The role of microglia in neuronal and cognitive function during high altitude acclimatization.

Due to their interactions with the neurovasculature, microglia are implicated in maladaptive responses to hypobaric hypoxia at high altitude (HA). To explore these interactions at HA, pharmacological depletion of microglia with the colony-stimulating factor-1 receptor inhibitor, PLX5622, was employed in male C57BL/6J mice maintained at HA or sea level (SL) for 3-weeks, followed by assessment of ex-vivo hippocampal long-term potentiation (LTP), fear memory recall and microglial dynamics/physiology. Our findings revealed that microglia depletion decreased LTP and reduced glucose levels by 25% at SL but did not affect fear memory recall. At HA, the absence of microglia did not significantly alter HA associated deficits in fear memory or HA mediated decreases in peripheral glucose levels. In regard to microglial dynamics in the cortex, HA enhanced microglial surveillance activity, ablation of microglia resulted in increased chemotactic responses and decreased microglia tip proliferation during ball formation. In contrast, vessel ablation increased cortical microglia tip path tortuosity. In the hippocampus, changes in microglial dynamics were only observed in response to vessel ablation following HA. As the hippocampus is critical for learning and memory, poor hippocampal microglial context-dependent adaptation may be responsible for some of the enduring neurological deficits associated with HA.

"How will I ever know I didn't bring it on myself?": Navigating personal responsibility in public health messaging on dementia risk.

BACKGROUND AND OBJECTIVES: Public health messaging increasingly emphasizes the importance of "lifestyle interventions" to reduce dementia risk. Our study aimed to understand how people interpret and respond to information about dementia risk. In a second sub-aim, we examined how these interpretations may contribute to dementia-related lifestyle stigma. RESEARCH DESIGN AND METHODS: We engaged in a secondary analysis of 50 semi-structured interviews using a framework approach to understand, from the perspective of community-dwelling middle-aged and older adults, how they may interpret, make sense of, and respond to information about dementia risk and risk reduction. During the interpretive and narrative phase, the authors began to elucidate participant responses analytically and identified that these responses could be interpreted within the health locus of control literature. RESULTS: Of the 23 participants who discussed dementia risk, 13 felt some sense of personal responsibility and control over their dementia risk. Of those 13, four participants believed they had personal responsibility and control and actively engaged in lifestyle interventions. The remaining nine participants also engaged in lifestyle interventions, aiming to find comfort in knowing they had done what they could to reduce their risk and working to alleviate self-attribution of blame if diagnosed with dementia. DISCUSSION AND IMPLICATIONS: The tendency to internalize responsibility may inadvertently contribute to the stigmatization of dementia as a 'lifestyle disease' creating dementia-related lifestyle stigma. Recognizing the multifaceted nature of dementia risk, including environmental and external factors beyond individual control, is essential to combatting the 'lifestyle stigma' increasingly associated with the condition.

Structural plasticity of pyramidal cell neurons measured after FLASH and conventional dose-rate irradiation.

Evidence shows that ultra-high dose-rate FLASH-radiotherapy (FLASH-RT) protects against normal tissue complications and functional decrements in the irradiated brain. Past work has shown that radiation-induced cognitive impairment, neuroinflammation and reduced structural complexity of granule cell neurons were not observed to the same extent after FLASH-RT (> MGy/s) compared to conventional dose-rate (CONV, 0.1 Gy/s) delivery. To explore the sensitivity of different neuronal populations to cranial irradiation and dose-rate modulation, hippocampal CA1 and medial prefrontal cortex (PFC) pyramidal neurons were analyzed by electron and confocal microscopy. Neuron ultrastructural analyses by electron microscopy after 10 Gy FLASH- or CONV-RT exposures indicated that irradiation had little impact on dendritic complexity and synapse density in the CA1, but did increase length and head diameter of smaller non-perforated synapses. Similarly, irradiation caused no change in PFC prelimbic/infralimbic axospinous synapse density, but reductions in non-perforated synapse diameters. While irradiation resulted in thinner myelin sheaths compared to controls, none of these metrics were dose-rate sensitive. Analysis of fluorescently labeled CA1 neurons revealed no radiation-induced or dose-rate-dependent changes in overall dendritic complexity or spine density, in contrast to our past analysis of granule cell neurons. Super-resolution confocal microscopy following a clinical dosing paradigm (3×10Gy) showed significant reductions in excitatory vesicular glutamate transporter 1 and inhibitory vesicular GABA transporter puncta density within the CA1 that were largely dose-rate independent. Collectively, these data reveal that, compared to granule cell neurons, CA1 and mPFC neurons are more radioresistant irrespective of radiation dose-rate.

