobacterium avium complex was present in 8 cultures. Sixty-eight percent of the MABC isolates were confirmed to be macrolide resistance; half (12/24, 50.0%) were evident by the presence of functional erm gene, while the other half by antimicrobial susceptibility (Table 3). Of the remaining isolates, 14% were macrolide-susceptible, while no information was reported in 17%. The median (IQR) treatment duration of OMC was 8 months (3.9 – 15.7). The most commonly co-administered antibiotics were intravenous amikacin, imipenem/cilastatin, inhaled amikacin and clofazimine with the same percentage (42.9%) (Table 1). Overall, MABC clinical success was observed in 71.4%, 89.7%, and 90.9% in 3-, 6- and 12 months, respectively (Table 3). Adverse effects reported in 34.3%. The most common side effects were gastrointestinal intolerance (25.7%) and hepatoxicity (11.4%), which led to drug discontinuation in 22.9%. Conclusion OMC treatment showed clinical success in > 70% of patients with pulmonary MABC including patients with macrolide resistant strains for more than 3 months. However, larger studies are needed to validate the outcomes beyond 12 months. Disclosures Kaylee E. Caniff, PharmD, BCIDP, T2Biosystems: Honoraria Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Advisor/Consultant|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Grant/Research Support|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Speaker

662 Background: Alkylating-based chemotherapy (ALK) is one of the main treatments used in patients with advanced pancreatic neuroendocrine tumors (PanNETs). Its use has been associated with an increased risk of grade progression and acquisition of a hypermutator phenotype, associated with frequent alterations of the mismatch repair (MMR) genes. This suggests a potential benefit of immune checkpoint inhibitors (ICI) that are otherwise ineffective in ALK-naïve PanNETs, which are mostly hypomutated. We aimed to describe the efficacy of ICI in patients with advanced PanNET pretreated with ALK. Methods: We assembled an international retrospective cohort of patients with advanced PanNET who received at least one cycle of ICI, and who had previously received at least 3 months of ALK. Patients with poorly-differentiated neuroendocrine carcinoma were excluded. The primary endpoint was progression-free survival (PFS) and the secondary endpoint was the objective response rate (ORR). The impact of tumor mutational burden (TMB, high being defined by >10 mut/Mb) and MMR alterations (mutations or IHC) was explored. Results: We included 39 patients (median age 58.7, male sex 62%). All PanNETs were progressive at baseline and presented a median of 3 (IQR, 2-4) metastatic sites. Tumors were predominantly classified as G2 (47%) or G3 (42%), with a median Ki-67 of 18.5% (IQR, 12-35). 23/27 patients with tumor tissue or ctDNA NGS testing had high TMB (median, 35 mut/Mb; IQR, 24-106) and 12/22 had MMR alterations. Patients had previously received an average of 14 cycles (IQR, 7-25) of ALK (temozolomide 78%, streptozotocin 18%, dacarbazine 4%), which had yielded objective response in 72% of cases. In addition, patients had received a median of 4 (IQR, 3-5) other treatments (including platinum drugs in 80% and PRRT in 51%). ICI mainly consisted in an anti-PDL1/PD1 + anti-CTLA4 combination (85%) or a monotherapy (15%), with a median of 3 (IQR, 2-8) cycles. The ORR was 18% and the disease control rate was 46%. Median PFS was 2.8 months (95% CI, 0.62-4.96) and 6-month PFS rate was 31%. 19% of patients had grade 3-4 toxicity. Patients with high TMB had higher ORR (30% vs. 0%, p=0.03) and longer median PFS (4.9 vs. 2.1 months, p=0.004) compared with patients with low/unknown TMB. Patients with altered MMR had higher ORR (42% vs. 7%, p=0.02) and longer median PFS (8.9 vs. 2.5 months, p=0.014) compared with patients with no/unknown MMR alterations. Conclusions: While ICI shows limited efficacy in unselected patients with advanced PanNETs pretreated with ALK, it may be an effective treatment option in case of high TMB and MMR alterations.

