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Background Mild cognitive impairment (MCI) represents a critical window for both pharmacological therapies and non-pharmacological interventions to delay cognitive decline. Objective To evaluate whether combining pharmacotherapy with multicomponent behavioral interventions enhances outcomes relative to behavioral interventions alone. Methods The sample included people with MCI (pwMCI) of any etiology who completed the HABIT Healthy Action to Benefit Independence & Thinking ® program. Baseline pharmacotherapy (acetylcholinesterase inhibitor and/or glutamate regulators) use was dichotomized (yes/no). Multivariate linear mixed-effects models examined changes from baseline in care partner-reported everyday functional skills, quality of life, self-efficacy, anxiety, depression, and HABIT compliance at post-intervention, 6 months, and 12 months, adjusting for baseline cognitive impairment severity and relevant demographic covariates. Results Among 1074 pwMCI, 413 (38.5%) were receiving pharmacotherapy at baseline. Pharmacotherapy use was more prevalent among White than non-White participants (39.4% versus 23.3%, p = 0.01). At baseline, pharmacotherapy users had more severe cognitive impairment and lower utilization of rehabilitation strategies (all p < 0.05). Both groups demonstrated significant improvements across all outcomes at post-intervention. During follow-up (mean score change compared to baseline), pharmacotherapy users showed greater increases in HABIT compliance at 6 months (3.2 versus 2.0) and 12 months (2.1 versus 1.4). In contrast, by 12 months, pharmacotherapy users experienced greater worsening of everyday functional skills related to memory (−2.1 versus −1.3) and executive function (−5.8 versus-3.7). Conclusions pwMCI undergoing pharmacotherapy entered the HABIT program with more advanced cognitive impairment. The pharmacotherapy was not associated with greater intervention-related benefit or attenuation of long-term cognitive decline.

Abstract Intercellular communication between multiple myeloma (MM) cells and osteoclast precursor cells (pre-OCs) contributes extensively to the occurrence and development of myeloma-related bone destruction. However, key interacting modes and the exchanged substances involved in this communication remain unclear. In this study, we discover that tunneling nanotubes (TNTs) directly connect MM and pre-OCs. Using the stable isotope labeling with amino acids in cell culture assay and a positive-negative double selection strategy, we identify filamin A (FLNA) as a major protein transported from MM to pre-OCs. FLNA acts as a molecular clutch linking extracellular matrix–bound MAC1 to the cytoskeleton, activating Rho and MAPK signaling pathways and promoting F-actin polymerization, which subsequently enhances osteoclast differentiation by modulating cellular stiffness, traction force, and deformability. In addition, FLNA directly binds vinculin and promotes its recruitment to podosomes, thereby enhancing the functions of podosomes and the bone resorption capacity of osteoclasts. The conditional depletion of Flna in mice suppresses podosome activity and reduces stiffness, traction force, and deformability in pre-OCs, leading to significantly impaired osteoclast differentiation and increased bone mass. In the Vk∗MYC mouse model of myeloma, the administration of the TNT inhibitor latrunculin B disrupts FLNA transport to osteoclasts and alleviates osteolytic bone disease. These findings highlight the critical role of MM-transferred FLNA in osteoclastogenesis and suggest that targeting TNTs may represent a therapeutic strategy to limit pathological bone resorption associated with MM.

