Difference In Rate Of Decline Research Articles

417P Comparison of changes in 6-minute walk distance for Colombian patients with Duchenne muscular dystrophy treated with Ataluren with different rates of decline

417P Comparison of changes in 6-minute walk distance for Colombian patients with Duchenne muscular dystrophy treated with Ataluren with different rates of decline

Dissecting unique and common variance across body and brain health indicators using age prediction

AbstractAgeing is a heterogeneous multisystem process involving different rates of decline in physiological integrity across biological systems. The current study dissects the unique and common variance across body and brain health indicators and parses inter‐individual heterogeneity in the multisystem ageing process. Using machine‐learning regression models on the UK Biobank data set (N = 32,593, age range 44.6–82.3, mean age 64.1 years), we first estimated tissue‐specific brain age for white and gray matter based on diffusion and T1‐weighted magnetic resonance imaging (MRI) data, respectively. Next, bodily health traits, including cardiometabolic, anthropometric, and body composition measures of adipose and muscle tissue from bioimpedance and body MRI, were combined to predict ‘body age’. The results showed that the body age model demonstrated comparable age prediction accuracy to models trained solely on brain MRI data. The correlation between body age and brain age predictions was 0.62 for the T1 and 0.64 for the diffusion‐based model, indicating a degree of unique variance in brain and bodily ageing processes. Bayesian multilevel modelling carried out to quantify the associations between health traits and predicted age discrepancies showed that higher systolic blood pressure and higher muscle‐fat infiltration were related to older‐appearing body age compared to brain age. Conversely, higher hand‐grip strength and muscle volume were related to a younger‐appearing body age. Our findings corroborate the common notion of a close connection between somatic and brain health. However, they also suggest that health traits may differentially influence age predictions beyond what is captured by the brain imaging data, potentially contributing to heterogeneous ageing rates across biological systems and individuals.

Pet Ownership, Living Alone, and Cognitive Decline Among Adults 50 Years and Older

It remains unclear whether pet ownership is associated with cognitive decline and to what extent pet ownership mitigates the association between living alone and cognitive decline. To explore the association of pet ownership with cognitive decline, the interaction between pet ownership and living alone, and the extent to which pet ownership mitigates the association between living alone and cognitive decline in older adults. This cohort study used data from waves 5 (June 2010 to July 2011) to 9 (from June 2018 to July 2019) in the English Longitudinal Study of Ageing. Participants included adults 50 years and older. Data were analyzed from April 1 to June 30, 2023. Pet ownership and living alone in wave 5. In waves 5 to 9, verbal memory and verbal fluency were assessed, and composite verbal cognition was further calculated. Of the 7945 participants included, the mean (SD) age was 66.3 (8.8) years, and 4446 (56.0%) were women. Pet ownership was associated with slower rates of decline in composite verbal cognition (β = 0.008 [95% CI, 0.002-0.014] SD/y), verbal memory (β = 0.006 [95% CI, 0.001-0.012] SD/y), and verbal fluency (β = 0.007 [95% CI, 0.001-0.013] SD/y). Three-way interaction tests showed that living alone was a significant modifier in all 3 associations. Stratified analyses showed that pet ownership was associated with slower rates of decline in composite verbal cognition (β = 0.023 [95% CI, 0.011-0.035] SD/y), verbal memory (β = 0.021 [95% CI, 0.008-0.034] SD/y), and verbal fluency (β = 0.018 [95% CI, 0.005-0.030] SD/y) among individuals living alone, but not among those living with others. Joint association analyses showed no significant difference in rates of decline in composite verbal cognition, verbal memory, or verbal fluency between pet owners living alone and pet owners living with others. In this cohort study, pet ownership was associated with slower rates of decline in verbal memory and verbal fluency among older adults living alone, but not among those living with others, and pet ownership offset the associations between living alone and declining rates in verbal memory and verbal fluency. Further studies are needed to assess whether pet ownership slows the rate of cognitive decline in older adults living alone.