566 Background: Immune checkpoint inhibitors (ICIs) have become the preferred treatment for unresectable hepatocellular carcinoma (HCC). Conflicting data exist regarding the prognostic value of immune-related adverse events (irAEs) in these patients. We aimed to explore potential the association between irAEs and prognosis in HCC patients treated with ICIs. Methods: We searched PubMed, Scopus, Web of Science, and CENTRAL databases for articles published from inception to June 2024 using keywords including ICI, HCC, and irAEs. Two reviewers independently screened studies for eligibility and relevant data. A random effects model was used for statistical analysis, and subgroup analysis was performed by the grade of irAEs. Results: Of 3,028 studies, 25 (n=4,116 patients) met criteria for inclusion. Atezolizumab plus bevacizumab was the most common treatment regimen (n=10 studies). About half (49.5%) of patients experienced irAEs. irAEs were associated with increased objective response rate (ORR) (pooled OR: 1.72; 95% CI: 1.36 – 2.19, I 2 =39%), higher complete response rate (pooled OR: 1.45; 95% CI: 1.21-1.74, I 2 =74%), and longer progression-free survival (PFS) (pooled HR: 0.66; 95% CI: 0.52-0.84, I 2 =71%). Although irAEs were associated with longer overall survival, this difference was not statistically significant (pooled HR: 0.83; 95% CI: 0.62 – 1.11, I 2 =73%). Subgroup analysis showed a survival benefit for patients with grade 1-2 irAEs (pooled HR: 0.50; 95% CI: 0.36-0.67, I 2 =0%) but not for those with grade 3-4 irAEs (pooled HR: 0.95; 95% CI: 0.24-3.72, I 2 =84%). Conclusions: The development of irAEs is associated with a favorable prognosis in HCC, including improved PFS and higher ORR. A survival benefit was noted in patients with mild irAEs, but not in those with severe irAEs. Future studies are needed to determine if a differential survival benefit relates to the continuation vs. discontinuation of ICI therapy.

496 Background: Incidence of early-onset gastroesophageal adenocarcinoma (eoGEA, ages <50 years) has been increasing in the United States since the 1990s, the etiology of which is still unclear, and limited data exists on molecular drivers. This study evaluates somatic and germline profiles in eoGEA compared to average-onset GEA (aoGEA, ages≥ 50 years). Methods: This is a retrospective, cross-sectional study utilizing data from de-identified records of GEA (esophageal, gastroesophageal junction and gastric adenocarcinomas) patients who underwent somatic NGS testing via the Tempus xT assay (595-648 gene DNA panel) from 12/2017 to 07/2024. This assay assesses somatic tumor mutations (including SNVs, Indels, CNVs, and select SVs), MSI, TMB, and incidentally detected germline SNVs and small indels in matched normal tissue. Clinical characteristics and immunotherapy markers were compared between eoGEA and aoGEA by Wilcoxon Rank Sum or Chi-squared test. Somatic and germline mutations were compared between two age groups with false discovery rate adjustments. Results: We compared the demographic, clinical, and molecular features of a total of 5863 patients with eoGEA (n=785, median age 43) and aoGEA (n=5078, median age 68). Over 80% of patients were diagnosed with stage IV disease. The eoGEA group had a higher proportion of females, non-white, and Hispanic or Latino patients compared to the aoGEA group (p<0.001). Prevalence of MSI-H/ dMMR, and TMB-H was lower in eoGEA vs aoGEA (p<0.001), while PD-L1 expression was similar. Prevalence of somatic CDH1 , CDKN2A , and TP53 SNVs, and FGFR2 and KRAS CNAs were higher in eoGEA vs aoGEA (q<0.001). In a subset of 3286 patients with tumor/normal match testing (eoGEA=464 and aoGEA=2822), eoGEA also had a higher prevalence of germline CDH1 mutations (q<0.001). Conclusions: eoGEA has a unique somatic and germline mutation profile compared to aoGEA; further study evaluating the molecular landscape including epigenetic changes could shed light on underlying mechanisms responsible for the rising incidence of eoGEA. eoGEA (n=785) aoGEA (n=5078) p-value/q-value* Baseline characteristics Median age at diagnosis (IQR) 43 (38, 47) 68 (61,74) <0.001 Gender: male 509 (65%) 3798 (75%) <0.001 Race (white) 280 (69%) 2347 (80%) <0.001 Ethnicity (not hispanic or latino) 206 (60%) 1768 (86% <0.001 Stage IV 495 (85%) 2883 (81%) 0.073 Immunologic markers TMB ≥ 10 25 (3.2%) 519(10%) <0.001 MSI-H 13 (1.7%) 261 (5.1%) <0.001 dMMR 7 (2.2%) 120 (5.9%) 0.007 Somatic mutations profiles * CDH1 126 (16%) 334 (6.6%) <0.001 TP53 515 (66%) 3764 (74%) <0.001 CDKN2A 101 (13%) 1011 (20%) <0.001 KRAS 92 (12%) 931 (18%) <0.001 NOTCH1 12 (1.5%) 228 (4.5%) 0.002 Germline mutation profiles * eoGEA (N=464) aoGEA (N= 2,822) Overall prevalence 46 (9.9%) 207 (7.3%) CDH1 10 (2.2%) 8 (0.3%) 0.001 TP53 3 (0.6%) 0 (0%) 0.039 BRCA2 2 (0.4%) 38 (1.3%) 0.6 BRIP1 4 (0.9%) 10 (0.4%) 0.6

