Search Results (1,768)

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are associated with immune-related adverse events (irAEs) and variable clinical outcomes. Clinical predictors of organ-specific irAEs remain indeterminate, particularly in real-world populations. Methods: We conducted a retrospective single-center cohort study including 751 adult patients with solid tumors treated with ICIs between 2018 and 2025. Clinical, demographic, and treatment-related variables were analyzed. Multivariable logistic regression identified predictors of irAEs, while associations with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed using logistic and Cox regression models. Results: The most frequent irAEs were endocrine (9.9%), dermatologic (9.1%), gastrointestinal (7.6%), and pulmonary (4.7%). Female sex independently predicted endocrine (aOR 1.98, p = 0.007) and rheumatologic irAEs (aOR 4.06, p = 0.007). Combination immunotherapy was associated with increased dermatologic (aOR 2.66, p = 0.013) and gastrointestinal irAEs (aOR 2.65, p = 0.016), while concurrent radiotherapy predicted gastrointestinal toxicity (aOR 1.82, p = 0.044). Atezolizumab was associated with higher pulmonary irAE risk (aOR 2.97, p = 0.048). Endocrine, dermatologic, gastrointestinal, and pulmonary irAEs were independently associated with improved ORR (OR range: 2.53–4.30, all p < 0.01). Conclusions: Organ-specific irAEs exhibit distinct clinical predictors and differential prognostic implications in patients receiving ICIs. Select irAEs are associated with improved treatment response and disease control, yet our results should be regarded as hypothesis-generating requiring further investigation. Full article

Seasonal variation in heart rate variability (HRV) reflects multiple interacting determinants rather than a single underlying determinant. In this study, we aimed to examine subgroup-level seasonal HRV variation in relation to physical activity (PA) using large-scale real-world data. We analyzed 133,747 24-h ECG recordings with tri-axial accelerometry from the ALLSTAR database across eight regions in Japan (after excluding regions with insufficient sample sizes) collected between 2015 and 2021. Seasonal variation (Δ) was defined as the difference between the maximum and minimum seasonal mean values. Weighted least squares models (WLS) were applied to examine associations between ΔPA and multiple HRV indices, including interaction terms for sex and region, while regional differences in residual variability were assessed using Levene’s test. During the normal period, significant associations between ΔPA and ΔHRV were observed for specific indices (ΔULF, ΔVLF, ΔHF, and ΔLF/HF), whereas other indices were not significant. During the Coronavirus Disease 2019 (COVID-19) period, significant associations were observed for ΔRRI, ΔSDRR, and ΔLF/HF, indicating that the association between PA and seasonal HRV variation was index-specific. Sex interactions were not statistically significant after FDR (False Discovery Rate) correction in either period, suggesting a limited role of sex in the PA–HRV relationship at the population level. Regional differences in HRV sensitivity to PA were statistically significant but heterogeneous across regions. In contrast, residual variability exhibited significant regional differences across multiple HRV indices in both periods. These patterns were not fully explained by sample size and showed stable regional heterogeneity. These findings suggest that subgroup-level regional heterogeneity in seasonal HRV variation is primarily reflected in the unexplained component rather than in the direct PA–HRV relationship, indicating the presence of region-specific variability in the unexplained component beyond behavioral influences. Full article

Background/Objectives: Executive functions and motor performance develop rapidly during early childhood and may be closely interconnected. However, it remains unclear whether specific motor domains are more strongly associated with executive functioning than others. This study examined the relationships among executive functions, motor performance, physical activity, and waist circumference in preschool children using structural equation modeling (SEM). Methods: A cross-sectional study was conducted in 364 preschool children aged 4–7 years from Temuco, Chile. Executive functions were assessed using the Childhood Executive Functioning Inventory (CHEXI). Motor performance included postural stability and strength–coordination indicators derived from the PREFIT battery and the Movement Assessment Battery for Children-2. Physical activity was assessed using the Krece Plus questionnaire. SEM was used to examine direct and indirect statistical associations among variables while adjusting for age and sex. Results: The final SEM showed acceptable fit to the data (CFI = 0.915; TLI = 0.882; RMSEA = 0.054). Postural stability was significantly associated with executive functions (β = −0.268, p = 0.016), whereas strength–coordination was not. Physical activity positively predicted postural stability (β = 0.099, p = 0.024), while waist circumference negatively predicted postural stability (β = −0.095, p = 0.032). An indirect statistical association between waist circumference and executive functions through postural stability was observed. The model explained 9.6% of the variance in executive functions. Conclusions: In preschool children, executive functioning appeared to be more closely associated with postural stability than with broader strength–coordination performance. Although the observed associations were modest in magnitude, the findings suggest that balance-related motor processes may be relevant for understanding motor–executive function associations during early childhood. Longitudinal and experimental studies are needed to clarify the nature and direction of these associations. Full article

