Obesity is highly prevalent among patients with cancer and is associated with increased risks of treatment-related complications, poorer oncological outcomes, and long-term morbidity. Despite this, current oncology nutrition guidelines primarily address malnutrition and provide limited direction for clinical management of patients with obesity. Intentional weight loss interventions during cancer treatment are uncommon, partly due to concerns about safety and feasibility. The CANOBESE study aims to address this evidence gap by evaluating the feasibility of implementing a structured, multimodal weight management programme for patients with obesity undergoing curative oncological treatment. This single-arm feasibility trial will recruit 50 adult patients with a BMI ≥ 30 kg/m2 and newly diagnosed stage II-IV solid tumours receiving chemotherapy, radiotherapy, immunotherapy, targeted therapy alone, or in combination with curative intent. The intervention includes a personalized hypocaloric and high-protein diet, a supervised home-based aerobic and resistance exercise programme, and integrated behavioural support delivered throughout the programme, with psycho-oncological input when more intensive individualized support is needed. Follow-up will continue for the duration of active treatment (3-9 months). The study will evaluate feasibility by examining key aspects such as recruitment and retention rates, intervention adherence and fidelity, participant acceptability, and the completeness of data collection throughout the intervention period. Secondary outcomes include exploratory changes in weight, body composition, physical performance, dietary intake, quality of life, and inflammatory biomarkers. The broad eligibility criteria were selected to evaluate feasibility in a pragmatic real-world oncology setting, while predefined exclusions were used to reduce baseline nutritional risk and improve safety. The CANOBESE study represents one of the first efforts to assess whether a comprehensive lifestyle intervention can be effectively delivered to patients with obesity during curative cancer treatment. This protocol incorporates patient and public involvement, a multidisciplinary team approach, and real-world implementation considerations. Findings will inform the scalability of the intervention, characterize implementation challenges across a pragmatic oncology population, and guide the design of a future randomized controlled trial. The study is not intended to provide subgroup-specific clinical recommendations, but to generate feasibility data that may help refine tailored approaches to intentional weight management in oncology settings. ClinicalTrials.gov identifier: NCT07058207. Registered on 9 July 2025. https://clinicaltrials.gov/study/NCT07058207.

Nutrition Services in Oncology: A Cross-Sectional Survey of Patient Experiences, Needs, and Gaps in Care.

Urinary incontinence (UI)-including stress (SUI), urge (UUI), and mixed (MUI) subtypes-is associated with obesity, and weight loss is commonly recommended for intervention. However, the comparative effects of intentionality and weight loss strategies on UI severity remain poorly defined. We analyzed 16,331 adults from the 2001-2020 NHANES cohorts who self-reported 1-year weight loss and completed the UI questionnaire. Our use of a large, diverse sample of U.S. men and women and self-reported intentionality and strategies (dietary changes, exercise, intermittent fasting, and diet pills) was unique. UI severity was defined by number of leakage episodes. Ordinal logistic regression, adjusted for age, sex, race/ethnicity, body mass index (BMI), and comorbidities, evaluated associations between weight loss intentionality and UI severity. Among 16,331 adults, 9581 (58.7%) reported intentional and 6750 (41.3%) unintentional weight loss. After adjustment, intentional weight loss was associated with lower odds of more frequent SUI (0.79 OR [95%CI 0.68-0.92]), UUI (0.85 OR [95%CI 0.73-0.99]), and MUI (0.79 OR [95%CI 0.64-0.98]) compared to unintentional weight loss. Commonly used strategies included dietary modification (n = 8818), exercise (n = 5714), intermittent fasting (n = 1584), and diet pills (n = 238). Exercise was associated with the lowest prevalence of frequent SUI, UUI, and MUI symptoms in both males and females. Stratified analysis demonstrated that exercise remained associated with lower UUI symptom frequency even among individuals achieving ≤ 5% weight loss. Intentional weight loss was associated with lower likelihood of frequent UI symptoms compared to unintentional weight loss. Exercise was the intervention associated with the lowest severity of SUI, UUI, and MUI in both males and females. Our findings are consistent with current recommendations for active behavioral modification for UI weight loss. Additional prospective comparative analysis of exercise and other weight loss strategies is warranted.