573 Background: Immunotherapy has shown great efficacy in hepatocellular carcinoma (HCC). No clear consensus exists on when to stop the immune checkpoint inhibitor (ICI) after complete response (CR), and clinical course after stopping ICI remains unknown. Methods: We identified 138 HCC patients who received ICI at Cedars-Sinai Medical Center and Mayo Clinic Rochester from 2016-2023. Modified Response Evaluation Criteria In Solid Tumors (mRECIST) was used to assess treatment response. We further described the clinical course of patients who achieved CR after ICI discontinuation, including cancer recurrence, subsequent treatment, liver transplantation (LT) listing and outcomes. Results: The median age at ICI initiation was 68 years; 79% were male; 55.9% were white; 51.5% were BCLC stage C. 9.4% CRs, 25.4% partial responses, 39.9% stable diseases, and 25.4% progressive disease. Hepatitis C etiology was associated with higher likelihood of CR (P=0.005). Among 13 patients who achieved CR, 10 stopped ICI (60% for LT evaluation, 40% for toxicity). After stopping ICI, 40% had recurrence (Table). 3 patients underwent local therapy for recurrent HCC within Milan criteria and 1 patient restarted ICI for recurrence beyond Milan criteria. Among CR patients, 9 patients underwent LT evaluation after stopping ICI and 7 patients were waitlisted. After listing, 3 dropouts were observed, due to recurrent HCC beyond Milan criteria, sepsis leading to death, and personal preference. 4 patients underwent LT. 2 patients underwent local therapy before LT for recurrent HCC (Table). All transplanted patients had the last dose of ICI more than 1 year before LT (12, 21, 24, and 29 months). On explanted livers, 2 patients had no residual viable tumor and 2 patients had residual HCC within Milan criteria. 1 patient developed acute cellular rejection and was treated with immunosuppressants and maintained stable graft function. None had graft loss or evidence of HCC recurrence in the follow-up period at 8, 20, 28, and 51 months. Conclusions: Immunotherapy demonstrated excellent effects on a subset of HCC patients, including 9.4% who achieved CR. After stopping ICI, 40% had cancer recurrence but 3 out of 4 were within Milan criteria. 4 underwent successful LTs (2.9%) with excellent post LT outcome. Larger prospective data is needed to establish a protocol for ICI use, especially to determine the optimal timing for ICI discontinuation after CR. BCLC at ICI initiation ICI cycles before stopping, ICI Recurrence after last ICI (days) Within Milan at recurrence Treatment(s) received after recurrence and outcomes OS (days) Patient 1 B 7, Nivolumab 730 No Nivolumab. Died from GI bleeding 1065 Patient 2 B 64, Atezo/Bev 149 Yes TACE with CR, followed by LT without recurrence. 1203 Patient 3 A 8, Nivolumab 1393 Yes Y90 with CR. No recurrence. 1984 Patient 4 C NA, Pembrolizumab 407 Yes TACE and MWA with CR, followed by LT without recurrence. 1722

Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, with nearly half of all patients diagnosed at an advanced stage. Immune checkpoint inhibitors (ICIs) harness the host immune system to combat malignant cells. ICIs, which target programmed death-ligand 1 (PD-L1), programmed cell death 1 (PD-1), and cytotoxic T-cell lymphocyte-4 (CTLA-4), have transformed the treatment landscape for advanced NSCLC. While a subset of patients experiences a long-term durable response, most patients will develop disease progression. New drugs targeting novel pathways are being tested in clinical trials to improve the efficacy of immunotherapy and overcome resistance patterns. This review aims to summarize the currently available ICIs for advanced NSCLC and describe emerging immunotherapies with recently published data from phase I/II clinical trials.