"Why miss today worrying about tomorrow?" A qualitative investigation of ways middle-aged and older adults manage dementia-related anxiety.

BACKGROUND AND OBJECTIVES: Dementia-related anxiety (DRA) is the fear or anxiety about a current or future diagnosis of Alzheimer's disease or another type of dementia. The purpose of the present study was to examine management of DRA. METHODS AND DESIGN: In semi-structured qualitative interviews, 50 community-dwelling adults (58-89 years old, M = 70.80, SD = 6.02) without dementia diagnoses reflected on their thoughts and feelings about dementia. A reflexive inductive thematic approach was used to examine ways people managed DRA. RESULTS: We identified five themes related to managing DRA: monitoring cognitive status (e.g., self-monitoring or objective assessment); active coping strategies (e.g., using external reminders, normalizing age-related change); interpersonal relationships and support (e.g., anticipating benefit of support from others); planning and preparing for potential outcomes (e.g., securing power of attorney, saying goodbyes); and personal responsibility to manage risk or accept diagnosis (e.g., lifestyle factors to reduce dementia risk, thereby reducing risk for burdening others). CONCLUSIONS: Findings suggest internal and external means for coping with DRA that are likely to vary in degrees of usefulness. We consider findings within the context of relevant, established theories, attending to potential clinical interventions for individuals experiencing DRA.

Needs of social isolation, loneliness, and intergenerational interventions in the United States: a scoping review.

Social isolation and loneliness are major health concerns for older adults in the United States. This scoping review examines the effectiveness of intergenerational interventions aimed at reducing social isolation and loneliness among older adults in the United States, specifically through programs that engage university students from healthcare-related fields in one-on-one settings with older adults, as reports of lacking geriatric training of healthcare students causes older adult neglect to persist in the healthcare workforce. The importance of addressing these issues is underscored by significant health risks and substantial economic burdens, with social isolation and loneliness potentially increasing mortality and costing Medicare an estimated $6.7 billion annually. Covering literature from 2010 to 2022, this review critically assesses the role of such interventions in fostering social connections and improving both physical and mental health outcomes. Despite the positive preliminary results indicating significant reductions in loneliness and enhancements in social networks among participants, the review highlights considerable gaps in current research, particularly in structured intervention curricula, demographic reporting and detailed intervention descriptions. This underscores the need for more rigorous and standardized research methodologies to better understand the effectiveness and potential of intergenerational programs as interventions against the detrimental effects of social isolation and loneliness among older adults.

Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study.

PURPOSE: To assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling. RESULTS: A total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%). CONCLUSION: Treatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.

Impact of distinct cognitive domains on gait variability in individuals with mild cognitive impairment and dementia.

BACKGROUND: Gait variability is a common feature in neurodegenerative diseases and has been linked to cognitive impairment. Despite this link, the influence of specific cognitive domains, such as memory, visual spatial skills, executive function, and verbal function on gait variability is not well-understood. OBJECTIVE: To investigate the predictive value of these specific cognitive domains on gait variability in people with mild cognitive impairment (MCI) and dementia during preferred and dual task walking. METHOD: One hundred and two participants with either MCI or dementia underwent a comprehensive cognitive assessment and completed preferred and dual-task walking trials on a pressure-sensing walkway. Gait variability was assessed using the PKMAS software. Lower extremity function was evaluated with a self-reported validated scale. RESULTS: Our findings indicate that only visual spatial abilities had a moderate predictive value on gait variability [F (1, 78) = 17.30, p < 0.01, r = 0.43], both in preferred pace walking (70% direct effect) and dual-task walking (90% direct effect) (p's < 0.05). Additionally, lower extremity functional skills had a significant indirect effect (30%) on gait variability in preferred walking contexts. CONCLUSION: For individuals diagnosed with MCI or dementia, increased gait variability may be driven by deficits in visual spatial processing. An increased understanding of the role of visual spatial processing in gait variability can aid in the assessment and management of individuals with MCI or dementia, potentially leading to targeted interventions to improve mobility and safety.

Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.

Uveal melanoma immunogenomics predict immunotherapy resistance and susceptibility.

Immune checkpoint inhibition has shown success in treating metastatic cutaneous melanoma but has limited efficacy against metastatic uveal melanoma, a rare variant arising from the immune privileged eye. To better understand this resistance, we comprehensively profile 100 human uveal melanoma metastases using clinicogenomics, transcriptomics, and tumor infiltrating lymphocyte potency assessment. We find that over half of these metastases harbor tumor infiltrating lymphocytes with potent autologous tumor specificity, despite low mutational burden and resistance to prior immunotherapies. However, we observe strikingly low intratumoral T cell receptor clonality within the tumor microenvironment even after prior immunotherapies. To harness these quiescent tumor infiltrating lymphocytes, we develop a transcriptomic biomarker to enable in vivo identification and ex vivo liberation to counter their growth suppression. Finally, we demonstrate that adoptive transfer of these transcriptomically selected tumor infiltrating lymphocytes can promote tumor immunity in patients with metastatic uveal melanoma when other immunotherapies are incapable.

Thermal Characterization and Preclinical Feasibility Verification of an Accessible, Carbon Dioxide-Based Cryotherapy System.

To investigate the potential of an affordable cryotherapy device for the accessible treatment of breast cancer, the performance of a novel carbon dioxide-based device was evaluated through both benchtop testing and an in vivo canine model. This novel device was quantitatively compared to a commercial device that utilizes argon gas as the cryogen. The thermal behavior of each device was characterized through calorimetry and by measuring the temperature profiles of iceballs generated in tissue phantoms. A 45 min treatment in a tissue phantom from the carbon dioxide device produced a 1.67 ± 0.06 cm diameter lethal isotherm that was equivalent to a 7 min treatment from the commercial argon-based device, which produced a 1.53 ± 0.15 cm diameter lethal isotherm. An in vivo treatment was performed with the carbon dioxide-based device in one spontaneously occurring canine mammary mass with two standard 10 min freezes. Following cryotherapy, this mass was surgically resected and analyzed for necrosis margins via histopathology. The histopathology margin of necrosis from the in vivo treatment with the carbon dioxide device at 14 days post-cryoablation was 1.57 cm. While carbon dioxide gas has historically been considered an impractical cryogen due to its low working pressure and high boiling point, this study shows that carbon dioxide-based cryotherapy may be equivalent to conventional argon-based cryotherapy in size of the ablation zone in a standard treatment time. The feasibility of the carbon dioxide device demonstrated in this study is an important step towards bringing accessible breast cancer treatment to women in low-resource settings.

NCCN Guidelines® Insights: Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

The Efficacy and Safety of Treating Acquired MET Resistance Through Combinations of Parent and MET Tyrosine Kinase Inhibitors in Patients With Metastatic Oncogene-Driven NSCLC.

