Modern surgical therapy for gastric cancer-Robotics and beyond.

The surgical paradigm for gastric cancer has been changed from extended surgery to minimally invasive surgery. Laparoscopic surgery is a practical method for minimally invasive surgery for early gastric cancer, and the indication is expanding to advanced gastric cancer. In recent years, robotic gastrectomy has been highlighted as a breakthrough to overcome the drawbacks of laparoscopic gastrectomy. Here, we discuss the recent updates of modern surgical therapy for gastric cancer-robotics and beyond.

Trends in clinical outcomes and long-term survival after robotic gastrectomy for gastric cancer: a single high-volume center experience of consecutive 2000 patients.

BACKGROUND: Minimally invasive surgery is now a standard treatment for gastric cancer. Many retrospective studies have reported that robotic gastrectomy is safe and feasible, with similar short- and long-term outcomes as laparoscopic gastrectomy. However, no studies have reported the details of surgical and survival outcomes for robotic gastrectomy. This study aimed to evaluate the surgical trends and techniques of robotic gastrectomy and analyze the surgical outcomes of 2000 consecutive patients with gastric cancer who underwent robotic gastrectomy over 14 years. METHODS: Between July 2005 and January 2019, 2000 consecutive robotic gastrectomies were performed. We evaluated short- and long-term outcomes as well as surgical trends after robotic gastrectomy. RESULTS: There were 1,560 subtotal gastrectomies (78%), 324 total gastrectomies (16.2%), 83 proximal gastrectomies (4.2%), and 33 completion total gastrectomies (1.7%). The rates of major complications and mortality were 3.1% and 0.3%, respectively. In a subgroup analysis, there were no significant differences in the rate of complications over time (P = 0.696). Five-year overall survival rates were 97.6% for stage I, 91.9% for stage II, and 69.2% for stage III, with a total recurrence rate of 5.3%. Since its adoption in 2005, the proportion of robotic gastrectomies, as well as technically demanding procedures have increased over time. CONCLUSIONS: Our 14 years' experience of 2000 robotic gastrectomies has shown the proportion, as well as the number of robotic gastrectomies, have tended to increase and trends toward to technically demanding procedures. Outcomes of robotic gastrectomy appear safe and feasible with acceptable short- and long-term outcomes.

Fluorescent lymphography during minimally invasive total gastrectomy for gastric cancer: an effective technique for splenic hilar lymph node dissection.

BACKGROUND: Fluorescent lymphography is an excellent technique for complete lymph node dissection during minimally invasive surgery for gastric cancer. This study aimed to evaluate the role of fluorescent lymphography in splenic hilar lymph node dissection during minimally invasive total gastrectomy. METHODS: We retrospectively analyzed 168 gastric cancer patients who underwent minimally invasive total gastrectomy with D2 + No. 10 lymph node dissection from 2013 to 2018. Fluorescent lymphography was used whenever it is possible. However, when near-infrared imaging system and endoscopic indocyanine green injection were not available, we performed surgery without fluorescent lymphography. A total of 74 patients underwent surgery with fluorescent lymphography (FL group) and 94 underwent surgery without it (non-FL group). Perioperative and long-term outcomes including the number of retrieved lymph nodes at each nodal station were compared between groups. RESULTS: The median number of retrieved lymph nodes at the splenic hilum was larger in the FL group {2.5 [Interquartile range (IQR), 1-5]} than in the non-FL group [1 (IQR, 1-3); P = 0.012]. The negative predictive value of fluorescent lymphography for lymph node metastasis at the splenic hilum was 97.1%, although the sensitivity was 66.7%. The overall survival (FL: 96.9% vs. non-FL: 88.9%; P = 0.334) and relapse-free survival (FL: 90.5% vs. non-FL: 65.5%; P = 0.054) were higher in the FL group, although there were no statistical differences. However, among the patients without lymph node metastasis, the relapse-free survival was significantly higher in the FL group (100%) than in the non-FL group (67.1%; P = 0.017). CONCLUSIONS: Fluorescent lymphography is an effective tool for complete lymph node dissection at the splenic hilum. Moreover, it may help select patients who do not need splenic hilar lymph node dissection during a total gastrectomy.