Background Resilience refers to the ability to adapt or recover from stress. There is increasing appreciation that it plays an important role in wholistic patient-centered care and may affect patient outcomes, including those of orthopaedic surgery. Despite being a focus of the current orthopaedic evidence, there is no strong understanding yet of whether resilience is a stable patient quality or a dynamic one that may be modified perioperatively to improve patient-reported outcome scores. Questions/purposes (1) Does resilience change postoperatively? (2) How do outcome measures change postoperatively in relation to resilience grouping? (3) For patients who do have resilience instability (change in resilience of ≥ 1 SD between any two follow-up points), how were patient-level factors, surgical characteristics, and outcome measures associated with instability? Methods In this single-surgeon, retrospective, comparative study, we identified all patients who underwent shoulder surgery between March 2021 and March 2023 from the medical records of one US military teaching hospital, resulting in 144 initial patients. Data on resilience (measured by the Brief Resilience Scale) and outcomes (assessed using the Numeric Rating Scale [NRS] and the Single Assessment Numeric Evaluation [SANE]) were collected for all patients and maintained in a longitudinal outcomes score database. Patients younger than 18 years of age (1% [1 of 144]) who underwent surgery for fracture, acute tendon rupture (8% [11 of 144]), or revision surgery (3% [4 of 144]); had concomitant shoulder conditions (such as, instability or rotator cuff tear) (1% [2 of 144]); or had incomplete follow-up data (4% [5 of 144]) were excluded, leaving 84% (121 of 144) of the original sample size for analysis. Among the patients, 12% (15 of 121) were women, the mean age was 41 ± 15 years, and the most common indication for surgery was instability (40% [48 of 121]) followed by rotator cuff repair (29% [35 of 121]). Based on their preoperative Brief Resilience Scale and its deviation from the mean, patients were stratified into low (> 1 SD below mean), intermediate (within 1 SD above and below mean), and high (> 1 SD above mean) resilience groups. Preoperatively, 19% (23 of 121) of patients were classified as low resilience, 62% (75 of 121) as intermediate resilience, and 19% (23 of 121) as high resilience. The mean ± SD preoperative Brief Resilience Scale score was 25 ± 4. The Brief Resilience Scale is a six-item scale with a calculated summary score ranging from 6 to 30. A higher score is suggestive of greater perceived resilience. There were no differences in the preoperative Brief Resilience Scale score with regard to age, gender, type of surgery performed, or outcome measures. Patient resilience was followed during the postoperative period for a minimum of 6 months, and instability in the scale was evaluated. Instability in resilience was defined as change in Brief Resilience Scale score by > 1 SD from one follow-up time point to another. Perioperative NRS and SANE outcomes, in addition to demographic data, were utilized to evaluate the relationship between resilience and patient-level factors. Results Brief Resilience Scale groups across all time points remained consistent with no change in grouping or crossover in groups except for patients with low resilience who had an increase in mean ± SD Brief Resilience Scale score by the final follow-up (18 ± 3 versus 20 ± 4; p < 0.05). Regardless of resilience group, there was a decrease in mean ± SD NRS (4.4 ± 2.2 versus 2.4 ± 2.3; p < 0.001) and an improvement in mean ± SD SANE (46 ± 19 versus 69 ± 21; p < 0.001) scores during the postoperative period. At the 1- to 2-month follow-up and the 6- to 10-month follow-up visits, patients with high resilience were more likely to have lower NRS scores than patients with intermediate resilience (1.8 ± 1.0 versus 3.8 ± 2.3; p = 0.003) and low resilience (1.5 ± 1.8 versus 3.3 ± 2.4; p < 0.001), respectively. No relationship was observed between resilience groups and SANE scores, surgical category, and percentage of patients meeting the minimum clinically important difference (MCID) of the NRS or the SANE. Regarding resilience instability, 46% (56 of 121) of patients were categorized as having a Brief Resilience Scale change of ≥ 1 SD from baseline during the postoperative period. Gender (r = 0.03; p = 0.21), age (p = 0.81), and surgical category (r = 0.01; p = 0.88) were not associated with the likelihood of resilience instability. Individuals whose resilience increased had a lower starting Brief Resilience Scale score than those whose resilience stayed the same (22 ± 4 versus 25 ± 4, respectively; p < 0.001) or those whose resilience decreased (22 ± 4 versus 26 ± 3, respectively; p < 0.001). Conclusion When evaluated by resilience group, the trait appears static; however, at the individual level, resilience appears dynamic and complex. Patients with high resilience may have less postoperative pain. Identification of patients with low resilience may indicate patients who experience more dynamic change in this psychometric property. Level of Evidence Level III, therapeutic study.

