Greater Impairment Research Articles

Longitudinal urinary neopterin is associated with hearing threshold change over time in independent older adults

Low-grade chronic inflammation is associated with many age-related conditions. Non-invasive methods to monitor low-grade chronic inflammation may improve the management of older people at risk of poorer outcomes. This longitudinal cohort study has determined baseline inflammation using neopterin volatility in monthly urine samples of 45 independent older adults (aged 65–75 years). Measurement of neopterin, an inflammatory metabolite, enabled stratification of individuals into risk categories based on how often in a 12-month period their neopterin level was raised. Hearing was measured (pure-tone audiometry) at baseline, 1 year and 3 years of the study. Results show that those in the highest risk category (neopterin raised greater than 50% of the time) saw greater deterioration, particularly in high-frequency, hearing. A one-way Welch’s ANOVA showed a significant difference between the risk categories for change in high-frequency hearing (W (3, 19.6) = 9.164, p = 0.0005). Despite the study size and duration individuals in the highest risk category were more than twice as likely to have an additional age-related morbidity than those in the lowest risk category. We conclude that volatility of neopterin in urine may enable stratification of those at greatest risk of progression of hearing loss.

Effects of Developmental Timing on Cognitive and Behavioral Profiles in Fetal Alcohol Spectrum Disorder: Considerations for Education.

Associations and families demand the need to raise awareness of the implications in the cognitive and behavioral development of children with Fetal Alcohol Spectrum Disorder (FASD) that affect their learning and school participation. This study aims to generate a profile of executive and behavioral functioning in children and adolescents diagnosed with FASD. A probabilistic sampling by clusters (associations for individuals with FASD) is applied. The sample is composed of 66 families from three associations. The BRIEF-2 and SENA tests were administered to assess executive and behavioral functioning domains. Data analysis found that the executive and behavioral functioning profile of individuals with FASD varies with age, with greater impairment in middle and late adolescence. Likewise, the domain of executive functioning most affected in any of the developmental stages is working memory. Finally, cognitive impairment in the executive functioning domains has a direct impact on the social and adaptive functioning of people with FASD.

The complementary dominance hypothesis: a model for remediating the 'good' hand in stroke survivors.

The complementary dominance hypothesis is a novel model of motor lateralization substantiated by decades of research examining interlimb differences in the control of upper extremity movements in neurotypical adults and hemisphere-specific motor deficits in stroke survivors. In contrast to earlier ideas that attribute handedness to the specialization of one hemisphere, our model proposes complementary motor control specializations in each hemisphere. The dominant hemisphere mediates optimal control of limb dynamics as required for smooth and efficient movements, whereas the non-dominant hemisphere mediates impedance control, important for countering unexpected mechanical conditions and achieving steady-state limb positions. Importantly, this model proposes that each hemisphere contributes its specialization to both arms (though with greater influence from either arm's contralateral hemisphere) and thus predicts that lesions to one hemisphere should produce hemisphere-specific motor deficits in not only the contralesional arm, but also the ipsilesional arm of stroke survivors - a powerful prediction now supported by a growing body of evidence. Such ipsilesional arm motor deficits vary with contralesional arm impairment, and thus individuals with little to no functional use of the contralesional arm experience both the greatest impairments in the ipsilesional arm, as well as the greatest reliance on it to serve as the main or sole manipulator for activities of daily living. Accordingly, we have proposed and tested a novel intervention that reduces hemisphere-specific ipsilesional arm deficits and thereby improves functional independence in stroke survivors with severe contralesional impairment.

Examining childhood experiences and personality functioning as potential predictors for the speed of recovery during psychotherapy of patients with anxiety disorders.