Abstract INTRODUCTION Multicomponent non‐pharmacological interventions, such as the HABIT Healthy Action to Benefit Independence & Thinking® program, have shown promise for improving emotional well‐being, functioning, and self‐efficacy in both people with mild cognitive impairment (pwMCI) and their care partners. However, limited research has examined whether outcomes differ based on type of care partner who co‐enrolls with the pwMCI. METHODS We analyzed data from 875 pwMCI−care partner dyads who completed the HABIT program. Multivariate linear mixed‐effects regression models evaluated changes from baseline in outcomes by care partner type (spouse vs. non‐spouse) at post‐intervention, 6‐months, and 12‐ months. RESULTS At post‐intervention, pwMCI with spousal care partners demonstrated significant improvements across all outcomes from baseline, whereas those with non‐spousal partners improved in five out of seven outcomes. Across subsequent follow‐ups, pwMCI with spousal care partners showed sustained mean reductions in anxiety (post‐intervention: −2.0; 12‐month: −0.9) and increased compliance (post‐intervention: 5.7; 12‐month: 0.9). Everyday functioning in memory (post‐intervention: −0.9; 12‐months: 1.8) and executive functioning (post‐intervention: −0.7; 12‐months: 4.8) improved at post‐intervention but declined thereafter. Spousal care partners reported reduced anxiety (−1.2) and depression (−1.3) at post‐intervention, but by 12‐months they experienced increased burden, anxiety, and depression relative to baseline. Non‐spousal pwMCI–care partner dyads did not show significant change at 6 or 12‐months. DISCUSSION The HABIT intervention may have more favorable outcomes for pwMCI and care partners in spousal compared to non‐spousal dyads. These findings highlight the potential impact of care partner characteristics on both immediate and long‐term response to behavioral interventions for MCI. Highlights At post‐intervention, people with mild cognitive impairment (pwMCI) with spousal care partners showed significant improvements across all outcomes, while those with non‐spousal partners improved in five of seven outcomes. Gains attenuated over time for both spousal and non‐spousal dyads Spousal care partners reported reduced anxiety and depression at post‐intervention, but by 12 months they experienced increased burden, anxiety, and depression relative to baseline. Non‐spousal pwMCI–care partner dyads did not show significant change at 6 or 12 months.

Background Dementia with Lewy bodies (DLB) is a common degenerative dementia, but no studies investigate bereaved caregiver experiences. Objective To investigate the experiences of caregivers three months after the death of persons with DLB using a mixed-methods approach. Methods Dyads of individuals with moderate-advanced DLB and their primary informal caregivers were followed prospectively every 6 months until the person with DLB died. Caregivers completed a study visit with questionnaires and a semi-structured interview ∼3 months later. Spearman correlation coefficients and Wilcoxon rank-sum tests evaluated the relationships of post-death measures with pre-death patient and caregiver variables. Thematic analysis was used to analyze the interviews. Results Seventy-three caregivers completed visits (mean 3.5 months post-death). Most of the caregivers were women (82.2%) and spouses (76.7%) or adult children (17.8%). Over 40% had scores indicating risk for clinical depression. Post-death caregiver experiences (depression, quality of life, grief, resilience) correlated with pre-death caregiver experiences. Post-death experiences did not associate with patient characteristics, disease-related symptoms, or healthcare services used in the last 6 months of life. Trajectories for caregiver measures from pre- to post-death visits varied widely. Interview themes included grief and sadness, anger, guilt and regret, relief, appreciation/gratitude, and adjusting to a new normal. Conclusions The finding that pre-death caregiving experiences have the strongest association with post-death experiences emphasizes the critical importance of accessible and evidence-based caregiver support before and after the death of a person with DLB. Research is needed to develop interventions for current and bereaved caregivers of individuals with DLB. Trial registration information NCT04829656 (submitted 2021-03-22).

Nonmedical stimulant use (NMSU) among adolescents poses significant public health concerns. Using cross-sectional design, this study examined risk and protective factors for NMSU among 20,576 Florida high school students using the 2020 Florida Youth Substance Abuse Survey, with 925 students reporting NMSU. Guided by Hawkins and Catalano’s Social Development Model, we employed multivariate logistic regression analyses to estimate adjusted odds ratios while controlling for demographics. Students engaged in extracurricular activities were 50% less likely to report NMSU. Higher academic performance was associated with lower NMSU likelihood. Students with friends who used stimulants nonmedically were significantly more likely to engage in NMSU (AOR, 7.60; 95% CI: 6.35, 9.10), as were those living with relatives who used substances (AOR, 3.54; 95% CI: 2.94, 4.26). Findings highlight the importance of extracurricular involvement and positive social networks in mitigating NMSU. Interventions addressing family, peers, and extracurricular involvement are crucial for prevention and evidence-based policies.

