Moderate Stage Research Articles

A - 124 A Case of Lewy Body Dementia and Charles Bonnet Syndrome in a Patient with Bilateral Enucleation

Abstract Objective The patient presented with a history of blindness due to bilateral enucleation (age 10 and 23) and visual hallucinations for approximately 2 years. Approximately 30% of visually impaired individuals are affected by Charles Bonnet syndrome, characterized by complex visual hallucinations in visually challenged patients, possibly stemming from the brain’s attempt to fill the visual void. Additionally, she was diagnosed with Lewy Body dementia (LBD) 2 years prior by her neurologist, and she reported challenges with completing instrumental activities of daily living (IADLs). Method The patient was a left-handed 83-year-old woman, with a history of total blindness and bilateral enucleation, who presented with progressive memory loss 3–4 years prior, along with balance/gait disturbances for 1–1.5 years. The patient and her family sought neuropsychological testing to clarify her cognitive functioning in light of her physical and neurologic symptoms. Results Premorbid functioning was estimated in the low average range, with 11 years of education. Due to her total vision loss, neuropsychological evaluation was limited. Her cognitive profile was marked by impairments in immediate memory, delayed memory, recognition, executive functioning, and language. Conclusions In light of the patient’s marked cognitive deficits in memory, attention, and executive functioning, along with visual hallucinations (although also attributed to possible Charles Bonnet syndrome), balance/gait disturbances, fluctuating awareness, autonomic dysfunction (i.e., bladder/bowel control), and sleep changes (i.e., acting out dreams), her presentation is consistent with LBD, in the moderate stage of severity. Given the symptomatology, it raises the possibility the patient may be experiencing Charles Bonnet syndrome along with LBD.

Correlation between salivary and serum biomarkers of kidney function in chronic kidney disease patients attending the nephrology clinics at Teaching Hospital Karapitiya, Sri Lanka

The present study was designed to determine the correlation between salivary and serum levels of creatinine and urea in patients with chronic kidney disease (CKD) and to propose the use of saliva as an alternative medium for the analysis of biochemical parameters of kidney function. Accordingly, an analytical cross-sectional study was carried out using 100 CKD patients attending the Nephrology Clinics at Teaching Hospital Karapitiya, Sri Lanka. Saliva and serum samples were collected from the patients for the estimation of creatinine and urea using spectrophotometric assay kits. Of the total, the majority of the patients were found within CKD stage 3 (82%). The salivary and serum concentrations of creatinine varied within the range of 0.20 - 2.10 mg/dL and 1.54 – 11.6 mg/dL, whereas the salivary and serum concentrations of urea varied within the range of 68.04 – 127.59 mg/dL and 60.14 – 168.25 mg/dL respectively within the study population. Significant positive correlations were observed between the salivary and serum concentrations of creatinine (r= 0.985, p=0.01), and urea (r= 0.942, p=0.01), and between salivary concentrations of creatinine and urea (r=0.887, p=0.01). A significant difference was observed in the salivary biomarkers between mild to moderate stages of CKD patients and severe to end-stage CKD patients. No significant association was observed in the salivary markers with the age and sex of the patients. The area under curve values in the receiver operating characteristic analysis was>0.9 (95% CI). These findings revealed high levels of diagnostic accuracy in salivary biomarkers suggesting the potential use of saliva for the assessment of kidney function in CKD patients.

Six-Month Outcomes of Goniotomy Performed with a Trapezoidal Dual Blade in Combination with Cataract Surgery.

To assess the efficacy and safety of goniotomy using a uniquely shaped trapezoidal, serrated dual blade (TDB), designed to accommodate variability in patient anatomy, in reducing intraocular pressure (IOP) or anti-glaucoma medications (AGM) in adult glaucoma patients when combined with cataract surgery. Retrospective consecutive case series of patients with glaucoma who underwent phacoemulsification with TDB-goniotomy were included. Preoperative, intraoperative, and postoperative data were collected over 6 months. The primary outcome measure was surgical success, defined as IOP reduction ≥20% from baseline at 6 months, and/or reduction of at least 1 AGM. Postoperative adverse events were collected as a secondary outcome measure. Sixty-five eyes of 46 patients were included with data available on 53 eyes at 6 months. Primary open-angle (38%), primary angle-closure (37%), and mixed-mechanism glaucoma (11%) were the most common diagnoses. Most cases were severe (48%) or moderate (32%) stage. At the 6-month mark, surgical success was achieved in 92% of eyes by either or both criteria. Mean preoperative IOP decreased from 18.4mmHg (SE 0.83) to 13.0mmHg (SE 0.37) (p<0.001) at postoperative month 6. Mean AGM decreased from 2.46 (SE 0.19) preoperatively to 1.45 (SE 0.17) (p<0.001). The most common postoperative complication was an IOP spike at postoperative week 1 (11%). No serious adverse events occurred related to the goniotomy. TDB-goniotomy in combination with cataract surgery safely and effectively lowered IOP and reduced AGM burden in adults with various types and severities of glaucoma over 6-months of follow-up.