Lymphovascular Invasion: Traditional but Vital and Sensible Prognostic Factor in Early Gastric Cancer.

BACKGROUND: Although patients with early gastric cancer have good prognosis, recurrence after treatment may occur. Lymphovascular invasion (LVI) in gastric cancer has long been suggested as a poor prognostic indicator. This study sought to evaluate the prognostic effect of LVI in patients with early gastric cancer. METHODS: From 2005 to 2016, 6516 patients with early gastric cancer who underwent radical gastrectomy were analyzed. The patients were categorized according to LVI and lymph node (LN) status. RESULTS: LVI was present in 853 patients (13.1%). Patients with LVI or LN metastasis had more aggressive tumor characteristics than patients without both LVI and LN metastasis. The overall and relapse-free survival in patients with LVI were significantly worse than in patients without LVI. When we compared the survival rate of patients stratified by LVI and LN status, there was a significant overall and relapse-free survival difference between patients without both LVI and LN metastasis compared with those with LVI but without LN metastasis (p < 0.001). The overall and relapse-free survival of patients with LVI but without LN metastasis were similar to those without LVI but with LN metastasis (p = 0.818). Patients with LVI or LN metastasis showed a high frequency of recurrence (p < 0.001). Multivariate analysis showed that LVI and LN status were independent risk factors for relapse-free survival of early gastric cancer patients. CONCLUSIONS: Early gastric cancer with LVI is associated with poor prognosis and frequent recurrence. When predicting the prognosis of patients with early gastric cancer, LVI should be considered.

Surgical Merits of Open, Laparoscopic, and Robotic Gastrectomy Techniques with D2 Lymphadenectomy in Obese Patients with Gastric Cancer.

BACKGROUND: Robotic surgery has been widely adopted for complex procedures to overcome technical limitations of open or laparoscopic methods. However, evidence of any subsequent benefit is lacking. This study was undertaken to compare open, laparoscopic, and robotic gastrectomy in technically demanding procedure-D2 dissection in obese patients with gastric cancer. METHODS: Data collected between 2010 and 2018 on D2 gastrectomy in obese patients with gastric cancer were used to conduct retrospective analysis, comparing short- and long-term outcomes of open, laparoscopic, and robotic techniques. RESULTS: In a total of 185 patients, there were 69 open, 62 laparoscopic, and 54 robotic gastrectomy procedures. Median ages for respective surgical groups were 66 (interquartile range [IQR]: 61-64 years), 63 (IQR: 59-63), and 59 years (IQR: 56-60 years) (p = 0.009). Early-stage gastric cancer ranked proportionately higher in the laparoscopic group (p = 0.005), but operative times were similar among groups. Estimated blood loss (p < 0.001) and drainage volumes (p = 0.001) were higher in the open group, relative to others. Although a robotic approach performed best in overall compliance and in mean number of retrieved lymph node, observed rates of early or late complications did not differ by technique. The open group experienced significantly poorer overall (p = 0.039) and relapse-free (p < 0.001) survival compared with the laparoscopic or robotic group. Robotic surgery emerged from multivariable Cox regression as a protective factor for relapse-free survival (HR = 0.314, 95% CI 0.116-0.851). CONCLUSIONS: In obese patients with gastric cancer, robotic gastrectomy with D2 lymphadenectomy proved comparable to open or laparoscopic technique short-term, yielding better long-term outcomes.

Assessment of diagnostic value of fluorescent lymphography-guided lymphadenectomy for gastric cancer.