Many individuals with obesity meet criteria for an eating disorder such as binge-eating disorder (BED) or bulimia nervosa (BN). However, the impact of behaviorally based weight management interventions such as behavioral weight loss (BWL) on eating disorder symptoms for individuals diagnosed with BED or BN is unclear, with one possibility being that encouraging intentional weight loss could exacerbate symptoms of these disorders. Thus, the purpose of this systematic review and meta-analysis was to evaluate the impact of behavioral weight management interventions on eating disorder symptoms among individuals diagnosed with BED or BN. Electronic database searches yielded 22 experimental groups across 11 trials that met inclusion criteria (890 participants). All trials reported that on average, baseline eating disorder symptoms decreased after weight management interventions at posttreatment. Random-effects meta-analyses revealed no significant difference between weight management interventions and comparison groups in posttreatment changes to binge-eating frequency (MD = 0.59, 95% CI [-0.86, 1.86]), global eating disorder symptom severity (MD = 0.03, 95% CI [-0.15, 0.21]), or pooled eating disorder symptom outcomes (g = 0.04, 95% CI [-0.20, 0.29]). Posttreatment symptom decreases were greater when weight management interventions were compared with no-treatment (vs. active) control groups, and outcomes were also moderated by the type of weight management intervention used. These findings, though limited by the small number of trials, heterogeneity in study design and outcome measures, and sparse long-term outcome data, suggest that behavioral weight management interventions may be an effective treatment modality for individuals diagnosed with full-threshold BED or BN.

Rapid and intentional weight loss can result from bariatric surgery, pharmacologic agents such as glucagon-like peptide-1 receptor agonists, and intensive lifestyle changes. Although effective in lowering body weight, these interventions often produce broader physiologic effects. Patients may experience changes beyond size, including decreased skin firmness, muscle loss, and reduced bone density. To describe the dermatologic and structural consequences of rapid weight loss and review current and emerging management strategies. A narrative review was conducted using PubMed and Google Scholar to identify English-language literature published between 2000 and 2025 on soft tissue changes associated with rapid weight loss. Rapid weight loss impacts collagen, elastic fibers, adipose tissue, muscle mass, and skeletal integrity. Management strategies include nutritional optimization, resistance-based physical activity, energy-based devices, biostimulatory injectables, and, in advanced cases, surgical procedures. Regenerative therapies are also under investigation. As rapid weight loss becomes increasingly common, dermatologists are encountering a broader range of cosmetic and structural concerns. A multidisciplinary, evidence-informed approach is critical for addressing these issues and improving patient outcomes.

The rapid evolution of obesity therapeutics, led by glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metabolic surgery, has achieved unprecedented weight loss. However, the skeletal consequences of such substantial weight reduction are of increasing clinical concern. This review explores the relationship between obesity, weight-loss modalities, and bone health. While obesity was historically viewed as bone-protective due to mechanical loading, recent evidence highlights qualitative bone deterioration and sitespecific fracture risks. Intentional weight loss through caloric restriction or bariatric surgery consistently accelerates bone turnover and reduces bone mineral density (BMD), with surgical interventions showing the most significant impact. Emerging data on GLP-1RAs suggest modest BMD declines, largely proportional to weight loss and likely driven by mechanical unloading. Conversely, preclinical studies indicate that GLP-1 signaling may exert direct osteoanabolic and anti-resorptive effects. To preserve skeletal integrity, obesity management must shift toward a holistic body composition framework. Integrating structured resistance exercise, optimizing nutrition (calcium, vitamin D, and protein), and implementing skeletal monitoring in high-risk individuals are essential. Future obesity care should prioritize the maintenance of bone quality and lean mass alongside fat reduction to ensure long-term skeletal resilience and prevent fragility fractures.

