Social health and subsequent cognitive functioning in people aged 50 years and older: examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies.

BACKGROUND: Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. METHODS: In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). FINDINGS: The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001-0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000-0·002]) and in delayed recall (PIE 0·001 [0·000-0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000-0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. INTERPRETATION: The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. FUNDING: EU Joint Programme-Neurodegenerative Disease Research (JPND) and Alzheimer's Society. TRANSLATION: For the Swedish translation of the abstract see Supplementary Materials section.

The association of physical activity and sedentary behaviour with low back pain disability trajectories: A prospective cohort study.

BACKGROUND: Multiple factors influence the recovery process of low back pain (LBP). The identification and increased knowledge of risk factors might contribute to a better understanding of the course of LBP. OBJECTIVES: To investigate the association of habitual physical activity (PA) and sedentary behaviour (SB), measured at baseline, with disability trajectories in adults with LBP. METHODS: A prospective cohort study where habitual PA levels were measured using the Short QUestionnaire to ASsess Health enhancing physical activity (SQUASH), SB was calculated as average sedentary hours per day, and LBP disability using the Oswestry Disability Index (ODI). Participants completed the questionnaires at one and a half, three, six, and twelve months. Linear mixed models were estimated to describe the association of habitual PA levels SB measured at baseline with disability trajectories. Other predictors were gender, education level, age, pain, number of previous episodes of LBP, and duration of LBP. RESULTS: Habitual SB measured at baseline in adults (n = 347) with LBP were not associated with disability trajectories. For PA, participants with one metabolic equivalent of task (MET) hour per day above average recovered 0.04 [95% CI 0.004 to 0.076] points on the ODI per month faster than participants with an average amount of MET hours per day. CONCLUSIONS: Habitual SB was not associated with LBP disability trajectories over a one-year follow-up. High levels of habitual PA at baseline were associated with improved recovery in LBP disability trajectory, but the finding is not clinically relevant.

The association of the STarT Back Screening Tool and type of leg pain with low back pain disability trajectories: a prospective cohort study.

BACKGROUND: Multiple factors influence the recovery process of low back pain (LBP). The identification and increased knowledge of prognostic factors might contribute to a better understanding of the course of LBP. The purpose of this study is to investigate the association of the STarT Back Screening Tool (SBST) risk score and the type of leg pain (non-radiating LBP, referred non-radicular, and radicular radiating leg pain) with the disability trajectory (at baseline, the slope, and recovery at one year) in adults with low back pain. METHODS: This is a prospective cohort study in 347 patients with low back pain who sought physiotherapy care at three primary care practices in the Netherlands. Linear mixed models were estimated to describe the association of the SBST risk score and the type of leg pain with disability at baseline, the slope in the disability trajectory, and at twelve months follow-up. RESULTS: A medium/high risk score on the SBST is associated with higher baseline disability scores on the Oswestry Disability Index (ODI), faster initial recovery, and still a higher disability ODI score at 12 months follow-up. Non-radicular referred and radicular radiating leg pain were associated with worse baseline disability ODI scores in LBP. This association was not present for the initial recovery or at the 12 months follow-up. CONCLUSION: The SBST is associated with the LBP recovery trajectory. The SBST might be a useful tool to predict the disability trajectory in a heterogeneous group of people with low back pain in primary care and might, therefore, be recommended in future clinical practice guidelines. The type of leg pain was not associated with the recovery trajectory of LBP. Future research might focus on evaluating different types of leg pain. TRIAL REGISTRATION: Clinicaltrials.gov: 109,643.

External validation of six COVID-19 prognostic models for predicting mortality risk in older populations in a hospital, primary care, and nursing home setting.