Background: Lung transplant recipients often live for years with residual respiratory symptoms and psychological distress, but the pathways through which these factors affect quality of life (QoL) are not fully understood. We examined how transplant-specific pulmonary symptom burden and psychological distress relate to generic and transplant-specific QoL in long-term lung transplant recipients. Methods: In this cross-sectional study, 76 adult lung transplant recipients from a single center completed the Lung Transplant Quality of Life (LT-QoL) questionnaire, EQ-5D-5L, SF-36, St George’s Respiratory Questionnaire (SGRQ), and Hospital Anxiety and Depression Scale (HADS). A composite psychological distress index was derived from HADS-Anxiety, HADS-Depression, and the LT-QoL Anxiety/Depression and Health Distress subscales. Associations were examined using Pearson correlations, hierarchical linear regression (adjusting for age, sex, and time since transplant), and statistical mediation models examining psychological distress as a potential mediator between pulmonary symptoms and QoL outcomes. Results: Pulmonary symptom burden (LT-QoL Pulmonary Symptoms) was in the low–moderate range yet showed robust correlations with poorer generic, transplant-specific, and respiratory-specific QoL (|r| up to 0.82). The psychological distress index demonstrated good internal consistency (α = 0.84) and was strongly associated with worse EQ-5D, SF-36, and LT-QoL General QoL scores. In regression models, pulmonary symptoms and psychological distress independently predicted SF-36 overall QoL (R² = 0.55), whereas psychological distress was the stronger predictor of the EQ-5D Index Value. Statistical mediation analyses were consistent with partial mediation of the association between pulmonary symptoms and SF-36 and the EQ-5D Index Value, while effects on the EQ-VAS and LT-QoL General QoL were largely direct. Conclusions: Even modest pulmonary symptom burden and psychological distress are tightly linked to QoL years after lung transplantation. Routine follow-up should include brief assessment of both domains, and integrated care models that combine optimization of pulmonary status with targeted psychological support may be needed to preserve long-term QoL in lung transplant recipients. Full article

Introduction: Previous research has suggested thiazolidinediones (TZDs) may be associated with certain solid tumors. We examined incidence rates over time for patients with solid tumors who received TZD treatment for diabetes. Methods: We identified medication use and diagnosis codes that were aggregated to phecode disease classifications derived from the nationwide Veterans Administration Health Record System from 2000 to 2021. We identified 148,139 patients who had ≥2 diabetes diagnoses and had no previous cancer diagnosis. Among these, 8981 subjects had ≥4 years of TZD exposure. We then identified subjects with ≥2 diagnosis codes for solid tumors including bladder (n = 3987), breast (n = 632), colorectal (n = 5139), esophageal (n = 482), glioma (n = 591), lung (n = 5142), melanoma (n = 1896), pancreatic (n = 726), prostate (n = 11,884), renal (n = 3145), testicular (n = 369), and thyroid (n = 513). We used multivariable Cox proportional hazards regressions to measure associations between TZD use and cancer incidence. TZD use was modeled as a time-varying covariate from the first to last prescription of TZD medication, and analyses were adjusted for age at diabetes diagnosis, self-reported race, self-reported ethnicity, sex, body mass index, and cancer site-specific polygenic risk scores. Results: Long-term (≥4 years) exposure to TZDs was significantly associated with increased risk of developing prostate cancer (HR = 1.24, p < 0.001) and decreased risk of developing lung (HR = 0.58, p < 0.001), bladder (HR = 0.51, p < 0.001), and renal cancer (HR = 0.75, p = 0.003). Conclusions: Decreased risk of developing several solid tumors (lung, bladder, and renal) indicate that TZDs may be strong candidates for drug repurposing strategies to manage these types of cancer. These results warrant replication attempts in external datasets. Full article

