Stages Of Decline Research Articles

The Relationships between Cerebrospinal Fluid Glial (CXCL12, CX3CL, YKL-40) and Synaptic Biomarkers (Ng, NPTXR) in Early Alzheimer's Disease.

In addition to amyloid and tau pathology in the central nervous system (CNS), inflammatory processes and synaptic dysfunction are highly important mechanisms involved in the development and progression of dementia diseases. In the present study, we conducted a comparative analysis of selected pro-inflammatory proteins in the CNS with proteins reflecting synaptic damage and core biomarkers in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). To our knowledge, no studies have yet compared CXCL12 and CX3CL1 with markers of synaptic disturbance in cerebrospinal fluid (CSF) in the early stages of dementia. The quantitative assessment of selected proteins in the CSF of patients with MCI, AD, and non-demented controls (CTRL) was performed using immunoassays (single- and multiplex techniques). In this study, increased CSF concentration of CX3CL1 in MCI and AD patients correlated positively with neurogranin (r = 0.74; p < 0.001, and r = 0.40; p = 0.020, respectively), ptau181 (r = 0.49; p = 0.040), and YKL-40 (r = 0.47; p = 0.050) in MCI subjects. In addition, elevated CSF levels of CXCL12 in the AD group were significantly associated with mini-mental state examination score (r = -0.32; p = 0.040). We found significant evidence to support an association between CX3CL1 and neurogranin, already in the early stages of cognitive decline. Furthermore, our findings indicate that CXCL12 might be a useful marker for tract severity of cognitive impairment.

Peculiarities and stages of development of sportsmanship of qualified athletes in the system of long- term performances in professional boxing

The article examines the peculiarities of the formation of the highest sportsmanship of athletes in professional boxing. A comparative analysis of the dynamics of competitive activity of men and women during many years of performances in the professional arena was carried out. Considered options for building a professional career of boxers, taking into account the experience of performances in prestigious amateur competitions, as well as existing trends of liberalization and globalization of the modern Olympic movement. The individual dynamics of the long-term career of famous male and female professional boxers, who at one time owned championship belts in various weight categories, are presented. The optimal age range for demonstrating the highest sports results in boxing has been determined. The influence of international sports organizations (WBC, WBA, WBO, IBF, etc.) on the formation of sports careers of athletes in professional boxing is analyzed.&#x0D; Systematized and considered stages of formation of the highest sportsmanship in professional boxing: 1) formative stage of 18-24 years (quantitative intensification of competitive activity); 2) - the stage of optimal opportunities (championship phase) - 25-35 years; 3) the stage of preservation and gradual decline of sports results - 35 years and more. It has been established that men have a longer formative phase of their professional career, which is characterized by a significantly greater number of preparatory matches in the initial stages of its formation and a longer period of time to maintain the achieved results in the final stages of multi-year improvement. The need to take into account the important regularities of the formation of the highest sportsmanship in boxing and the rational logistics of planning matches during the annual training cycle, taking into account the stage of the sports career and the age of the athletes, is substantiated.

Epidemiology of Motoric Cognitive Risk Syndrome in the Kerala Einstein Study: Protocol for a Prospective Cohort Study.