OBJECTIVES: To systematically evaluate the performance of COVID-19 prognostic models and scores for mortality risk in older populations across three health-care settings: hospitals, primary care, and nursing homes. STUDY DESIGN AND SETTING: This retrospective external validation study included 14,092 older individuals of ≥70 years of age with a clinical or polymerase chain reaction-confirmed COVID-19 diagnosis from March 2020 to December 2020. The six validation cohorts include three hospital-based (CliniCo, COVID-OLD, COVID-PREDICT), two primary care-based (Julius General Practitioners Network/Academisch network huisartsgeneeskunde/Network of Academic general Practitioners, PHARMO), and one nursing home cohort (YSIS) in the Netherlands. Based on a living systematic review of COVID-19 prediction models using Prediction model Risk Of Bias ASsessment Tool for quality and risk of bias assessment and considering predictor availability in validation cohorts, we selected six prognostic models predicting mortality risk in adults with COVID-19 infection (GAL-COVID-19 mortality, 4C Mortality Score, National Early Warning Score 2-extended model, Xie model, Wang clinical model, and CURB65 score). All six prognostic models were validated in the hospital cohorts and the GAL-COVID-19 mortality model was validated in all three healthcare settings. The primary outcome was in-hospital mortality for hospitals and 28-day mortality for primary care and nursing home settings. Model performance was evaluated in each validation cohort separately in terms of discrimination, calibration, and decision curves. An intercept update was performed in models indicating miscalibration followed by predictive performance re-evaluation. MAIN OUTCOME MEASURE: In-hospital mortality for hospitals and 28-day mortality for primary care and nursing home setting. RESULTS: All six prognostic models performed poorly and showed miscalibration in the older population cohorts. In the hospital settings, model performance ranged from calibration-in-the-large -1.45 to 7.46, calibration slopes 0.24-0.81, and C-statistic 0.55-0.71 with 4C Mortality Score performing as the most discriminative and well-calibrated model. Performance across health-care settings was similar for the GAL-COVID-19 model, with a calibration-in-the-large in the range of -2.35 to -0.15 indicating overestimation, calibration slopes of 0.24-0.81 indicating signs of overfitting, and C-statistic of 0.55-0.71. CONCLUSION: Our results show that most prognostic models for predicting mortality risk performed poorly in the older population with COVID-19, in each health-care setting: hospital, primary care, and nursing home settings. Insights into factors influencing predictive model performance in the older population are needed for pandemic preparedness and reliable prognostication of health-related outcomes in this demographic.

Assessing dynamical resilience indicators in older adults: a prospective feasibility cohort study.

PURPOSE: Measuring dynamical resilience indicators based on time series data may improve the prediction of health deterioration in older adults after hospital discharge. We examined the feasibility of an intensive prospective cohort study examining dynamical resilience indicators based on time series data of symptoms and physical activity in acutely ill older adults who visited the Emergency Department (ED). METHODS: This is a prospective cohort study with time series data from symptom questionnaires and activity trackers. Thirty older adults (aged 75.9 ± 5.5 years, 37% female) who were discharged from the ED of a tertiary hospital in the Netherlands were included in the study. We monitored self-reported symptoms using a daily online questionnaire, and physical activity using an activity tracker for 30 days. Descriptive data on participant eligibility and adherence to and acceptability of the assessments were collected. RESULTS: Of 134 older patients visiting the ED, 109/134 (81%) were eligible for inclusion and 30/109 (28%) were included. Twenty-eight (93%) of the included participants completed follow-up. Regarding the adherence rate, 78% of participants filled in the questionnaire and 80% wore the activity tracker. Three (10%) participants completed fewer than three questionnaires. Most participants rated the measurements as acceptable and seven (23%) participants experienced an adverse outcome in the 30 days after discharge. CONCLUSION: Such an intensive prospective cohort study examining dynamical resilience indicators in older adults was feasible. The quality of the collected data was sufficient, some adjustments to the measurement protocol are recommended. This study is an important first step to study resilience in older adults.

The need for systems thinking to advance Alzheimer's disease research.

Despite extensive research efforts to mechanistically understand late-onset Alzheimer's disease (LOAD) and other complex mental health disorders, curative treatments remain elusive. We emphasize the multiscale multicausality inherent to LOAD, highlighting the interplay between interconnected pathophysiological processes and risk factors. Systems thinking methods, such as causal loop diagrams and systems dynamic models, offer powerful means to capture and study this complexity. Recent studies developed and validated a causal loop diagram and system dynamics model using multiple longitudinal data sets, enabling the simulation of personalized interventions on various modifiable risk factors in LOAD. The results indicate that targeting factors like sleep disturbance and depressive symptoms could be promising and yield synergistic benefits. Furthermore, personalized interventions showed significant potential, with top-ranked intervention strategies differing significantly across individuals. We argue that systems thinking approaches can open new prospects for multifactorial precision medicine. In future research, systems thinking may also guide structured, model-driven data collection on the multiple interactions in LOAD's complex multicausality, facilitating theory development and possibly resulting in effective prevention and treatment options.