Hepatitis E virus (HEV) is an emerging zoonotic pathogen in Europe, mainly transmitted via consumption of naturally contaminated food or contact with infected animals. People living in the Balkans have diverse dietary habits, with high pork consumption in some countries, making this region a relevant setting for investigating HEV seroprevalence and its possible determinants. The current study aimed to estimate pooled HEV seroprevalence among adults in the general population and blood donors and to assess factors associated with regional variation. Twenty-eight eligible studies were identified from PubMed, Scopus, and Web of Science following the PRISMA guidelines. Pooled prevalence estimates were calculated using a random-effects meta-analysis of proportions implemented via a generalized linear mixed model (GLMM) with logit transformation. Potential factors associated with HEV seroprevalence, including national pork consumption, serological assay type, population group, year of publication, sex, and country, were evaluated. The pooled anti-HEV seroprevalence was estimated to be 5.68% (95% CI: 3.48–9.12%), with substantial heterogeneity. Country-specific estimates ranged from 1.01% in Greece to 26.66% in Bulgaria. Subgroup analyses showed significant variation according to national pork consumption category, serological assay type, year of publication, and country. However, meta-regression indicated that methodological and temporal factors, particularly serological assay type and year of publication, were the main significant moderators, whereas national pork consumption was not independently associated with seropositivity. Therefore, pork consumption should be interpreted as an exploratory ecological indicator rather than as evidence of a direct association. The methodological differences contribute substantially to the variability in HEV seroprevalence across the Balkans, emphasizing the need for standardized diagnostic approaches within a One Health framework. Full article

Sleep is a multidimensional health domain influenced by behavioural, psychological, and lifestyle factors. However, multinational evidence integrating insomnia severity and multiple sleep outcomes within the Mediterranean lifestyle framework remains limited. This study examined correlates of insomnia severity and key sleep outcomes in adults from Mediterranean and neighbouring countries participating in the MEDIET4ALL survey. Data were collected from 4010 adults (59.5% female) across 10 countries using a standardized multilingual e-survey. Insomnia severity was assessed as primary outcome using the Insomnia Severity Index (ISI), while sleep characteristics were assessed using sleep duration, sleep latency, sleep efficiency, and subjective sleep quality. Regression analyses examined sociodemographic, health-related, Mediterranean dietary, movement-related, psychological, and social correlates. Exploratory statistical indirect association analyses involving life satisfaction were also conducted. Insomnia severity showed the highest explained variance among sleep outcomes (adjusted R² ≈ 0.29). Higher insomnia severity was associated with female sex, higher body mass index, and greater depression, anxiety, and stress (β ≈ 0.15–0.17), whereas lower insomnia severity was associated with older age, better self-reported health status, higher life satisfaction, and greater adherence to Mediterranean dietary consumption patterns (β ≈ −0.04 to −0.11). Models for secondary sleep outcomes explained more modest variance and should be interpreted as exploratory. Across these outcomes, psychological well-being and distress showed the most consistent associations, while Mediterranean dietary dimensions and social participation showed smaller and outcome-specific associations. Exploratory indirect association analyses showed small but statistically significant indirect associations involving life satisfaction between Mediterranean dietary dimensions, social participation, and selected sleep outcomes, particularly sleep quality and insomnia severity. The findings confirm and contextualize established associations between sleep, psychological well-being, distress, Mediterranean lifestyle-related behaviours, and regional context within a large multinational sample. Psychological well-being and distress emerged as the most consistent correlates. Insomnia severity was the most robustly explained sleep outcome, whereas secondary sleep dimensions reflected more modest exploratory correlational profiles. Full article

Background/Objectives: Dynamic balance during the Y-Balance Test (YBT) relies on coordinated multi-joint control of the lower extremity. Although hip muscle strength is considered important for YBT performance, the relative contribution of individual hip muscle groups remains insufficiently understood. This study aimed to examine the associations between isometric hip abduction, external rotation, and extension strength and YBT performance in healthy adults. Methods: In this cross-sectional study, 104 healthy adults underwent assessment of isometric hip abduction, external rotation, and extension strength using strap-stabilized handheld dynamometry. Hip extension strength was measured in the prone position with the knee flexed to 90°. Strength values were normalized and expressed as joint torque (Nm/kg). YBT performance was assessed in the anterior, posteromedial, and posterolateral directions and as a composite score. Associations were examined using Pearson correlation coefficients. To account for the dependency of bilateral measurements, a linear mixed model (LMM) was used to evaluate the collective and independent contribution of hip strength components to YBT performance, with sex, age, and BMI included as covariates. Results: All hip strength measures showed significant positive correlations with YBT performance (r = 0.19–0.49, p < 0.05). Hip extension strength demonstrated the strongest associations, particularly with posterolateral reach (r = 0.49). After adjustment for demographic covariates, sex was the strongest predictor of YBT performance across all directions (β = 7.8–8.9, p < 0.001), with males achieving higher scores than females. Hip extension and abduction strength were significant predictors of posterolateral reach (p < 0.05), whereas no hip strength variable independently predicted anterior reach or composite score after adjustment for demographic factors. No significant differences in YBT performance were observed between limbs. Conclusions: Sex was the strongest predictor of YBT performance in healthy adults. Hip extension and abduction strength were independently associated with posterolateral reach performance after controlling for demographic factors, suggesting that the association between hip muscle strength and dynamic balance may be direction-specific. These findings highlight the importance of accounting for sex when interpreting the relationship between hip strength and YBT performance. Full article

