Dynamic establishment and maintenance of the human intestinal B cell population and repertoire following transplantation in a pediatric-dominated cohort.

Introduction: It is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of recipient gut lymphocyte populations in immunosuppressed conditions. Methods: Using polychromatic flow cytometry that includes HLA allele group-specific antibodies distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients. Results: We confirm the early presence of naïve donor B cells in the circulation (donor age range: 1-14 years, median: 3 years) and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa (recipient age range at the time of transplant: 1-44 years, median: 3 years). Recipient B cell repopulation of the allograft was most rapid in infant (<1 year old)-derived allografts and, unlike T cell repopulation, did not correlate with rejection rates. While recipient memory B cell populations were increased in graft mucosa compared to circulation, naïve recipient B cells remained detectable in the graft mucosa for years. Comparisons of peripheral and intra-mucosal B cell repertoires in the absence of rejection (recipient age range at the time of transplant: 1-9 years, median: 2 years) revealed increased BCR mutation rates and clonal expansion in graft mucosa compared to circulating B cells, but these parameters did not increase markedly after the first year post-transplant. Furthermore, clonal mixing between the allograft mucosa and the circulation was significantly greater in ITx recipients, even years after transplantation, than in deceased adult donors. In available pan-scope biopsies from pediatric recipients, we observed higher percentages of naïve recipient B cells in colon allograft compared to small bowel allograft and increased BCR overlap between native colon vs colon allograft compared to that between native colon vs ileum allograft in most cases, suggesting differential clonal distribution in large intestine vs small intestine. Discussion: Collectively, our data demonstrate intestinal mucosal B cell repertoire establishment from a circulating pool, a process that continues for years without evidence of stabilization of the mucosal B cell repertoire in pediatric ITx patients.

Prestroke Physical Activity Matters for Functional Limitations: A Longitudinal Case-Control Study of 12,860 Participants.

OBJECTIVE: In the chronic phase after a stroke, limitations in activities of daily living (ADLs) and instrumental activities of daily living (IADLs) initially plateau before steadily increasing. The benefits of prestroke physical activity on these limitations remain unclear. To clarify this relationship, the effect of physical activity on the long-term evolution of functional limitations in a cohort of people with stroke compared to a cohort of matched adults without stroke was examined. METHODS: Longitudinal data from 2143 people with stroke and 10,717 adults without stroke aged 50 years and older were drawn from a prospective cohort study based on the Survey of Health, Ageing and Retirement in Europe (2004-2022; 8 data collection waves). Physical activity was assessed in the prestroke wave. Functional limitations were assessed in the poststroke waves. Each person with stroke was matched with 5 adults without stroke who had similar propensity scores computed on the basis of key covariates, including baseline age, sex, body mass index, limitations in ADLs and IADLs, chronic conditions, and country of residence, before any of the participants from either cohort had experienced a stroke. RESULTS: Results showed an interaction between stroke status and physical activity on ADL limitations (b = -0.076; 95% CI = -0.142 to -0.011), with the effect of physical activity being stronger in people with stroke (b = -0.345; 95% CI = -0.438 to -0.252) than in adults without stroke (b = -0.269; 95% CI = -0.269 to -0.241). CONCLUSION: The beneficial effect of prestroke physical activity on ADL limitations after stroke is stronger than its effect in matched adults without stroke followed for a similar number of years. IMPACT: Physical activity, an intervention within the physical therapist's scope of practice, is effective in reducing the risk of functional dependence after stroke. Moreover, prestroke levels of physical activity can inform the prognosis of functional dependence in people with stroke.

Latent change scores models for applied research: A practical guide using Mplus.

The present article provides a practical guide for modelling and interpreting several basic applications of the latent change scores (LCS) model, a useful and flexible approach for the analysis of change. The article is addressed to students, researchers and practitioners who are familiar with structural equation modelling but new to LCS. We first provided a gentle introduction to the LCS model using non-technical language and minimal mathematical formalism. We illustrated the basic ideas behind this approach, introducing LCS in its simplest form. We show how this model can be straightforwardly extended to more complex applications, including the dual change score (DCS) model and some of its variants (i.e., the proportional change and the constant change models). We illustrated how the univariate LCS model can be used to determine the growth trajectory of a variable across multiple waves of assessment. Next, we focused on the bivariate case, which allows for the modelling of the dynamic relations between two variables. For each model, we provided easy-to-follow examples of applications based on Schwartz's theory of basic personal values. The examples are accompanied by annotated syntax and output showing how they can be implemented with the Mplus software and how results can be interpreted.