Background . Despite the potential of palliative care (PC) to enhance the quality of life for patients with advanced dementia, there is limited knowledge of its inpatient utilization patterns. This study investigated inpatient PC consultation utilization patterns and evaluated its impact on hospital length of stay (LOS) and medical costs among older patients diagnosed with Alzheimer’s Disease and Related Dementia who were at a high risk of mortality (ADRD-HRM). Methods . Using the 2016-2019 National Inpatient Sample database, we conducted multivariable logistic regression analyses to identify individual and hospital characteristics influencing PC consultation utilization. We subsequently performed generalized linear models to estimate LOS (using Poisson distribution) and hospital charges (via log-transformation). Results . Our sample encompassed 965,644 hospital discharges (weighted n = 4,828,219) of patients aged 65 years and above with ADRD-HRM. Among them, 14.6% received inpatient PC. There was a notable uptrend in PC consultation utilization from 13.3% in 2016 to 16.3% in 2019 ( p trend<.001). Factors positively influencing and associated with PC utilization included patients that are older, non-Hispanic White, with higher income, receiving care from teaching hospitals, and facilitated with greater bed capacity (all P < .05). Although patients who received PC were more likely to have 3.0% longer LOS ( P < .001), they had 19.2% lower hospital charges ( P < .001). Conclusions . PC substantially reduced hospital expenditures for older patients with ADRD-HRM, but the prevalence remained low at 14.6% in the study period. Future studies should explore the unmet needs of patients with lower sociodemographic status and those in rural hospitals to further increase their PC consultation utilization.

AbstractINTRODUCTIONLittle is known regarding quality of life (QoL) in dementia with Lewy bodies (DLB), particularly in advanced stages.METHODSDyads of individuals with moderate–advanced DLB and their primary caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease‐related measures, and measures of patient/caregiver experiences.RESULTSThe Quality of Life in Alzheimer's Disease (QoL‐AD) was completed by the person with DLB and the caregiver (proxy) in 61 dyads; 85 dyads had only a proxy‐completed QoL‐AD. Patient‐ and proxy‐reported scores were moderately correlated (r = 0.57, P < 0.0001). Worse patient‐reported QoL correlated with daytime sleepiness, autonomic symptom burden, and behavioral symptoms. Proxy ratings correlated with dementia severity, daytime sleepiness, behavioral symptoms, dependence in activities of daily living, and caregiver experience measures.DISCUSSIONPatient‐ and proxy‐reported quality of life (QoL) should be assessed separately in advanced DLB. Some symptoms associated with QoL have available therapeutic options. Research is needed regarding strategies to optimally improve QoL in DLB.Highlights Patient and proxy quality of life (QoL) ratings had moderate correlation in advanced dementia with Lewy bodies. Daytime sleepiness affected patient‐ and proxy‐reported QoL. Behavioral symptoms affected patient‐ and proxy‐reported QoL. Autonomic symptom burden affected patient‐reported QoL. Dementia severity, dependence, and caregiver experiences affected proxy ratings.

Background: Left bundle branch area pacing (LBBAP) has rapidly emerged as a promising modality of physiologic pacing and has demonstrated excellent lead stability. In this retrospective study, we evaluate whether this pacing modality can allow concomitant atrioventricular node (AVN) ablation and same-day dismissal. Methods: Twenty-four consecutive patients (female 63%, male 37%) with an average age of 78 ± 5 years were admitted for pacemaker (75%)/defibrillator (25%) implantations and concomitant AVN ablation. Device implantation with LBBAP was performed first, followed by concomitant AVN ablation through left axillary vein access to allow for quicker post-procedure ambulation. The patients were discharged on the same day after satisfactory post-ambulation device checks. Results: LBBAP was successful in 22 patients (92% in total, 20 patients had an LBBP and two patients had a likely LBBP), followed by AVN ablation from left axillary vein access (21/24, 88%). All patients had successful post-op chest x-rays, post-ambulation device checks, and were discharged on the same day. After a mean follow up of three months, no major complications occurred, such as LBBA lead dislodgement requiring a lead revision. The LBBA lead pacing parameters immediately after implantation vs. three-month follow up were a capture threshold of 0.8 ± 0.3 V@0.4 ms vs. 0.6 ± 0.3 V@0.4 ms, sensing 9.9 ± 3.9 mV vs. 10.4 ± 4.1 mV, and impedance of 710 ± 216 ohm vs. 544 ± 110 ohm. The QRS duration before and after AVN ablation was 117 ± 32 ms vs. 123 ± 14 ms. Mean LVEF before and three months after the implantation was 44 ± 14% vs. 46 ± 12%. Conclusion: LBBA pacing not only offers physiologic pacing, but also allows for a concomitant AVN ablation approach from the left axillary vein and safe same-day hospital dismissal.