Research on food avoidance behaviors in individuals with chronic spinal cord injuries and disorders (SCI/D) is scarce. The objective was to assess food avoidance, reasons, and associated variables in persons with chronic SCI/D. A cross-sectional survey was conducted. Bivariate and multivariable analyses identified variables associated with food avoidance. Of 365 respondents, 63% engaged in food avoidance behaviors. Reasons included intentional weight loss (49%), lack of hunger cues (40%), fear of bowel complications (32%), fear of gastrointestinal concerns (26%), uninterested in food (26%), and lack of help needed to prepare/eat food (11%). Bivariate analysis showed that a greater proportion of individuals with SCI/D who engaged in food avoidance behaviors compared with those who did not had low blood pressure (29% vs. 19%), heart problems (13% vs. 5%), sleep problems (86% vs. 66%), musculoskeletal pain (82% vs. 63%), bowel complications (78% vs. 69%), bladder complications (77% vs. 65%), gastroesophageal reflux disease (49% vs. 30%), osteoporosis (37% vs. 24%), posttraumatic stress (35% vs. 16%), and loneliness (31% vs. 14%; all p < .05). Variables that remained independently associated with food avoidance in multivariable analysis included: heart conditions (OR = 3.09, 95% confidence interval [CI]: 1.18-8.12), gastroesophageal reflux disease (OR = 1.77, 95% CI: 1.05-2.97), musculoskeletal pain (OR = 2.00, 95% CI: 1.11-3.62), sleep problems (OR = 1.81, 95% CI: 1.01-3.30), and loneliness (OR = 2.19, 95% CI: 1.17-4.10; all p < .05). Many individuals with SCI/D engaged in food avoidance behaviors. Food avoidance may be a strategy people use to modify their diet to manage health conditions, or it may suggest disordered avoidant eating behaviors. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Obesity is associated with increased risk of at least 13 adult cancer types and is the second most common cause of cancer (after tobacco) in many populations. Uncertainty about the extent to which intentional weight loss leads to reduced cancer risk represents a gap in knowledge. Evidence from bariatric surgery studies shows that sustained weight reduction of 20% to 30% in individuals with severe obesity is associated with reduced risk of obesity-related cancers over 10 years. However, in terms of population health, this is not a viable cancer prevention strategy. Recently, glucagon-like peptide-1 receptor agonists (GLP-1RA), known to be effective antidiabetes drugs, have been shown in randomized trials to cause substantial weight loss (in the order of 15%) in obese individuals with or without diabetes. This is a rapidly evolving field, which has revolutionized the modern management of obesity. Much clinical experience has been with semaglutide (a GLP-1RA) and tirzepatide (a dual agonist of the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor), but newer drugs in the class are being developed. We review available data that provide a strong rationale for evaluating incretin-mimetic drugs in a cancer prevention trial but show that the feasibility of such a trial is questionable.

To synthesize current evidence supporting intentional weight reduction as a cardiometabolic strategy for treating and preventing heart failure (HF) across the ejection-fraction spectrum, examine the influence of baseline obesity on treatment effects of established HF therapies, and highlight key knowledge gaps and future research directions. Visceral adipose tissue, central obesity, and dysfunctional adipose mass are linked to the development and progression of HF with preserved ejection fraction (HFpEF). Recent trials show that incretin-based therapies (semaglutide, tirzepatide) improve exercise capacity, symptoms, and quality of life in HFpEF, and potentially reduce HF events. Patients with higher degrees of obesity may derive greater benefit from incretin-based therapies and other guideline-directed therapies, including mineralocorticoid receptor antagonists (MRA), sodium-glucose transport 2 (SGLT2) inhibitors, and angiotensin receptor-neprilysin inhibitor (ARNI). While observational studies suggest intentional weight loss may lower HF risk, randomized trials of antiobesity medications have yet to further clarify this potential benefit. Weight loss is currently recommended as an optimal strategy for individuals with obesity and HFpEF, given consistent benefits for exercise capacity, functional status, and quality of life, with a potential for reducing clinical events. Intentional weight loss impact in HFrEF and its role in primary HF prevention remains uncertain. Large, well designed cardiovascular outcome trials of intentional weight-loss interventions in populations with obesity and HF, or obesity and elevated HF risk, are needed to establish clinical efficacy and better define individuals who benefit from those interventions across the spectrum of ejection fraction.