Longitudinal relationships between early-life homelessness and school-aged asthma and wheezing.

BACKGROUND: Homelessness is a disruptive life event with profound impacts on children's health. It remains unclear, however, whether homelessness in early life has an enduring association with asthma and wheezing among school-aged children. OBJECTIVE: To test whether early-life homelessness is prospectively associated with asthma and wheezing during school-aged years. METHODS: We draw on data from 9242 children from the Avon Longitudinal Study of Parents and Children. Children were categorised as 'ever' or 'never' homeless based on maternal reports from the prenatal period through age 5 years. Children were assigned a binary indicator of asthma/wheezing based on maternal reports of asthma and wheezing at ages 6.8, 7.6 and 8.6 years. We used multilevel logistic regression models to test the association of interest in both bivariate analyses and models adjusted for a broad set of potential confounders. We conducted sensitivity analyses using generalised estimating equations and considering asthma and wheezing separately to test the robustness of the results. RESULTS: Between 12.1% and 14.3% of children had asthma or wheezing at ages 6.8, 7.6 and 8.6 years, and these conditions were more common among ever homeless participants. Ever-homeless children displayed higher odds of asthma or wheezing than never-homeless children (OR: 1.59, 95% CI 1.02 to 2.48) after adjustment for child, maternal and household risk factors. Sensitivity analyses yielded similar results. CONCLUSION: Early-life homelessness is prospectively associated with asthma and wheezing among school-aged children and should be prioritised by interventions promoting healthy child development.

Life changes and symptoms of depression and anxiety among Chinese children and adolescents before, during, and after the COVID-19 pandemic lockdown: a combination of cross-sectional, longitudinal, and clustering studies.

The measures to prevent COVID-19 pandemic had caused significant life changes, which may have caused stress on the mental health of children and adolescents. We aimed to evaluate the short- and long-term effects of life changes on children's mental health in a large Chinese cohort. Survey-based life changes during COVID-19 lockdown were measured among 7,829 Chinese students at Grade 1-9, including social contacts, lifestyles and family financial status. Clustering analysis was applied to identify potential patterns of these changes. Depressive and anxiety symptoms were measured using the Center for Epidemiologic Studies Depression Scale and Screen for Child Anxiety Related Emotional Disorders. Logistic regression models were used to investigate the associations between these changes, their patterns and the presence of depression/anxiety symptoms using both cross-sectional and longitudinal designs. We found that the prevalence of depression and anxiety symptoms decreased during pandemic (34.6-32.6%). However, during and shortly after lockdown, students who reported negative impacts on their study, social and outside activities, and diet had increased risks of depressive/anxiety symptoms. Decreased electronic time and sugar-sweetened consumption, as well as family income decline and unemployment, were also associated with higher risks of these symptoms. Additionally, students with changed sleep time had increased depressive symptoms. These associations attenuated or disappeared one year later. Similar patterns were observed in clustering analysis, while only the group with severe impact on family financial status showed a sustained increase in depression symptoms. In summary, restrictive measures that changed children and adolescents' daily life during COVID-19 lockdown showed negative effects on their mental health, with some commonalities and distinctions patterns in the manifestation of depression and anxiety symptoms.

Exploring nursing student self-esteem change and its predictors: Cohort study and its methodological challenges.

OBJECTIVE: Considering methodological difficulties and inconsistent results of previous studies on it, the objective was to describe the change in nursing student self-esteem over time and its predictors, using a sound theoretical framework and relevant tools to measure and analyse the data. METHOD: Cohort study. Self-esteem and related factors were assessed in nursing students in a 4-year bachelor's program at the beginning of each academic year from 2017 to 2019 and at the end of the academic year in May 2020, using he revised version of Self-liking/Self-competence scale of Tafarodi and Swann. Univariate and multivariate analyses were performed via generalized linear mixed modelling. RESULTS: Self-esteem was moderate at the beginning of the program: 50.40 (9.10). It increased slightly over time: 51.15 (9.11) at T1; 51.64 (0.49) at T2; and 51.39 (10.79) at T3 (P = .002). Baseline variables that predicted self-esteem change were gender, secondary school graduation level, state anxiety, intent to continue, and self-efficacy. Assessing and improving those last variables via a strong career plan could boost student achievement and increase retention during and after training. CONCLUSION: Nursing student self-esteem can be assessed using a bidimensional model, with a two-factor scale like Tafarodi & Swann's self-liking/self-competence scale. Generalized linear mixed model is a useful way to correlate large sets of longitudinal data.