Adverse childhood experiences were previously identified as relevant risk factors for the development of anxiety disorders. Furthermore, anxiety disorders were shown to be associated with impairments of personality functioning. The objective of this study was to investigate adverse and protective childhood experiences as well as personality functioning, as defined by the Operationalized Psychodynamic Diagnosis system, as potential predictors for the speed of recovery during psychotherapy for patients with anxiety disorders. The sample consisted of n = 312 completed psychotherapies. The speed of recovery, defined as symptom abatement over time, was calculated using a two-stage hierarchical linear model. The effects of adverse and protective childhood experiences as well as personality functioning on the speed of recovery during psychotherapy were then examined using a structural equation model. The presence of adverse childhood experiences predicted a lower speed of recovery during psychotherapy. In addition, a higher number of adverse childhood experiences was associated with greater impairments in the abilities of perception and regulation as dimensions of personality functioning. A higher number of protective childhood experiences was associated with fewer impairments in the communication and attachment dimensions. Impairments in personality functioning in patients with anxiety disorders did not predict the speed of recovery during psychotherapy. Among patients with anxiety disorders, adverse childhood experiences lead to a lower speed of recovery during psychotherapy. Therefore, childhood adversity should be routinely assessed before and thoroughly addressed during psychotherapy in patients with anxiety disorders.

Patients with more complex ankle fractures are associated with poorer patient-reported outcome: an observational study of 11,733 patients from the Swedish Fracture Register.

Patient-reported outcome measures (PROMs) following ankle fractures, including all fracture types, have not been reported. It is therefore unclear whether fracture morphology correlates with outcome. We aimed to analyze PROMs in patients with an ankle fracture in relation to the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture classification using population-based register data from the Swedish Fracture Register (SFR). All patients aged ≥ 18 years with an ankle fracture (AO/OTA 44A1-C3) registered in the SFR between 2012 and 2019 were retrieved from the register. Patients with completed PROM questionnaires (Short Musculoskeletal Function Assessment and EuroQol-Visual Analogue Scale) on both day 0 (pre-trauma) and 1-year post-trauma were included. The difference in PROMs between day 0 and 1 year was calculated for each patient (delta value) and mean delta values were calculated at group level, based on the AO/OTA fracture classification. 11,733 patients with 11,751 fractures with complete PROMs were included. According to the AO/OTA classification, 21% were A fractures, 67% were B fractures and 12% were C fractures. All groups of patients, regardless of fracture class (A1-C3), displayed an impairment in PROMs after 1 year compared with day 0. Type C fractures displayed a larger impairment in PROMs at group level than type B, which in turn had a greater impairment than type A. The same pattern was seen in groups 3, 2, and 1 for A and B fractures. We found that the AO/OTA classification is prognostic, where more complex fractures were associated with poorer PROMs.

Description of a Murine Model of Pneumocystis Pneumonia.

Pneumocystis pneumonia is a serious lung infection caused by an original ubiquitous fungus with opportunistic behavior, referred to as Pneumocystis jirovecii. P. jirovecii is the second most common fungal agent among invasive fungal infections after Candida spp. Unfortunately, there is still an inability to culture P. jirovecii in vitro, and so a great impairment to improve knowledge on the pathogenesis of Pneumocystis pneumonia. In this context, animal models have a high value to address complex interplay between Pneumocystis and the components of the host immune system. Here, we propose a protocol for a murine model of Pneumocystis pneumonia. Animals become susceptible to Pneumocystis by acquiring an immunocompromised status induced by iterative administration of steroids within drinking water. Thereafter, the experimental infection is completed by an intranasal challenge with homogenates of mouse lungs containing Pneumocystis murina. The onset of clinical signs occurs within 5weeks following the infectious challenge and immunosuppression can then be withdrawn. At termination, lungs and bronchoalveolar lavage (BAL) fluids from infected mice are analyzed for fungal load (qPCR) and immune response (flow cytometry and biochemical assays). The model is a useful tool in studies focusing on immune responses initiated after the establishment of Pneumocystis pneumonia.

The relationship between bullying victimization and impairment in personality functioning in a clinical adolescent sample.