BACKGROUND: Indocyanine green fluorescent lymphography helps visualize the lymphatic drainage pattern in gastric cancer; however, it is unknown whether fluorescent lymphography visualizes all metastatic lymph nodes. This study aimed to evaluate the sensitivity of fluorescent lymphography to detect metastatic lymph node stations and lymph nodes and the risk of false-negative findings. METHODS: Patients with clinical T1-4a gastric cancer were included. Indocyanine green was peritumorally injected the day prior to surgery by endoscopy. Gastrectomy with systematic D1+ or D2 lymphadenectomy was performed. Stations and lymph nodes were retrieved at the back-table using near-infrared imaging and classified as "fluorescent" or "non-fluorescent" and later matched with histopathological findings. RESULTS: Among 592 patients who underwent minimally invasive gastrectomy from September 2013 until December 2016, lymph node metastases were present in 150. The sensitivity of fluorescent lymphography in detecting all metastatic lymph node stations was 95.3% (143/150 patients), with a false-negative rate of 4.7% (7/150 patients) and the sensitivity in detecting all metastatic lymph nodes was 81.3% (122/150 patients). The negative predictive value was 99.3% for non-fluorescent stations and 99.2% for non-fluorescent LNs. For detecting all metastatic LN stations, subgroup analysis revealed 100% sensitivity for pT1a, 96.8% for pT1b, 100% for pT2, 91.3% for pT3, and 93.6% for pT4a tumors. CONCLUSIONS: Fluorescent lymphography-guided lymphadenectomy can be a useful method for radical lymphadenectomy by facilitating the complete dissection of all potentially positive LN stations. Fluorescent lymphography-guided lymphadenectomy appears to be a reasonable alternative to conventional systematic lymphadenectomy for gastric cancer.

Lower rate of conversion using robotic-assisted surgery compared to laparoscopy in completion total gastrectomy for remnant gastric cancer.

BACKGROUND: Completion total gastrectomy with radical lymphadenectomy for remnant gastric cancer is a technically demanding procedure. No previous studies have compared laparoscopic to robotic-assisted completion gastrectomy, whereas a few small case series have reported benefits of minimally invasive surgery over open surgery. The aim of this study is to assess the effectiveness and feasibility of robotic-assisted compared with laparoscopic completion gastrectomy for the treatment of remnant gastric cancer. METHODS: We retrospectively reviewed data from 55 patients who underwent minimally invasive completion gastrectomy for remnant gastric cancer at the Severance Hospital of Yonsei University Health System from April 2005 to July 2017. Of the 55 patients, 30 patients underwent laparoscopic and 25 underwent robotic-assisted completion total gastrectomy. We compared the patients' demographics, operative outcomes, and postoperative outcomes. RESULTS: Operation time was longer in the robotic-assisted surgery group (225 vs 292 min, P < 0.001), but both groups had similar estimated blood loss. The laparoscopic surgery group had a 13.3% (four patients) rate of conversion to open surgery because of severe adhesions, whereas no patients in the robotic group underwent conversion to laparoscopic or open surgery (P = 0.058). Mean hospital stay, postoperative complications, and recovery were similar in both groups. Pathology results, including the number of retrieved lymph nodes, did not differ between groups. CONCLUSION: Laparoscopic and robotic approaches are both feasible and safe for remnant gastric cancer, with comparable short-term outcomes. However, the robotic approach demonstrated a lower conversion rate than laparoscopy, although the statistical difference was marginal.

Intracorporeal esophagojejunostomy using a linear stapler in laparoscopic total gastrectomy: comparison with circular stapling technique.