Identifying early language predictors: A replication of Gasparini et al. (2023) confirming applicability in a general population cohort.

BACKGROUND: Identifying language disorders earlier can help children receive the support needed to improve developmental outcomes and quality of life. Despite the prevalence and impacts of persistent language disorder, there are surprisingly no robust predictor tools available. This makes it difficult for researchers to recruit young children into early intervention trials, which in turn impedes advances in providing effective early interventions to children who need it. AIMS: To validate externally a predictor set of six variables previously identified to be predictive of language at 11 years of age, using data from the Longitudinal Study of Australian Children (LSAC) birth cohort. Also, to examine whether additional LSAC variables arose as predictive of language outcome. METHODS & PROCEDURES: A total of 5107 children were recruited to LSAC with developmental measures collected from 0 to 3 years. At 11-12 years, children completed the Clinical Evaluation of Language Fundamentals, 4th Edition, Recalling Sentences subtest. We used SuperLearner to estimate the accuracy of six previously identified parent-reported variables from ages 2-3 years in predicting low language (sentence recall score ≥ 1.5 SD below the mean) at 11-12 years. Random forests were used to identify any additional variables predictive of language outcome. OUTCOMES & RESULTS: Complete data were available for 523 participants (52.20% girls), 27 (5.16%) of whom had a low language score. The six predictors yielded fair accuracy: 78% sensitivity (95% confidence interval (CI) = [58, 91]) and 71% specificity (95% CI = [67, 75]). These predictors relate to sentence complexity, vocabulary and behaviour. The random forests analysis identified similar predictors. CONCLUSIONS & IMPLICATIONS: We identified an ultra-short set of variables that predicts 11-12-year language outcome with 'fair' accuracy. In one of few replication studies of this scale in the field, these methods have now been conducted across two population-based cohorts, with consistent results. An imminent practical implication of these findings is using these predictors to aid recruitment into early language intervention studies. Future research can continue to refine the accuracy of early predictors to work towards earlier identification in a clinical context. WHAT THIS PAPER ADDS: What is already known on the subject There are no robust predictor sets of child language disorder despite its prevalence and far-reaching impacts. A previous study identified six variables collected at age 2-3 years that predicted 11-12-year language with 75% sensitivity and 81% specificity, which warranted replication in a separate cohort. What this study adds to the existing knowledge We used machine learning methods to identify a set of six questions asked at age 2-3 years with ≥ 71% sensitivity and specificity for predicting low language outcome at 11-12 years, now showing consistent results across two large-scale population-based cohort studies. What are the potential or clinical implications of this work? This predictor set is more accurate than existing feasible methods and can be translated into a low-resource and time-efficient recruitment tool for early language intervention studies, leading to improved clinical service provision for young children likely to have persisting language difficulties.

Gender Inequalities of Health and Quality of Life in Informal Caregivers in Spain: Protocol for the Longitudinal and Multicenter CUIDAR-SE Study.