Problematic interpersonal relationships may represent both, a risk factor for the development or trigger of personality disorder (PD) symptoms and its consequences. Since peer relationships become more and more important in adolescence, the current study explores the cross-sectional association between recent bullying experiences and levels of impairment in personality functioning according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) alternative model of personality disorders (AMPD; Criterion A) in help-seeking adolescents (N = 493). Logistic and multiple regression analyses revealed that patients who were frequently bullied in the past 3 months (i.e., at least once a week) were more likely to reach the diagnostic threshold for PD according to the AMPD (OR = 1.71, p = .025) and showed higher levels of impairment in identity (β = .41, p < .001), empathy (β = .26, p = .002), and intimacy (β = .30, p = .001), but not self-direction, compared to patients who did not report any bullying experiences. Occasional bullying in the past 3 months (i.e., every few weeks) was neither associated with a greater likelihood to reach the diagnostic threshold for PD nor with greater impairments in identity, self-direction, empathy, or intimacy compared to no bullying. While the current study provides support for a correlation between bullying experiences and personality dysfunction (particularly in the elements identity and intimacy), longitudinal research is needed to clarify whether experiences of bullying cause or trigger personality dysfunction or/and vice versa. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Spontaneous Sympathetic Baroreflex Sensitivity Is Impaired in Patients with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have chronic overactivation of the sympathetic nervous system that contributes to hypertension and increased cardiovascular risk. The sympathetic baroreflex is a major regulator of sympathetic activity in response to changes in blood pressure; however, limited information is available regarding sympathetic baroreflex control in non-dialysis patients with CKD. In the present study we tested the hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA) is attenuated in non-dialysis patients with CKD. In 17 sedentary patients with CKD stages III-IV (76% hypertensive and 29% with diabetes) [12 male/5 female, age: 57 ± 13 yr, 13 Black/4 White, systolic/diastolic BP: 122 ± 17/75 ± 7 mmHg, BMI: 31 ± 5 kg/m2, eGFR: 40 ± 14 mL/min/1.73m2] and 9 controls (CON) (89% hypertensive and 22% with diabetes) [7 male/2 female, age: 51 ± 13 yr, 8 Black/1 White, systolic/diastolic BP: 123 ± 6/79 ± 6 mmHg, BMI: 30 ± 6 kg/m2, eGFR: 95 ± 12 mL/min/1.73m2], resting beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA, microneurography) were continuously recorded during 10 min of semi-recumbent rest. Weighted linear regression analysis between MSNA burst incidence and diastolic blood pressure was used to determine the spontaneous sympathetic baroreflex sensitivity (sBRS). Resting MSNA burst incidence was higher in patients with CKD [CKD: 70 ± 19 bursts (100 heart beats)−1. mmHg−1 versus CON: 47 ± 9 bursts (100 heart beats)−1. mmHg−1; p&lt;0.001], and a higher MSNA burst frequency was observed in CKD (CKD: 43 ± 11 bursts. min−1 versus CON: 32 ± 10 bursts. min−1; P=0.021], whereas resting mean arterial blood pressure (91 ± 9 mmHg versus 94 ± 5 mmHg; P=0.317) and heart rate were similar between groups. Patients with CKD had reduced sBRS compared to controls [CKD: -1.37 ± 0.59 bursts (100 heart beats)−1 mmHg−1 versus CON: -2.79 ± 1.33 bursts (100 heart beats)−1 mmHg−1; P=0.013]. The MSNA burst incidence (r = -0.63, p&lt;0.001) and the sBRS (r = -0.57, P=0.002) were significantly associated with the estimated glomerular filtration rate (eGFR). Overall, these preliminary findings suggest an attenuated sympathetic baroreflex sensitivity in patients with CKD compared with age and-comorbidities matched controls, with greater impairment in those with more severe kidney dysfunction. This work was supported by National Institutes of Health Grants R01HL135183 and R61AT010457 (J.P). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effect of nintedanib on health-related quality of life in Japanese patients with progressive fibrosing interstitial lung diseases: A subset analysis of the INBUILD trial