The southern India state of Kerala has among the highest proportion of older adults in its population in the country. An increase in chronic age-related diseases such as dementia is expected in the older Kerala population. Identifying older individuals early in the course of cognitive decline offers the best hope of introducing preventive measures early and planning management. However, the epidemiology and pathogenesis of predementia syndromes at the early stages of cognitive decline in older adults are not well established in India. The Kerala Einstein Study (KES) is a community-based cohort study that was established in 2008 and is based in the Kozhikode district in Kerala state. KES aims to establish risk factors and brain substrates of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of slow gait and subjective cognitive concerns in individuals without dementia or disability. This protocol describes the study design and procedures for this KES project. KES is proposing to enroll a sample of 1000 adults ≥60 years old from urban and rural areas in the Kozhikode district of Kerala state: 200 recruited in the previous phase of KES and 800 new participants to be recruited in this project. MCR is the cognitive phenotype of primary interest. The associations between previously established risk factors for dementia as well as novel risk factors (apathy and traumatic brain injury) and MCR will be examined in KES. Risk factor profiles for MCR will be compared between urban and rural residents as well as with individuals who meet the criteria for mild cognitive impairment (MCI). Cognitive and physical function, medical history and medications, sociodemographic characteristics, lifestyle patterns, and activities of daily living will be evaluated. Participants will also undergo magnetic resonance imaging and electrocardiogram investigations. Longitudinal follow-up is planned in a subset of participants as a prelude to future longitudinal studies. KES (2R01AG039330-07) was funded by the US National Institutes of Health in September 2019 and received approval from the Indian Medical Council of Research to start the study in June 2021. We had recruited 433 new participants from urban and rural sites in Kozhikode as of May 2023: 41.1% (178/433) women, 67.7% (293/433) rural residents, and 13.4% (58/433) MCR cases. Enrollment is actively ongoing at all the KES recruitment sites. KES will provide new insights into risk factors and brain substrates associated with MCR in India and will help guide future development of regionally specific preventive interventions for dementia. DERR1-10.2196/49933.

Electrochemical magneto-immunoassay for detection of ADAM10 Alzheimer's biomarker using gold nanoparticles as label

Alzheimer's disease (AD), a neurodegenerative and progressive illness with no known cure, is the most frequent cause of dementia in older adults. Dementia in AD is usually preceded by a stage of cognitive decline known as mild cognitive impairment (MCI). MCI has gained attention as an ideal target for prevention and early interventions, considering its reversible characteristic. Here, we propose a magneto-immunoassay based on a low-cost screen-printed electrode for detecting soluble ADAM10 in plasma samples, a potential biomarker for early AD diagnosis. We present a sandwich immunoassay using magnetic beads modified with antibodies to capture ADAM10 from plasma samples and using gold nanoparticles (AuNPs) as an electrochemical label. The assay was designed to accurately detect ADAM10 in diluted plasma with a limit of detection (LoD) of 32.5 pg/mL and a dynamic linear range of 10.0–1000.0 pg/mL. Twenty-three plasma samples from the elderly, including patients with AD, MCI, and healthy subjects (negative control), were analyzed by the magneto-immunoassay and enzyme-linked immunosorbent assay (ELISA), and the ADAM10 levels correlated. This work shows the potential of this protein as a biomarker in the early diagnosis and progression of AD and provides an interesting disposable device with capabilities for applications as point-of-care (PoC) to measure ADAM10 levels.

Trends in age at menarche from 1943 through 1989 in Taiwan: A retrospective population-based analysis

Recent studies have demonstrated a global decline in the age at menarche. Our study aimed to determine the age at menarche of Taiwanese women born between 1943 and 1989. Data were obtained from the Taiwan Biobank. To view the trends in age at menarche, we analyzed data from 74,799 women. The mean, standard deviation, and annual percentage change in age at menarche were calculated for birth-year cohorts. The mean age at menarche of Taiwanese women born in 1943 was 14.85 years. The age at menarche decreased to 12.20 years for those born in 1989. The mean age at menarche declined by 2.65 years across the 47-year study period; hence, the reduction rate was 0.56 years per decade. This study demonstrated a downward secular trend in the age at menarche of Taiwanese women born between 1943 and 1989. This trend occurred in three stages of decline: fast (1943-1953), slow (1953-1965), and moderate (1965-1989). The age at menarche decreased by 2.65 years among Taiwanese women born in 1943 compared with those born in 1989. This decline occurred in three stages: fast (1943-1953), slow (1953-1965), and moderate (1965-1989). This significant downward secular trend in age at menarche reflects Taiwan's socioeconomic development.