The modifying effects of cardiovascular risk factors on the relationship between lifetime discrimination and cognitive function: Study of Healthy Aging in African Americans (STAR)

AbstractBackgroundDiscrimination is a root cause of health inequities contributing to the excess burden of cognitive impairment among Black Americans. Using the Study of Healthy Aging in African Americans (STAR) we examined whether the effect of lifetime discrimination on late‐life cognitive decline was magnified by early adulthood cardiovascular risk factors.MethodSTAR enrolled long‐term Kaiser Permanente Northern California members ages 50+ who identify as Black/African American. In early adulthood, participants completed Multiphasic Health Check‐ups (MHC; 1964‐1985) where systolic blood pressure (BP), total cholesterol, and body mass index (BMI) were assessed. A latent class analysis identified groups based on responses to the Major Experiences of Discrimination Scale and gender. Standardized z‐scores for executive function (EF) and verbal episodic memory (VEM) were measured over 3 waves (2018‐2022) using the Spanish and English Neuropsychological Assessment Scales. Linear mixed models with random intercepts and slopes associated latent class with cognitive decline adjusting for age at MHC, age at baseline cognitive assessment, education, and assessment mode (in‐person/telephone). Separate models tested class*cardiovascular risk factor interactions.ResultParticipants (n = 646) averaged 27.7(SD = 7.3) years of age at MHC and 68.5(SD = 8.8) at baseline cognitive assessment (Table 1). Four latent classes were identified: men reporting widespread discrimination (Class‐1men; 12%), women reporting widespread discrimination (Class‐2women; 22%), men and women reporting unfair police treatment (Class‐3police; 17%), and men and women reporting little/no discrimination (Class‐4no_discimination; 49%). Using Class‐4no_discimination as reference, those in Class‐2women had significantly higher baseline EF (β(95% CI):0.18(0.03,0.34)) while Class‐1men (β:0.04(‐0.15,0.23)) and Class‐3police (β:‐0.08(‐0.25,0.09)) did not differ (Figure 1). Class‐2women (β:0.17(0.00,0.33)) had higher baseline VEM compared to Class‐4no_discrimination while Class‐1men (β:‐0.40(‐0.60,‐0.19)) and Class‐3police (β:‐0.27(‐0.46,‐0.09)) had significantly lower (Figure 1). There were no differences in rate of decline. There was a systolic BP*class interaction (p = 0.04) where 5 mm Hg higher systolic BP in early adulthood was associated with worse EF for Class‐3police (β:‐0.07(‐0.12,‐0.02)) compared to Class‐4no_discrimination while Class‐1men and Class‐2women did not differ (Figure 2). This pattern was similar for VEM but non‐significant (interaction p = 0.07). We found no interactions with total cholesterol or BMI.ConclusionFor Black Americans, discriminatory experiences may differentially impact late‐life cognition, and elevated systolic BP in early adulthood may exacerbate this harm.

Assessing spatial heterogeneous response of ecosystem service relationships to land use intensification

Sustainable land use should balance the competing needs for development and protection. Land-use intensification facilitates material benefits from ecosystem, while potentially undermining the capacity of regulate the life-support environment and thus altering trade-offs between ecosystem services (ES). However, there remains a limited understanding of how land-use intensity (LUI) affects the spatial heterogeneity of ES relationships. To address this issue, we first propose an ES synergies (ESS) index, to clarify site-specific ES relationships, based on a combination of the production possibility frontier (PPF) and the technique for order preference by similarity to the ideal solution (TOPSIS). Then, we assess the nonlinear impacts of LUI on ESS, using the generalized additive models (GAMs). A case study was conducted in the Three Gorges region of central China, due to the dilemma between intensive development for poverty alleviation and water-soil retention for ecological protection. The results showed that an increase in LUI caused different rates of decline in ESS. Land-use intensification increased resource inputs and anthropogenic disturbances within entire land parcels, thus disrupting the synergistic relationships between several ES. Specifically, the synergies between water retention and carbon sequestration or biodiversity conservation decreased by more than three times as much as those between water retention and food production. Excessive LUI will reduce the provision of carbon sequestration and biodiversity conservation compared to that of food production for the same level of water retention. However, moderate LUI can promote the synergistic provision of multiple services. For example, an LUI threshold of 2.5, which maximized the synergies of water-soil retention with other ES, showed the optimal balance of diverse ecological benefits at the highest level of intensity. Our study is expected to extend existing knowledge on the spatial heterogeneity of ES relationships by considering site-specific land use, and to mitigate the costs of land management due to ES trade-offs.