BackgroundIn previous Japanese subgroup/subset analyses of the global INBUILD trial, nintedanib reduced the annual rate of forced vital capacity (FVC) decline and the risk of disease progression in patients with progressive fibrosing interstitial lung diseases (PF-ILDs). This exploratory subset analysis assessed the effect of nintedanib on symptoms and impacts of pulmonary fibrosis in Japanese patients with PF-ILDs, including those with usual interstitial pneumonia (UIP)-like fibrotic pattern on high-resolution computed tomography (HRCT). MethodsThis analysis included Japanese patients who received at least one dose of study treatment in the randomized, double-blind, placebo-controlled INBUILD trial. The Living with Pulmonary Fibrosis (L-PF) questionnaire was used to assess pulmonary fibrosis symptoms and impacts (higher scores indicated greater impairment) at baseline and weeks 12–52. ResultsIn total, 108 Japanese patients (nintedanib: n = 52; placebo: n = 56) were included; 84 patients had UIP-like fibrotic pattern on HRCT. In the total Japanese subgroup and in those with UIP-like fibrotic pattern, numerically greater increases in L-PF total, symptoms total, symptoms fatigue domain, and impacts scores were observed in the placebo group than in the nintedanib group at all timepoints, starting from week 12. A numerically greater increase in the symptoms dyspnea domain score was observed with placebo versus nintedanib starting from week 36. Throughout the study, the symptoms cough domain score increased in the placebo group but decreased in the nintedanib group. ConclusionsOur findings demonstrate that nintedanib has the potential to reduce the worsening of symptoms and impacts of pulmonary fibrosis in Japanese patients with PF-ILDs.

Cognitive profile in multiple sclerosis and post-COVID condition: a comparative study using a unified taxonomy

Post-COVID condition (PCC) and multiple sclerosis (MS) share some clinical and demographic features, including cognitive symptoms and fatigue. Some pathophysiological mechanisms well-known in MS, such as autoimmunity, neuroinflammation and myelin damage, have also been implicated in PCC. In this study, we aimed to compare the cognitive phenotypes of two large cohorts of patients with PCC and MS, and to evaluate the relationship between fatigue and cognitive performance. Cross-sectional study including 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol and were categorized according to the International Classification of Cognitive Disorders system. Fatigue and depression were also assessed. Cognitive profiles of PCC and MS largely overlapped, with a greater impairment in episodic memory in MS, but with small effect sizes. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC. Still, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. There were no differences in the severity of depression among groups. Our study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS. Further comparative studies addressing the mechanisms related to cognitive dysfunction and fatigue may be of interest to advance the knowledge of these disorders and develop new therapies.

Sex-specific differences in myocardial glucose metabolic rate in non-diabetic, pre-diabetic and type 2 diabetic subjects

BackgroundEvidence has shown that women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than men with T2DM. Subjects with either T2DM or prediabetes exhibit myocardial insulin resistance, but it is still unsettled whether sex-related differences in myocardial insulin resistance occur in diabetic and prediabetic subjects.MethodsWe aimed to evaluate sex-related differences in myocardial glucose metabolic rate (MRGlu), assessed using dynamic PET with 18F-FDG combined with euglycemic-hyperinsulinemic clamp, in subjects with normal glucose tolerance (NGT; n = 20), prediabetes (n = 11), and T2DM (n = 26).ResultsWomen with prediabetes or T2DM exhibited greater relative differences in myocardial MRGlu than men with prediabetes or T2DM when compared with their NGT counterparts. As compared with women with NGT, those with prediabetes exhibited an age-adjusted 35% lower myocardial MRGlu value (P = 0.04) and women with T2DM a 74% lower value (P = 0.006), respectively. Conversely, as compared with men with NGT, men with T2DM exhibited a 40% lower myocardial MRGlu value (P = 0.004), while no significant difference was observed between men with NGT and prediabetes. The statistical test for interaction between sex and glucose tolerance on myocardial MRGlu (P < 0.0001) was significant suggesting a sex-specific association.ConclusionsOur data suggest that deterioration of glucose homeostasis in women is associated with a greater impairment in myocardial glucose metabolism as compared with men. The sex-specific myocardial insulin resistance could be an important factor responsible for the greater effect of T2DM on the excess risk of cardiovascular disease in women than in men.