Introduction: Acquired MET gene amplification, MET exon 14 skip mutations, or MET fusions can emerge as resistance mechanisms to tyrosine kinase inhibitors (TKIs) in patients with lung cancer. The efficacy and safety of combining MET TKIs (such as crizotinib, capmatinib, or tepotinib) with parent TKIs to target acquired MET resistance are not well characterized. Methods: Multi-institutional retrospective chart review identified 83 patients with metastatic oncogene-driven NSCLC that were separated into the following two pairwise matched cohorts: (1) MET cohort (n = 41)-patients with acquired MET resistance continuing their parent TKI with a MET TKI added or (2) Chemotherapy cohort (n = 42)-patients without any actionable resistance continuing their parent TKI with a platinum-pemetrexed added. Clinicopathologic features, radiographic response (by means of Response Evaluation Criteria in Solid Tumors version 1.1), survival outcomes, adverse events (AEs) (by means of Common Terminology Criteria for Adverse Events version 5.0), and genomic data were collected. Survival outcomes were assessed using Kaplan-Meier methods. Multivariate modeling adjusted for lines of therapy, brain metastases, TP53 mutations, and oligometastatic disease. Results: Within the MET cohort, median age was 56 years (range: 36-83 y). Most patients were never smokers (28 of 41, 68.3%). Baseline brain metastases were common (21 of 41, 51%). The most common oncogenes in the MET cohort were EGFR (30 of 41, 73.2%), ALK (seven of 41, 17.1%), and ROS1 (two of 41, 4.9%). Co-occurring TP53 mutations (32 of 41, 78%) were frequent. Acquired MET alterations included MET gene amplification (37 of 41, 90%), MET exon 14 mutations (two of 41, 5%), and MET gene fusions (two of 41, 5%). After multivariate adjustment, the objective response rate (ORR) was higher in the MET cohort versus the chemotherapy cohort (ORR: 69.2% versus 20%, p < 0.001). Within the MET cohort, MET gene copy number (≥10 versus 6-10) did not affect radiographic response (54.5% versus 68.4%, p = 0.698). There was no difference in ORR on the basis of MET TKI used (F [2, 36] = 0.021, p = 0.978). There was no difference in progression-free survival (5 versus 6 mo; hazard ratio = 0.64; 95% confidence interval: 0.34-1.23, p = 0.18) or overall survival (13 versus 11 mo; hazard ratio = 0.75; 95% confidence interval: 0.42-1.35, p = 0.34) between the MET and chemotherapy cohorts. In the MET cohort, dose reductions for MET TKI-related toxicities were common (17 of 41, 41.4%) but less frequent for parent TKIs (two of 41, 5%). Grade 3 AEs were not significant between crizotinib, capmatinib, and tepotinib (p = 0.3). The discontinuation rate of MET TKIs was 17% with no significant differences between MET TKIs (p = 0.315). Among pre- and post-treatment biopsies (n = 17) in the MET cohort, the most common next-generation sequencing findings were loss of MET gene amplification (15 of 17, 88.2%), MET on-target mutations (seven of 17, 41.2%), new Ras-Raf-MAPK alterations (three of 17, 17.6%), and EGFR gene amplification (two of 17, 11.7%). Conclusions: The efficacy and safety of combining MET TKIs (crizotinib, capmatinib, or tepotinib) with parent TKIs for acquired MET resistance are efficacious. Radiographic response and AEs did not differ significantly on the basis of the underlying MET TKI used. Loss of MET gene amplification, development of MET on-target mutations, Ras-Raf-MAPK alterations, and EGFR gene amplification were molecular patterns found on progression with dual parent and MET TKI combinations.

Patient perspectives of weight stigma across the cancer continuum: A scoping review.

BACKGROUND: Weight stigma has been defined as the social devaluation and denigration of individuals because of their weight. The purpose of this scoping systematic review was to assess and understand patient experiences with weight stigma in the cancer care setting. METHODS: We conducted a systematic scoping review of studies examining shame, prejudice, bias, and stigma in relation to weight and cancer-related care using five databases: PubMed, CINAHL Plus Full Text (ProQuest), Cochrane Library, PsycINFO (EBSCO), and Scopus. Articles were uploaded into Covidence for de-duplication and screening. Included studies were peer reviewed, reported adult patient experiences in cancer-related care, and were published in English between October 2012 and February 2023. Study characteristics and key findings were abstracted and qualitatively synthesized. RESULTS: Publications meeting inclusion criteria yielded five studies (n = 113 participants). Most focused on the experiences of women (n = 4) and cancers which predominantly impact women (i.e., breast, cervical, endometrial; n = 4). All stages of the cancer continuum were included with studies examining screening (n = 2), treatment (n = 1), and post-treatment survivorship (n = 2). Weight discrimination was discussed in four studies and weight-biased stereotypes were discussed in three studies. Experiences of weight bias internalization were reported in four studies. One study described an instance of implicit weight bias. CONCLUSIONS: Limited studies examine patient experiences of weight stigma in cancer care; however, current evidence suggests that patients do experience weight stigma in cancer-related care. This review highlights critical gaps and a need for more research on the prevalence and impact of weight stigma in cancer screening and care.

