State Examination Research Articles

Using real‐world general practitioner data to study the diagnosis and management of dementia: rationale and design

AbstractBackgroundGeneral practitioners (GPs) play a critical role in the early recognition of cognitive deficits and management of dementia. Timely diagnosis is important in light of potential disease‐modifying therapies and the potential to improve patient outcomes. We aimed to establish a real‐world data cohort utilizing data from GPs on individuals with dementia as a starting point, with the goal of gaining valuable insights into trajectories and management of dementia and patient outcomes. Here we describe the rationale and design.MethodWe selected individuals with dementia using Dutch GP data from the PHARMO Data Network, which includes diagnoses, symptoms, examinations, prescriptions, and communication between GPs and specialists. Diagnosis of dementia was defined as a diagnosis code or prescription of anti‐dementia drugs between January 1, 2011 and December 31, 2020. Persons were included if they had one year of history prior to dementia diagnosis. We described the cohort in terms of demographics and screening tests for cognitive impairment.ResultA total of 52,911 individuals with dementia were selected from a source population of 4.7 million persons. The mean age was 81 years (standard deviation [SD] = 8.65) and 31,343 (59%) were female (Table 1). On average, patients have 8.6 years (SD = 4.09) of data available prior to dementia diagnosis and can be followed‐up for 2.8 years (SD = 2.19) after diagnosis. The reason for end of follow‐up was death for 16,978 persons (32%), end of data availability for 21,314 persons (40%), and 14,699 (28%) reached December 31, 2020 and are still registered (i.e., active). We found the Mini‐Mental State Examination (MMSE) in GP records of 31,759 persons (60%), and the Montreal Cognitive Assessment (MoCA) and Rowland Universal Dementia Assessment Scale (RUDAS) for only 1,777 (3%), and 29 persons (<0.5%), respectively.ConclusionWe created a cohort of 52,991 individuals with dementia, providing a starting point for further research on trajectories and management of AD in primary care and patient outcomes. Next steps include matching the cohort with dementia‐free controls, enriching the cohort by established linkages to other data sources (e.g. hospital data), and examining healthcare resource utilization, indicators of cognitive decline, treatment, and young‐onset dementia.

Discriminant Validity and Time‐effectiveness of A Stepwise Dementia Case‐finding Approach in an Asian Elderly Community

AbstractBackgroundTo investigate the discriminant validity and time‐effectiveness of a stepwise dementia case‐finding approach in a community‐based Singaporean older adult population.MethodParticipants who completed the Progressive Forgetfulness Question (PFQ) and the Abbreviated Mental Test (AMT) were invited to phase II and administered the Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a formal neuropsychological battery. Participants were diagnosed by cognitive performance and DSM‐IV criteria into No Cognitive Impairment (NCI), Cognitive Impairment‐No Dementia (CIND) mild (≤2 cognitive domains impaired), CIND moderate (>2 domains impaired) and dementia. Receiver Operating Characteristic were conducted for different cognitive instruments (AMT, MoCA, MMSE) between PFQ = Yes and PFQ = No groups. All discriminant indices including sensitivity, specificity, positive (PPV), negative predictive values (NPV) and accuracy were calculated. Bayesian correction methods were used to adjust the verification bias. Screening time saving and number of subjects further evaluated was estimated in two scenarios with or without the PFQ.ResultThe PFQ showed an NPV of 94.2% for excluding dementia‐free cases after adjustment. After excluding PFQ = No participants, all cognitive tools achieved optimal NPV (>99%). Furthermore, the number of people requiring further evaluation decreased by 129 (42.7%), 58 (36.5%), 25 (14.3%) subjects, corresponding to 48.2%, 48.2%, and 47.8% of screening time being saved, when the PFQ was conducted prior to the MoCA, MMSE, and AMT, respectively.ConclusionUsing a single‐question assessment as the first step of a case‐finding approach, followed up a cognitive test such as the MoCA, could minimize time and resources for further investigation in the community.

AD8 revisited: what’s the optimal cutoff value?