Increased Intestinal Inflammation and Permeability in Glaucoma.

Evidence suggests that dysbiosis of the gut microbiota plays a pivotal role in the development of glaucoma. This dysbiosis is commonly associated with chronic intestinal inflammation and increased intestinal permeability. However, the understanding of intestinal inflammation and permeability in glaucoma remains insufficient. This study aims to investigate the potential relationship between fecal inflammation and permeability markers and glaucoma. We recruited 114 glaucoma patients and 75healthy controls. Levels of fecal lactoferrin (Lf) and alpha-1 antitrypsin (AAT) were quantified using enzyme linked immunosorbent assay (ELISA) to compare both biomarkers between groups and across different severity grades of glaucoma. Logistic regression analysis was used to assess the association between these fecal biomarkers and glaucoma. The severity of glaucoma was assessed based on the mean deviation (MD) in the visual field. In this study, we observed elevated levels of fecal Lf and AAT in glaucoma patients. The proportion of glaucoma patients with abnormal fecal Lf levels (≥ 7.25µg/g) was significantly higher than that of the controls (p = 0.012). A positive correlation was noted between fecal Lf and AAT (rho = 0.20, p = 0.006). After adjusting for age and sex, multivariable logistic regression analysis indicated that both fecal Lf (OR = 1.11, 95% CI: 1.01-1.21, p = 0.026) and AAT (OR = 1.01, 95% CI: 1.01-1.02, p < 0.001) positively correlated with glaucoma. These biomarkers might reflect glaucoma severity, with significant differences in fecal Lf levels observed between moderate and severe stages, but not in the early stage. Furthermore, increasing levels of fecal AAT correlated with greater severity of glaucomatous injury and a larger vertical cup-to-disc ratio (VCDR) (p < 0.05). This study suggests an increase in intestinal inflammation and permeability in glaucoma, further indicating the importance of the 'gut-retina axis' in the pathogenesis of the disease and potentially offering new therapeutic avenues.

Performance and grazing behavior of Gyr dairy heifers in integrated production systems in the Cerrado biome

The study aimed to assess the performance of Gyr dairy heifers in four pasture systems: renovated pasture (RP), non-renovated pasture (NRP), crop-livestock integration (CLI) and crop-livestock-forest integration (CLFI). For our study, we used a Marandu Palissadegrass pasture with a slight to moderate stage of degradation. The experimental area had 7.5 hectares which were divided into 3 blocks with four grazing systems: RP, NRP, CLI and CLFI. Thirty-four Gyr dairy heifers with an initial body weight (BW) of 206.9 kg were used. There was no difference in total forage production between the grazing systems. The RP system had a higher % of leaves, while the NRP showed a lower % of leaves and a higher % of dead material. The CLFI showed the highest % of crude protein (CP) in the forage, and lowest levels in the NRP. There was no difference between the grazing systems in the % of neutral detergent fiber (NDF) and acid detergent fiber (ADF). When the BW factor was analyzed in isolation, it was observed that the NRP had a higher BW and there was a linear increase in BW as the grazing cycles progressed. There was an interaction between grazing systems and evaluation periods for the variables related to grazing behavior, with emphasis on the heifers in the NRP system, which ruminated for longer and grazed for less time during the evaluation period. The RP, CLI, and CLFI systems, when established, promoted a pasture of better morphological and nutritional quality for rearing Gyr dairy heifers.