Photothermal enhanced salinity-gradient osmotic energy conversion for sustainable power generation with phase change material

Salinity-gradient osmotic energy conversion is one of the key energy-effective strategies to alleviate global power scarcity and is highly dependent on the saline solution temperature. In this study, a solar thermal boosted salinity-gradient osmotic energy conversion with phase change thermal storage is proposed. Phase change materials (PCMs) are integrated into a solar-driven salinity-gradient osmotic energy conversion system to overcome intermittent solar illumination during the entire diurnal cycle. A graphene oxide membrane (GOM)-based experiment is conducted to study the time-dependent solution temperature, current, and power density with three thermal management materials: Cu/PCM composite, pure PCM, and a reference case without PCM in one diurnal cycle, as well as their periodic stability. The solution temperature can be effectively improved by the solar thermal effect. The utilized PCMs, which absorb solar heat during the daytime and release latent heat at nighttime, can effectively maintain the solution temperature to suppress the power decline at night, thereby improving the power generation capacity of the osmotic system during the entire cycle. The combined interaction mechanism of temperature and solution evaporation on the solution concentration, ion diffusivity, ion conductance, ion selectivity, and power density is revealed. The contributions of ion diffusivity, ion conductance, ion selectivity and solution concentration on the power density are obtained. In an illumination cycle, the power density undergoes three processes of growth stage (0 < t < 5 h), high power output stage (5 < t < 13h), and decline stage (13 < t < 23 h). In addition, the present design also demonstrates a consistent solution temperature and short-current stability during successive cycles.

What drives change in children receiving telephone-delivered Common Elements Treatment Approach (t-CETA)? A multiple n = 1 study with Syrian refugee children and adolescents in Lebanon

BackgroundAlthough the evidence-base for mental health and psychosocial support (MHPSS) interventions in humanitarian settings is growing rapidly, their mechanisms of change remain poorly understood despite the potential to improve the effectiveness and reach of interventions. ObjectiveThis study aimed to explore the mechanisms or factors that drive change in a modular transdiagnostic telephone-delivered mental health intervention, Common Elements Treatment Approach (t-CETA). Participants and settingParticipants were Syrian refugee children and adolescents living in tented settlements in Lebanon. MethodsWe used a multiple n = 1 design, drawing on secondary data from 9 children who completed t-CETA during a pilot randomized controlled trial. ResultsChildren with historical war-related trauma were more likely to show significant improvement across symptom clusters by the end of treatment compared to children presenting with depression related to daily living conditions. Children also showed fluctuating symptoms during the early stages of treatment (engagement and cognitive restructuring) but significant decline in symptoms after the trauma module (prolonged imaginal exposure) and depression module (behavioral activation). Salient external life events identified were starting or dropping out of school, working, change in living conditions, family conflict and the October Revolution; and interpersonal factors of parental engagement (with or without full attendance) and counsellor skills in building rapport were also identified as having an impact on treatment success. ConclusionsImplications of our findings are discussed in terms of integrating active ingredients into MHPSS programming, and building on parental and multi-sector involvement in child and adolescent mental health care in humanitarian settings.

Cognitive training based on functional near-infrared spectroscopy neurofeedback for the elderly with mild cognitive impairment: a preliminary study.

Mild cognitive impairment (MCI) is often described as an intermediate stage of the normal cognitive decline associated with aging and dementia. There is a growing interest in various non-pharmacological interventions for MCI to delay the onset and inhibit the progressive deterioration of daily life functions. Previous studies suggest that cognitive training (CT) contributes to the restoration of working memory and that the brain-computer-interface technique can be applied to elicit a more effective treatment response. However, these techniques have certain limitations. Thus, in this preliminary study, we applied the neurofeedback paradigm during CT to increase the working memory function of patients with MCI. Near-infrared spectroscopy (NIRS) was used to provide neurofeedback by measuring the changes in oxygenated hemoglobin in the prefrontal cortex. Thirteen elderly MCI patients who received CT-neurofeedback sessions four times on the left dorsolateral prefrontal cortex (dlPFC) once a week were recruited as participants. Compared with pre-intervention, the activity of the targeted brain region increased when the participants first engaged in the training; after 4 weeks of training, oxygen saturation was significantly decreased in the left dlPFC. The participants demonstrated significantly improved working memory compared with pre-intervention and decreased activity significantly correlated with improved cognitive performance. Our results suggest that the applications for evaluating brain-computer interfaces can aid in elucidation of the subjective mental workload that may create additional or decreased task workloads due to CT.