BACKGROUND: The aging population and increased disability prevalence in Spain have heightened the demand for long-term care. Informal caregiving, primarily performed by women, plays a crucial role in this scenario. This protocol outlines the CUIDAR-SE study, focusing on the gender-specific impact of informal caregiving on health and quality of life among caregivers in Andalusia and the Basque Country from 2013 to 2024. OBJECTIVE: This study aims to analyze the gender differences in health and quality of life indicators of informal caregivers residing in 2 Spanish autonomous communities (Granada, Andalusia, and Gipuzkoa; Basque Country) and their evolution over time, in relation to the characteristics of caregivers, the caregiving situation, and support received. METHODS: The CUIDAR-SE study uses a longitudinal, multicenter design across 3 phases, tracking health and quality of life indicators among informal caregivers. Using a questionnaire adapted to the Spanish context that uses validated scales and multilevel analysis, the research captures changes in caregivers' experiences amid societal crises, notably the 2008 economic crisis and the COVID-19 pandemic. A multistage randomized cluster sampling technique is used to minimize study design effects. RESULTS: Funding for the CUIDAR-SE study was in 3 phases starting in January 2013, 2017, and 2021, spanning a 10-year period. Data collection commenced in 2013 and continued annually, except for 2016 and 2020 due to financial and pandemic-related challenges. As of March 2024, a total of 1294 participants have been enrolled, with data collection ongoing for 2023. Initial data analysis focused on gender disparities in caregiver health, quality of life, burden, perceived needs, and received support, with results from phase I published. Currently, analysis is ongoing for phases II and III, as well as longitudinal analysis across all phases. CONCLUSIONS: This protocol aims to provide comprehensive insights into caregiving dynamics and caregivers' experiences over time, as well as understand the role of caregiving on gender inequality in health, considering regional variations. Despite limitations in participant recruitment, focusing on registered caregivers, the study offers a detailed exploration of the health impacts of caregiving in Spain. The incorporation of a gender perspective and the examination of diverse contextual factors enrich the study's depth, contributing significantly to the discourse on caregiving health complexities in Spain. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/58440.

Maximizing Insights from Longitudinal Epigenetic Age Data: Simulations, Applications, and Practical Guidance.

Background: Epigenetic Age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk. Limited by available data, most studies investigating these relationships have been cross-sectional - using a single EA measurement. However, the recent growth in longitudinal DNAm studies has led to analyses of associations with EA over time. These studies differ in (i) their choice of model; (ii) the primary outcome (EA vs. EAA); and (iii) in their use of chronological age or age-independent time variables to account for the temporal dynamic. We evaluated the robustness of each approach using simulations and tested our results in two real-world examples, using biological sex and birthweight as predictors of longitudinal EA. Results: Our simulations showed most accurate effect sizes in a linear mixed model or generalized estimating equation, using chronological age as the time variable. The use of EA versus EAA as an outcome did not strongly impact estimates. Applying the optimal model in real-world data uncovered an accelerated EA rate in males and an advanced EA that decelerates over time in children with higher birthweight. Conclusion: Our results can serve as a guide for forthcoming longitudinal EA studies, aiding in methodological decisions that may determine whether an association is accurately estimated, overestimated, or potentially overlooked.

Trajectory Patterns of Weight and Length in Children: From Birth Until 2-Years of Age.

OBJECTIVE: The aim was to identify trajectory patterns of weight and length in children from birth until two years of life and establish associations with maternal and child characteristics. METHODS: A mixed-cohort study was conducted in public health services in Colombo-PR, Brazil, between 2018 and 2022. Pregnancy information was gathered through anthropometric data collection and questionnaires. Birth data were extracted from birth record forms, while weight and length data in the first two years of life were obtained from physical and electronic health service records. Weight and length trajectory patterns were identified using a group-based trajectory model. The definition of the number of trajectory patterns to be selected considered the model fit to the type of variable, its practical utility, as well as the probabilities of group membership. RESULTS: Two trajectory patterns of weight and length were identified among the children. The majority exhibited a pattern of weight (67.8%, n = 382) and length (90.9%, n = 472) considered high and stable, with a tendency to decelerate from one and a half years of age. The probability of belonging to the lower weight gain group was associated with female sex (41.5%, p < 0.001), smoking during pregnancy (48.7%, p = 0.008), prematurity (65.0%, p = 0.001), cesarean delivery (36.4%, p = 0.009), small for gestational age (69.0%, p < 0.001), and twinning (69.2%, p = 0.002). Similarly, the probability of belonging to the lower length gain group was associated with female sex (11.7%, p < 0.001), smoking during pregnancy (20.6%, p = 0.003), cesarean delivery (10.1%, p = 0.048), born small for gestational age (46.4%, p < 0.001), and twinning (46.1%, p < 0.001). CONCLUSION: Conditions during pregnancy and childbirth can impact growth patterns in the first two years of life.

Choroid plexus volume as a novel candidate neuroimaging marker of the Alzheimer's continuum.