AbstractBackgroundThe 8‐item Informant Interview to Differentiate Aging and Dementia (AD8) was developed as a screening tool for dementia with a cutoff of 2 suggested by the initial study. However, various studies found different cutoff values, and many suggested a cutoff of 2 might result in a high false positive rate (up to > 80%). A higher false positive rate in Taiwan was repeatedly shown when AD8 was self‐administered in local government screening programs. This study aimed to examine the performance of AD8, determine its best cutoff value, and discuss factors that may affect the performance of AD8.MethodWe recruited 119 participant‐informant dyads from a psychiatric outpatient clinic of a university medical center. For each dyad, the AD8 was administered first, and then Mini‐Mental Status Examination (MMSE) and the Clinical Dementia Rating (CDR) to minimize contamination effect. Two geriatric psychiatrists made a consensus clinical diagnosis for each subject based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5) using all available clinical information, including MMSE, CDR, clinical history, other past neuropsychological tests, and neuroimaging examinations (if available).ResultThere were 37 subjects with normal cognition, 44 with mild neurocognitive disorder (mild NCD), and 28 with major neurocognitive disorder (major NCD). When the cutoff value was 2 for the differentiation between major NCD and no‐dementia subjects (including normal cognition and mild NCD), the AD8 had an AUC of 0.756, a sensitivity of 0.929, and a specificity of 0.582. But the optimal cutoff value was 4 according to the Youden index, with an AUC of 0.888, a sensitivity of 0.786, and a specificity of 0.835.ConclusionAlthough many studies recommended 2 as the best cutoff value for screening dementia, our findings and those of others suggest a cutoff of 2 may result in a high false positive rate. Many factors could affect the performance of AD8, including sample characteristics (e.g. education level), region, conduct of the test, flow of the administration (whether AD8 is administered first or contaminated by other tests), etc. Details will be discussed during the AAIC meeting.

Development of a cognitive composite for preclinical Alzheimer’s disease (CPAD) in Korean older adults

AbstractBackgroundAs tracking subtle cognitive declines in the preclinical stage of Alzheimer’s disease (AD) is difficult with traditional individual outcome measures, need for cognitive composite for preclinical AD is widely recognized. We aimed to develop culturally appropriate cognitive composite that sensitively identifies subtle cognitive decline of preclinical AD in Korean older adults.MethodA total 225 cognitively normal elderly individuals, who completed baseline and 2‐year follow‐up evaluation including clinical assessments and comprehensive neuropsychological tests and baseline amyloid positron emission tomography (PET) in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), were included. Tests of episodic memory, orientation, and executive function were carefully selected through review of previously established composite scores. Three candidate composites including Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word list recall (WLR), logical memory (LM) II, and Mini‐mental status examination (MMSE) in common, and letter fluency test, category fluency test, or Stroop color and word test, were selected.ResultStudent t‐tests demonstrated that only the composite composed of WLR, LM II, MMSE, and LF (Composite 1) showed a significant difference in score decline over two‐year follow‐up period between Aβ positive and negative group (P = 0.03). Linear mixed model analyses also showed that the Aβ x time interaction effect was significant only for Composite 1 (P = 0.026). In contrast, we did not find any significant results for other two candidate composites (Composite 2 and 3). Based on the results, Composite 1 was chosen as the final CPAD.ConclusionCPAD can be used to assess subtle cognitive decline of preclinical AD in clinical research settings, especially in clinical trials with Korean older adults with preclinical AD. It also may be used for monitoring progression or treatment benefits in clinical practices.

Early changes of fecal short‐chain fatty acid levels in patients with mild cognitive impairments

AbstractBackgroundMild cognitive impairment (MCI) is with great risk for the conversion to Alzheimer’s disease (AD). The aim of present study wanted to explore whether fecal Short‐chain fatty acids (SCFAs) could be used as the biomarker for the identification of MCI patients and to examine the relationship between fecal SCFAs and amyloid‐β deposition in the brain.MethodsA cohort of 32 MCI patients and 27 NC were recruited in our study. Fecal levels of SCFAs were measured using chromatography and mass spectrometry. Disease duration, ApoE genotype, body mass index, constipation, and diabetes were evaluated. To assess cognitive impairment, we used the Mini‐Mental Status Examination (MMSE). To assess brain atrophy, the degree of medial temporal atrophy (MTA score, Grade 0‐4) was measured by structural MRI. β‐amyloid positron emission tomography (PET) with 18F‐AV‐45 was performed in seven MCI patients to detect and quantify Aβ deposition in the brain.ResultsCompared with NC, MCI patients had significantly lower fecal levels of acetic acid, butyric acid, and caproic acid. Among fecal SCFAs, acetic acid performed the best in discriminating MCI from NC, achieved an AUC of 0.752 (p = 0.001, 95% CI: 0.628‐0.876), specificity of 66.7% and sensitivity of 75%. By combining fecal levels of acetic acid, butyric acid and caproic acid, the diagnostic specificity was significantly improved, reaching 88.9%. To better verify the diagnostic performance of SCFAs, we randomly assigned 80% of participants into training dataset and 20% into testing dataset. Only acetic acid showed significantly difference between these two groups in the training dataset. Based on the fecal levels of acetic acid, we achieved the ROC curve. Next, the ROC curve was evaluated in the independent test data and 66.7% (4 in 6) of MCI patients, and 80% (4 in 5) of NC could be identified correctly. Subgroup analysis showed that reduced fecal SCFAs in MCI group were negatively associated with Aβ deposition in cognition‐related brain regions.ConclusionOur findings suggest that gut metabolite SCFAs have the potential to serve as early diagnostic biomarkers for distinguishing patients with MCI from NC and could serve as potential targets for preventing AD.