The “real life” efficacy of dupilumab is independent of initial polyp size and concomitant steroids in CRSwNP

BackgroundDupilumab significantly improves symptom control in chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with large polyps at the initiation of treatment (total polyp score (TPS) ≥ 5) have been the focus in published studies. Patients with significant burden of disease but small polyps (TPS ≤ 4) have not yet been evaluated for clinical response. This study set out to evaluate the benefit of dupilumab treatment on cohorts of small (TPS ≤ 4) compared to large polyps (TPS ≥ 5). Furthermore, benefit of concomitant oral and/or nasal steroid therapy has been evaluated.Methods97 patients with CRSwNP, who were begun on dupilumab between January 2020 and October 2021, were included. All patients were followed-up for 6 months. At each visit they underwent nasal endoscopy, smell identification tests and filled out validated patient questionnaires.ResultsSignificant drops in TPS were seen in both patient groups after 6 months of therapy, dropping from a median score of 3 to 0 and from 6 to 2 in patients with small and large polyps respectively. Furthermore, a linear mixed model calculated a drop of 22% and 24% in TPS per month in patients with small and large polyps respectively with no significant difference in rate of decline. Finally the model showed that neither oral nor nasal steroids influenced the rate of response to dupilumab therapy.ConclusionsPolyp size at the initiation of dupilumab therapy and whether patients continue to take steroid therapy does not appear to influence effectiveness of dupilumab treatment.

Study of the structure and development of oil deposits in carbonate reservoirs using field data and X-ray microtomography

At present, a large number of scientific works devoted to the study of the features of the geological structure and the development of oil deposits in complex carbonate reservoirs are based on the use of any one research method. This article shows the advantages of the integrated use of modern methods of core research, including X-ray microtomography and electron microscopy, as well as data from hydrodynamic and field studies of wells. The advantage of the approach used is the ability to study the deposit at three levels: core-well-development object, it is reasonable to transfer micro-survey data to the regularities of the implementation of technological processes of oil production. The objects of research in this article are the Famennian oil deposits of two neighboring fields, which, at first glance, are analogues in terms of the similarity of the enlarged geological and physical characteristics. Comprehensive studies of core samples from these deposits made it possible to establish differences both in the mineral composition of rocks and in the structure of their void space, especially in the size and distribution of pore channels. So, with approximately equal porosity for one of the deposits, the presence of two types of voids and a twofold prevalence of the size of the largest of them were established. According to the complex of laboratory methods for studying the core, the reservoir is classified as a porous type (no cracks were found). The performed interpretation of the hydrodynamic studies confirmed this fact, made it possible to establish the presence of a dependence of the reservoir permeability on the formation pressure (deformation of the void space of the reservoir), and also to build the corresponding individual dependence for each well. Comparison of the equations approximating the dependence data showed a more pronounced deformation of the reservoir, which is characterized by the presence of large pores and caverns. That is, a complex of laboratory and hydrodynamic studies made it possible to establish the probability of deformation of the void space of a carbonate reservoir even in the absence of cracks in it. In turn, the reservoir deformation is singled out as the most probable cause explaining the different rates of decline in well flow rates of the fields under consideration.