BACKGROUND: Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer's disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear. METHODS: This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aß42, Aß40, Aß42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman's correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aß42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models. RESULTS: The participants' mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P < 0.05). ChP volume enlargement correlated with decreased Aß42 and Aß40 levels; lower MMSE and MoCA and higher NPI and ADL scores; and lower volume, cortical thickness, and cCBF in other cognition-related regions (all P < 0.05). ChP volume mediated the association of Aß42 and Aß40 levels with MMSE scores (19.08% and 36.57%), and Aß42 levels mediated the association of ChP volume and MMSE or MoCA scores (39.49% and 34.36%). ChP volume alone better identified cerebral Aß42 changes than LVV alone (AUC = 0.81 vs. 0.67, P = 0.04) and EC thickness alone (AUC = 0.81 vs.0.63, P = 0.01) and better differentiated patients with MCI from HCs than hippocampal volume alone (AUC = 0.85 vs. 0.81, P = 0.01), and LVV alone (AUC = 0.85 vs.0.82, P = 0.03). Combined ChP and hippocampal volumes significantly increased the ability to differentiate cerebral Aß42 changes and patients among AD dementia, MCI, and HCs groups compared with hippocampal volume alone (all P < 0.05). After correcting for age, sex, years of education, APOE ε4 status, eTIV, and hippocampal volume, ChP volume was associated with MMSE, MoCA, NPI, and ADL score at baseline, and rapid ChP volume enlargement was associated with faster deterioration in NPI scores with an average follow-up of 10.03 ± 4.45 months (all P < 0.05). CONCLUSIONS: ChP volume may be a novel neuroimaging marker associated with neurodegenerative changes and clinical AD manifestations. It could better detect the early stages of the AD and predict prognosis, and significantly enhance the differential diagnostic ability of hippocampus on the AD continuum.

Risk and protective factors for cognitive decline in Brazilian lower educated older adults: A 15-year follow-up study using group-based trajectory modelling.

BACKGROUND: Patterns of cognitive change and modifiable factors for cognitive decline versus stable cognitive trajectories have rarely been described in lower-educated older adults. OBJECTIVES: We aimed to identify long-term trajectories of cognitive functioning and possible factors associated with cognitive decline. DESIGN AND PARTICIPANTS: We used data from 1,042 adults aged ≥ 60 participating in the Health, Welfare and Aging Study (SABE), São Paulo, Brazil, without cognitive impairment at baseline. Data were collected across four waves (2000-2015). Group-based trajectory modelling was used to identify cognitive trajectories. Associations with socioeconomic variables, childhood background, lifestyle, and cardiovascular risk factors were explored using weighted multinomial logistic regressions. MEASUREMENTS: The abbreviated Mini-Mental State Examination was used to measure cognition. RESULTS: Three cognitive trajectories were identified: stable (n= 754, 68.6%), mild-decline (n= 183, 20.8%), and strong-decline (n= 105, 10.7%). At baseline, respondents in the strong-decline group were more likely to be older than those with stable and mild-decline trajectories. Furthermore, participants in both the mild and strong-decline groups were more likely to have no schooling, be divorced/separated, receive less than 4 monthly wages, and be underweight (BMI < 18.5) compared to the stable group. Finally, the mild-decline group was more likely to have lived in rural areas during childhood than participants located in a stable trajectory. CONCLUSIONS: Our findings suggest that interventions to reduce cognitive decline for low-educated older adults might include strategies addressing inequalities and improving modifiable risk factor burden.

Defining Trajectories of Linguistic, Cognitive-Communicative, and Quality of Life Outcomes in Aphasia: Longitudinal Observational Study Protocol.