Association of estimated white matter hyperintensity age with cognition in hypertensive elderly

AbstractBackgroundHypertension is associated with white matter hyperintensity (WMH) and cognitive impairment. Further, WMH is associated with cognitive impairment including executive, attention and visuospatial functions. The aim of this study was to investigate the effects of controlled hypertension (cHT) and previously developed concept, ‘WMH age’ on cognitive function and the mediating role of WMH in the effect of cHT on cognitive impairment.MethodWe enrolled 855 Koreans without dementia aged 60 years or older, 326 of whom completed 2‐year follow‐up assessment. We measured their blood pressure thrice in a sitting position using an automated blood pressure monitoring device. We estimated ‘WMH age’ of every participant using previously developed WMH probability map of healthy older Koreans. We analyzed the mediating effect of WMH age in the association of cHT and cognitive function using the PROCESS Macro model.ResultOld WMH age was associated with a faster decline in the Mini‐Mental Status Examination (MMSE; p = .003), Consortium to Establish a Registry for Alzheimer’s Disease total score (CERAD‐TS; p = .003), and Frontal Assessment Battery (FAB; p = .007). Old WMH age showed an approximately‐six times higher risk of incident mild cognitive impairment (OR = 6.47, 95% CI = 1.37 – 9.50, p = .024) compared to young or normal WMH age over the 2‐year follow‐up period in the cHT group. WMH age mediated the effects of cHT on the MMSE, CERAD‐TS, and FAB scores at baseline and two‐year follow‐up period.ConclusionWMH mediates the adverse effect of hypertension on cognitive function. Elders with cHT who have older WMH age may be at a higher risk of cognitive decline.

A comparative study of medication profiles from AD, MCI, and non‐demented patients

AbstractBackgroundThe ever‐increasing incidence of Alzheimer’s disease (AD) and the lack of effective therapeutics to treat the disease are leading to a “silver tsunami”. Current FDA‐approved drugs to treat the disease are limited as their benefit is simply momentary relief of the symptoms. Due to the chronic and progressive nature of AD, patients are routinely prescribed multiple non‐AD medications to preserve their ability to perform daily activities and to improve their quality of life. However, how those medications affect AD pathology remains unknown. In the present study, we have compared medication profiles of AD (n = 135), mild cognitive declined (MCI; n = 120), and non‐demented (n = 259) patients, with an aim to determine the effects of top‐ranked drugs on AD pathology.MethodsStudy subjects (≥65 years) were recruited from an academic geriatric practice that is heavily focused on memory disorders. All subjects underwent for the following cognitive assessments: a) Clinical dementia rating scale (CDR), b) Mini‐Mental Status Examination (MMSE), c) logical memory test, d) digit span forward and backward, e) category fluency test, f) ordering test, g) trails A&B, and finally the Geriatric Depression Scale. Individual medication for each subject was listed and they were categorized into major drug classes. Statistical analysis was performed to determine the frequency of each drug in each class.ResultsEight top‐ranked drug classes were categorized from a list of 453 individual medications. Vitamins (30‐40%) and anti‐inflammatory (∼30%) drugs were the major categories for each cohort. Interestingly, 11% of drugs were proton pump inhibitors in non‐demented patients, and this decreased by 8% in MCI, and 5% in AD. We found a reduced (8%) Lipitor prescriptions for AD patients compared MCI (11%) and non‐demented (13%) patients. We are investigating the effects of these highly prescribed drugs on β‐amyloid production/aggregation, cytotoxicity, plaque load, and tau phosphorylation in vitro and in vivo using cell culture and AD mouse models.ConclusionWhile the effects of routinely prescribed drugs on AD pathology are not well known, we found reduced vitamins, proton pump inhibitors, and Lipitor in the medication profiles of AD patients compared to the non‐AD population.