Experimental Study on the Effect of CO2 Injection Pressure on the Migration Characteristics and Extraction Effects of Replacement CH4.

To study the effect of CO2 injection pressure on gas migration characteristics and coalbed methane (CBM) extraction, a platform for the experimental replacement of CH4 with CO2 was used to conduct experiments on the replacement of CH4 under different CO2 injection pressures and analyze the gas transport characteristics and CH4 extraction during the experiment. The results reveal that the rate of gas migration out of the coal seam accelerates with increasing gas injection pressure, as determined by comparisons of the migration rates between adjacent monitoring points. The change trend of the CH4 desorption rate under different gas injection pressures is divided into slow decline, sharp decline, and stability stages, and the maximum value of the effective diffusion coefficient increases from 2.3 × 10-5 to 3.4 × 10-5 and 4.6 × 10-5 cm2/s as the gas injection pressure increases from 0.6 to 0.8 and 1.0 MPa. Similarly, the change pattern of coal seam permeability can be divided into slow decline, sharp decline, and stability stages. After the gas injection pressure was increased from 0.6 to 0.8 and 1.0 MPa, the CH4 desorption volume increased from 90.2 to 94.1 and 97.8 L, whereas the coal seam CO2 sequestration volume increased from 269.2 to 274.2 and 322.8 L, respectively. In contrast, the CH4 extraction efficiency increased from 76.9 to 80.2 and 82.9%, respectively. The research results have important reference value and practical significance for optimizing the CO2 injection pressure and improving the CBM extraction.

Significance of cell culture phases for utilizing 3D cultures of A549 cells for in vitro studies.

Three-dimensional (3D) culture systems of human cancer cell lines have become popular experimental models for a variety of applications including drug screening. It is understood that the 2D and 3D cultures of the same cell line behave differently in several aspects. One such difference is in the duration of cell culture phases (the lag, log, plateau and the decline stages). We obtained 3D cultures of A549 cells on agarose hydrogels. We observed and compared the morphological differences in the progression of 2D and 3D cultures of A549 cells in a time-dependent manner. The morphological features along with the cell counts and viabilities obtained for the 2D and 3D cultures at different time intervals clearly indicate that the cell culture phases occurred as more extended one for the 3D cultures compared to that of the 2D counterparts. The plateau stage for the 2D and 3D cultures occurred at 48 and 69 h, respectively. Such cell culture phase durations can be different for different cell lines as a function of their doubling times. We propose that the cell culture phase durations for any cell line should be first established before using them for drug testing or for studies involving toxicity to obtain useful results from 3D cell cultures. Also, we propose that the late-exponential (lag) phase of 3D cultures of cancer cell lines is the most ideal one for drug testing owing to the various optimal features of the aggregates in this cell culture phase.

Digital transformation, life cycle and internal control effectiveness: Evidence from China

Based on corporate life cycle theory, this paper investigates the impact of digital transformation on the effectiveness of internal control by analyzing data from Chinese listed companies from 2007–2021. The empirical results show that digital transformation can improve internal control effectiveness by alleviating information asymmetry and reducing agency costs, and that this effect is significant to firms in growth and maturity stage, but not firms in decline stage. In addition, digital transformation has a more significant effect on the effectiveness of internal control in high-tech enterprises and manufacturing firms. This paper provides insights into the impact of digital transformation on corporate governance and have policy implications for promoting smooth capital market operation.

The Role of Financial Distress on Company Life Cycle and Stock Return

This study aims to see how the company life cycle affects stock returns with financial distress as a moderating variable in companies listed on the Indonesia Stock Exchange between 2017 and 2021. Purposive sampling was used to obtain a sample of 71 companies. A panel regression analysis with a fixed effect model was used for the analysis. The study's findings show that the decline stage of a company's life cycle hurts stock returns, whereas the introduction, growth, and maturity stages do not affect stock returns. Financial distress can mitigate the impact of the company's decline stage on stock returns. However, it needs to mitigate the impact of the company's introduction, growth, and maturity stages on stock returns.