Objective: To describe the trajectories of linguistic, cognitive-communicative, and health-related quality of life (HRQOL) outcomes after stroke in persons with aphasia. Design: Longitudinal observational study from inpatient rehabilitation to 18 months after stroke. Setting: Four US mid-west inpatient rehabilitation facilities (IRFs). Participants: We plan to recruit 400 adult (older than 21 years) English speakers who meet the following inclusion criteria: (1) Diagnosis of aphasia after a left-hemisphere infarct confirmed by CT scan or magnetic resonance imaging (MRI); (2) first admission for inpatient rehabilitation due to a neurologic event; and (3) sufficient cognitive capacity to provide informed consent and participate in testing. Exclusion criteria include any neurologic condition other than stroke that could affect language, cognition or speech, such as Parkinson's disease, Alzheimer's disease, traumatic brain injury, or the presence of right-hemisphere lesions. Interventions: Not applicable. Main Outcome Measures: Subjects are administered a test battery of linguistic, cognitive-communicative, and HRQOL measures. Linguistic measures include the Western Aphasia Battery-Revised and the Apraxia of Speech Rating Scale. Cognitive-communicative measures include the Communication Participation Item Bank, Connor's Continuous Performance Test-3, the Communication Confidence Rating Scale for Aphasia, the Communication Effectiveness Index, the Neurological Quality of Life measurement system (Neuro-QoL) Communication short form, and the Neuro-QoL Cognitive Function short form. HRQOL measures include the 39-item Stroke & Aphasia Quality of Life Scale, Neuro-QoL Fatigue, Sleep Disturbance, Depression, Ability to Participate in Social Roles & Activities, and Satisfaction with Social Roles & Activities tests, and the Patient-Reported Outcome Measurement and Information System 10-item Global Health short form. The test battery is administered initially during inpatient rehabilitation, and at 3-, 6-, 12-, and 18-months post-IRF discharge. Biomarker samples are collected via saliva samples at admission and a subgroup of participants also undergo resting state fMRI scans. Results: Not applicable. Conclusions: This longitudinal observational study will develop trajectory models for recovery of clinically relevant linguistic, cognitive-communicative, and quality of life outcomes over 18 months after inpatient rehabilitation. Models will identify individual differences in the patterns of recovery based on variations in personal, genetic, imaging, and therapy characteristics. The resulting models will provide an unparalleled representation of recovery from aphasia resulting from stroke. This improved understanding of recovery will enable clinicians to better tailor and plan rehabilitation therapies to individual patient's needs.

Neuropsychiatric Symptom Profile in Alzheimer's Disease and Their Relationship With Functional Decline.

OBJECTIVE: Understanding the course of individual neuropsychiatric symptoms (NPS) and their relationship with function is important for planning targeted interventions for preventing and delaying functional decline. This study aims to disentangle relative contributions of individual NPS on functional decline. METHODS: Longitudinal study of 9,358 well-characterized participants with baseline diagnoses of Mild Cognitive Impairment or AD in the National Alzheimer's Coordinating Center Uniform Data Set. Function was measured using the Functional Assessment Questionnaire (FAQ). Clinician judgment of seven common behavioral symptoms were examined simultaneously: apathy-withdrawal, depressed mood, visual or auditory hallucinations, delusions, disinhibition, irritability, and agitation. RESULTS: Apathy was the most common NPS at baseline (33.7%) and throughout follow-up, endorsed by clinicians in 63.7% of visits. Apathy was the most persistent with 36.7% of participants having clinician-endorsed apathy in ≥50% of their visits. Apathy strongly correlated with faster rate of functional decline. Compared to those who never had apathy, baseline FAQ was worse in those with intermittent or persistent/always apathy (intermittent: estimated coefficient ±SE=1.228±0.210, 95% CI=[0.817, 1.639]; persistent/always: 2.354±0.244 (95% CI=[1.876, 2.832], both p <0.001). Over time, rate of functional decline was faster in those with intermittent and persistent/always apathy (intermittent: 0.454±0.091, 95% CI=[0.276, 0.632]; persistent/always: 0.635±0.102, 95% CI=[0.436, 0.835], both p <0.001). Worse agitation, delusions, and hallucinations also correlated with functional decline, but magnitudes of the estimates were smaller. CONCLUSION: Individual NPS may be sensitive targets for tracking longitudinal change in function. The study raises awareness of the need for more comprehensive assessment of functional decline in AD patients with noncognitive symptoms.

The Longitudinal Relationship between Edentulism and the Progress of Multimorbidity.