Study of the possibility of producing brine-ripened cheeses from frozen sheep’s milk

The article presents the results of a study of the quality indicators of brine-ripened cheeses produced from defrosted sheep’s milk. The objects of the study were natural and defrosted sheep’s milk, brine-ripened cheeses from this milk. The study of defrosted sheep’s milk (experiment) was carried out after 10 days of its storage at a temperature of –18 °C followed by defrostation at a temperature of 20 ± 2 °C. The composition of natural sheep’s milk (control) was examined after storage for 24 ± 12 hours at a temperature of 4 ± 2 °C. It has been found that the freezing of milk and its subsequent defrostation did not have a significant effect on the milk solids content, the mass fraction of protein and fat, titrated acidity; however, the mass fraction of calcium decreased, on average, by 20%. Freezing milk did not significantly affect the total number of micro- organisms, including spore aerobic microorganisms and molds. A decrease in the number of somatic cells (from 3.0 to 4.5 times) was found. There were no differences between the control and experimental milk samples in the renneting ability. The level of syneresis of clots in the control sample was 16 ± 1% higher compared to the experimental sample. The cheeses were produced according to the traditional technological scheme of brine-ripened cheese using a production mesophilic bacterial starter culture. The control and experimental cheeses did not differ significantly in physical and chemical parameters. According to the degree of proteolysis, there were no significant differences between the control and experimental variants. In the experimental sample, a decrease in the buffer capacity of the cheese mass was noted in comparison with the control cheeses. The freezing of milk did not have a significant effect on the taste characteristics of the cheeses: in both variants, the cheeses were characterized by a weakly expressed cheese, fermented milk taste with original taste of sheep’s milk. More noticeable differences were found in the consistency of the cheeses. In the control version, the consistency was characterized as tender, slightly brittle; in the experimental version, it was less tender, but brittle and slightly powdery. The greatest deterioration in consistency was observed in the samples of frozen cheese made from natural milk after defrosting; it was characterized as brittle, powdery, crumbly.

Auditory Changes in Occupational Health Associated With Metabolic Diseases in Adult Workers

Introduction: The most common hearing losses in the population are associated with genetic conditions, use of ototoxic substances or medications, infectious diseases, metabolic diseases and chronic ear diseases and the association of exposure to occupational risks or the natural aging process. Objective: Verify the association between hearing loss in workers and metabolic diseases. Method: Retrospective cross-sectional study with analysis of secondary data of subjects exposed to occupational noise and undergoing drug treatment for metabolic disease, attended in two occupational health clinics (C1 and C2) from January 2020 to December 2022, considering the data of reference examinations from the year 2005. Results: Of the n = 97 subjects evaluated, 73.20% were male, exposed to occupational noise (64.90%), with medication use for treating cardiovascular diseases (89.70%). The most recurrent auditory complaint was tinnitus (28.90%), n = 53 subjects presented sensorineural hearing loss with a statistical association between the decline of hearing loss and medications used for metabolic and hormonal regulation. Conclusion: Here was a higher frequency in the use of medications for treating cardiovascular diseases with a risk of triggering or worsening hearing loss in these subjects and greater impairment and decline of hearing thresholds were observed in the results of C2.

Performance and perceived fatigability across the intensity spectrum: role of muscle mass during cycling.