Availability of Cognitive Resources in Early Life Predicts Transitions Between Cognitive States in Middle and Older Adults From Europe.

Background and Objectives: The existing literature highlights the importance of reading books in middle-to-older adulthood for cognitive functioning; very few studies, however, have examined the importance of childhood cognitive resources for cognitive outcomes later in life. Research Design and Methods: Using data from 11 countries included in the Survey of Health, Ageing, and Retirement in Europe (SHARE) data set (N = 32,783), multistate survival models (MSMs) were fit to examine the importance of access to reading material in childhood on transitions through cognitive status categories (no cognitive impairment and impaired cognitive functioning) and death. Additionally, using the transition probabilities estimated by the MSMs, we estimated the remaining years of life without cognitive impairment and total longevity. All models were fit individually in each country, as well as within the pooled SHARE sample. Results: Adjusting for age, sex, education, and childhood socioeconomic status, the overall pooled estimate indicated that access to more books at age 10 was associated with a decreased risk of developing cognitive impairment (adjusted hazard ratio = 0.79, confidence interval: 0.76-0.82). Access to childhood books was not associated with risk of transitioning from normal cognitive functioning to death, or from cognitive impairment to death. Total longevity was similar between participants reporting high (+1 standard deviation [SD]) and low (-1 SD) number of books in the childhood home; however, individuals with more access to childhood books lived a greater proportion of this time without cognitive impairment. Discussion and Implications: Findings suggest that access to cognitive resources in childhood is protective for cognitive aging processes in older adulthood.

Understanding multimorbidity requires sign-disease networks and higher-order interactions, a perspective.

Background: Count scores, disease clustering, and pairwise associations between diseases remain ubiquitous in multimorbidity research despite two major shortcomings: they yield no insight into plausible mechanisms underlying multimorbidity, and they ignore higher-order interactions such as effect modification. Objectives: We argue that two components are currently missing but vital to develop novel multimorbidity metrics. Firstly, networks should be constructed which consists simultaneously of signs, symptoms, and diseases, since only then could they yield insight into plausible shared biological mechanisms underlying diseases.Secondly, learning pairwise associations is insufficient to fully characterize the correlations in a system. That is, synergistic (e.g., cooperative or antagonistic) effects are widespread in complex systems, where two or more elements combined give a larger or smaller effect than the sum of their individual effects. It can even occur that pairs of symptoms have no pairwise associations whatsoever, but in combination have a significant association. Therefore, higher-order interactions should be included in networks used to study multimorbidity, resulting in so-called hypergraphs. Methods: We illustrate our argument using a synthetic Bayesian Network model of symptoms, signs and diseases, composed of pairwise and higher-order interactions. We simulate network interventions on both individual and population levels and compare the ground-truth outcomes with the predictions from pairwise associations. Conclusion: We find that, when judged purely from the pairwise associations, interventions can have unexpected 'side-effects' or the most opportune intervention could be missed. The hypergraph uncovers links missed in pairwise networks, giving a more complete overview of sign and disease associations.

Association between Muscle Fatigability, Self-Perceived Fatigue and C-Reactive Protein at Admission in Hospitalized Geriatric Patients.

Background: The capacity to perceived vitality (CPV) ratio is a novel measure for intrinsic capacity or resilience based on grip work and self-perceived fatigue. CPV has been associated with pre-frailty in older adults and post-surgery inflammation in adults. To better understand the utility of this measure in a frail population, we examined the association between CPV and inflammation in geriatric inpatients. Methods: Data were obtained from 104 hospitalized geriatric patients. The average age of participants was 83.3 ± 7.5 years, and 55.8% of participants were women. In the cross-sectional analyses, associations between C-reactive protein (CRP), grip work (GW), self-perceived fatigue (SPF) and the CPV ratio (higher values indicate better capacity) were examined using linear regression adjusted for confounders. Results: The adjusted association between CRP (abnormal vs. normal) and the CPV ratio was not statistically significant (B = -0.33, 95% CI = -4.00 to 3.34). Associations between CRP and GW (B = 25.53, 95% CI = -478.23 to 529.30) and SPF (B = 0.57, 95% CI = -0.64 to 1.77) were also not statistically significant. Similar results were found in unadjusted models and analyses of cases with complete data. Conclusions: In this frail group of geriatric inpatients, inflammation, routinely assessed with CRP, was not associated with CPV or its components, GW and SPF. Further research is needed to explore whether CPV is a useful indicator of frailty or recovery capacity in hospitalized geriatric patients.