OBJECTIVES: To examine the longitudinal relationship between edentulism, nutritional intake, and the progress of multimorbidity among older Americans. METHODS: We used data from the Health and Retirement Study (2006-2018), a longitudinal survey of older Americans that has collected data biennially since 1992. Edentulism was assessed in 2006 while nutritional intake was assessed in 2013. Multimorbidity was indicated by five self-reported chronic conditions: diabetes, heart conditions, lung diseases, cancer, and stroke. Individuals with two or more conditions at baseline were excluded from the analysis. Nutritional intake was calculated by summing 10 nutrients (protein, vitamins C, D, B12 and E, calcium, zinc, polyunsaturated fatty acids, folate, and ß-carotene). Structural equation modelling (SEM) was used to examine the nutritional pathway between edentulism (2006) and the increase in multimorbidity from 2006 to 2018. RESULTS: The number of individuals included in the analysis was 3463. The incidence of multimorbidity between 2006 and 2018 was 24.07%, while the percentage of edentate participants in 2006 was 16.42%. The mean total nutrition in 2013 was 4.50 (4.43, 4.55). The SEM analysis showed that edentulism was negatively associated with nutritional intake {estimate -0.15 (95%CI: -0.30, -0.01)}. A negative association was found between total nutrition and multimorbidity {estimate -0.008 (95%CI: -0.01, -0.002)}. Age, wealth, and smoking were included in the analysis and had statistically significant associations with multimorbidity. CONCLUSION: The analysis demonstrated a longitudinal association between edentulism, nutritional intake, and the progress of multimorbidity.

Caries trajectories from childhood to adolescence: Analysis of data from a nationwide school dental service.

OBJECTIVES: The aim of the study was to assess patterns of longitudinal changes in caries status among school-going children in Singapore. METHODS: Dental records for a single cohort of students who received dental examinations in six standard examination years between 2009 and 2017 were analysed (n = 24 699). Group-based trajectory modelling with a zero-inflated Poisson distribution was carried out to determine dental caries trajectories in the permanent dentition. Associations between sociodemographic factors and trajectory group membership were assessed using multinomial logistic regression. RESULTS: The predicted population distribution across the four caries trajectory groups identified was 65.0% ('none'), 16.8% ('low'), 14.8% ('medium') and 3.4% ('high'). The 'none' trajectory group had a decayed, missing and filled teeth (DMFT) score of 0 throughout the 8 years. Higher baseline DMFT counts and nonlinear increases in DMFT scores were noted for the 'low', 'medium' and 'high' trajectory groups. The correlation coefficient between DMFT counts in years 6 and 8 was 0.91, as compared to 0.77 between baseline and year 1. Factors associated with the 'high' caries trajectory include lower socio-economic status, female gender, Chinese race (compared to the Indian race), enrolment in primary schools in the Eastern and Western regions of Singapore, and enrolment in public secondary schools. CONCLUSIONS: Under a nationwide school dental service, four trajectory patterns of caries counts in the permanent dentition were identified over 8 years. Among students in the 'low', 'medium' and 'high' trajectory groups, greater caries increment was noted during the transition from primary to secondary school. The correlation between DMFT counts in successive examinations was stronger in older than younger ages.

Two-Year Longitudinal Outcomes of Subjective Cognitive Decline in Hispanics Compared to Non-hispanic Whites.

BACKGROUND: Subjective cognitive decline (SCD), considered a preclinical dementia stage, is less understood in Hispanics, a high-risk group for dementia. We investigated SCD to mild cognitive impairment (MCI) progression risk, as well as baseline and longitudinal features of depressive symptoms, SCD complaints, and objective cognitive performance among Hispanics compared to non-Hispanic Whites (NHW). METHODS: Hispanic (n = 23) and NHW (n = 165) SCD participants were evaluated at baseline and 2-year follow-up. Evaluations assessed function, depressive symptoms, SCD, and objective cognitive performance. RESULTS: Hispanics were at increased risk of progression to MCI (OR: 6.10, 95% CI 1.09-34.20, P = .040). Hispanic participants endorsed more depressive symptoms at baseline (P = .048) that worsened more longitudinally (OR: 3.16, 95% CI 1.18-8.51, P = .023). Hispanic participants had increased SCD complaints on the Brief Cognitive Rating Scale (BCRS) (ß = .40 SE: .17, P = .023), and in specific BCRS domains: concentration (ß = .13, SE: .07, P = .047), past memory (ß = .13, SE: .06, P = .039) and functional abilities (ß = .10, SE: .05, P = .037). In objective cognitive performance, Hispanic ethnicity associated with decline in MMSE (ß = -.27, SE: .13, P = .039), MoCA (ß = -.80 SE: .34, P = .032), Trails A (ß = 2.75, SE: .89, P = .002), Trails B (ß = 9.18, SE: 2.71, P = .001) and Guild Paragraph Recall Delayed (ß = -.80 SE: .28, P = .005). Conclusions: Hispanic ethnicity associated with a significantly increased risk of 2-year progression of SCD to MCI compared to NHW. This increased risk associated with increased depressive symptoms, distinctive SCD features, and elevated amnestic and non-amnestic objective cognitive decline. This supports further research to refine the assessment of preclinical dementia in this high-risk group.