Glucagon-like peptide 1 receptor agonists (GLP1RAs) are widely used for the treatment of type 2 diabetes mellitus (T2DM) and, at higher doses, obesity. Both T2DM and obesity are associated with a higher risk of cancer, which can be reduced by intentional weight loss, whereas effects of a reduction in hyperglycaemia are uncertain. GLP1RAs might have further direct effects, either beneficial or detrimental, on the development of specific malignancies. Evidence from preclinical and clinical studies suggests heterogeneous effects of GLP1RAs on cancer risk: the incidence of hepatocellular, oesophageal, endometrial, ovarian and prostate cancers might be reduced, whereas safety concerns persist with respect to thyroid (both medullary and non-medullary) carcinomas. Conversely, initial concerns on the risk of pancreatic cancer have not been confirmed. Nonetheless, the interpretation of current data is limited by detection and prescription biases in observational studies as well as insufficient follow-up and number of events in randomized trials. In this Review, we summarize current preclinical and clinical evidence, showing that the risk-benefit profile of GLP1RAs remains favourable in individuals withT2DM and obesity, although caution is warranted in those with a low cardiometabolic risk, for whom the potential risks of cancer might outweigh any expected benefits; conversely, the potential use of GLP1RAs as adjuvant therapies for certain forms of cancer needs to be further investigated.

The Physiology Of the WEight Reduced State (POWERS) study is a multi-center clinical trial designed to understand the physiological basis for observed variability in weight regain following intentional weight loss among US adults. The primary dependent variable is weight regain over one year following a 7% or greater supervised weight loss. The overarching design and study organization, along with rationale and history of the POWERS study and outcomes measures are described in accompanying papers. This paper provides the rationale for and description of biospecimens samples that will ultimately inform on the molecular and cellular basis of the physiological variability that contributes to the regulation of energy balance in the weight reduced state. Participants will be 205 healthy adults (n = 205), aged 25-59 years, with body mass index (BMI) 30- ≤ 40 kg/m2. Biospecimens will be collected prior to weight loss (baseline, BL), immediately following weight loss via lifestyle intervention (T0), and then four (T4) and twelve (T12) months after weight loss. Blood will be collected in the fasting state and following a meal challenge designed to induce hormones related to satiety. Weight change from T0 to T12 will be the primary outcome variable. Biospecimens to be collected include plasma, serum, peripheral blood mononuclear cells (PBMCs), DNA, urine, feces, adipose and skeletal muscle tissue. All samples will be biobanked at each site. This manuscript describes the rationale for the biospecimens chosen to assess contributors to homeostatic mechanisms that drive observed variability of weight regain after weight loss.

Obesity is increasingly prevalent in patients undergoing gastrointestinal (GI) cancer surgery and is associated with higher rates of intraoperative and postoperative complications. Preoperative weight loss has been proposed as a potential strategy to optimise surgical outcomes, but evidence regarding its safety, efficacy, and feasibility remains unclear. A systematic search was conducted across MEDLINE, PubMed, EMBASE, and Cochrane from inception to 28th May 2025, following PRISMA 2020 guidelines and a registered protocol (PROSPERO ID: CRD42020154074). Eligible studies included adults (≥ 18 years) with obesity (BMI ≥ 30 kg/m²) undergoing surgery for GI cancers who received a structured preoperative weight loss intervention. Primary outcomes were feasibility and overall postoperative complication rates. Secondary outcomes included anastomotic leak, operative time, and adverse events. Meta-analysis was performed per outcome measure. Eight observational cohort studies comprising 532 patients (213 weight loss intervention vs. 319 control) were included. Completion rates for preoperative weight loss were ≥ 96.9%, with no intervention-related harms or surgical delays reported. Pooled analysis demonstrated a significant reduction in overall postoperative complications (OR 0.37, 95% CI 0.16–0.85; p = 0.02) and anastomotic leak (OR 0.26, 95% CI 0.12–0.60; p = 0.002) in the intervention group. Where assessed, skeletal muscle mass and nutritional parameters were preserved. Intentional preoperative weight loss appears feasible, safe, and may improve postoperative outcomes in patients with obesity undergoing GI cancer surgery. Integration of such strategies, particularly during neoadjuvant therapy windows, offers a modifiable opportunity to optimise surgical risk. Prospective trials are warranted to define optimal protocols, timing, and oncologic safety.