Serum and urinary monocyte chemoattractant protein-1 as markers of inflammation and renal damage in dogs with naturally occurring leishmaniosis

BackgroundRenal disease in canine leishmaniosis is of great importance owing to increased risk of mortality. In human visceral leishmaniosis, monocyte chemoattractant protein-1 (MCP-1) has been used as a marker of renal damage and inflammation. The purpose of this study was first to determine the serum MCP-1 and urinary MCP-1-to-creatinine ratio (uMCP-1/Cr) in healthy dogs and dogs with leishmaniosis at diagnosis, and second to determine whether these markers can differentiate disease severity at diagnosis.MethodsIn total, 19 healthy seronegative dogs and 38 dogs with leishmaniosis were included in the study. Dogs with leishmaniosis were classified as LeishVet clinical staging and as International Renal Interest Society (IRIS) staging. Serum and urinary MCP-1 concentrations were measured with an enzyme-linked immunosorbent assay. A receiver operating characteristic (ROC) curve determined disease severity at diagnosis between two LeishVet groups (Stage II versus stage III and IV).ResultsDogs in Leishvet stages IIb, III, and IV had a median serum MCP-1 and uMCP-1/Cr concentration higher than healthy dogs (P < 0.0001). No statistical differences were found in serum MCP-1 and uMCP-1/Cr between dogs in LeishVet stage IIa and healthy dogs. The dogs in LeishVet stage IV had significantly higher serum MCP-1 and uMCP-1/Cr compared with the dogs in LeishVet stage IIa (P < 0.0001). Serum MCP-1 and uMCP-1 were significantly higher in dogs in IRIS stage I and II + III + IV compared with healthy dogs. Dogs stage II + III + IV of IRIS had a significantly higher serum MCP-1 compared with dogs in IRIS stage I (P < 0.0001). The area under the ROC curve for serum MCP-1 was 0.78 [95% confidence interval (CI) 0.64–0.93] and for uMCP-1/Cr it was 0.86 (95% CI, 0.74–0.99). The optimal cutoff value for serum MCP-1 and uMCP-1/Cr was 336.85 pg/ml (sensitivity of 79% and specificity of 68%) and 6.89 × 10−7 (sensitivity of 84% and specificity of 79%), respectively.ConclusionsSerum MCP-1 and uMCP-1/Cr are increased in dogs with leishmaniosis compared with healthy dogs, suggesting the presence of inflammation and renal injury. Serum MCP-1 and uMCP-1/Cr were more elevated in the advanced stages of the disease compared with the moderate stages and, therefore, can be markers of the severity of the disease process.Graphical

Comparison of Automated and Manual Measurement of Corneal Epithelial Thickness in Eyes With Limbal Stem Cell Deficiency.

The purpose of this study was to compare the outcomes of manual and automated corneal epithelial thickness (CET) assessments using anterior segment optical coherence tomography in eyes with limbal stem cell deficiency (LSCD). Eighty-seven eyes from 64 patients with LSCD and 65 eyes from 39 healthy subjects were included in this cross-sectional study. OCT images of corneas were acquired using a Fourier-domain anterior segment optical coherence tomography. The automated measurement of CET was obtained using the manufacturer's program and the manual measurements were obtained by 2 masked observers. The average CET was obtained from 3 consecutive epithelial profile maps. The average CET of manual measurement was obtained from 3 consecutive cross-line scans using 3-point measurement as previously described. The central CET was thinner in patients with LSCD compared with healthy individuals by both manual and automated measurements. Automated CET measurements were similar to the manually obtained CET in the healthy controls (r = 0.911). However, there is a lower correlation between the automated and manually obtained CET in the LSCD group (r = 0.497). Manual measurements of CET (39.8 ± 11 μm) in eyes with LSCD were significantly lower than the automated measurements (48.8 ± 7.2 μm, P = 0.001, 95% CI -11.0 to -6.9). The correlations between the automated and manually obtained measurements in the mild, moderate, and severe stages of LSCD were 0.623, 0.632, and 0.378, respectively. There is a large discrepancy between the manual and automated measurements in eyes with LSCD but not in normal eyes. Automated measurements in LSCD exhibited a higher rate of errors and nonuniform measurements due to the presence of subepithelial scars. Automated CET measurements appear to be unreliable in eyes with corneal scars in LSCD.

Bilirubinemia and retinopathy of prematurity in infants ≤ 29 weeks' gestational age.