Impact of Intermittent Fasting and/or Caloric Restriction on Aging-Related Outcomes in Adults: A Scoping Review of Randomized Controlled Trials.

Intermittent fasting (IF) and caloric restriction (CR) are dietary strategies to prevent and attenuate obesity associated with conditions and aging-related outcomes. This scoping review examined the cardiometabolic, cancer, and neurocognitive outcome differences between IF and CR interventions among adults. We applied a systematic approach to scope published randomized controlled trials (databases: PubMed, CINAHL Plus, PsychInfo, Scopus, and Google Scholar) from inception through August 2023. The initial search provided 389 unique articles which were critically appraised. Thirty articles met the eligibility criteria for inclusion: 12 were IF, 10 were CR, and 8 were combined IF and CR interventions. IF and CR were associated with weight loss; however, IF studies tended to report greater adherence compared with CR. Overall, IF and CR were equivalently effective across cardiometabolic, cancer, and neurocognitive outcomes. Our findings suggest that IF has health benefits in a variety of conditions and may be better accepted and tolerated than CR, but more comparative research is required.

"Terror Is a Better Word": A Qualitative Analysis of Dementia-Related Anxiety.

BACKGROUND AND OBJECTIVES: Dementia-related anxiety (DRA) is the fear of a current or future diagnosis of Alzheimer's disease or another type of dementia. Previous studies suggest diverse factors contribute to DRA, including emotional, social, and cognitive concerns. A mixed-methods investigation was designed to explore DRA's underlying causes; we present a thematic analysis of these causes. RESEARCH DESIGN AND METHODS: A semistructured qualitative interview design was used to explore participant's thoughts, feelings, and reactions about dementia. Fifty community-dwelling adults (aged 58-89, M = 70.80, SD = 6.02) without dementia diagnoses were interviewed, with a focus on why dementias are anxiety-provoking diagnoses. We engaged in a reflexive inductive thematic approach. RESULTS: We identified 7 themes positioned within previously established antecedents of DRA. Anticipated consequences were conveyed in statements identifying dementia as a feared diagnosis and its connection to how one would be treated if diagnosed. Low perceived control was associated with dementia's anticipated effects including the ability of dementia to undermine core aspects of one's personhood, limit independence, and increase reliance on others. Perceived risk was connected to past familial experiences with dementia and the implications of receiving different diagnoses with different trajectories and treatments. DISCUSSION AND IMPLICATIONS: Findings offer insight into diverse factors contributing to DRA, which can be used to inform public health messaging and develop applicable and clinically relevant interventions to meet the needs of individuals experiencing DRA and their social support systems.

Therapeutic efficacy of an alpha-particle emitter labeled anti-GD2 humanized antibody against osteosarcoma-a proof of concept study.