ImportanceBlood culture (BC) use benchmarks in US hospitals have not been defined.ObjectiveTo characterize BC use in adult intensive care units (ICUs) and wards in US hospitals.Design, Setting, and ParticipantsA retrospective cross-sectional study of BC use in adult medical ICUs, medical-surgical ICUs, medical wards, and medical-surgical wards from acute care hospitals from the 4 US geographic regions was conducted. Critical access hospitals, less than 6 months of BC data, and non-US hospitals were excluded. The study included BC use data from September 1, 2019, to August 31, 2021. Data were analyzed from February 23 to July 14, 2024.Main Outcomes and MeasuresThe primary outcome was BC use per 1000 patient-days. Adjusted means with 95% CIs were calculated using mixed-effects negative binomial regression models adjusted for unit type, hospital bed size, geographic region, seasonality, and state COVID-19 case load, with random intercepts accounting for clustering at unit and hospital levels. Secondary outcomes included blood culture positivity, single BCs, BC contamination, and minimum threshold for BC use where blood culture positivity would be optimized.ResultsA total of 362 327 blood cultures were analyzed from 27 medical ICUs, 35 medical-surgical ICUs, 121 medical wards, and 109 medical-surgical wards from 48 hospitals in 19 states and the District of Columbia. The adjusted mean BC use per 1000 patient-days was 273.1 (95% CI, 270.2-275.9) for medical ICUs, 146.0 (95% CI, 144.5-147.5) for medical-surgical ICUs, 80.3 (95% CI, 79.8-80.7) for medical wards, and 65.1 for medical-surgical wards. Blood culture use was significantly higher across all 4 unit types in hospitals with more than 500 beds compared with 500 or less beds and in the West-Midwest compared with other regions. Single blood culture and positive blood culture rates were below 10% across all 4 unit types. Of the 292 units, 97% had a mean BC contamination rate within 3% of the recommended threshold, and 51% were within 1%. The minimum BC use thresholds (ie, BC use below this number may represent undertesting) were 120 BCs per 1000 patient-days for medical ICUs, 80 BCs per 1000 patient-days for medical-surgical ICUs, and 30 BCs per 1000 patient-days for medical-surgical wards.Conclusions and RelevanceThe findings of this study suggest that blood culture positivity may help determine appropriate BC use for individual unit types.

Abstract The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate ‘pro-aging’ or ‘pro-youthful’ effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear. We examined five previously identified brain rejuvenation factors in cerebrospinal fluid of adults with autosomal dominant forms of frontotemporal dementia and sporadic Alzheimer’s disease. Our frontotemporal dementia cohort included 100 observationally followed adults carrying autosomal dominant frontotemporal dementia mutations (Mage = 49.6; 50% female; 43% C9orf72, 24% GRN, 33% MAPT) and 62 non-carriers (Mage = 52.6; 45% female) with cerebrospinal fluid analysed on Somascan, and longitudinal (Mvisits = 3 years, range 1–7 years) neuropsychological and functional assessments and plasma neurofilament light chain. Our Alzheimer’s disease cohort included 35 adults with sporadic Alzheimer’s disease (Mage = 69.4; 60% female) and 56 controls (Mage = 68.8, 50% female) who completed the same cerebrospinal fluid and clinical outcome measures cross-sectionally. Levels of C-C motif chemokine ligand 11, C-C motif chemokine ligand 2, beta-2-micorglobulin, bone gamma-carboxyglutamate protein (aka Osteocalcin) and colony stimulating factor 2 in cerebrospinal fluid were linearly combined into a composite score, with higher values reflecting ‘pro-youthful’ levels. In genetic frontotemporal dementia, higher baseline cerebrospinal fluid rejuvenation proteins predicted slower decline across cognitive, functional, and neurofilament light chain trajectories; estimates were similar across genotypes. In transdiagnostic analyses, higher cerebrospinal fluid rejuvenation proteins associated with better functional, cognitive, and neurofilament light chain outcomes in adults with sporadic Alzheimer’s disease. Proteins with pre-clinical evidence for brain rejuvenation show translational clinical relevance in adults with Alzheimer’s disease and related dementias and warrant further investigation.