Bilirubin is a known antioxidant. We hypothesized that the degree of bilirubinemia is inversely associated with oxidative stress-mediated retinopathy of prematurity (ROP). A prospective study was performed to determine if bilirubinemia is associated with ROP in infants ≤ 29 wks' gestational age and birth weights ≤ 1000 g. Total serum bilirubin (TSB) levels were measured at least twice daily during the first week and at least daily during the second week to determine peak and mean TSB levels. The outcomes were the incidence and severity of ROP. Of 193 infants studied, 110 developed ROP: 53 had mild (stage 1 in zone 2 or 3); 31 had moderate (stage 2 in zone 2 or 3); and 26 had severe ROP ( ≥ stage 3 in any zone or any stage in zone 1). Mean TSB levels were associated with the severity (adjusted odds ratio [AOR] 0.68, 95% confidence interval [CI]:0.47-0.98, p = 0.04), but not with the incidence of ROP (AOR 0.81, 95% CI:0.52-1.27, p = 0.3). Peak TSB levels were also associated with the severity (AOR 0.71, 95% CI:0.52-0.96, p = 0.02), but not with the incidence of ROP (AOR 0.71, 95% CI:0.48-1.01, p = 0.07). Bilirubinemia may be protective against severity of ROP. Retinopathy of prematurity (ROP) is a disease mediated by oxidative stress. Increasing antioxidant status may decrease the incidence and severity of ROP. Bilirubin is a known antioxidant; however, findings from observational studies evaluating the role of bilirubinemia against the incidence and/or severity of ROP in premature infants are conflicting. Our findings from this prospective study suggests that bilirubinemia may be protective against the severity of ROP.

Geochemical distribution of major and trace elements in hydromorphic soil profiles developed on recent alluvium

Geochemical composition and distribution of major elements study is vital in terms of investigating the major soil forming compounds and to know the fate of trace elements in soils. Particle size distribution (PSD), pH, organic carbon (OC), and major and trace elements of hydromorphic soils formed on recent alluvium in Obafemi-Owode Local Government Area of Ogun state, Nigeria were analysed using standard procedures. Three profiles pits were dug based on the mapping units identified, and samples were collected for laboratory analysis. Data were subjected descriptive statistics and Pearson’ correlation coefficients using IBM SPSS version 27. The PSD was dominated by sand content, followed by clay and silt, and soil pH in KCl was strongly acid (3.17–4.30) and pH in H2O was moderately acid (4.74–5.80), while OC contents were low to moderate (1.22–6.69 g/kg). The major elemental results showed higher concentration of SiO2 (>50 %) connotes presence quartz, feldspar, and clay minerals. Manganese, Cu, Ba, Zr, and Zn have higher concentrations among the trace elements. Major elements ratios (SiO2/Al2O3, K2O/Al2O3) showed moderate weathering stage, while trace elements ratios (Ni/Co and Cu/Zn) revealed deposition under humid conditions and anoxic environment. The statistical analysis revealed that most elements have skewness closed to zero except MgO and K2O. Correlation coefficients between the elements are positive and significant (p < 0.05 and p < 0.01) indicating that their presence can be accounted for by similar lithology, though some have negative relationship which could be as a result of anthropogenic activities. The study found that elements were potential tracers for the presence of human activities and environmental changes.

Ultrasound assessment of diaphragmatic excursion in chronic obstructive pulmonary disease patients with different severities