Study on evaporation rate of steel slag pervious concrete based on CT scanning

Pervious concrete can reduce the surface temperature and improve the outdoor environment through its own evaporation capacity. The unique pore structure makes pervious concrete different from ordinary concrete and has a great impact on its macro performance, such as mechanical, penetration, fatigue, durability, noise reduction performance. In this study, the correlation between water evaporation rate and pore structure parameters of steel slag pervious concrete (SPC) was analyzed, and an empirical model formula was proposed to characterize the water evaporation rate at different evaporation time. Evaporation experiments at different temperatures and different specimen heights were designed, and the evaporation of each specimen was obtained. The porosity and surface porosity of each specimen were determined by water replacement method and computed tomography (CT) scanning. The results show that the evaporation and initial evaporation rate of SPC increase with the increase of specimen height and temperature. The relationship between evaporation rate and evaporation time conforms to the exponential function distribution, showing a rapid decline stage and a gentle decline stage, with obvious inflection points. The pore size distribution and sphericity of SPC were analyzed, and its influence on evaporation rate was negligible. With the increase of height ratio, the tortuosity of SPC increases relatively, while the surface porosity decreases. The evaporation rate model of SPC considering the influence of specimen height, temperature, tortuosity and surface porosity is constructed. The research is helpful to improve the ecological design of SPC pavement and promote the application of SPC materials.

Alpine meadow patches unevenly regulate runoff and sediment yield generation on the Qinghai-Tibetan Plateau

Meadow patches are caused by the fragmentation and disappearance of mattic epipedons, and can serve as evidence of degradation. This is a gradual decline in meadow patch coverage, which can result in soil and surface water loss due to increased bare soil surface. However, little is known about how the loss of mattic epipedons alters soil erosion processes in alpine regions. This study sheds light on this topic by conducting simulated rainfall experiments with different rainfall intensities to assess runoff and sediment generation. We selected representative degraded alpine meadows on the eastern Qinghai-Tibetan Plateau in China. The observed temporal variations of runoff and soil loss rates were explained by the presence of two stages of meadow patch coverage decline: an increasing and a relatively stable stage. Compared to 30% and 60% meadow patch coverage, 90% meadow patch coverage displayed an extended increasing stage with delayed entrance into the stable stage during the rainfall period. The runoff coefficients were significantly higher in 90% and 30% meadow patch coverage than in 60%. The sediment concentrations were significantly lower in 90% and 60% meadow patch coverage than in 30%. It is worth stressing that 90% meadow patch coverage could prompt more rainfall flowing as runoff and reduce sediment under different rainfall intensities. The complex mosaic-pattern formed by meadow and bald patches changed the hydrological response of the soil, decreasing runoff coefficient in 60% meadow patch coverage. The destruction, reduction or even disappearance of some mattic epipedons led to a higher sediment concentration in 30% meadow patch coverage. The meadow patch coverage exerted a greater influence on sediment yield than on runoff volume, although it was generally affected by rainfall intensity. Our findings highlight the importance of maintaining runoff and reducing sediment through the presence of mattic epipedons. Mattic epipedons appear as an effective soil erosion control feature, and this study offers a theoretical guidance for planning adaptive management strategies for degraded alpine meadows on the Qinghai-Tibetan Plateau.

Tools for the Development of Regional Medical Tourism Programs: International Experience