A community mobilisation intervention to improve engagement in HIV testing, linkage to care, and retention in care in South Africa: a cluster-randomised controlled trial

Community mobilisation, engaging communities in a process to collectively enact change, could improve HIV testing and care engagement. In South Africa, current rates fall below those needed for epidemic control. We assessed whether community mobilisation increased HIV testing, linkage to care, and retention in care over time in intervention relative to control communities. We conducted a cluster-randomised controlled trial in villages in the Agincourt sub-district of the rural Mpumalanga Province in South Africa. 15 villages were randomly assigned to either a community mobilisation intervention engaging residents to address social barriers to HIV testing and treatment (intervention arm) or to a control arm using balanced randomisation. Villages were eligible if they had been fully enumerated in 2014, had not been included in previous mobilisation activities, and included over 500 permanent adult residents aged 18-49 years. Primary outcomes included quarterly rates of HIV testing, linkage to care, and retention in care documented from health facility records among residents of the intervention and control communities over the 3-year study period. Intention-to-treat analyses employed generalised estimating equations stratified by sex. This trial is registered with ClinicalTrials.gov, NCT02197793. Between Aug 1, 2015, and July 31, 2018, residents in eight intervention communities (n=20 544 residents) and seven control communities (n=17 848) contributed data; 92 residents contributed to both arms. Among men, HIV testing increased quarterly by 12·1% (relative change [RC] 1·121, 95% CI 1·099 to 1·143, p<0·0001) in the intervention communities and 9·5% (1·095, 1·075 to 1·114, p=0·011) in the control communities; although increases in testing were greater in the intervention villages, differences did not reach significance (exponentiated interaction coefficient 1·024, 95% CI 0·997 to 1·052, p=0·078). Among women, HIV testing increased quarterly by 10·6% (RC 1·106, 95% CI 1·097 to 1·114, p<0·0001) in the intervention communities and 9·3% (1·093, 1·084 to 1·102, p=0·053) in the control communities; increases were greater in intervention communities (exponentiated interaction coefficient 1·012, 95% CI 1·001 to 1·023, p=0·043). Quarterly linkage increased significantly among women in the intervention communities (RC 1·013, 95% CI 1·002 to 1·023, p=0·018) only. Quarterly linkage fell among men in both arms, but decreased significantly among men in the control communities (0·977, 0·954 to 1·002, p=0·043). Quarterly retention fell among women in both arms; however, reductions were tempered among women in the intervention communities (exponentiated interaction coefficient 1·003, 95% CI <1·000 to 1·006, p=0·062). Retention fell significantly among men in both arms with difference in rates of decline. Community mobilisation was associated with modest improvements in select trial outcomes. The sum of these incremental, quarterly improvements achieved by addressing social barriers to HIV care engagement can impact epidemic control. However, achieving optimal impacts will probably require integrated efforts addressing both social barriers through community mobilisation and provision of improved service delivery. US National Institutes of Health, National Institute of Mental Health, and United States President's Emergency Plan for AIDS Relief through Right to Care and Project SOAR.

Analysis of the incidence of children in social isolation during the period of COVID-19