BackgroundChronic obstructive pulmonary disease (COPD) is associated with dysfunctional diaphragmatic breathing we assess the diaphragmatic excursion at different stages of COPD patients by transthoracic ultrasound.ObjectiveThe present study aimed to assess the diaphragmatic excursion at different stages of COPD patients by transthoracic ultrasound.Patients and methodsIn this observational case–control study, 80 COPD patients were included according to GOLD guidelines 2020 attending the Chest Clinic in Badr Hospital, Helwan University. All patients were divided equally into 5 groups according to FEV1 measured by spirometer: group (1) normal person; group (2) mild stage FEV1_80% predicted; group (3) moderate stage 50%_FEV1 < 80% predicted; group (4) severe stage 30%_FEV1 < 50% predicted; and group (5) very severe stage FEV1 < 30% predicted. We measured diaphragmatic movement in all these patients using ultrasound.ResultsThe outcomes result of normal, mild, moderate, severe, and very severe groups in terms of post-bronchodilator FEV1/FVC are 0.66 ± 0.05, 0.65 ± 0.05, 0.63 ± 0.04, 0.51 ± 0.068 respectively showed was a significant difference. There was a significant difference of FEV1 are 86.70 ± 5.62, 63.00 ± 13.81, 43.00 ± 6.78, 24.00 ± 4.17, respectively (P < 0.001). There was a significant difference in diaphragmatic thickness at the end of normal expiration are 0.49 ± 0.12, 0.51 ± 0.09, 0.47 ± 0.16, 0.37 ± 0.07, respectively (P < 0.001). There was a significant difference in the diaphragmatic thickness during maximum inspiration are 0.70 ± 0.16, 0.8 ± 0.17, 0.64 ± 0.19, and 0.47 ± 0.08, respectively (P < 0.001). There was a significant difference in the diaphragmatic excursion during normal breathing are 2.45 ± 0.39, 1.78 ± 0.67, 1.86 ± 0.67, 1.09 ± 0.16, respectively (P < 0.001). There was a significant difference in diaphragmatic Excursion during maximum inspiration are 4.41 ± 0.91, 3.83 ± 0.78, 3.36 ± 0.74, 2.36 ± 0.66 respectively (P < 0.001).ConclusionThe use of ultrasonography for assessing the diaphragmatic excursion. Sonographically determined diaphragmatic excursion strongly correlates with FEV1/FVC.

Implementing Advance Care Planning and Care Coordination in the Care for People With Parkinson Disease: A Feasibility Study.

BACKGROUND: For people with a moderate stage of Parkinson disease (PD), dedicated care coordination combined with advance care planning (ACP) is highly needed. However, evidence is lacking. The objective of this study was to assess the feasibility and acceptability of the study processes to inform a larger randomized controlled trial, aiming the effectiveness of a combined intervention on ACP and care coordination for people with PD. METHODS: Two nurse practitioners with expertise in PD followed training on a combined intervention on ACP and care coordination. Patients were invited to participate in several sessions for a period of 12 months. Feasibility of the study was surveyed covering sample recruitment, attrition rate, eligibility, intervention delivery, number of ACP sessions, type of intervention administration, and satisfaction with the intervention. RESULTS: In total, 27 patients were invited to participate, and 20 (74%) enrolled into the study, together with 11 family caregivers; 7 patients (35%) dropped out. Most patients were men (n = 20), with a mean age of 73.4 (SD 8.2) years. In total, 71 ACP sessions were held (3.6 sessions per patient on average), of which 41% of the sessions were conducted face-to-face at home, 44% at the hospital, 11% over telephone, and 4% via a videoconference call. Patients perceived the intervention not only as supportive but also as confronting. CONCLUSION: The ACP aspect of the intervention was useful and feasible to stimulate patients to think about their current care situation as well as about future care. Care coordination was less profoundly provided and discussed.

Erratum in the article “Results from the open-label, single-center, clinical study assessing the efficacy and safety of a group cognitive stimulation therapy in Russian-speaking patients with the moderate dementia stage of Alzheimer's disease”

Erratum in the article “Results from the open-label, single-center, clinical study assessing the efficacy and safety of a group cognitive stimulation therapy in Russian-speaking patients with the moderate dementia stage of Alzheimer's disease”

2248 Clinical relevance of Donanemab treatment

Abstract Objective To assess in Alzheimer’s disease (ad), the treatment impact of donanemab, an amyloid plaque-reducing monoclonal antibody, on readily interpretable item-measures and constructs that matter to patients, care-partners, and clinicians. Background Positive outcomes were reported from TRAILBLAZER-ALZ2, a randomised, double-blind, placebo-controlled, 18-month, phase 3 study evaluating donanemab as an investigational treatment for mild cognitive impairment (MCI) or mild dementia due to ad. In 1736 participants, donanemab significantly slowed the rate of clinical decline (by 22–36%) as measured by the integrated ad Rating Scale (iADRS) and the Clinical Dementia Rating Scale—Sum-of-Boxes (CDR-SB); both measures of cognition and function as indications of global clinical severity. In these subsequent post-hoc exploratory analyses, the impact of donanemab treatment on individual iADRS cognition and function items, CDR domains, and risks of advancing to greater disease severity were assessed. Methods Mixed model repeated measures and Cox proportional hazard modelling methodology assessed treatment effects on iADRS items and CDR domains. Results Donanemab treatment was associated with significant beneficial effects on: 1) iADRS cognitive items related to episodic memory and executive function, and instrumental activities of daily living items related to communication and others (e.g. being left alone, making a meal, using household appliances); 2) all CDR-SB cognitive and functional domains (i.e. memory, orientation, judgement/problem solving, community affairs, home/hobbies, and personal care); and 3) lowering risk of progression to a more advanced clinical stage of disease. Conclusions These analyses explored the impact of donanemab treatment on constructs that matter to and are considered more readily interpretable by patients, care-partners, and clinicians. These results provide further support that treating those with MCI or mild dementia due to ad with donanemab can meaningfully reduce risk of progression to more severe clinical stages (e.g. moderate stage dementia), and potentially allow greater independence for a longer period of time.