Background. Internationalization of global healthcare and, in particular, the development of international medical tourism, informs the creation of a strategy for the development of domestic medical tourism programs in regions, states, or provinces using various tools for each stage of market development. &#x0D; Purpose. This article aims to identify, classify, and analyze the development tools for regional medical tourism programs applied in the countries recognized as international destinations for medical tourism. &#x0D; Methods and materials. The study data are based on foreign and domestic scientific publications in the field of international medical tourism and the export of medical services. The authors analyzed publications on the development of regional medical tourism programs in the media and performed content analysis of scientific publications in peer-reviewed scientific journals.&#x0D; Results. The internationalization of global healthcare has a significant influence on cross-border private medical travel (medical tourism), thus encouraging the development of both national and regional healthcare. The existing global practice of 19 countries in regional medical tourism provides an extensive development toolkit that includes more than 70 tools focusing on various aspects of the elaboration and implementation of opportunities for regional medical tourism and the export of medical services. The tools can be implemented in one of the four stages of market development: introduction, growth, maturity, and decline. The first stage is characterized by the prevalence of tools related to analysis and the development of the market base. The growth stage focuses on market expansion. At the third stage, the first tools aimed at offering better price for medical services appear. The stage of market decline is focused on the expansion of the target consumers by increasing the financial accessibility of medical tours. At the same time, the third and fourth stages are characterized by a limited number of support tools, which can be explained by the relative immaturity of the global medical tourism market and the focus on programs designed for the international market rather than on increasing economic efficiency. Therefore, in the following years, the scientific and professional communities will focus on the development and implementation of tools that can increase the reflow of financial resources expended on market development.&#x0D; The results of this study can be useful to the subjects of the Russian Federation that are interested in the development of regional strategies in terms of the federal project on the development of the export of medical services as part of the “Healthcare” national project.

Eye movement changes as an indicator of mild cognitive impairment.

Early identification of patients at risk of dementia, alongside timely medical intervention, can prevent disease progression. Despite their potential clinical utility, the application of diagnostic tools, such as neuropsychological assessments and neuroimaging biomarkers, is hindered by their high cost and time-consuming administration, rendering them impractical for widespread implementation in the general population. We aimed to develop non-invasive and cost-effective classification models for predicting mild cognitive impairment (MCI) using eye movement (EM) data. We collected eye-tracking (ET) data from 594 subjects, 428 cognitively normal controls, and 166 patients with MCI while they performed prosaccade/antisaccade and go/no-go tasks. Logistic regression (LR) was used to calculate the EM metrics' odds ratios (ORs). We then used machine learning models to construct classification models using EM metrics, demographic characteristics, and brief cognitive screening test scores. Model performance was evaluated based on the area under the receiver operating characteristic curve (AUROC). LR models revealed that several EM metrics are significantly associated with increased odds of MCI, with odds ratios ranging from 1.213 to 1.621. The AUROC scores for models utilizing demographic information and either EM metrics or MMSE were 0.752 and 0.767, respectively. Combining all features, including demographic, MMSE, and EM, notably resulted in the best-performing model, which achieved an AUROC of 0.840. Changes in EM metrics linked with MCI are associated with attentional and executive function deficits. EM metrics combined with demographics and cognitive test scores enhance MCI prediction, making it a non-invasive, cost-effective method to identify early stages of cognitive decline.

The Role of The Company Life Cycle on Chief Executive Officer Power and Earnings Management

Purpose : This study aims to re-examine whether chief executive officer (CEO) power affects earnings management and whether company life cycles can moderate the effect of CEO power on earnings management.&#x0D; Method : This study used publicly listed companies in the Indonesia Stock Exchange period 2017-2021, are 74 companies, or 370 data, were picked using a purposive sampling method that eliminates companies with outliers. This research uses panel data regression with a random effect model to examine CEO power on earnings management with the company’s life cycle as moderating variables.&#x0D; Findings : This study finds that CEO power does not affect earnings management, and the decline stage can moderate the effect of CEO power on earnings management. However, the introduction, growth, and mature stage cannot moderate the effect of CEO power on earnings management.&#x0D; Novelty : This study contributes to the literature on earnings management by highlighting CEO power in Indonesian companies with different life cycles. This study provides a unique perspective on earnings management, especially in emerging markets like Indonesia.&#x0D; Keywords : CEO’s Power, Earnings Management, Company Life Cycle

Life Cycle Stages and Debt Maturity in Brazilian Listed Companies

We have analyzed the association between firms’ life cycle stages (LCSs) and their debt maturity (DM). This paper deepens the discussion on capital structure from the perspective of the LCSs’ dynamic effect associated with DM. The sample was composed by secondary data from 370 (non-financial) Brazilian listed companies in the period from 2010 to 2019, gathered quarterly. The data were analyzed through descriptive statistics, tests of differences between means and regression analysis from panel data. The results showed that the DM presents no association with LCS, following an inverted U-shape. It has been observed that the maturity stage had a positive effect on the DM, however, as companies move towards the shake-out and decline stages, DM experiences successive reductions. The findings are relevant for providing insights for future research. In addition, they have the potential to contribute to managers, board members, credit committees, capital providers in general, risk management process, and resource allocation.