Meningkatkan Hasil Belajar Kreatif Siswa Melalui Model PBL Gereja Sebagai Umat Allah FaseF SMKN 1 Kelam Permai

Education is very important in this era of globalization and is even included in the basic needs of every human being because by obtaining education humans will be able to improve their quality of life. Education is also one of the supporting factors for a country's progress, with a country's high level of education it can produce quality human resources and contribute to developing the country. Catholic Religious Education is an effort made so that students have the ability to build a more faithful life. Christian and devoted to God Almighty in accordance with the teachings of the Catholic Church. Building a life of Christian faith means building loyalty to the Gospel of Jesus Christ, which has a single concern, namely the Kingdom of God. The Kingdom of God is a situation and event of salvation: a situation and struggle for peace and justice, happiness and prosperity, brotherhood and loyalty as well as environmental preservation, which is longed for by everyone from various religions and beliefs. Catholic Religious Education lessons are also not included in the subjects that take part in the State Examination. This causes students to underestimate Catholic Religious Education lessons. In situations like that, teachers must be good at creating situations, creative and good at having methods so that PAK learning can be more interesting and arouse students' interest. Based on the researcher's experience of teaching at SMK N 1 Kelam Permai, many students obtained below average learning outcomes and students had little interest in the Catholic religious learning process. They were less interested in participating in PAK learning. They also underestimate PAK learning because they prioritize other subjects. To overcome the problems mentioned above, one of the alternatives proposed by researchers is learning using the Problem Based Learning model with the reward method, which aims to ensure that students' learning outcomes are good and they have a high interest in learning. The Redward method intended in this research is an educational tool for educational efforts to achieve satisfactory learning outcomes and change students' interest in learning for the better. By giving this prize, it is hoped that students will be more interested in participating in lessons, especially in studying material about the Church as God's people. The objectives of this research are 1). PBL learning using the reward method on Church material as God's people can improve student learning outcomes creatively. 2). Increasing creative student learning outcomes in Catholic Religious Education by providing rewards for church material as God's people.3). Knowing students' reactions to the use of the Problem Based Learning (PBL) method by providing rewards to improve students' creative learning outcomes and interest in phase F of SMK N 1 Kelam Permai. In particular, in the material "The Church as God's people" it is hoped that students will be able to find themselves, recognize and accept themselves as members of God's people, and work together in efforts to develop themselves as members of the Church in accordance with God's plan. The Problem Based Learning (PBL) learning model by providing rewards can overcome problems in motivating students to be more creative in learning. Redward's way of working is in accordance with the way students learn and encourages students to be more enthusiastic and creative in learning so as to improve student learning outcomes, especially in Catholic religious education.

Neural responses to acute stress predict chronic stress perception in daily life over 13 months

The importance of amygdala, hippocampus, and medial prefrontal cortex (mPFC) for the integration of neural, endocrine, and affective stress processing was shown in healthy participants and patients with stress-related disorders. The present manuscript which reports on one study-arm of the LawSTRESS project, aimed at investigating the predictive value of acute stress responses in these regions for biopsychological consequences of chronic stress in daily life. The LawSTRESS project examined law students either in preparation for their first state examination (stress group [SG]) or in the mid-phase of their study program (control group [CG]) over 13 months. Ambulatory assessments comprising perceived stress measurements and the cortisol awakening response (CAR) were administered on six sampling points (t1 = − 1 year, t2 = − 3 months, t3 = − 1 week, t4 = exam, t5 = + 1 week, t6 = + 1 month). In a subsample of 124 participants (SG: 61; CG: 63), ScanSTRESS was applied at baseline. In the SG but not in the CG, amygdala, hippocampus, and (post-hoc analyzed) right mPFC activation changes during ScanSTRESS were significantly associated with the trajectory of perceived stress but not with the CAR. Consistent with our finding in the total LawSTRESS sample, a significant increase in perceived stress and a blunted CAR over time could be detected in the SG only. Our findings suggest that more pronounced activation decreases of amygdala, hippocampus, and mPFC in response to acute psychosocial stress at baseline were related to a more pronounced increase of stress in daily life over the following year.

Skolēnu rakstu valoda latviešu valodas un vēstures valsts pārbaudes darbos 2021. gadā Kurzemē

The research aims to examine pupils’ text creation skills in the Latvian language and history state examinations (SE). The source of the research is the examination papers of pupils in Kurzeme in the 2021 Latvian language SE (an opinion; 250 words) and history SE (task 3 of part 3 – an essay; 200 words). Examination of the evaluation criteria of both examinations shows that the evaluation criteria of the Latvian language examination pay more attention to the quality of spelling (10 points out of 34 (approx. 30%) can be obtained for orthography and punctuation). The article summarizes the main types of errors in morphology and syntax in both examinations. Several types of errors are distinguished in morphology: unjustified use of macrons or their absence, spelling of consonants, words written incorrectly together and separately, spelling of onyms, and errors in the spelling of verbs and foreign words. A number of syntactic constructions were studied in the pupils’ examination papers – coordinated parts of sentence, coordinated parts of sentence with a generalising word, participial clauses, insertions and explanatory word groups –, as wethe frequency of their use in the pupils’ examination papers and the most frequently detected cases of errors. The use of punctuation marks in the sentence, separating the subordinate clause, has also been studied. A comparison of the two examination papers leads to the conclusion that there are no statistically significant differences in the text creation task in Latvian or history SE in Kurzeme. Spelling and punctuation skills are solid, and the number of errors is equal. As pupils take the examinations, caution is observed in using more complex syntactic constructions. In the analysis, examples from pupils’ examination papers are presented in italics, preserving their style, spelling and punctuation errors.