BACKGROUND: Laparoscopic total gastrectomy for gastric cancer is feasible but less commonly performed compared to laparoscopic distal gastrectomy due to technical difficulties such as reconstruction. There is no standard esophagojejunal anastomosis technique in laparoscopic total gastrectomy due to a lack of evidence. METHODS: We retrospectively analyzed data from 213 patients with gastric cancer who underwent laparoscopic total gastrectomy from October 2012 to December 2016. Of these, 109 and 104 patients underwent esophagojejunostomy with linear and circular stapling, respectively. We compared short-term postoperative outcomes, including surgical complications and anastomosis costs between both groups. RESULTS: The mean operation time in the linear stapler group was longer than the circular stapler group (Linear stapler, 235.3 ± 57.9 vs. Circular stapler, 217.1 ± 55.8 min; P = 0.021); however, D2 lymph node dissection was performed more in the linear stapler group (Linear stapler, 36.7% vs. Circular stapler, 23.1%; P = 0.030). There were two anastomosis leakages in each group (Linear stapler, 1.8% vs. Circular stapler, 1.9%; P > 0.999). Anastomosis stenosis only occurred in the circular stapler group (Linear stapler, 0% vs. Circular stapler, 7.7%; P = 0.003). Although the linear stapling technique used more stapler cartridges (Linear stapler, 7.6 ± 1.1 vs. Circular stapler, 4.8 ± 0.9; P < 0.001), costs related to anastomosis were lower in the linear stapler group (Linear stapler, 1,904,679 ± 342,116 vs. Circular stapler, 2,246,150 ± 427,136KRW; P < 0.001). CONCLUSIONS: Esophagojejunostomy with the linear stapling technique reduces anastomosis stenosis in laparoscopic total gastrectomy. It can be recommended as a safe and more cost-effective method for esophagojejunal anastomosis.

Multi-institutional validation of the 8th AJCC TNM staging system for gastric cancer: Analysis of survival data from high-volume Eastern centers and the SEER database.

BACKGROUND: The clinical relevance and general applicability of the 8th American Joint Committee on Cancer TNM gastric cancer staging system vs the 7th version have not been examined using datasets from both the East and West. METHODS: Patients (n = 29 984) treated for gastric adenocarcinoma at two high-volume centers (Severance Hospital [SH] and Gangnam Severance Hospital [GSH]) in Korea and data from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. Survival curves, the performance of tumor staging, and the homogeneity of modified subgroups were compared. RESULTS: Minute changes were noted in the stage IIB subgroup; most changes were noted in stage III. Applying the 8th staging system facilitated better prediction of survival than applying the 7th version for SH data according to the log-rank test, C-index, and AIC (8444.5 vs 9263.8, 0.796 vs 0.798, and 104152 vs 103909, respectively). Its performance was also superior for GSH and SEER data. In a subgroup analysis of stages IIB to IIIC in SH, GSH, and SEER data, the 8th staging system showed similar or more homogeneous survival for each sub-classification than the 7th version. CONCLUSION: Compared with the 7th gastric cancer staging system, the newer version more accurately predicted prognosis and stratified subgroups more homogeneously.

Robotic spleen-preserving splenic hilar lymph node dissection during total gastrectomy for gastric cancer.

BACKGROUND: Robotic system may have potential advantages to facilitate the technically challenging splenic hilar lymphadenectomy during gastrectomy for gastric cancer. However, robotic spleen-preserving splenic hilar lymphadenectomy is performed infrequently not only because of the limited availability of the robot but also because of its technical difficulty. In this study, we describe our technique of performing robotic spleen-preserving splenic hilar lymphadenectomy in detail to facilitate wider application and present operative outcomes and the follow-up results of the procedure. METHODS: From 2005 to 2015, 93 patients underwent robotic total gastrectomy with D2 lymphadenectomy. One patient with obvious lymph node (LN) metastasis received splenectomy and was excluded from the analysis. Intraoperative complications, operation and console time, estimated blood loss, postoperative morbidity and mortality, the number of harvested LNs in total and at the splenic hilum, and 5-year overall survival were analyzed, retrospectively. RESULTS: Among the 92 patients, robotic spleen-preserving splenic hilar lymphadenectomy was successfully performed in 91 patients except one who experienced intraoperative splenic artery injury which demanded splenectomy to be performed simultaneously. The overall mean operation time and console time were 287.2 ± 66.0 and 180.2 ± 47.2 min, respectively. Mean estimated blood loss was 141.1 ± 227.0 ml. The mortality was 1.1% (1/92). The overall postoperative morbidity rate was 16.3% (15/92). There was no case of pancreatic fistula, whole splenic infarction, or the delayed aneurysm of splenic artery. The mean numbers of harvested LNs in total and at the splenic hilum were 50.8 ± 18.1 and 1.9 ± 2.6. The 5-year overall survival was 86.3% and 5-year recurrence-free survival was 87.4%. CONCLUSION: This study suggests that robotic application for spleen-preserving splenic hilar lymphadenectomy could be a feasible and safe method.