Amyloid accumulation and functional connectivity in normal aging and preclinical Alzheimer’s Disease: a longitudinal analysis of the OASIS‐3 cohort

AbstractBackgroundPathological changes in the brain begin accumulating decades before the appearance of cognitive symptoms in Alzheimer’s Disease (AD). The deposition of amyloid‐beta (Aβ) proteins and other neurotoxic changes occur, leading to disruption in functional connections between brain networks. Discrete characterization of the changes that take place in preclinical AD has the potential to help treatment development by targeting the neuropathological mechanisms to prevent cognitive decline and dementia from occurring entirely. Previous research has focused on cross sectional differences in the brains of patients with mild cognitive impairment (MCI) or AD and healthy controls or has concentrated on the stages immediately preceding cognitive symptoms. The present study emphasizes early preclinical phases of neurodegeneration.MethodWe use a longitudinal approach to examine the brain changes that take place during early stages of cognitive decline in the OASIS‐3 dataset. Among 1098 participants, 274 passed the inclusion criteria (i.e. had at least two repeated measures of cognitive status and amyloid levels). We use mixed‐effect linear models to examine rates of amyloid accumulation in those who showed cognitive decline compared to those who did not change in cognitive status.ResultOver 90% of participants were healthy at baseline. Over 8‐10 years, some participants progressed to very mild dementia (n = 48) while others stayed healthy (n = 226). Participants with cognitive decline have faster amyloid accumulation and greater increases in functional connectivity in similar brain regions, namely among lateral temporal, motor, and some lateral prefrontal cortex areas. These changes were linked to increases in functional connectivity of select default mode, frontoparietal and motor components.ConclusionOur findings advance the understanding of initial amyloid staging in preclinical Alzheimer’s, as well as contribute to the determination of the functional changes that occur among brain network components as the disease progresses.

Combining data and mathematical models for the design of personalised light interventions to improve sleep timing in aging

AbstractBackgroundMore than 70% of people living with dementia (PLWD) experience sleep disturbances (e.g., early bedtime, long time in bed) even in the early stages of cognitive decline. Light interventions have been proposed as a promising non‐pharmacological approach to improve sleep timing, but current implementations are burdensome and not personalised. Quantitative tools for designing pragmatic light interventions for the home‐setting could benefit PLWD and their carers.Here, we report on a quantitative computational tool which combines readily collectable data with a new mathematical model to provide personalised advice on light interventions. Our focus is on designing low‐burden interventions requiring minimal changes to lifestyle or sleep‐wake routines.MethodEighteen older adults (65‐80 y) monitored their light exposure and sleep for a period of 7‐10 days at home using a wristworn monitor (Actiwatch Spectrum) and a sleep diary from which we calculated daily sleep timing and duration.We constructed a new mechanistic mathematical model for sleep timing that incorporates sleep homeostasis, circadian rhythmicity and light data (HCL). For each participant, we fitted the model to their sleep timing and duration data. We then used simulations to predict the effect of different light interventions on sleep timing and used optimisation to determine light exposure patterns that promote a target sleep onset time.ResultIndividuals varied in their sleep duration (07:18 ± 0:56 hh:mm; mean ± SD) and mid‐sleep timing (03:22 ± 01:00 hh:mm). We successfully retrieved ‘personal’ model parameters that accurately captured sleep duration and timing for 17 of the 18 participants. Our simulations indicated that the effect of a given light exposure pattern on sleep timing depends on the personalised model parameters, suggesting that an intervention that works for one person may not work for someone else. We were able to propose light exposure patterns requiring minimal behavioural change, facilitating adherence.ConclusionIt is possible to extract individual physiological parameters for sleep‐wake regulation from data collected in the field. These individual parameters can be used to design personalised light interventions. Our fully‐documented code could be combined with passive sleep monitors and environmental light sensors to unobtrusively recommend personalised light exposure patterns in close‐to real time.