Voice analysis results in individuals with Alzheimer's disease: How do age and cognitive status affect voice parameters?

Reports of acoustic changes in the voice in individuals with Alzheimer's disease (AD) and the relationship of acoustic changes with age and cognitive status are still limited. This study aims to determine the changes in voice analysis results in AD, as well as the effects of age and cognitive status on voice parameters. The study included 47 (AD: 30; healthy: 17) women with a mean age of 76.13 years. The acoustic voice parameters mean fundamental frequency (F0), relative average perturbation (RAP), jitter percent (Jitt), shimmer percent (Shim), and noise-to-harmonic ratio were detected. The mini-mental state examination (MMSE) was utilized. F0, Shim, Jitt, and RAP values were found to be statistically significantly higher in individuals with AD compared to healthy individuals. There was a significant negative correlation between MMSE and F0, Jitt, RAP and Shim, and the MMSE score had a significant negative effect on F0, Jitt, and RAP (p<.05). Cognitive status was discovered to significantly impact the voice, with fundamental frequency and frequency and amplitude perturbations increasing as cognitive level decreases. In order to contribute to the therapy process for voice disorders, cognitive functions can be focused on in addition to voice therapy.

Daytime dysfunction may be associated with postoperative delirium in patients undergoing total hip/knee replacement: The PNDABLE study.

Postoperative delirium (POD) is a usual complication after total hip/knee replacement, which may be affected by sleep characteristics. However, up to now, preoperative sleep characteristics have not been evaluated as risk factors of POD. The relationship between self-reported sleep characteristics and POD in patients has been investigated in this study. We recruited 495 cognitively intact individuals in the final analysis from the Perioperative Neurocognitive Disorder and Biomarker Lifestyle study. Sleep characteristics were tested by the Pittsburgh Sleep Quality Index (PSQI). Mini-mental state examination was applied to assess preoperative mental status of patients. Postoperatively, we used confusion assessment method and memorial delirium assessment scale to evaluate the incidence of POD and POD severity, respectively. The cerebrospinal fluid (CSF) levels of T-tau, P-tau, Aβ40, and Aβ42 were detected by enzyme-linked immune-sorbent assay before the operation. Logistic regression, multiple linear regression, and mediation effects were performed to analyze the relationship between self-reported sleep characteristics and POD. POD was detected in 11.31% (56/495) of the patients, with logistic regression analysis showing that daytime dysfunction, P-tau, and T-tau were risk factors of POD, and Aβ42 was a protective factor of POD. Multiple linear regression analysis confirmed that daytime dysfunction was positively correlated with P-tau in patients with POD. Meanwhile, compared to the patients with no postoperative delirium, the CSF levels of P- and T-tau were higher in patients with POD. Furthermore, mediation analysis showed that it was probable that daytime dysfunction mediated POD through P-tau (proportion: 12.90%) partially. Daytime dysfunction is a risk factor of POD preoperatively. To sum up, CSF P-tau protein might partially mediate the influence of daytime dysfunction on POD. This study was registered at Chinese Clinical Trial Registry (ChiCTR2000033439).

Association of dietary patterns with cognitive function in older people: Results from the Chinese longitudinal healthy longevity survey