Associations between white matter lesions, adiposity, and systemic inflammation in late adulthood: Results from the IGNITE study.

Excess weight increases morbidity risk after colorectal cancer surgery. Weight loss might reduce this risk. However, the period between diagnosis and treatment in colorectal cancer is typically less than 1 month, necessitating an intensive weight loss intervention. We tested the feasibility of an intensive preoperative weight loss intervention.

Unintentional weight loss (UWL) is the primary diagnostic parameter for cancer cachexia in the clinic. Prompt identification of UWL can lead to earlier diagnoses and interventions for cancer. This study investigates the frequency and timing of UWL documentation and diagnoses in a cohort of cancer patients with measured UWL and sought to understand how recognition of UWL is related to stage of disease at cancer diagnosis. A retrospective cohort of adult gastrointestinal and non-small cell lung cancer patients with measured UWL was evaluated. Body weight histories were manually reviewed for UWL. Patients with intentional weight loss, weight loss related to fluid status or weight loss with unclear intention were excluded. Records were assessed for the use of UWL-related International Classification of Diseases codes and documentation of UWL. ULW was considered missed if it was not documented or diagnosed by a healthcare provider. Associations between weight loss over time, documentation and/or diagnosis of UWL and stage of disease at cancer diagnosis were investigated through repeated measures mixed models and univariate and multivariate tests. In total, 374 patients (24%) met the definition of UWL with an average weight loss of 8.6% ± 0.3%. UWL was missed in 161 (43%) patients with cancer cachexia. The odds of undetected UWL were greater in patients < 65 years old, with NSCLC, with obesity and who were White. In the 213 patients with recognized UWL, the documentation of UWL occurred approximately 7 months after their initial weight loss. The magnitude of weight loss was associated with cancer stage at cancer diagnosis (p < 0.0001). Patients who experienced ≥ 7.5% UWL pre-cancer diagnosis had a median cancer stage of 3 whereas patients who experienced < 7.5% UWL had a median cancer stage of 2 at cancer diagnosis (p < 0.0001). Relative to patients with ≥ 7.5% weight loss, the < 7.5% weight loss group had 73.7% more patients with Stage 1 disease (p < 0.0001) and 32.5% fewer patients with Stage 4 disease (p = 0.0006) resulting in median cancer stage increasing from Stages 2 to 3. UWL was missed in 43% of cancer cachexia patients despite 8.6% ± 0.3% body weight loss prior to cancer diagnosis. When recognized, documentation of UWL did not occur until 7 months after weight loss initiation. A greater magnitude of UWL was associated with more advanced disease at cancer diagnosis. Recognition and timely diagnosis of UWL will increase the percentage of patients with curable, early-stage disease.