Multimorbidity patterns in older persons and their association with self-reported quality of life and limitations in activities of daily living.

BACKGROUND: As populations age, multimorbidity (the presence of two or more chronic morbidities) is increasingly more common. These evolving demographics demand further research into the identification of morbidity patterns in different settings as well as the longitudinal effects of these patterns. METHODS: Prospectively collected data on 12,755 older persons aged 65+ years were derived from The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS, www.topics-mds.eu). Latent class analyses were performed to identify unobserved relationship patterns between morbidities in older persons. Using linear mixed models, the average difference in health-related quality of life (EQ-5D) and general quality of life scores (Cantril's Self Anchoring Ladder) as well as limitations in Activities of Daily Living and Instrumental Activities of Daily Living (ADL/IADL) were examined over a 12-month period. RESULTS: Five multimorbidity patterns were identified: sensory (n = 3882), cardio-metabolic (n = 2627), mental health (n = 920), osteo-articular (n = 4486), and system decline (n = 840). Relative to older persons in the sensory group, multimorbidity patterns did not have a strong effect on health-related quality of life, general quality of life or ADL/IADLs over a one-year period. CONCLUSIONS: The observed multimorbidity patterns are similar to others based on different methodologies and study populations. When examining the effect of such patterns on quality of life, the EQ-5D and Cantril's Ladder may be insufficient outcome measures. Further investigations into the prognostic value of morbidity patterns would be of benefit.

Exploring the potential impact of multi-factor precision interventions in Alzheimer's disease with system dynamics.

Numerous clinical trials based on a single-cause paradigm have not resulted in efficacious treatments for Alzheimer's disease (AD). Recently, prevention trials that simultaneously intervened on multiple risk factors have shown mixed results, suggesting that careful design is necessary. Moreover, intensive pilot precision medicine (PM) trial results have been promising but may not generalize to a broader population. These observations suggest that a model-based approach to multi-factor precision medicine (PM) is warranted. We systematically developed a system dynamics model (SDM) of AD for PM using data from two longitudinal studies (N=3660). This method involved a model selection procedure in identifying interaction terms between the SDM components and estimating individualized parameters. We used the SDM to explore simulated single- and double-factor interventions on 14 modifiable risk factors. We quantified the potential impact of double-factor interventions over single-factor interventions as 1.5 [95% CI: 1.5-2.6] and of SDM-based PM over a one-size-fits-all approach as 3.5 [3.1, 3.8] ADAS-cog-13 points in 12 years. Although the model remains to be validated, we tentatively conclude that multi-factor PM could come to play an important role in AD prevention.

Social Health and Change in Cognitive Capability among Older Adults: Findings from Four European Longitudinal Studies.

INTRODUCTION: In this study, we examine whether social health markers measured at baseline are associated with differences in cognitive capability and the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies. METHODS: We applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline. RESULTS: Pooled estimates show distinct relationships between markers of social health and cognitive domains, e.g., a large network size (≥6 people vs. none) was associated with higher executive function (0.17 standard deviation [SD] [95% CI: 0.00, 0.34], I2 = 27%) but not with memory (0.08 SD [95% CI: -0.02, 0.18], I2 = 19%). We also observed pooled associations between being married or cohabiting, having a large network size, and participating in social activities with slower decline in cognitive capability. However, estimates were close to zero, e.g., 0.01 SD/year (95% CI: 0.01, 0.02) I2 = 19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous, and results for average memory were the most heterogeneous. CONCLUSION: Overall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between-study differences and considering the context specificity of findings in developing and deploying interventions.

Determinants of quality of life in family caregivers in MCI: a comparison with mild dementia.