Introduction. Children's health is an important integral indicator and criterion for the socio- conomic wellbeing of society and the state, and is also included in the system of global indicators for achieving the goals in the field of sustainable development of countries. In terms of statistical research and forecasting in health care, children's health indicators can be assessed as the most stable and reliably reflecting the actual situation. The article contains information that allows one to form an idea of the health status of children of various age groups in Moscow in conditions of social isolation and distance learning during the COVID-19 period.&#x0D; Purpose of the study. To identify the main trends in the level of general morbidity among children aged 0-17 in Moscow during the COVID-19 pandemic, both in general and by age groups. Assess how the lockdown associated with the coronavirus outbreak has affected the health of children.&#x0D; Materials and methods. The review used population data, as well as data from federal statistical observation form No. 12 “Information on the number of diseases registered in patients living in the service area of a medical organization” for 2016–2020. Morbidity was analyzed for age groups 0-4 years, 5-9 years, 10-14 years, 15-17 years per 100,000 of the corresponding population.&#x0D; Results and discussion. In 2020, the overall level of child morbidity in the capital amounted to 189.1 thousand cases per 100,000 children, a decrease of 15.6% compared to 2019, in general, for the period from 2016 to 2020 – by 18.6 %. An analysis of the incidence of children showed that in 2020, the conditions of temporary isolation and a decrease in contacts during the COVID-19 pandemic led to a decrease in the registration of a number of diseases: SARS, acute bronchitis, acute conjunctivitis and diseases of the digestive system, as well as a decrease in childhood injuries in all age groups. A characteristic feature for children of all ages was the decrease in the overall incidence in 2020, however, it is worth noting the different rates of decline in indicators for individual classes of diseases depending on age.

Quantifying societal emotional resilience to natural disasters from geo-located social media content.

Natural disasters can have devastating and long-lasting effects on a community's emotional well-being. These effects may be distributed unequally, affecting some communities more profoundly and possibly over longer time periods than others. Here, we analyze the effects of four major US hurricanes, namely, Irma, Harvey, Florence, and Dorian on the emotional well-being of the affected communities and regions. We show that a community's emotional response to a hurricane event can be measured from the content of social media that its population posted before, during, and after the hurricane. For each hurricane making landfall in the US, we observe a significant decrease in sentiment in the affected areas before and during the hurricane followed by a rapid return to pre-hurricane baseline, often within 1-2 weeks. However, some communities exhibit markedly different rates of decline and return to previous equilibrium levels. This points towards the possibility of measuring the emotional resilience of communities from the dynamics of their online emotional response.

Ескалація глобальних ризиків і загроз в умовах пандемії: фінансовий і макроекономічний аспекти

Potentially threatening phenomena on the way to stabilizing and overcoming depressive trends in the global economy in the medium and long term in the context of the COVID-19 pandemic have been identified and systematized, taking into account the identification of areas of global risk. The reformatting of the global socio-economic landscape is substantiated, which is determined by the course of the pandemic, the different rates of decline and recovery of the economic growth in general and in individual industries, the destabilization of public finances, the exacerbation of social protection problems. This is confirmed by the dynamics of international trade in goods and services, the aggravation of the global debt problem. Emphasis is placed on the need to form in each country the anti-crisis potential on a scientifically sound basis in order to counter external and internal threats and stimulate sustainable socio-economic development.

Sex Differences in the Association Between Metabolic Dysregulation and Cognitive Aging: The Health and Retirement Study.

Dysregulation of some metabolic factors increases the risk of dementia. It remains unclear if overall metabolic dysregulation, or only certain components, contribute to cognitive aging and if these associations are sex specific. Data from the 2006-2016 waves of the Health and Retirement Study (HRS) was used to analyze 7 103 participants aged 65 and older at baseline (58% women). We created a metabolic-dysregulation risk score (MDRS) composed of blood pressure/hypertension status, glycosylated hemoglobin (HbA1c)/diabetes status, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and waist circumference, and assessed cognitive trajectories from repeated measures of the HRS-Telephone Interview for Cognitive Status (HRS-TICS) over 10 years of follow-up. Linear mixed-effects models estimated associations between MDRS or individual metabolic factors (biomarkers) with mean and change in HRS-TICS scores and assessed sex-modification of these associations. Participants with higher MDRSs had lower mean HRS-TICS scores, but there were no statistically significant differences in rate of decline. Sex stratification showed this association was present for women only. MDRS biomarkers revealed heterogeneity in the strength and direction of associations with HRS-TICS. Lower HRS-TICS levels were associated with hypertension, higher HbA1c/diabetes, and lower HDL-C and TC, whereas faster rate of cognitive decline was associated with hypertension, higher HbA1c/diabetes, and higher TC. Participants with higher HbA1c/diabetes presented worse cognitive trajectories. Sex differences indicated that women with higher HbA1c/diabetes to have lower HRS-TICS levels, whereas hypertensive males presented better cognitive trajectory. Our results demonstrate that metabolic dysregulation is more strongly associated with cognition in women compared with men, though sex differences vary by individual biomarker.