Similar hematologic and nutritional outcomes after proximal gastrectomy with double-tract reconstruction in comparison to total gastrectomy for early upper gastric cancer.

BACKGROUND: Proximal gastrectomy offers theoretical benefits over total gastrectomy in terms of hematologic and nutritional outcomes. However, little evidence confirming these benefits has been reported. The aim of this study was to assess the hematologic and nutritional outcomes of proximal gastrectomy with double-tract reconstruction in comparison to those of total gastrectomy. METHODS: We retrospectively analyzed data from 80 patients with stage I gastric cancer who underwent proximal gastrectomy with double-tract reconstruction (n = 38) or total gastrectomy (n = 42) from September 2014 to December 2015. We compared hematologic (including hemoglobin, ferritin, vitamin B12, etc.) and nutritional outcomes [including body mass index (BMI), serum total protein, albumin, total cholesterol, and total lymphocyte count] between the two groups. RESULTS: We found no significant differences in changes in hemoglobin (P = 0.250) or cumulative incidence of iron deficiency anemia (P = 0.971) during a median follow-up period of 24 months (range 18-30 months) after surgery. Cumulative incidence of vitamin B12 deficiency also did not differ significantly between the proximal and total gastrectomy groups (P = 0.087). BMI changes from baseline were not significantly different between the two groups (P = 0.591). Likewise, there were no statistically significant differences in nutritional outcomes. CONCLUSIONS: Proximal gastrectomy with double-tract reconstruction exhibited similar outcomes in terms of hematologic and nutritional features in comparison to total gastrectomy.

A prospective observational study of pigmented naevi changes in psoriasis patients on biologic therapy.

BACKGROUND/OBJECTIVES: Patients on biologic therapy are thought to be at increased risk of developing non-melanoma skin cancers and melanomas. It is unknown whether biologic therapy alters the natural history of melanocytic naevi. Therefore, a prospective observational study was conducted to determine whether psoriasis patients on biologic therapy develop changes in naevi. METHODS: Clinical and dermoscopic assessment of all melanocytic naevi was performed in 45 psoriasis patients on biologic therapy versus a control cohort of 43 subjects, using sequential digital dermoscopic imaging and total body photography. The mean follow-up period was 1.5 years. RESULTS: The study and control patients had comparable age, gender, previous and family history of non-melanoma skin cancers and melanomas, as well as previous sun exposure and total number of naevi. The number of naevi with major dermoscopic changes was 3% in the study and 1.9% in the control group, with an adjusted incidence rate ratio of 1.45 (95% confidence interval 0.90-2.33; P = 0.125). The rate of minor changes was 15.9% in the study group versus 19.4% in the control (adjusted incidence rate ratio 0.77, 95% confidence interval 0.57-1.08; P = 0.14). There were six new dysplastic naevi in 4/45 biologic patients and four in 4/43 controls; however, the difference was not significant (relative risk 0.96, 95% confidence interval -0.12 to 0.12; P = 0.95). There were no melanomas in either group. CONCLUSION: Over a mean follow-up period of 1.5 years there was no evidence of significantly different changes in naevi or development of new dysplastic naevi in psoriasis patients on biologic treatment compared to controls.

Parameters for Predicting Surgical Outcomes for Gastric Cancer Patients: Simple Is Better Than Complex.