Background/Objectives: Prediction is a fundamental mechanism of language comprehension, enabling readers to generate expectations about upcoming words during sentence processing. Event-related potentials (ERPs), particularly the N400 and P300, provide sensitive electrophysiological markers of semantic integration and expectancy-related processing. However, the contributions of individual sentence elements to semantic prediction and the influence of sex differences on these processes remain poorly understood. Methods: Forty-six healthy right-handed young adults (23 females) performed a semantic decision task with six-word Spanish sentences ending in congruent or incongruent final words while EEG activity was recorded. ERP components associated with anticipatory and integrative stages of sentence processing were analyzed during the sequential presentation of sentence words. Behavioral performance and sex-related ERP differences were assessed using repeated-measures ANOVAs and correlational analyses. Results: Behavioral findings showed that males committed significantly more errors in detecting semantic incongruities, although overall performance exceeded 92%. Congruent sentence endings elicited a centro-parietal P300, whereas incongruent endings produced a robust N400 followed by a late positive component (LPC). Sex differences emerged, beginning at the third word of the sentence. Males exhibited greater P2 amplitudes and a larger anticipatory P300-like positivity preceding the final word, whereas females showed enhanced N2 and N400 negativities associated with contextual processing and semantic incongruity. Correlations between anticipatory ERP activity and later semantic components supported functional continuity between predictive and integrative stages of language processing. Despite earlier differences, males and females exhibited comparable LPC amplitudes, suggesting convergence during later elaborative processing stages. Conclusions: These findings support predictive models of language comprehension by demonstrating that semantic expectations are progressively constructed throughout sentence processing. Sex-related ERP differences were observed across anticipatory, attentional, and semantic integration stages, indicating quantitative and stage-specific neurophysiological variations rather than qualitatively distinct language-processing strategies. Full article

Background/Objectives: Long COVID-19 (LC) has been associated with persistent inflammation and impaired vascular health. Dietary minerals are involved in oxidative stress, endothelial homeostasis, and arterial stiffness; however, their relationship with vascular health in LC remains poorly explored. This study aimed to examine the association between energy-adjusted dietary mineral intake and markers of vascular stiffness and vascular aging in adults with LC, while exploring potential sex-specific patterns. Methods: A total of 304 adults with LC from the BioICOPER study were included. Dietary mineral intake was assessed using a validated 7-day dietary record from the EVIDENT tool and expressed as mineral density per 1000 kcal for the regression analyses. Vascular assessment included carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (cfPWV), brachial-ankle pulse wave velocity (baPWV), and the vascular aging index (VAI). Hierarchical multivariable linear regression models, false discovery rate (FDR) correction, restricted cubic spline analyses, sensitivity analyses excluding supplement users, and formal sex × mineral interaction tests were performed. Results: In descriptive adequacy analyses, adequate iron intake was associated with lower baPWV. In energy-adjusted linear regression models, no mineral-outcome association remained statistically significant after FDR correction. In the fully adjusted sensitivity model, zinc density showed a nominal positive association with cfPWV, but this association did not survive FDR correction. Restricted cubic spline analyses suggested possible non-linear associations of magnesium and potassium density with cfPWV and VAI. Formal interaction analyses did not provide robust evidence of sex-related effect modification. Conclusions: After energy adjustment and correction for multiple testing, the evidence for independent linear associations between dietary mineral density and vascular outcomes in adults with LC was limited. These exploratory findings suggest that mineral intake, dietary sources, and non-linear patterns deserve further evaluation in prospective studies and nutritional intervention trials. Full article

