Sex-differences in the association of social health and marital status with blood-based immune and neurodegeneration markers in a cohort of community-dwelling older adults.

BACKGROUND: The immune system has been proposed to play a role in the link between social health and all-cause dementia risk. We explored cross-sectional and longitudinal associations between social health, immune system balance and plasma neurodegeneration markers in community-dwelling older adults, and explored whether the balance between innate and adaptive immunity mediates associations between social health and both cognition and total brain volume. METHODS: Social health markers (social support, marital status, loneliness) were measured in the Rotterdam Study between 2002-2008. Immune system cell counts and balance were assessed repeatedly from 2002 to 2016 using white blood-cell-based indices and individual counts (granulocyte-to-lymphocyte ratio (GLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)). Plasma neurodegeneration biomarkers (amyloid-ß40, amyloid-ß42, total tau and neurofilament light chain) were measured once from blood samples collected between 2002-2008. Global cognitive function and total brain volume (MRI) were measured at the follow-up visit between 2009-2014. We used linear mixed models to study longitudinal associations and performed causal mediation analyses. RESULTS: In 8374 adults (mean age 65.7, 57 % female), never married participants (n = 394) had higher GLR, PLR and SII compared to married peers at baseline and during follow-up, indicating imbalance towards innate immunity. Being never married was associated with higher plasma amyloid-ß40, and being widowed or divorced with higher plasma total tau levels at baseline. Widowed or divorced males, but not females, had higher GLR, PLR and SII at baseline. Higher social support was associated with lower PLR in females, but higher PLR in males. Loneliness was not associated with any of the immune system balance ratios. Never married males had higher levels of all plasma neurodegeneration markers at baseline. Immune system balance did not mediate associations between social health and cognition or total brain volume, but does interact with marital status. CONCLUSION: This study indicates that marital status is associated with blood-based immune system markers toward innate immunity and higher levels of plasma neurodegeneration markers. This is particularly evident for never married or previously married male older adults compared to married or female peers.

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.

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.

No association between markers of systemic inflammation and endothelial dysfunction with Alzheimer's disease progression: a longitudinal study.

INTRODUCTION: Systemic inflammation and endothelial dysfunction are potentially modifiable factors implicated in Alzheimer's disease (AD), which offer potential therapeutic targets to slow disease progression. METHODS: We investigated the relationship between baseline circulating levels of inflammatory (TNF-α, IL-1ß) and endothelial cell markers (VCAM-1, ICAM-1, E-selectin) and 18-month cognitive decline (ADAS-cog12) in 266 mild-to-moderate AD patients from the NILVAD study. We employed individual growth models to examine associations, potential mediation, and interaction effects while adjusting for confounders. RESULTS: The average increase in ADAS-cog12 scores over all patients was 8.1 points in 18 months. No significant association was found between the markers and the rate of cognitive decline. Mediation analysis revealed no mediating role for endothelial cell markers, and interaction effects were not observed. DISCUSSION: Our results do not support the role of systemic inflammation or endothelial dysfunction in progression in persons with AD.