OBJECTIVES: The aim of the current study was to investigate the health-related quality of life (HRQol) of the family caregiver in MCI, explore possible determinants and study possible differences with mild dementia. METHODS: This secondary data analysis included 145 persons with MCI and 154 persons with dementia and their family caregivers from two Dutch cohort studies. HRQoL was measured with the VAS of the EuroQol-5D-3L version. Regressions analyses were conducted to examine potential demographic and clinical determinants of the caregiver's HRQoL. RESULTS: The mean EQ5D-VAS in family caregivers of persons with MCI was 81.1 (SD 15.7), and did not significantly differ from family caregivers in mild dementia (81.9 (SD 13.0)). In MCI, patient measurements were not significantly associated with caregiver mean EQ5D-VAS. Concerning caregiver characteristics, being a spouse and a lower educational level were associated with a lower mean EQ5D-VAS (in a multiple linear regression model: unstandardized B -8.075, p = 0.013 and unstandardized B -6.162, p = 0.037 resp.). In mild dementia, the NPI item irritability showed an association with caregiver EQ5D-VAS in bivariate linear regression analyses. CONCLUSION: Results indicate that especially family caregiver characteristics seem to influence family caregiver HRQoL in MCI. Future research should include other potential determinants such as burden, coping strategies and relationship quality.

Trajectories of Physical Function and Behavioral, Psychological, and Social Well-Being in a Cohort of Swedish Older Adults.

Background and Objectives: Successful aging has been described as a multifactorial and dynamic process. The aims of the study were to detect aging trajectories of physical function and behavioral, psychological, and social well-being; and to explore the correlations between functional versus well-being trajectories by age group. Research Design and Methods: Data were gathered from the Swedish National Study on Aging and Care in Kungsholmen (N = 1,375). Subjects' physical function was assessed through walking speed and chair-stand tests, behavioral well-being through participation in mental and physical activities, psychological well-being through life satisfaction and positive affect, and social well-being through social connections and support. All exposures were standardized (z-scores). Linear mixed models were used to estimate trajectories of physical function and well-being over a 12-year follow-up. Results: The steepest declines were seen for physical function (relative change [RC] in z-scores across ages; RC = 3.01), followed by behavioral well-being (RC = 2.15), psychological well-being (RC = 2.01), and social well-being (RC = 0.76). Correlations between physical function and the different well-being domains were weak, especially for slopes. Stronger intercept correlations were observed among the oldest-compared to the youngest-old, especially with behavioral (r = 0.39 vs r = 0.24) and psychological (r = 0.33 vs r = 0.22) well-being. Discussion and Implications: Physical function declines the fastest throughout aging. The different well-being domains decline at a slower rate, which may be a possible sign of compensation against age-related functional decline, especially among the youngest-old, for whom discordances between physical function and the different well-being domains were more common.

DementiaNet facilitates a sustainable transition toward integrated primary dementia care: A long-term evaluation.

INTRODUCTION: Care integration is a promising strategy to achieve sustainable health-care systems. With DementiaNet, a 2-year program, we facilitated collaboration between primary health-care professionals. We studied changes in primary dementia care integration during and after DementiaNet participation. METHODS: A longitudinal follow-up study was performed. Networks started between 2015 and 2020; follow-up ended in 2021. Quantitative and quantitative data were collected annually to assess quality of care, network collaboration, and number of crisis admissions. Growth modeling was used to identify changes over time. RESULTS: Thirty-five primary care networks participated. Network collaboration and quality of care of newly formed networks increased significantly in the first 2 years (respectively, 0.35/year, P < .001; 0.29/year, P < .001) and thereafter stabilized. CONCLUSION: Primary care networks improved their collaboration and quality of care during DementiaNet participation, which persisted after the program ended. This indicates that DementiaNet facilitated a sustainable transition toward integrated primary dementia care.

Comparing Continuous with Periodic Vital Sign Scoring for Clinical Deterioration Using a Patient Data Model.

To evaluate a minute-by-minute monitoring algorithm against a periodic early warning score (EWS) in detecting clinical deterioration and workload. Periodic EWSs suffer from large measurement intervals, causing late detection of deterioration. This might be prevented by continuous vital sign monitoring with a real-time algorithm such as the Visensia Safety Index (VSI). This prospective comparative data modeling cohort study (NCT04189653) compares continuous algorithmic alerts against periodic EWS in continuous monitored medical and surgical inpatients. We evaluated sensitivity, frequency, number of warnings needed to evaluate (NNE) and time of initial alert till escalation of care (EOC): Rapid Response Team activation, unplanned ICU admission, emergency surgery, or death. Also, the percentage of VSI alerting minutes was compared between patients with or without EOC. In 1529 admissions continuous VSI warned for 55% of EOC (95% CI: 45-64%) versus 51% (95% CI: 41-61%) by periodic EWS. NNE for VSI was 152 alerts per detected EOC (95% CI: 114-190) compared to 21 (95% CI: 17-28). It generated 0.99 warnings per day per patient compared to 0.13. Time from detection score till escalation was 8.3 hours (IQR: 2.6-24.8) with VSI versus 5.2 (IQR: 2.7-12.3) hours with EWS (P=0.074). The percentage of warning VSI minutes was higher in patients with EOC than in stable patients (2.36% vs 0.81%, P<0.001). Although sensitivity of detection was not significantly improved continuous vital sign monitoring shows potential for earlier alerts for deterioration compared to periodic EWS. A higher percentage of alerting minutes may indicate risk for deterioration.