The role of muscle mass in modulating performance and perceived fatigability across the entire intensity spectrum during cycling remains unexplored. We hypothesized that at task failure (Tlim), muscle contractile function would decline more following single- (SL) versus double-leg (DL) cycling within severe and extreme intensities, but not moderate and heavy intensities. After DL and SL ramp-incremental tests, on separate days, 11 recreationally active males (V̇o2max: 49.5 ± 7.7 mL·kg-1·min-1) completed SL and DL cycling until Tlim within each intensity domain. Power output for SL trials was set at 60% of the corresponding DL trial. Before and immediately after Tlim, participants performed an isometric maximal voluntary contraction (MVC) coupled with one superimposed and three resting femoral nerve stimulations [100 Hz; 10 Hz; single twitch (Qtw)] to measure performance fatigability. Perceived fatigue, leg pain, dyspnea, and effort were collected during trials. Tlim within each intensity domain was not different between SL and DL (all P > 0.05). MVC declined more for SL versus DL following heavy- (-42 ± 16% vs. -30 ± 18%; P = 0.011) and severe-intensity cycling (-41 ± 12% vs. -31 ± 15%; P = 0.036). Similarly, peak Qtw force declined more for SL following heavy- (-31 ± 12% vs. -22 ± 10%; P = 0.007) and severe-intensity cycling (-49 ± 13% vs. -40 ± 7%; P = 0.048). Except for heavy intensity, voluntary activation reductions were similar between modes. Similarly, except for dyspnea, which was lower for SL versus DL across all domains, ratings of fatigue, pain, and effort were similar at Tlim between exercise modes. Thus, the amount of muscle mass modulates the extent of contractile function impairment in an intensity-dependent manner.NEW & NOTEWORTHY We investigated the modulatory role of muscle mass on performance and perceived fatigability across the entire intensity spectrum. Despite similar time-to-task failure, single-leg cycling resulted in greater impairments in muscle contractile function within the heavy- and severe-intensity domains, but not the moderate- and extreme-intensity domains. Perceived fatigue, pain, and effort were similar between cycling modes. This indicates that the modulatory role of muscle mass on the extent of performance fatigability is intensity domain-dependent.

Survey of hereditary angioedema episodes and quality of life impairment through a patient-participatory registry

Hereditary angioedema (HAE) adversely affects patients’ social and daily life significantly, and the disease burden is high. We recruited study participants from a patient-participatory registry, Rare and Undiagnosed Diseases Study (RUDY) Japan, to better understand the broader effect of HAE on patients’ lives. Thirteen patients with HAE who registered between January 2019 and March 2021 completed an online questionnaire to record details of episodes and the angioedema quality of life (AE-QoL) questionnaire, in which they described the degree to which QoL was impaired. In all, 58 episodes were recorded, and self-reported data were accumulated from 24 returned AE-QoL questionnaires. The episodes peaked between approximately 06:00 and 07:00 h and between approximately 16:00 and 20:00 h. Of the 58 episodes, 38 (65.5%) were treated; 24 (63.2%) were treated at patients’ homes. The drugs used in treatment were hospital-administered human C1-inhibitor preparations for 14 episodes and home-administered icatibant for 26 episodes. Time between episode onset and treatment initiation and between episode onset and full recovery tended to be shorter with icatibant treatment at home. The total AE-QoL score was 37.1 ± 22.9, indicating great impairment of QoL, with particularly high scores in the fatigue/mood and fears/shame domains. Most previous studies of real-world HAE episodes have been retrospective, based on patients’ memories. Collaboration between patients and researchers revealed the location of episodes, the time of day they appeared, treatments for episodes, and the degree to which patients’ QoL was impaired by HAE in this prospective study.

Scope of a short &amp; obese patient for thymoma surgery with the risk of difficulty in weaning from general anaesthesia

Obese patients had more difficulty with tracheal intubation and a higher incidence of post-extubation stridor. Obesity is such a ubiquitous issue in our culture, and it is a significant risk factor for many diseases, thus it is not surprising that many obese patients are treated in ICU. The objective of this article is to explore challenges for short, obese patients (Little’s) in the critical care setting. Obese patients have a strong correlation between lung function and body fat distribution, with greater impairment when fat accumulates in the chest and abdomen. Mediastinal masses, particularly those located in the anterior mediastinum, can cause perioperative morbidity and mortality by causing major airway and vascular compression, which may be exacerbated under general anesthesia.