AbstractBackgroundDietary patterns are crucial for maintaining cognitive health among older people and can be modified through lifestyle interventions. We investigated the associations between dietary patterns, changes in these patterns over time, and cognitive function.MethodsThis cohort study utilized data from the Chinese Longitudinal Healthy Longevity Survey conducted between 2005 and 2014. The sample included 7472 participants (mean age: 81.45 ± 10.88 years). Dietary patterns were derived using cluster analysis. Cognitive function was assessed using the Mini‐Mental State Examination (MMSE). The relationships between dietary patterns/changes, MMSE scores, changes in MMSE scores, and cognitive impairment were analyzed using the generalized estimating equation method, linear regression, and logistic regression.ResultsCluster analysis identified three major dietary patterns: balanced diet, relatively balanced diet, and unbalanced diet. Mean MMSE scores decreased from 24.71 ± 7.24 in 2005 to 22.22 ± 9.29 in 2008, then increased to 24.10 ± 7.76 in 2014. Participants who adhered to balanced diet patterns exhibited significantly higher MMSE scores (1.56; 95% confidence interval: 1.34, 1.78) than those who followed unbalanced diet patterns. This association was particularly prominent among older individuals, women, individuals with no education, and underweight individuals. Participants with relatively balanced or balanced diets showed a significantly lower risk of cognitive impairment (adjusted odds ratio (OR) = 0.72, 95% CI: 0.65, 0.80; OR = 0.47, 95% CI: 0.42, 0.53, respectively) than those with unbalanced diets. Transitioning from an unhealthy diet to a healthy diet was associated with a smaller decline in MMSE scores and reduced risk of cognitive impairment.ConclusionsThese findings emphasize the importance of balanced or relatively balanced diets in preserving cognitive health in older individuals. These patterns relate to better MMSE scores and reduced cognitive impairment risk. Shifting from unhealthy to healthy diets is linked to improved MMSE scores and lower cognitive impairment risk. These results underscore the importance of dietary interventions in mitigating cognitive decline in older adults. Further research is warranted to understand the underlying mechanisms and develop targeted strategies for promoting healthy dietary habits in this population.

Meningkatkan Kemandirian Belajar dalam pembelajaran Pendidikan Agama Katolik dengan Model Discovery learning AKU MEMILIKI KEMAMPUAN Fase D Kelas VII SMP Negeri 1 Girsang Sipangan Bolon

This research was carried out as a form of solving student problems in increasing student learning independence. The independence of student learning in learning is closely related to the quality and ability of the teacher as a designer of learning in the classroom, as well as implementing learning in the classroom. This research was carried out so that students were active in learning Catholicism at SMP Negeri 1 Girsang Sipangan Bolon, Simalungun Regency, learning Catholicism was less attractive to some students because it was not in the State Examination and the number of students was minimal. So the authors conducted research to increase student learning independence at SMP Negeri 1 Girsang Sipangan Bolon with the Discovery Learning learning model

Evaluation of the eOSCE for testing clinical skills.

The OSCE is a proven instrument for testing practical skills of students, not only in the (veterinary) medical field. At the University of Veterinary Medicine Hannover, Foundation (TiHo), students must complete a 10-week rotation in one of the university’s own clinics during the practical year in the 9th and 10th semesters in addition to other practical training. Within this framework, the first training for acquiring clinical practical skills with a formative examination (OSCE; Objective Structured Clinical Examination) was developed in the Clinical Skills Lab (CSL) in 2014. Since 2018, the TiHo has been the first veterinary medical training institution in Germany to conduct electronic OSCEs (eOSCEs). In the future, eOSCEs will also be introduced as a summative examination at the TiHo. For this reason, students in the practical year of the winter semester 2021/2022 and summer semester 2022 as well as former and current examiners were surveyed regarding their satisfaction with the eOSCE examination format as part of this study. The 175 analyzed questionnaires from students and 27 analyzed questionnaires from examiners showed a high level of satisfaction with the eOSCE overall, but at the same time indicated problems that should be ironed out before it is introduced as a summative examination in the state examination. In addition to its standardization and objectivity, the examination format also convinced with its quality-assurance review procedure and the direct feedback possibility with regard to the students’ performance.

Early-Onset/Young-Onset Colorectal Carcinoma: A Comparative Analysis of Morphological Features and Biomarker Profile.