LONGITUDINAL EXAMINATION OF THE ASSOCIATION BETWEEN HORMONAL CONTRACEPTIVE USE AND ANTI-MÜLLERIAN HORMONE (AMH) LEVELS IN REPRODUCTIVE-AGED AFRICAN-AMERICAN WOMEN

To determine the impact of hormonal contraceptive (HC) use on trends in AMH levels in a longitudinal cohort of reproductive-aged African American women (AAW). This study used an established cohort of AAW from Detroit, MI aged 25 to 35 years, who were recruited as a part of the Study of the Environment, Lifestyle and Fibroids. Anthropometric measurements, self-reported health history, and serum AMH levels (picoAMH assay, Ansh Labs, Webster, TX) were collected from participants at 4 visits over 5 years. All types of HC were included. Percent changes in AMH levels were calculated from baseline to final visit and compared across groups with different patterns of HC use using linear regression models, adjusting for age, BMI, history of abnormal menstrual bleeding, thyroid disorder, and a history of infertility. The effect of starting, continuing, or stopping HC on rate of change in AMH for all follow up visits was also assessed using linear mixed models adjusted for age. A total of 1531 women were included with a mean age of 29.2 ± 3.4 years and a median AMH of 4.07 (IQR 2.29 - 6.70) ng/mL at baseline. At the final follow-up visit, mean age was 34.1 ± 3.4 years and median AMH was 2.97 (IQR 1.52 - 5.15) ng/mL, with a 19.8% average decline in AMH. Women who started and continued HC during the study period had significantly greater % decrease in AMH levels (-23.1%, 95% CI -40.3%, -5.9%) compared with women who never used HC. When compared with women who never used HC, the % change in AMH levels among women who started and stopped HC during the study was -14.4% (95% CI -29.3%, 0.5%), among women who only used HC prior to the study was -13.5%, (95% CI -26.9%, -0.1%) , and among long-term users of HC (on HC before and throughout study period) was -8.7% (95% CI -24.6%, 7.2%). We next sought to determine whether the rate of decline in AMH was impacted by the recency of HC start or discontinuation. Women who started HC between study visits had a faster rate of decline in AMH levels compared with women not on HC at their previous or current visit, (-11.9%; 95% CI -15.5%, -8.0%), while women who used HC at a previous visit but discontinued prior to the most recent visit had a slower rate of decline in AMH (10.7% 95% CI 6.7%, 15.0%). There was no difference in rate of decline among women who continued HC between visits (2.3%, 95% CI -0.6%, 5.7%) compared to those who were not on HC between visits. In this study, the % decline in AMH levels with age was greatest among those who started and continued HC during the study period. This finding, along with the non-significant difference in % decrease with age in AMH levels among long-term HC users, suggests that the impact of HC use on AMH may be most significant after initiation with recovery of AMH following stoppage of HC suggested by the smaller decline with age in this subset of women. Thus, the impact of HC on AMH levels appears reversible. In addition, being on HC neither increases nor protects against the age related rate of decline.

Effect of nusinersen on respiratory function in paediatric spinal muscular atrophy types 1–3

IntroductionNusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown.AimTo assess the effects of nusinersen on respiratory function in paediatric SMA...

Coordinated changes in cellular behavior ensure the lifelong maintenance of the hippocampal stem cell population.