Mental health in Ireland during the Covid pandemic: Evidence from two longitudinal surveys.

The Covid pandemic arrived in Ireland on February 29, 2020. In the following weeks various restrictions were introduced to stem the spread of the disease. Anxiety over the spread of the disease and over the restrictions introduced had an adverse effect upon mental health. This study examines the change in mental health for two groups: young adults aged around 23 at the time of onset of Covid (the 1998 cohort) and a sample of principal carers (PCs) of children who were aged 13 at the onset of Covid (the 2008 cohort). Data were obtained from the two cohorts of the longitudinal Growing Up In Ireland (GUI) survey. The sample included 1953 young adults (from the 1998 cohort) and 3547 principal carers (from the 2008 cohort). Mental health as measured by the Centre for Epidemiological Studies Depression-8 scale was obtained for the last pre-Covid wave and for the Covid wave (surveyed in December 2020). Observations for which CES-D8 was not available in either pre or post Covid waves were excluded. Post-Covid sampling weights were applied. The change in depression rates was decomposed into a growth and distribution effect using a Shapley decomposition. The socioeconomic gradient of CES-D8 was examined pre and post Covid using concentration indices and a transition matrix was constructed to examine the dynamics of changes in CES-D8 and depression pre and post-Covid. Relative to the last pre-Covid survey, mental health, as measured by CES-D8 deteriorated for both the young adults of the 1998 cohort and the PCs of the 2008 cohort. For young adults, the deterioration was more pronounced for females. There was no observable socioeconomic gradient for poor mental health amongst young adults, both pre and post Covid. For mothers from the 2008 cohort, a gradient was observed during the pre-COVID-19 pandemic period with poorer mental health status for lower-income and less educated mothers. This gradient was less pronounced post-Covid, the levelling-off arising from a greater deterioration in mental health for higher-income and better-educated PCs. Both observed cohorts showed a significant deterioration in mental health post Covid. For young adults the effect was significantly more pronounced among females and this is consistent with generally poorer mental health amongst females in this age group. There was little or no socioeconomic gradient observed for young adults, but the gradient became more shallow for principal carers. Care must be taken in terms of drawing policy implications from this study as the Covid-19 pandemic was arguably a unique event, even allowing for the likelihood of future pandemics. However, the study highlights the vulnerability of young adults, especially females, to the mental health effects arising from major public health shocks.

Apraxia Patterns for the Differentiation between Alzheimer's Disease and Frontotemporal Dementia Variants.

Background and Objectives: Despite the increasing use of biomarkers, differentiation between Alzheimer's disease (AD), behavioral variant Frontotemporal Dementia (bvFTD), and Primary Progressive Aphasia (PPA) remains a challenge. Apraxia is a supportive feature for diagnosing AD but is underrepresented in other dementia types. Herein, we investigated the presence and characteristic profiles of limb, verbal, and non-verbal apraxia in three major dementia types. Materials and Methods: Test for Upper Limb Apraxia (TULIA) and Apraxia Battery for Adults-2 (ABA-2) were administered in patients with AD (n = 22), bvFTD (n = 41), and PPA (n = 22), with 20 individuals serving as healthy controls (HC). Composite and subdomain scores were compared between each patient group and the HC. Praxis profiles indicative of each dementia type and a possible predictive value were sought. Results: Apraxia provided high diagnostic accuracy for detecting dementia compared with HC (sensitivity: 63.6-100%, specificity: 79.2-100%). Patients with AD performed worse when imitating intransitive gestures as well as pantomiming transitive gestures (mean differences: 2.10 and 3.12, respectively), compared with bvFTD. PPA patients, compared with bvFTD, had comparable results in limb, verbal, and non-verbal praxis assessments, despite the greater deterioration in the outcome. Compared with patients with AD, PPA had increased pathological outcomes in verbal (86.4% vs. 40.9%) and non-verbal apraxia (31.8% vs. 0%), while bvFTD had increased pathological outcomes in verbal apraxia (85.4% vs. 44.5%). Finally, apraxia is correlated with cognitive decline. Conclusions: Apraxia profile evaluation could contribute to the differentiation between AD and Frontotemporal Dementia (FTD). Both TULIA and ABA-2 are reliable tools that can be performed as bed-side tests in clinical practice.