Introduction Colorectal carcinoma (CRC) is one of the most common cancers that involve the human body. Young-onset CRC (YO-CRC) or early-onset CRC (EO-CRC) is defined as CRC that develops before the age of 50 years, as opposed to CRC that is diagnosed after the age of 50, referred to as late-onset CRC (LO-CRC). EO-CRC is sparsely studied in our population. Therefore, in this study, we evaluated the clinicopathological parameters and biomarker profile of EO-CRC and compared them with those of LO-CRC. Methods This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan. A total of 254 biopsy-proven cases of CRC, reported over a period of nine years, were enrolled in the study. The specimens collected during surgery were sent to the laboratory for histopathological and immunohistochemical (IHC) status examinations. IHC staining of the specimens was performed using antibodies, namely, MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), and human epidermal growth factor receptor 2 (HER2/neu), on representative tissue blocks. A comparison of morphological and biomarker profiles between EO-CRC and LO-CRC was performed. Results The mean age at diagnosis was 46.27±17.75 years, with female predominance (59.8%). A significant difference between the two groups (EO-CRC and LO-CRC) was noted with respect to laterality, tumor site, tumor grade, tumor type, presence of pre-existing polyps, perineural invasion (PNI), lymphovascular invasion (LVI), and IHC markers. EO-CRC (as opposed to LO-CRC) significantly affected the left colon (92.6% vs. 72.9%, p<0.001), with the rectosigmoid being the most common site in the majority of cases (72.1% in EO-CRC vs. 61% in LO-CRC). EO-CRC showed a higher frequency of PNI and LVI than LO-CRC (42.6% vs. 23.7%, p=0.001; 29.4% vs. 18.6%, p=0.046, respectively). A significantly higher proportion of EO-CRCs were mucinous (42.6%) and medullary carcinoma (11.8%). Although the majority (54.4%) of cases of EO-CRC weregrade 2 tumors at the time of diagnosis, a significantly higher proportion of them were grade 3 (44.1%) compared with LO-CRC. IHC comparisons between the two age groups showed that a significantly higher proportion of cases of EO-CRC showed positive HER2/neu expression (27.1%) compared with LO-CRC (13.2%). Conversely, the loss of expression of microsatellite instability (MSI) markers was more commonly seen in LO-CRS compared with EO-CRC. Conclusions We found a relatively higher frequency of EO-CRC in our population. Moreover, compared with LO-CRCs, EO-CRCs were associated with prognostically poor histological parameters, such as mucinous and medullary carcinoma, high-grade, PNI, and LVI. Similarly, EO-CRC had a higher positive expression of HER2/neu with intact MSI markers compared with AO-CRC; all these characteristics indicate poor biological behavior in EO-CRC.

A call for utilizing various screening tools in dementia diagnosis: A systematic review

AbstractBackgroundDementia is a disorder distinguished by progressive and irreversible global cognitive impairment. About 45 million live with dementia globally, with an estimated increase to 75 million by 2030. Early recognition and diagnosis of dementia could enhance the efficiency of health care and quality of life. Hence, Medicare implemented a covered visit for assessing cognitive function for eligible patients as of January 2021. Previous studies described many tests and screening tools that clinicians can use to diagnose dementia. However, choosing a suitable test is solely left for clinicians to decide. We conducted a systematic review to provide an evidence‐based screening tool guide to facilitate dementia diagnosis.MethodA systematic review of studies published between 2010 and 2020 in English that targeted older patients. The search included multiple global databases; Cambridge Core, Cochrane Library, Google Scholar, PubMed, and Wiley online library. Keywords: “Dementia” “Screening” “Older people” “General Hospital” and “Inpatient''. Seven independent reviewers checked the studies to avoid bias.Result32 articles met the review criteria. More than ten dementia screening tools and tests were identified in the various clinical settings. However, the Mini‐Mental State Examination (MMSE) is the leading test with three times usage compared to other tests, followed by Montreal Cognitive Assessment (MoCA).ConclusionThe Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are the commonly used tools in diagnosing dementia. The review revealed other tests with a higher potential for early detection of dementia in various clinical settings. Thus, this is a call for clinicians to benefit and diversify the tools in diagnosing dementia and enrich the evidence‐based research with more confirmatory studies.

Prediction of the 3‐year survival in patients with cognitive impairment based on demographics, neuropsychological data, and comorbidities

AbstractBackgroundTo develop and validate a prediction model for the 3‐year survival of patientwith cognitive impairment based on demographics, neuropsychological assessment data, and comorbidities.MethodFive‐hundred‐and‐eighty‐seven patients with cognitive impairment were included from our memory clinic. Demographic information, comorbidities, the Mini‐Mental State Examination (MMSE), Instrumental Activity of Daily Living (IADL) score, and Neuropsychiatric Inventory Questionnaire sub‐item scores were collected. Survival conditions were obtained by telephone from the caregivers in the third year after the neuropsychological tests. Patients were randomly divided into training set and validation set with a ratio of 7:3. Variables that achieved statistical significance (P &lt; 0.05) in the single‐factor analysis were incorporated in the binary logistic regression model. A nomogram was established according to the multivariate analysis. The receiver operating characteristic curve, area under the curve, C‐index, calibration curve, and the Hosmer–Lemeshow test were performed to validate the nomogram.ResultYounger age, higher MMSE score, lower IADL score, no symptom of disinhibition, and Charlson Comorbidity Index score equal or less than 1 are associated with 3‐year survival. These predictors yielded good discrimination with C‐indexes of 0.80 (0.73–0.87) and 0.85 (0.77–0.94) in the training and validation cohorts, respectively. The Hosmer–Lemeshow test showed no statistical significance in either cohort, and calibration curves displayed a good consistency between the prediction and the actual observation.