Background/Objectives: Insulin resistance is increasingly recognized as a cause of colorectal neoplasms, but its measurement requires fasting insulin, which is not routinely available in clinical settings. The triglyceride–glucose (TyG) index, derived from fasting triglyceride and glucose, has emerged as a simple surrogate of insulin resistance. We aimed to evaluate the association of the TyG index with colorectal adenoma, identify a clinically usable cut-off, and examine whether the association is preserved across major subgroups. Methods: We conducted a cross-sectional analysis of 7251 asymptomatic adults who underwent screening colonoscopy and same-day biochemistry at university hospital health care centers in Daejeon and Chungcheong province of South Korea between November 2019 and June 2022. The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariable logistic regression was used to estimate odds ratios (ORs) for adenoma; discrimination was evaluated by area under the receiver-operating-characteristic curve (AUC), and the optimal cut-off was identified by Youden’s J. Large adenoma (≥10 mm) was analyzed as a secondary outcome. Results: Among 7251 participants (mean age 54.1 ± 11.2 years; 59.7% male; mean BMI 24.7 ± 3.4 kg/m²), 2402 (33.1%) had at least one colorectal adenoma. Adenoma prevalence rose monotonically across TyG quartiles (Q) (Q1, 26.3%; Q2, 32.0%; Q3, 35.5%; Q4, 38.7%; p for trend <0.001). A 1-standard deviation (SD) increase in TyG index was associated with adenoma prevalence in the fully adjusted model (OR 1.13, 95% confidence interval (CI) 1.06–1.20), and the Q4-versus-Q1 OR was 1.29 (1.09–1.53). The optimal cut-off for adenoma was TyG index = 8.55 (AUC 0.564, sensitivity 59.1%, specificity 50.8%); the association was modestly stronger for large adenoma (AUC 0.585; adjusted OR per 1-SD 1.25, 1.09–1.43). Subgroup analyses showed consistent effects across sex, age, body mass index, hypertension, diabetes, and metabolic-syndrome strata (all p for interaction >0.17). Conclusions: In a large screening cohort, an elevated TyG index was associated with the presence of colorectal adenoma, with a graded dose–response relationship and a modestly more pronounced association for large adenoma. Although discrimination by TyG index alone is too modest to support its use as a stand-alone screening tool, the index may serve as a low-cost adjunct within a multifactorial risk-stratification framework. Full article

Background/Objectives: Diabetic neuropathy is a prevalent complication of type 2 diabetes mellitus (T2DM), but the contribution of dietary factors to neuropathy severity remains insufficiently characterized. This study investigated associations between dietary patterns, nutrient intake, and neuropathy severity in 300 adults with T2DM from Northeastern Romania. Methods: Dietary intake was assessed using a validated food frequency questionnaire, and five dietary patterns were derived using principal component analysis. Neuropathy severity was analyzed as an ordinal outcome using logistic regression models adjusted for age, sex, HbA1c, diabetes duration, and treatment. Results: Higher adherence to Western/fast-food and alcohol and animal fat dietary patterns was associated with greater neuropathy severity in unadjusted analyses, whereas a healthy/prudent pattern showed inverse associations; however, these relationships were attenuated after multivariable adjustment. In contrast, higher intakes of protein (OR = 0.98, 95% CI: 0.97–0.99), magnesium (OR = 0.99, 95% CI: 0.98–1.00), zinc (OR = 0.80, 95% CI: 0.69–0.94), vitamin B3 (OR = 0.94, 95% CI: 0.89–0.99), and vitamin B12 (OR = 0.76, 95% CI: 0.62–0.93) remained independently associated with lower neuropathy severity after adjustment. Conclusions: These findings suggest that specific nutrient intakes may be more strongly associated with diabetic neuropathy severity than overall dietary patterns, highlighting potential nutritional targets for neuropathy risk reduction and clinical management in patients with T2DM. Full article