Phenotypic clusters of type 2 diabetes mellitus among North Indians reveal higher levels of insulin deficiency along with insulin resistance

BackgroundType 2 diabetes is now considered a heterogenous disease. Distinct clusters have been identified with patterns varying between Europeans and South Asians as well as between South Indians who have described a novel cluster; Combined Insulin-Resistant and Deficient Diabetes, and individuals from West and East India who have reported that insulin deficiency is the primary driver of heterogeneity. Therefore, North Indian patients may also have a distinct, novel clustering pattern due to unique genetic, epigenetic, and environmental factors. We aim to identify clusters of type 2 diabetes in North Indians and to describe the different characteristics of these clusters. MethodsThe K value for the optimal number of clusters was obtained from two-step clustering. K means clustering was done with this K value using SPSS 29.0 software. Variables used for clustering were age, BMI, HbA1c, HOMA-beta, HOMA-IR, and waist circumference. ResultsFour phenotypically different clusters were identified in 469 individuals with type 2 diabetes. Cluster 1 was severe insulin deficient diabetes (15%), Cluster 2 was severe insulin resistant diabetes (22%), Cluster 3 was moderate obesity-related diabetes (35%), and Cluster 4 was moderate age-related diabetes (27%). Clusters 1 and 2 were similar to earlier studies but in different proportions. Clusters 3 and 4 characteristics were different from earlier studies, with greater impairment in beta cell function and higher HbA1c levels. Significant insulin resistance was noted in all clusters. ConclusionThe phenotypic clusters of type 2 diabetes identified in the present study were characterized by high levels of insulin deficiency along with important contributions from insulin resistance.

The Bio-Hermes Study: Biomarker database developed to investigate blood-based and digital biomarkers in community-based, diverse populations clinically screened for Alzheimer's disease.

Alzheimer's disease (AD) trial participants are often screened for eligibility by brain amyloid positron emission tomography/cerebrospinal fluid (PET/CSF), which is inefficient as many are not amyloid positive. Use of blood-based biomarkers may reduce screen failures. We recruited 755 non-Hispanic White, 115 Hispanic, 112 non-Hispanic Black, and 19 other minority participants across groups of cognitively normal (n=417), mild cognitive impairment (n=312), or mild AD (n=272) participants. Plasma amyloid beta (Aβ)40, Aβ42, Aβ42/Aβ40, total tau, phosphorylated tau (p-tau)181, and p-tau217 were measured; amyloid PET/CSF (n=956) determined amyloid positivity. Clinical, blood biomarker, and ethnicity/race differences associated with amyloid status were evaluated. Greater impairment, older age, and carrying an apolipoprotein E (apoE) ε4 allele were associated with greater amyloid burden. Areas under the receiver operating characteristic curve for amyloid status of plasma Aβ42/Aβ40, p-tau181, and p-tau217 with amyloid positivity were ≥ 0.7117 for all ethnoracial groups (p-tau217, ≥0.8128). Age and apoE ε4 adjustments and imputation of biomarker values outside limit of quantitation provided small improvement in predictive power. Blood-based biomarkers are highly associated with amyloid PET/CSF results in diverse populations enrolled at clinical trial sites. Amyloid beta (Aβ)42/Aβ40, phosphorylated tau (p-tau)181, and p-tau 217 blood-based biomarkers predicted brain amyloid positivity. P-tau 217 was the strongest predictor of brain amyloid positivity. Biomarkers from diverse ethnic, racial, and clinical cohorts predicted brain amyloid positivity. Community-based populations have similar Alzheimer's disease (AD) biomarker levels as other populations. A prescreen process with blood-based assays may reduce the number of AD trial screen failures.