BACKGROUND: Various parameters are used to predict perioperative surgical outcomes. However, no comprehensive studies in gastrectomy have been conducted. This study aimed to compare the performance of each parameter in patients with gastric cancer. METHODS: The medical records of 1032 gastric cancer patients who underwent curative gastrectomy between 2009 and 2015 were reviewed. Laboratory values and associated parameters (neutrophil count, lymphocyte count, platelet count, albumin level, Prognostic Nutritional Index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and Systemic Immune-Inflammation Index) as well as body weight-related data and associated parameters [body mass index (BMI), percentage of weight loss, Nutritional Risk Screening 2002 assessment, the Malnutrition Universal Screening Tool, and the Nutritional Risk Index] were measured and calculated. The study end points were major complications, operative mortality, prolonged hospital stay, overall survival (OS), and recurrence-free survival (RFS). RESULTS: Multivariable logistic regression analysis showed that male gender, total gastrectomy, advanced-stage gastric cancer, and low albumin level were risk factors for major complications. Old age, total gastrectomy, advanced-stage cancer, and high BMI were risk factors for operative mortality. Old age, open approach, and total gastrectomy were risk factors for prolonged hospital stay. Multivariable Cox proportional hazards models showed that old age, total gastrectomy, advanced-stage cancer, and high neutrophil count were unfavorable risk factors for OS. Old age, advanced-stage cancer, high neutrophil count, and high BMI were unfavorable risk factors for RFS. CONCLUSIONS: Albumin level, BMI, and neutrophil count are the most useful parameters for predicting short- and long-term surgical outcomes. Compared with complex parameters, simple-to-measure parameters are better for predicting surgical outcomes for gastric cancer patients.

Clinical usefulness of the SARC-F questionnaire to assess sarcopenia in patients with Parkinson's disease.

OBJECTIVE: To investigate the accuracy of the SARC-F questionnaire to identify sarcopenia in patients with Parkinson's disease (PD). METHODS: We prospectively recruited patients with PD who had a score of 3 or lower on the Hoehn and Yahr (H&Y) scale. Appendicular skeletal muscle mass (ASM), hand grip strength, and the SARC-F were used to assess sarcopenia. The cutoffs for the ASM index and hand grip strength to diagnose sarcopenia were based on the Asian Working Group for Sarcopenia 2019 consensus. A score ≥4 on the SARC-F was considered at risk for sarcopenia. RESULTS: A total of 365 patients with PD were included (mean age, 71.1 years; men, 53.2 %), and 73 (20.0 %) were diagnosed with sarcopenia. The area under the receiver operating characteristic curve of the SARC-F was 0.702 (95 % confidence interval, 0.634-0.770). Using the recommended cutoff score of ≥4, the SARC-F showed a sensitivity of 38.4 %, specificity of 85.6 %, positive predictive value (PPV) of 40.0 %, and negative predictive value (NPV) of 84.7 %. The Youden's index was the highest at a cutoff score of ≥2, in which the SARC-F showed a sensitivity of 67.1 %, specificity of 65.4 %, PPV of 32.7 %, and NPV of 88.8 %. These predictive values were similar to those obtained using a cutoff score of ≥2.5 or 3 on the H&Y scale. CONCLUSION: The application of the SARC-F to the mild-to moderate PD population is not appropriate as a first-step screening tool to diagnose sarcopenia. Given the comparable predictive values of the SARC-F and H&Y scale, this questionnaire may be considered only for ruling out sarcopenia in patients with similar disease severity.

NOX4 and its association with myeloperoxidase and osteopontin in regulating endochondral ossification.

IMPORTANCE: Endochondral ossification plays an important role in skeletal development. Recent studies have suggested a link between increased intracellular reactive oxygen species (ROS) and skeletal disorders. Moreover, previous studies have revealed that increasing the levels of myeloperoxidase (MPO) and osteopontin (OPN) while inhibiting NADPH oxidase 4 (NOX4) can enhance bone growth. This investigation provides further evidence by showing a direct link between NOX4 and MPO, OPN in bone function. OBJECTIVE: This study investigates NOX4, an enzyme producing hydrogen peroxide, in endochondral ossification and bone remodeling. NOX4's role in osteoblast formation and osteogenic signaling pathways is explored. METHODS: Using NOX4-deficient (NOX4-/-) and ovariectomized (OVX) mice, we identify NOX4's potential mediators in bone maturation. RESULTS: NOX4-/- mice displayed significant differences in bone mass and structure. Compared to the normal Control and OVX groups. Hematoxylin and eosin staining showed NOX4-/- mice had the highest trabecular bone volume, while OVX had the lowest. Proteomic analysis revealed significantly elevated MPO and OPN levels in bone marrow-derived cells in NOX4-/- mice. Immunohistochemistry confirmed increased MPO, OPN, and collagen II (COLII) near the epiphyseal plate. Collagen and chondrogenesis analysis supported enhanced bone development in NOX4-/- mice. CONCLUSIONS AND RELEVANCE: Our results emphasize NOX4's significance in bone morphology, mesenchymal stem cell proteomics, immunohistochemistry, collagen levels, and chondrogenesis. NOX4 deficiency enhances bone development and endochondral ossification, potentially through increased MPO, OPN, and COLII expression. These findings suggest therapeutic implications for skeletal disorders.