Coupling Coordination Relationship between Cultural Landscape Conservation and Socio-Economic System in Ethnic Villages of Southeast Guizhou

Amidst the transition from agriculture to tourism, ethnic villages are facing issues of “misalignment” and “disequilibrium” between economic growth and cultural heritage conservation. Previous research has often isolated the effects of cultural heritage conservation or socio-economic development, neglecting their reciprocal influences within the coupling coordination. This study addresses this gap by assessing 43 villages in Leishan County, quantifying the preservation status of the cultural landscape (PSCL) and socio-economic level (SEL) using a comprehensive evaluation model and revealing the coupling coordination relationship between PSCL and SEL in each village with the coupling coordination degree (CCD) model. Spatial autocorrelation and the geographical detector model reveal the spatial agglomeration characteristics and influential factors of the CCD. The results highlight three findings. (1) The majority of villages (93%) are in a moderate imbalance stage or a serious imbalance stage, underscoring an urgent need for targeted policies. (2) Spatial autocorrelation analysis exposes significant clustering, with the northwest corner exhibiting the most pronounced high-value aggregation, which contrasts with the southern region’s low-value clustering. A ‘low–high’ clustering pattern is observed in the northern region, while the southwestern corner presents a ‘high–low’ distribution. (3) Key determinants affecting the CCD include the tourism revenue, tourist volume, resident participation in tourism, village hollowing level, and number of historical buildings. The interactions between driving factors show non-linear and two-factor enhancement effects. This study concludes with policy recommendations advocating for context-specific strategies to enhance the CCD, emphasizing the importance of aligning cultural preservation with economic progress in ethnic villages.

Pure argyrophilic grain disease revisited: independent effects on limbic, neocortical, and striato-pallido-nigral degeneration and the development of dementia in a series with a low to moderate Braak stage

Agyrophilic grains (AGs) are age-related limbic-predominant lesions in which four-repeat tau is selectively accumulated. Because previous methodologically heterogeneous studies have demonstrated inconsistent findings on the relationship between AGs and dementia, whether AGs affect cognitive function remains unclear. To address this question, we first comprehensively evaluated the distribution and quantity of Gallyas-positive AGs and the severity of neuronal loss in the limbic, neocortical, and subcortical regions in 30 cases of pure argyrophilic grain disease (pAGD) in Braak stages I–IV and without other degenerative diseases, and 34 control cases that had only neurofibrillary tangles with Braak stages I–IV and no or minimal Aβ deposits. Then, we examined whether AGs have independent effects on neuronal loss and dementia by employing multivariate ordered logistic regression and binomial logistic regression. Of 30 pAGD cases, three were classified in diffuse form pAGD, which had evident neuronal loss not only in the limbic region but also in the neocortex and subcortical nuclei. In all 30 pAGD cases, neuronal loss developed first in the amygdala, followed by temporo-frontal cortex, hippocampal CA1, substantia nigra, and finally, the striatum and globus pallidus with the progression of Saito AG stage. In multivariate analyses of 30 pAGD and 34 control cases, the Saito AG stage affected neuronal loss in the amygdala, hippocampal CA1, temporo-frontal cortex, striatum, globus pallidus, and substantia nigra independent of the age, Braak stage, and limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) stage. In multivariate analyses of 23 pAGD and 28 control cases that lacked two or more lacunae and/or one or more large infarctions, 100 or more AGs per × 400 visual field in the amygdala (OR 10.02, 95% CI 1.12–89.43) and hippocampal CA1 (OR 12.22, 95% CI 1.70–87.81), and the presence of AGs in the inferior temporal cortex (OR 8.18, 95% CI 1.03–65.13) affected dementia independent of age, moderate Braak stages (III–IV), and LATE-NC. Given these findings, the high density of limbic AGs and the increase of AGs in the inferior temporal gyrus may contribute to the occurrence of dementia through neuronal loss, at least in cases in a low to moderate Braak stage.