SummaryNeural stem cell numbers fall rapidly in the hippocampus of juvenile mice but stabilize during adulthood, ensuring lifelong hippocampal neurogenesis. We show that this stabilization of stem cell numbers in young adults is the result of coordinated changes in stem cell behavior. Although proliferating neural stem cells in juveniles differentiate rapidly, they increasingly return to a resting state of shallow quiescence and progress through additional self-renewing divisions in adulthood. Single-cell transcriptomics, modeling, and label retention analyses indicate that resting cells have a higher activation rate and greater contribution to neurogenesis than dormant cells, which have not left quiescence. These changes in stem cell behavior result from a progressive reduction in expression of the pro-activation protein ASCL1 because of increased post-translational degradation. These cellular mechanisms help reconcile current contradictory models of hippocampal neural stem cell (NSC) dynamics and may contribute to the different rates of decline of hippocampal neurogenesis in mammalian species, including humans.

Effectiveness of three brief treatments for recent traumatic events in a low-SES community setting.

To determine whether brief treatments provide psychological relief after traumatic events in low-resource communities. Participants (n = 105) who had experienced a traumatic event within the past 6 months were randomly assigned to 1 of 3 4-session treatments: individual eye movement desensitization and reprocessing (EMDR), group-administered stress management with a trauma focus (SMT), or group-administered psychological first aid (PFA). Measures administered pretreatment and at 1-, 3-, and 6-month posttreatment included posttraumatic stress disorder (PTSD) symptoms, posttraumatic cognitions (PTCI), and depressive symptoms (BDI). The 3 treatment groups all showed significant declines in PTSD, PTCI, and BDI symptoms over time with large prepost effect sizes (median 1-month: 0.96, 3-month: 1.38, 6-month: 1.10). However, the treatment groups showed significantly different rates of decline, with the EMDR group showing the fastest declines-interaction PTCI: F(1, 237) = 5.85, p = .016; depression:, F(1, 239) = 4.90, p = .028-followed by the SMT and then PFA group. While there were significant differences between the EMDR and PFA groups at the 1- and 3-month follow-ups, there were no significant differences in any of the 3 outcome measures at the 6-month follow-up, nor were there significant differences between groups on PTSD symptoms, F(1, 239) = 2.30, p = .131. This study provides preliminary evidence that any of these 3 approaches may be useful in low-resource community settings. Because it gives the quickest relief, EMDR is the preferred approach, followed by SMT, due its ease of administration. PFA provides a reasonable alternative. Where possible, booster sessions should be planned. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Identifying and predicting heterogeneity in cognitive decline among individuals with prodromal Alzheimer's disease using a latent class analysis

AbstractBackgroundIndividuals with prodromal Alzheimer’s disease (AD) show heterogeneity in their rates of cognitive decline, which is problematic for measuring (therapeutic) effects on cognition. We aimed to identify subgroups with homogeneous cognitive trajectories among individuals with prodromal AD in two large independent cohorts, and investigate which clinical and/or biological AD risk factors predict progression rate.MethodIndividuals with an abnormal amyloid marker (determined by either CSF Aβ‐42 levels or Florbetaben/Flutametamol/Florbetapir‐AV45 PET imaging) and mild cognitive impairment who had longitudinal cognitive data available were selected from the Amsterdam Dementia Cohort and ADNI (N=340, age =71.5±8.4, 43% female). We performed latent class mixed models (LCMM) to identify subgroups based on similarity of their trajectories on the Mini‐Mental State Examination (MMSE), and performed mixture modelling using individual MMSE slopes to validate those subgroups. We compared subgroups on baseline age, sex, years of education, ApoE‐e4 status, CSF tau and phosphorylated tau (p‐tau) and hippocampal volume using univariate logistic regression, and subsequently performed stepwise logistic regression with backward elimination to identify which baseline characteristics best predicted progression.ResultParticipants had 2.3±1.8 repeated assessments and a follow‐up of 2.3±1.6 [range=1‐8] years. LCMM identified three subgroups of MMSE progression, which were confirmed by mixture modelling: Group 1 (n=303, 88%) showing slowest progression (i.e. average 0.7 [range=0.4–1.9] points annual decline on MMSE); Group 2 (n=30, 10%) intermediate progression (average 2.6 [range=1.9–4.2] points annual decline on MMSE) and Group 3 (n=7, 2%) showing fastest progression (average 4.7 [range=3.3–6.2] points annual decline on MMSE) (Figure 1). No effects on progression were observed for age, sex, education and ApoE‐e4 (Table 1). Compared to individuals who slowly progressed, those with intermediate‐to‐fast progression had higher tau (OR=1.01, 95%CI=[1.01‐1.02], p&lt;.001) and p‐tau (OR=1.03, 95%CI=[1.02‐1.05], p&lt;.001) levels and lower hippocampal volume (OR=0.57, 95%CI=[.37‐.84], p=.006) at baseline. The model including both p‐tau (OR=1.03, 95%CI=[1.02‐1.05], p&lt;.001) and hippocampal volume (OR=0.55, 95%CI=[.34‐.85], p=.01) best predicted fast progression.ConclusionAmong individuals with prodromal AD, we identified three subgroups with different rates of decline on the MMSE, and demonstrated that baseline neurodegeneration markers were associated with faster decline. These findings have practical implications for clinical trial enrollment and predicting disease progression.