PURPOSE: Current treatments for osteosarcoma (OS) have a poor prognosis, particularly for patients with metastasis and recurrence, underscoring an urgent need for new targeted therapies to improve survival. Targeted alpha-particle therapy selectively delivers cytotoxic payloads to tumors with radiolabeled molecules that recognize tumor-associated antigens. We have recently demonstrated the potential of an FDA approved, humanized anti-GD2 antibody, hu3F8, as a targeted delivery vector for radiopharmaceutical imaging of OS. The current study aims to advance this system for alpha-particle therapy of OS. METHODS: The hu3F8 antibody was radiolabeled with actinium-225, and the safety and therapeutic efficacy of the [225Ac]Ac-DOTA-hu3F8 were evaluated in both orthotopic murine xenografts of OS and spontaneously occurring OS in canines. RESULTS: Significant antitumor activity was proven in both cases, leading to improved overall survival. In the murine xenograft's case, tumor growth was delayed by 16-18 days compared to the untreated cohort as demonstrated by bioluminescence imaging. The results were further validated with magnetic resonance imaging at 33 days after treatment, and microcomputed tomography and planar microradiography post-mortem. Histological evaluations revealed radiation-induced renal toxicity, manifested as epithelial cell karyomegaly and suggestive polyploidy in the kidneys, suggesting rapid recovery of renal function after radiation damage. Treatment of the two canine patients delayed the progression of metastatic spread, with an overall survival time of 211 and 437 days and survival beyond documented metastasis of 111 and 84 days, respectively. CONCLUSION: This study highlights the potential of hu3F8-based alpha-particle therapy as a promising treatment strategy for OS.

Prospective Clinical Prognostication of Endometrial Carcinomas Based on Next-Generation Sequencing and Immunohistochemistry-Real-World Implementation and Results at a Tertiary Care Center.

Based on findings from The Cancer Genome Atlas and the Proactive Molecular Risk Classifier for Endometrial Cancer algorithm, endometrial carcinoma can now be stratified into 4 prognostically distinct subgroups based on molecular alterations and immunohistochemical (IHC) aberrations. In this study, we describe the de novo adoption and clinical reporting of prognostic subgroup classification based on next-generation sequencing (NGS) and IHC analyses of all endometrial carcinoma resections at a single institution, framed by the Exploration, Preparation, Implementation, and Sustainment model. Results from the first 13 months show 188 tumors underwent analysis by a combination of IHC and a medium-sized (56 analyzed genes) NGS-based assay. All cases were assigned as either POLE (POLE-mutated) (5.3%), mismatch repair deficient (27.7%), no specific molecular profile (45.7%), or p53 abnormal (21.3%) inclusive of multiple-classifier cases. NGS-based analysis revealed additional distinctions among the subgroups, including reduced levels of PI3K pathway activation in the p53 abnormal subgroup, an increased rate of CTNNB1 activating mutation in the no specific molecular profile subgroup, and lower TP53 mutation variant allele frequencies in POLE and mismatch repair deficient subgroups compared with the p53 abnormal subgroup. Overall, we describe the testing protocol, reporting, and results of a combination of NGS and IHC to prospectively prognosticate endometrial carcinomas at a single tertiary care center.

Mechanisms of improved body composition among perimenopausal women practicing Meditative Movement: a proposed biobehavioral model.

OBJECTIVES: Weight gain and unfavorable body composition are prevalent among midlife/older women throughout menopause. These shifts may negatively impact health, well-being, and longevity. Efforts to attenuate weight and body composition changes are traditionally driven by manipulation of diet and/or exercise; however, sustained results are limited, possibly because the full spectrum of biobehavioral systems is not addressed by diet and exercise alone. We propose a biobehavioral model detailing mechanisms of body composition decline among perimenopausal women and the associated components of Meditative Movement (ie, tai chi, qigong, yoga) that address each of these factors. METHODS: Based on our previous work and extensive review of the literature, we developed a multifactorial and multidimensional biobehavioral model including factors that most directly relate to body composition among perimenopausal women: 1) psychological (ie, stress and mood, mindfulness and self-compassion, body awareness), 2) behavioral (ie, sleep, physical activity, eating behaviors), and 3) physiological (ie, cortisol, estrogen). Relationships between each factor, Meditative Movement practice components, and predicted effects on body composition were explored in detail. RESULTS: Our model describes select psychological, behavioral, and physiological factors, and potential mechanistic pathways of Meditative Movement practice driving improved changes in body composition and weight outcomes for perimenopausal women. CONCLUSIONS: The proposed model details a novel, evidence-supported means to reduce the risk of deleterious shifts in body composition throughout perimenopause and menopause thereafter. We suggest that these changes may occur directly and/or indirectly through psychological, behavioral, and physiological mechanisms that facilitate the desired changes in body composition.