Capturing postural blood pressure dynamics with near-infrared spectroscopy-measured cerebral oxygenation.

Orthostatic hypotension (OH) is highly prevalent in older adults and associated with dizziness, falls, lower physical and cognitive function, cardiovascular disease, and mortality. OH is currently diagnosed in a clinical setting with single-time point cuff measurements. Continuous blood pressure (BP) devices can measure OH dynamics but cannot be used for daily life monitoring. Near-infrared spectroscopy (NIRS) has potential diagnostic value in measuring cerebral oxygenation continuously over a longer time period, but this needs further validation. This study aimed to compare NIRS-measured (cerebral) oxygenation with continuous BP and transcranial Doppler-measured cerebral blood velocity (CBv) during postural changes. This cross-sectional study included 41 participants between 20 and 88 years old. BP, CBv, and cerebral (long channels) and superficial (short channels) oxygenated hemoglobin (O2Hb) were measured continuously during various postural changes. Pearson correlations between BP, CBv, and O2Hb were calculated over curves and specific characteristics (maximum drop amplitude and recovery). BP and O2Hb only showed good curve-based correlations (0.58-0.75) in the initial 30 s after standing up. Early (30-40 s) and 1-min BP recovery associated significantly with O2Hb, but no consistent associations were found for maximum drop amplitude and late (60-175 s) recovery values. Associations between CBv and O2Hb were poor, but stronger for long-channel than short-channel measurements. BP associated well with NIRS-measured O2Hb in the first 30 s after postural change. Stronger associations for CBv with long-channel O2Hb suggest that long-channel NIRS specifically reflects cerebral blood flow during postural transitions, necessary to better understand the consequences of OH such as intolerance symptoms.

A study protocol of external validation of eight COVID-19 prognostic models for predicting mortality risk in older populations in a hospital, primary care, and nursing home setting.

BACKGROUND: The COVID-19 pandemic has a large impact worldwide and is known to particularly affect the older population. This paper outlines the protocol for external validation of prognostic models predicting mortality risk after presentation with COVID-19 in the older population. These prognostic models were originally developed in an adult population and will be validated in an older population (≥ 70 years of age) in three healthcare settings: the hospital setting, the primary care setting, and the nursing home setting. METHODS: Based on a living systematic review of COVID-19 prediction models, we identified eight prognostic models predicting the risk of mortality in adults with a COVID-19 infection (five COVID-19 specific models: GAL-COVID-19 mortality, 4C Mortality Score, NEWS2 + model, Xie model, and Wang clinical model and three pre-existing prognostic scores: APACHE-II, CURB65, SOFA). These eight models will be validated in six different cohorts of the Dutch older population (three hospital cohorts, two primary care cohorts, and a nursing home cohort). All prognostic models will be validated in a hospital setting while the GAL-COVID-19 mortality model will be validated in hospital, primary care, and nursing home settings. The study will include individuals ≥ 70 years of age with a highly suspected or PCR-confirmed COVID-19 infection from March 2020 to December 2020 (and up to December 2021 in a sensitivity analysis). The predictive performance will be evaluated in terms of discrimination, calibration, and decision curves for each of the prognostic models in each cohort individually. For prognostic models with indications of miscalibration, an intercept update will be performed after which predictive performance will be re-evaluated. DISCUSSION: Insight into the performance of existing prognostic models in one of the most vulnerable populations clarifies the extent to which tailoring of COVID-19 prognostic models is needed when models are applied to the older population. Such insight will be important for possible future waves of the COVID-19 pandemic or future pandemics.