A concern with intentional weight loss among middle-aged and older adults with obesity and type 2 diabetes mellitus (T2DM) is the loss of lean mass, which may lead to declining physical function. However, the association between changes in body composition with intentional weight loss and physical function over the long-term is unknown. Thus, we examined the association between changes in body composition and physical function 8 years following an intensive lifestyle intervention (ILI). We conducted a secondary analysis of participants at the Baton Rouge site within the Look AHEAD study. Participants (n = 220) were middle-aged and older adults with overweight/obesity and T2DM randomized to an ILI or diabetes support and education (DSE). Body composition was measured by dual-energy X-ray absorptiometry at baseline and Year 8. Physical performance (expanded Short Physical Performance Battery [SPPBexp], 20- and 400-m walk) and strength (grip and knee extensor) were assessed at Year 8. Percent change (mean ± SD) from baseline in weight, fat and lean mass over 8 years were -4.0 ± 7.3%, 0.2 ± 12.5% and -6.5 ± 5.3% in ILI and -3.0 ± 9.7%, 1.2 ± 17.1% and -5.8 ± 6.6% in DSE, respectively. ILI had better SPPBexp scores and faster gait speed than DSE at 8-year follow-up (p < 0.05). Increases in fat mass were associated with worse SPPBexp scores in ILI and DSE (p = 0.03) and with slower gait speed in DSE (p = 0.01). Decreases in lean mass were associated with weaker grip strength in ILI (p = 0.04) and knee extensor strength in ILI and DSE (p < 0.05). There were no significant interactions by intervention group. Although the overall intervention effect on physical function was positive, increases in fat mass were associated with poorer physical performance while lean mass loss was associated with weaker strength 8 years post-randomization. Findings highlight the importance of minimizing fat mass gain/regain and loss of lean mass during intentional weight loss.

Obesity is a multifactorial disease caused by physiological and environmental factors. Adults who have obesity are at increased risk for several additional chronic and infectious diseases, resulting in reduced life expectancy, compared to those with lower body mass indices. Weight loss (WL) has several clinical benefits to reducing these risks. However, among those who intentionally lose weight, it is common for some, or all, of the lost weight to be regained. There is evidence that changes affecting energy intake or expenditure, including metabolic adaptations in the weight-reduced state, work against maintaining WL. The Physiology Of the WEight Reduced State consortium (POWERS) designed a study to describe behavioral and metabolic adaptations to the weight reduced state and to examine their contributions to weight variability following WL. This is accomplished by quantifying physiological, psychosocial, behavioral and other factors before and after a behavioral intervention that induces WL. The primary goal of POWERS is to identify factors that explain the variability in weight change following intentional weight loss. This multi-center project includes a POWERS-designed WL intervention implemented at two clinical centers for 205 enrolled participants. Those losing at least 7% of their pre-intervention weight and attaining weight stability are followed in a 1-year observational phase that includes sequential physiological and behavioral phenotyping. It is anticipated that 70% of those enrolled in the WL program will enter the observational phase of the study and that 100 will complete the study. The primary outcome is weight change during the observational period with primary independent variables measuring energy intake and energy expenditure. Detailed endophenotypes of energy intake and energy expenditure are assessed using a combination of biospecimens, neuroimaging, objective measures (e.g., doubly labeled water, calorimetry, accelerometry, polysomnography), self-report questionnaires, and interviews to address their contributions to weight change variability up to 1 year following WL.

This study aimed to evaluate the impact of intentional weight loss on the risk of microvascular and macrovascular complications in people with obesity and type 2 diabetes (T2D), while accounting for changes in glycaemic control. Data from adults living with obesity (body mass index [BMI] ≥30 kg/m2) and T2D were extracted from Clinical Practice Research Datalink (CPRD) Aurum database from 2006 to 2022. Incidence of microvascular (retinopathy, neuropathy, and chronic kidney disease [CKD]) and macrovascular (myocardial infarction [MI], peripheral artery disease [PAD], and stroke) complications following a 4-year intentional weight loss period were quantified, and risk of outcomes estimated using Cox proportional hazard regression. Data from 100 507 people (mean age 53.3 years; 58% male) was included. Mean [SD] relative reduction in BMI was -2.2% [9.1%] and mean [SD] absolute change in HbA1c was 0.0% [1.9%]. Risk of composite microvascular and macrovascular complications was significantly reduced per 1% BMI reduction (hazard ratio [HR] 0.990 [95% CI 0.988, 0.992] and 0.996 [95% CI 0.994, 0.998], respectively) and per 1%-point decrease in HbA1c (HR 0.875 [95% CI 0.866, 0.884] and 0.872 [95% CI 0.862, 0.883]). Results were consistent across all subgroups. Reductions in BMI and HbA1c were associated with reduced risk of retinopathy, neuropathy, CKD, and PAD. Reductions in HbA1c-only were associated with reduced risk of MI and stroke. A reduction in BMI and HbA1c by intentional weight loss, independently and concomitantly, was associated with a reduced risk of microvascular and macrovascular complications in people with obesity and T2D.