Long-Term Pulmonary Function Post-Spinal Cord Injury.

OBJECTIVE: To investigate mean values of pulmonary function tests at specific time points to assess long-term progression in patients with spinal cord injury (SCI). DESIGN: Retrospective cohort study from 1997 to 2022. SETTING: National rehabilitation hospital, providing scheduled admission for potential SCI-related issues. Follow-up assessments are recommended annually, guiding the observation period into consecutive one-year intervals. PARTICIPANTS: This study included 1,394 adult patients who were admitted at least twice to the National Rehabilitation Center between 1997 and 2022, selected from an initial pool of 1,510. Overall, 116 patients were excluded due to the absence of any pulmonary function test (PFT) results. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Changes in PFT values over time, specifically assessing for a potential two-phase pattern post-injury. The hypothesis that PFT values would initially improve before declining was formulated based on existing literature. RESULTS: Significant changes in pulmonary function were noted among 1,394 adults with SCI. FVC and FEV1 initially increased within the first 1-2 years post-injury but declined to below baseline levels after 6 years. Pronounced changes occurred between <1 year and 1-2 years post-injury (FVC: Δ = 4.89, SE = 0.87, p < 0.001; FEV1: Δ = 4.28, SE = 1.09, p = 0.002) and 1-2 years to >6 years (FVC: Δ = -5.83, SE = 0.94, p < 0.001; FEV1: Δ = -6.49, SE = 1.18, p < 0.001). No significant changes in the FEV1/FVC ratio. Motor completeness was significantly associated with the increase and decline phase, showing a steeper increase and less decline compared to the motor-incomplete group. CONCLUSIONS: Pulmonary function in SCI initially increases but declines over time, falling below initial levels by 6 years. Further evaluation with more complete datasets is warranted to elucidate factors influencing these changes.

Falls and patterns of physical activity participation over 18 years in the Australian Longitudinal Study on Women's Health.

OBJECTIVE: To explore the relationship between long-term physical activity (PA) participation and falls. METHODS: Participants in the Australian Longitudinal Study of Women's Health born 1946-1951 self-reported amounts of PA every 3 years since 1998 (mean age: 54 years, n=11 796). Latent class analysis described profiles of self-reported PA participation over 18 years. Associations between patterns of PA participation and self-reported falls measured in 2019 were examined using multinomial logistic regression adjusted for directed-acyclic graph-informed potential confounders, with the highly active group as the reference category. RESULTS: Women were grouped into five PA participation profiles. Compared with consistently highly active patterns (maintaining ≥300 min/week, 22%), consistently lower levels of PA<100 min/week (18%), consistently some PA<150 min/week (18%) and decreasing PA but maintaining≥150 min/week (n=3540, 30%) had higher odds of non-injurious falls (odds Ratiolower level (OR): 1.59, 95% CI 1.29 to 1.97; ORsome PA: 1.27, 95% CI 1.04 to 1.55; ORdecreasing activity:1.29, 95% CI 1.02 to 1.63) and injurious falls (ORlow level: 1.32, 95% CI 1.06 to 1.64; ORsome PA: 1.27, 95% CI 1.04 to 1.54; ORdecreasing activity: 1.47, 95% CI 1.18 to 1.83). No association was found between increasing PA (≥150 min/week, 11%) for non-injurious (OR 1.07, 95% CI 0.89 to 1.29) and injurious falls (OR 1.07, 95% CI 0.90 to 1.29). After adjusting for potential confounders, consistently lower levels of PA remained associated with increased non-injurious falls odds (OR1998 survey: 1.40, 95% CI 1.11 to 1.77; OR2016 survey: 1.35, 95% CI 1.07 to 1.71). CONCLUSION: The increased odds of falls among women with consistently lower levels of PA over 18 years supports ongoing participation of 150+ min/week of PA.