Background: Elite cycling can be dichotomised into road (endurance cycling) and track (sprint cycling) events that are associated with different training components and athlete physiology. Evidence of disproportionate right ventricular (RV) remodelling in endurance athletes places importance on defining physiological and athletic phenotypes. Therefore, the elite cyclist serves as an ideal model to study training-specific adaptations in the right heart. Methods: One hundred and eighty-six (110 males and 76 females) elite international-level cyclists (mean age 23 ± 5 years) were grouped by discipline (endurance cycling and sprint cycling) and sex (male cyclists and female cyclists). RV and right atrial (RA) structure and function was assessed with 2D, tissue Doppler, and strain echocardiography. Structural data were scaled allometrically to body size. Group comparisons were made with a two-way ANOVA. Results: Significantly larger absolute and scaled RV and RA structural values were seen in male and endurance cyclists (RV end diastolic area index: male endurance 14 ± 2 cm²/m², male sprint 13 ± 2 cm²/m²) than female and sprint cyclists (female endurance 13 ± 2 cm²/m², female sprint 11 ± 2 cm²/m²), respectively. Endurance training exposure was significantly correlated to structural parameters (RA area index: r = 0.53; p < 0.001). Sex and discipline showed significant impact on resting RV function with reduced RV strain values in male and endurance cyclists (RV basal strain: male endurance −17.5 ± 4.0%, male sprint −19.4 ± 4.6%) compared to female and sprint cyclists (female endurance −19.9 ± 3.9%, female sprint −22.1 ± 5.1%), respectively. There were no significant correlations between training exposure and resting RV function. Conclusions: Athlete sex and cycling discipline exert significant effects on RV and RA structure and function in elite cyclists. The strong correlations observed between endurance training exposure and right heart structure emphasise the importance of consideration of sporting discipline in elite athletes. Full article

Background/Objectives: Dementia poses a major public health challenge in South Korea, where population ageing has accelerated rapidly. We aimed to describe national 2016–2025 dementia prevalence trends and to generate a one-year 2026 forecast using NHIS-linked administrative data. Methods: We performed a retrospective longitudinal analysis of de-identified aggregate administrative data from the Ministry of Health and Welfare Municipal and District Dementia Status Report (2016–2025) and NHIS age–sex pivot table records. This was a purely descriptive and forecasting analysis; no inferential statistical tests were applied. Descriptive statistics were computed for national, sex-stratified, regional, and age-stratified outcomes. For the 2026 forecast, we used a prespecified demographic-offset time-series approach: the population aged 65 years or older and the estimated prevalence rate were modelled separately using damped-trend Holt exponential smoothing, then recombined to estimate patient count. Residual bootstrap resampling (20,000 iterations) was used to derive a 95% prediction interval for the patient count. A sensitivity analysis using ARIMA(1,1,0). Results: 602,633 (8.89%) in 2016 to 955,585 (9.09%) in 2025, a 58.6% increase. Females consistently showed higher prevalence than males (2025: 9.55% vs. 8.52%), and regional analysis identified South Jeolla Province (10.17%) as the highest-prevalence region and Ulsan Metropolitan City (8.10%) as the lowest. The female-to-male cumulative rate ratio reached 2.49 in the ≥85-year group. The primary 2026 forecast estimated 1,003,407 dementia patients among adults aged 65 years or older, with an estimated prevalence of 9.19% and a 95% prediction interval of 983,838–1,022,158. Conclusions: South Korea’s rising dementia burden is primarily driven by population ageing rather than a sharp increase in age-specific prevalence. The 2026 forecast supports urgent planning for a national dementia care population of approximately one million people. Full article

Variants in the glucocerebrosidase gene (GBA1) are the predominant genetic risk factor for Parkinson’s disease (PD), often accelerating disease progression. While biological sex modulates PD progression, the longitudinal association between rasagiline (a monoamine oxidase-B [MAO-B] inhibitor) and motor outcomes in GBA1-associated Parkinson’s disease (GBA1-PD) remains unclear. This retrospective cohort study (2019–2026) analyzed 259 patients with PD (106 females, 153 males) with a median follow-up of 1.56 years to evaluate the association between rasagiline use and motor decline, emphasizing sex-stratified outcomes. Motor progression was evaluated using the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS-III). Rates of change were calculated using sex-stratified Generalized Estimating Equations models, with adjustment for age at diagnosis to evaluate treatment effects and sex-specific associations. Among 259 patients, rasagiline use was associated with a significantly slower annual rate of motor decline (Slope Difference: −0.95; p = 0.03). In the GBA1-PD subgroup, females using rasagiline exhibited a clinically relevant slower rate of progression (approximately 1 point/year on the MDS-UPDRS-III) compared with non-users, although not statistically significant (p = 0.08); no association was observed in males. These findings suggest a potential sex-specific association of rasagiline with motor progression in GBA1-PD. Results highlight the importance of sex-stratified analyses to support personalized therapeutic approaches for PD genetic variants. Full article