Accuracy of Clinical Staging of Localized Colon Cancer: A National Cancer Database Cohort Analysis.

This study aimed to assess concordance between clinical and pathologic assessment of colon cancer. A retrospective cohort analysis of patients with stage I-III colon cancer in the National Cancer Database (2010-2019) was conducted. Concordance between clinical and pathologic assessment of colon cancer was calculated using Kappa coefficients and 95% confidence intervals (CIs). A total of 125,473 patients (51.2% female; mean age 68.2 years) were included. There was moderate concordance between clinical and pathologic T stage (Kappa = 0.606, 95%CI: 0.602-0.609) and between clinical and pathologic N stage (Kappa = 0.506, 95%CI: 0.501-0.511). For right-sided colon cancer, there was moderate agreement between clinical and pathologic T stage (Kappa = 0.594, 95%CI: 0.589-0.599) and N stage (Kappa = 0.530, 95%CI: 0.523-0.537). For left-sided colon cancer, there was substantial agreement between clinical and pathologic T stage (Kappa = 0.624, 95%CI: 0.619-0.630) and moderate agreement between N stage (Kappa 0.472, 95%CI: 0.463-0.480). Sensitivity of clinical assessment of T and N stage ranged from 64.3% to 77.2% and 41.6% to 54.5%, respectively. Specificity ranged from 96.7% to 97.7% for T stage and 95.7% to 97.3% for N stage. Clinical assessment of T and N stages of colon cancer had good diagnostic accuracy with moderate concordance withthe final pathologic stage. While clinical assessment was highly specific with < 3% of patients being over-staged, it had modest sensitivity, especially for detection of nodal involvement. Diagnostic accuracy of clinical assessment of right and left colon cancers was similar, except for higher sensitivity and accuracy of assessment of nodal involvement in right than left colon cancers.

Age-Related Retinal Layer Thickness Changes Measured by OCT in APPNL-F/NL-F Mice: Implications for Alzheimer's Disease.

In Alzheimer's disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining quantitative parameters from optical coherence tomography (OCT) in AD. The aim of this study was to analyze, in a transversal case-control study using manual retinal segmentation via SD-OCT, the changes occurring in the retinal layers of the APPNL/F-NF/L AD model in comparison to C57BL/6J mice (WT) at 6, 9, 12, 15, 17, and 20 months of age. The analysis focused on retinal thickness in RNFL-GCL, IPL, INL, OPL, and ONL based on the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Both APPNL-F/NL-F-model and WT animals exhibited thickness changes at the time points studied. While WT showed significant changes in INL, OPL, and ONL, the AD model showed changes in all retinal layers analyzed. The APPNL-F/NL-F displayed significant thickness variations in the analyzed layers except for the IPL compared to related WT. These thickness changes closely resembled those found in humans during preclinical stages, as well as during mild and moderate AD stages, making this AD model behave more similarly to the disease in humans.

Identification of profiles associated with conversions between the Alzheimer’s disease stages, using a machine learning approach