Self-Reported Hearing Loss and Longitudinal Cognitive Function in a Cohort Enriched with Risk for Alzheimer's Disease.

Growing evidence suggests hearing loss is a risk factor for mild cognitive impairment and dementia, but few studies have examined its relationship to sub-clinical cognitive outcomes. To investigate the effect of self-reported hearing loss on longitudinal cognitive function in a risk-enriched cohort of clinically-unimpaired, late middle-aged adults. 579 participants from the Wisconsin Registry for Alzheimer's Prevention (WRAP) were included. Hearing status was determined via self-reported history of diagnosed hearing loss. Each participant with self-reported hearing loss was age- and sex-matched to two participants who never reported hearing loss using nearest-neighbor matching. Linear mixed-effects models were used to examine associations between self-reported hearing loss and age-related cognitive trajectories with covariates of sex, literacy, and ethnicity, person-level random intercepts and age-related slopes. Cognitive outcomes encompassed measures of speed and flexibility, visuospatial memory, and verbal fluency. Participants with self-reported hearing loss exhibited significantly poorer performance on a speed and flexibility factor score and single test of psychomotor speed and executive function, relative to participants who never reported hearing loss. There was no association between self-reported hearing loss and visuospatial memory or verbal fluency. Longitudinally, self-reported hearing loss was associated with less rapid decline in speed and flexibility and no difference in rate of decline for any other cognitive measure. Self-reported hearing loss was associated with poorer speed and flexibility but not with accelerated decline in any domain studied, contrary to previous findings. Further studies involving behavioral auditory measures in this cohort would clarify the robustness of these findings.

Longitudinal Evaluation of Lung Function in Gulf War I Veterans Exposed to Depleted Uranium.

Gulf War I (GWI) Veterans exposed to depleted uranium (DU) have undergone biennial surveillance to assess for DU-related health effects. No DU-specific respiratory effects have been observed cross-sectionally, but longitudinal lung function decline has not been assessed. A dynamic cohort of 71 Veterans underwent spirometry testing between 1999 and 2019. Longitudinal rates of decline of spirometry values were compared among Veterans with high versus low uranium levels using a linear mixed model. There was no significant difference in rate of decline of spirometry values between Veterans with high versus low uranium levels. The overall rate of decline was similar to that of the general population. In 20 years of follow-up, there does not appear to be an accelerated rate of decline of lung function among veterans exposed to depleted uranium.

Impact of incremental versus conventional initiation of haemodialysis on residual kidney function: study protocol for a multicentre feasibility randomised controlled trial

IntroductionPreserving residual kidney function (RKF) may be beneficial to patients on haemodialysis (HD) and it has been proposed that commencing dialysis incrementally rather than three times a week may preserve...