Associations between modifiable and non‐modifiable risk factors and domain‐specific cognitive decline over a 17‐year period

AbstractBackgroundModifiable risk factors account for 40% of worldwide dementias. However, to what extent different risk factors are associated with different types of cognitive decline remains unclear. The aim of this study was to investigate how different risk factors contribute to future decline in memory and attention/executive function, respectively.MethodBaseline examination of individuals without dementia in the prospective Swedish population‐based Malmö Diet and Cancer Study (MDCS) took place in 1991‐1996. In 2007‐2012, a randomly selected subsample was invited to a re‐examination using cognitive assessments (the Mini‐Mental State Examination [MMSE], A Quick Test of cognitive speed (AQT) and, for a sub‐population, The Montreal Cognitive Assessment (MoCA). Participants with complete data on cognitive assessments, body measurements, education and APOE genotype were included in the study (n = 2,881; n = 720 with MoCA). Linear regression models were used to examine the modifiable risk factors (hypertension, body mass index [BMI], long‐term glucose levels [HbA1c], lipid levels, physical activity and alcohol consumption) and non‐modifiable risk factor (APOE‐genotype). Follow‐up outcomes were 1) AQT‐color/form (processing speed and executive function, higher scores indicating worse function), 2) delayed recall and orientation scores from MMSE (memory function), and 3) subscores from MoCA. All models were adjusted for age, sex, education and time between baseline and cognitive assessments.ResultMedian follow‐up time was 17.3 (inter‐quartile range [IQR] 2.2) years. APOE‐e4 and higher HbA1c levels were independently associated with worse future memory function in a multivariable model (Table 1). Mean arterial blood pressure, obesity, lower HDL‐C, and higher HbA1c levels were independently associated with worse future processing speed/executive function (Table 2). Higher alcohol consumption was associated better performance in executive function (Table 2). Similar results were found using corresponding MoCA subscores (delayed recall and orientation subscores; visuospatial/executive and attention subscores).ConclusionIn this prospective, population‐based, 17‐years follow‐up study, cardiovascular risk factors in mid‐life were associated with future decline in processing speed and executive functions, while an APOE‐e4 genotype was associated with worse memory function. Alcohol consumption in mid‐life was associated with better performance in both cognitive domains. These results suggest that targeting cardiovascular risk factors in interventions may have a greater effect on future executive function than memory.

The novel visual cognitive assessment test correlates well with plasma oligomeric amyloid beta in patients with mild cognitive impairment

AbstractBackgroundOligomeric Amyloid Beta (OAβ), is representative of a soluble, neurotoxic and pathogenic form of Aβ, which has been found to function as upstream drivers of Alzheimer’s Disease pathology (Tolar et al., 2021). It serves as a contributory factor towards the formation of cortical Aβ plaques and neurofibrillary Tau tangles, and has been found to induce oxidative stress, synaptic toxicity and neuroinflammation (Tolar et al., 2021). The pathology culminates in neuronal dysfunction/death and resultant neurodegeneration which has been found to manifest clinically as symptoms of cognitive decline. OAβ has been found to correlate with the severity of cognitive performance, as well as brain volume reduction (An et al., 2017, Wang et al., 2017, Meng et al., 2019, Youn et al., 2019, Babapour Mofrad et al., 2021). Nevertheless, its effect on language neutral cognitive tests ‐ the novel Visual Cognitive Assessment Test (VCAT) developed and validated by our team of neurologist and neuropsychologists; remains to be evaluated (Kandiah et al., 2016, Lim et al., 2018, Low et al., 2020).MethodsA cross‐sectional pilot study was conducted in a cohort of 63 patients, clinically diagnosed with mild cognitive impairment (MCI). The patients underwent cognitive evaluation tests, Multimer Detection System (MDS) based plasma OAβ analysis and MRI based cortical grey matter evaluations (Wang et al., 2017, Youn et al., 2019, Pyun et al., 2021, Vipin et al., 2021). Pearson’s correlation evaluated associations between plasma OAβ, cognitive scores [Mini‐Mental State Examination (MMSE), VCAT] and brain volume measures [Grey Matter Volume (GMV) / Intracranial Volume (ICV)].ResultsIncreasing plasma OAβ expression associated with decreasing, VCAT scores (r = ‐0.291, 95% CI = ‐0.504 to ‐0.044, p = 0.022) and MMSE scores (r = ‐0.272, 95% CI = ‐0.489 to ‐0.024, p = 0.032), in MCI patients (Figure 1A, B). Additionally increasing plasma OAβ expression also associated with decreasing and GMV/ ICV ratio (r = ‐0.264, 95% CI = ‐0.489 to ‐0.007, p = 0.045), in MCI patients (Figure 1C).ConclusionFindings from this study, emphasise on the promising clinical utility of plasma OAβ as a biomarker. Future longitudinal studies will validate these associations across the Alzheimer’s disease spectrum.