Association between prediabetes and cognitive function in Parkinson's disease.

INTRODUCTION: It remains largely unknown whether prediabetes is related to cognitive impairment in Parkinson's disease (PD). This study aimed to assess the association between prediabetes and cognitive function in PD patients. METHODS: In this cross-sectional study, 262 PD patients (age, 69.8 ± 10.3 years; Hoehn-Yahr stage, 2.3 ± 0.8) were classified into diabetes (glycated hemoglobin [HbA1c] ≥6.5% or previously diagnosed, n = 76), prediabetes (5.7%-6.4%, n = 90), or diabetes free (≤5.6%, n = 96) groups. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) test. RESULTS: Both the diabetes and prediabetes groups had significantly lower MoCA scores (17.0 ± 6.6 and 18.0 ± 6.1, respectively) than the diabetes free group (20.0 ± 5.7), even after adjusting for potential confounders (p = .002 and p = .008, respectively). In the combined group of prediabetes and diabetes free patients, higher HbA1c levels significantly correlated with lower MoCA scores (p = .031). There was a significant interaction of diabetes status with age, but not with the duration of PD, on cognitive function. CONCLUSION: In addition to diabetes, prediabetes may negatively affect cognitive function in PD patients. Further prospective longitudinal studies are necessary to clarify the impact of prediabetes on the cognitive trajectory of these patients.

Association of Early Weight Change With Cognitive Decline in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVE: To examine whether early weight change is associated with subsequent deterioration in cognitive function, including overall performance and specific domains, in Parkinson disease (PD). METHODS: This observational study used data from the Parkinson Progression Markers Initiative cohort. The patients underwent annual nonmotor assessments covering neuropsychiatric, sleep-related, and autonomic symptoms for up to 8 years of follow-up. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and detailed neuropsychological testing. Linear mixed-effects models were applied to investigate the association of early weight change with longitudinal evolution of cognitive and other nonmotor symptoms. RESULTS: A total of 358 patients with early PD were classified into weight loss (decrease of >3% body weight during the first year; n = 98), weight maintenance (within ±3%; n = 201), and weight gain (increase of >3%; n = 59) groups. The weight loss group showed a significantly faster decline in MoCA scores than the weight maintenance group (ß = -0.19, 95% CI -0.28 to -0.10). With respect to specific cognitive domains, the weight loss group showed a steeper decline in sematic fluency test scores (ß = -0.37, 95% CI -0.66 to -0.08) and MoCA phonemic fluency scores (ß = -0.18, 95% CI -0.31 to -0.05) and, to a lesser extent, Letter-Number Sequencing scores (ß = -0.07, 95% CI -0.14 to 0.01) compared with the weight maintenance group. Conversely, the weight gain group showed a slower decline in the Symbol Digit Modalities Test scores (ß = 0.34, 95% CI 0.05 to 0.63), although no association was found with longitudinal changes in MoCA scores. We did not find any significant effects of weight change on the progression of other nonmotor symptoms. DISCUSSION: Early weight loss was associated with a faster progression of decline in global cognitive function and executive function in patients with PD, whereas early weight gain was associated with a slower progression of decline in processing speed and attention. The impact of early weight change on nonmotor symptoms seemed to be specific to cognition.