BackgroundThe identification of factors involved in the conversion across the different Alzheimer’s disease (AD) stages is crucial to prevent or slow the disease progression. We aimed to assess the factors and their combination associated with the conversion across the AD stages, from mild cognitive impairment to dementia, at a mild, moderate or severe stage and to identify profiles associated with earliest/latest conversion across the AD stages.MethodsIn this study conducted on the real-life MEMORA cohort data collected from January 1, 2013, and December 31, 2019, three cohorts were selected depending on the baseline neurocognitive stage from a consecutive sample of patients attending a memory center, aged between 50 and 90 years old, with a diagnosis of AD during the follow-up, and with at least 2 visits at 6 months to 1 year of interval. A machine learning approach was used to assess the relationship between factors including socio-demographic characteristics, comorbidities and history of diseases, prescription of drugs, and geriatric hospitalizations, and the censored time to conversion from mild cognitive impairment to AD dementia, from the mild stage of dementia to the moderate or severe stages of AD dementia, and from the moderate stage of AD dementia to the severe stage. Profiles of earliest/latest conversion compared to median time to conversion across stages were identified. The median time to conversion was estimated with a Kaplan-Meier estimator.ResultsOverall, 2891 patients were included (mean age 77±9 years old, 65% women). The median time of follow-up was 28 months for mild cognitive impairment (MCI) patients, 33 months for mild AD dementia and 30 months for moderate AD dementia. Among the 1264 patients at MCI stage, 61% converted to AD dementia (median time to conversion: 25 months). Among the 1142 patients with mild AD dementia, 59% converted to moderate/severe stage (median time: 23 months) and among the 1332 patients with moderate AD dementia, 23% converted to severe stage (Q3 time to conversion: 22 months). Among the studied factors, cardiovascular comorbidities, anxiety, social isolation, osteoporosis, and hearing disorders were identified as being associated with earlier conversion across stages. Symptomatic treatment i.e. cholinesterase inhibitors for AD was associated with later conversion from mild stage of dementia to moderate/severe stages.ConclusionThis study based on a machine learning approach allowed to identify potentially modifiable factors associated with conversion across AD stages for which timely interventions may be implemented to delay disease progression.

Computer-aided diagnosis of Alzheimer’s disease and neurocognitive disorders with multimodal Bi-Vision Transformer (BiViT)

Cognitive disorders affect various cognitive functions that can have a substantial impact on individual’s daily life. Alzheimer’s disease (AD) is one of such well-known cognitive disorders. Early detection and treatment of cognitive diseases using artificial intelligence can help contain them. However, the complex spatial relationships and long-range dependencies found in medical imaging data present challenges in achieving the objective. Moreover, for a few years, the application of transformers in imaging has emerged as a promising area of research. A reason can be transformer’s impressive capabilities of tackling spatial relationships and long-range dependency challenges in two ways, i.e., (1) using their self-attention mechanism to generate comprehensive features, and (2) capture complex patterns by incorporating global context and long-range dependencies. In this work, a Bi-Vision Transformer (BiViT) architecture is proposed for classifying different stages of AD, and multiple types of cognitive disorders from 2-dimensional MRI imaging data. More specifically, the transformer is composed of two novel modules, namely Mutual Latent Fusion (MLF) and Parallel Coupled Encoding Strategy (PCES), for effective feature learning. Two different datasets have been used to evaluate the performance of proposed BiViT-based architecture. The first dataset contain several classes such as mild or moderate demented stages of the AD. The other dataset is composed of samples from patients with AD and different cognitive disorders such as mild, early, or moderate impairments. For comprehensive comparison, a multiple transfer learning algorithm and a deep autoencoder have been each trained on both datasets. The results show that the proposed BiViT-based model achieves an accuracy of 96.38% on the AD dataset. However, when applied to cognitive disease data, the accuracy slightly decreases below 96% which can be resulted due to smaller amount of data and imbalance in data distribution. Nevertheless, given the results, it can be hypothesized that the proposed algorithm can perform better if the imbalanced distribution and limited availability problems in data can be addressed.Graphical abstract

The Re-socialization Path of the Community Elderly from the Perspective of Active Aging: Take Community B as an Example

The 20th report pointed out that “implement the national strategy of actively responding to the aging of the population, develop the pension cause and industry, optimize the services for the elderly, and promote the realization of all the elderly enjoy the basic pension services”. It is estimated that during the 14th Five-Year Plan period, China’s population will enter a moderate stage of aging. In the current situation of the population aging trend, in addition to the establishment of relevant institutional guarantees for the elderly, we should also promote the social participation of the elderly and promote the re-socialization of the elderly. Community is the basic unit of social organizations and social population gathering. With the functions of socialization, psychological support, social participation and mutual assistance, it is an important field for the re-socialization of the elderly. Community social work is based on the community, through the use of relevant resources, mobilize the community strength, promote the social participation of the elderly in the form of community activities and volunteer services of the elderly. Based on the theory of active aging and re-socialization, this study conducted a questionnaire survey and in-depth interview on the B community in Lanzhou to understand the re-socialization level and re-socialization dilemma of the elderly in community B. On the basis of the analysis of relevant data, from the three dimensions of “participation”, “health” and “guarantee”, the beneficial measures of the community in promoting the re-socialization of the elderly are summarized, and targeted suggestions are put forward.