BackgroundIntentional weight loss improves cardiometabolic risk factors, which by associated neuroprotective effects may reduce dementia risk. However, assessing change in dementia risk directly demands long‐term follow‐up. In this study, we assessed whether a recently validated 25‐protein signature for dementia risk could detect changes in dementia risk in response to an intentional weight loss program in people with type 2 diabetes (T2D) and associated cardiometabolic features.MethodsA potential impact of intentional weight loss on dementia risk was explored in two randomized controlled clinical trials in patients with obesity and T2D, DiRECT and DIADEM‐I; both demonstrated that a diet program to induce and maintain weight loss led to diabetes remissions of 46% and 61% at 1 year. The proteomic dementia risk test (derived from the SomaScan™ assay, predicting the probability of incident dementia diagnosis within 20‐years of blood draw) was applied to plasma samples at baseline and 1‐year in intervention (DiRECT n=118; DIADEM‐I n=56) and control (DiRECT n=144; DIADEM‐I n=66) participants. This model includes measurements of 25 plasma proteins, but not HbA1c, which might otherwise dominate a prediction of dementia risk in people with T2D. Dementia risk scores were compared within and between trial arms and the association between weight loss amount and the magnitude of dementia risk score change was explored.ResultsIn both DiRECT and DIADEM‐I a significant difference in the change in dementia risk score from baseline to 1‐year between the trial arms was observed (p =1.8x10‐7 and p =8.79x10‐8, respectively), with risk scores either remaining stable or decreasing in the intervention arm over the trial duration. Furthermore, in DiRECT there was a significant (p =9.06x10‐3) association between the amount of weight lost and the reduction in dementia risk in the intervention arm with greater weight loss associating with a greater reduction in dementia risk.ConclusionsThese results support epidemiological evidence that non‐pharmacological weight loss may protect against dementia risk, particularly in those with cardiometabolic features. Furthermore, the proteomic dementia risk test was robust to identifying changes in dementia risk in response to intentional weight loss. These findings suggest that the proteomic model has value to evaluate pharmacologic and non‐pharmacological interventions to reduce dementia.

Abstract Weight regain following intentional weight loss in older adults is a near expected occurrence. The gravitostat theory suggests that gravitational loading – in the form of a weighted vest, for instance – might dampen the body’s perception of weight loss, thus mitigating signals driving weight regain, such as reduced resting energy expenditure (REE). The 12-month INVEST in Bone Health Trial (NCT04076618), compared WL alone (targeting 10% WL), WL plus weighted vest use (WL+VEST; 8 hours/day, weight replacement up to 10% total WL), or WL plus resistance training (WL+RT; 3 supervised sessions/week) on bone health in 150 older adults, is an ideal platform to examine this concept. A subset of participants (n = 21) with baseline characteristics similar to the original cohort (66.9±5.4 years; 71% women; 67% white; body mass index [BMI] 33.3±3.5 kg/m²) returned for a 24-month follow up visit (12 months post-intervention) to collect REE and body weight. At intervention end (12-months), REE was better preserved in WL+VEST [+146.9 kcal/day (95% CI: 32.4, 222.4)] compared to WL alone [-52.5 kcal/day (95% CI: -137.5, 32.5)] and WL+RT [-89.7 kcal/day (95% CI: -160.5, -18.8)]; p = 0.02. From 12 to 24 months, WL+VEST regained the least weight [+0.74 kg (95% CI:(-3.75, 5.23)], compared to WL+RT [+4.74 kg (95% CI: 0.51, 8.96)] and WL alone [+4.40 kg (95% CI (2.03, 6.77)]; p = 0.084. Findings suggest that weighted vest use may attenuate long-term weight regain in older adults by preserving REE. Future work will examine other measures of energy balance, including physical activity energy expenditure and appetite hormones.