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Objective: To investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and changes in cognition and global brain structure. Methods: In the Rotterdam Study, baseline NT-proBNP was assessed at baseline from 1997 to 2008. Between 1997 and 2016, participants without dementia or stroke at baseline (n = 9566) had repeated cognitive tests (every 3–6 years) for global cognitive function, executive cognitive function, fine manual dexterity, and memory. Magnetic resonance imaging of the brain was performed repeatedly at re-examination visits between 2005 and 2015 for 2607 participants to obtain brain volumes, focal brain lesions, and white matter microstructural integrity as measures of brain structure. Results: Among 9566 participants (mean age 65.1 ± 9.8 years), 5444 (56.9%) were women, and repeated measures of cognition were performed during a median follow-up time of 5.5 (range 1.1–17.9) years, of whom 2607 participants completed at least one brain imaging scan. Higher levels of NT-proBNP were associated with a faster decline of scores in the global cognitive function (p value = 0.003) and the Word-Fluency test (p value = 0.003) but were not related to a steeper deterioration in brain volumes, global fractional anisotropy, and mean diffusivity, as indicators of white matter microstructural integrity, or focal brain lesions. Conclusions: Higher baseline NT-proBNP levels were associated with a faster decline in cognition; however, no association with global brain structure was found.

Background Poor social health has been linked to a risk of neuropsychiatric disorders. Neuroimaging studies have shown associations between social health and global white matter microstructural integrity. We aimed to identify which white matter tracts are involved in these associations. Methods Social health markers (loneliness, perceived social support, and partnership status) and white matter microstructural integrity of 15 white matter tracts (identified with probabilistic tractography after diffusion magnetic resonance imaging) were collected for 3352 participants (mean age 58.4 years, 54.9% female) from 2002 to 2008 in the Rotterdam Study. Cross-sectional associations were studied using multivariable linear regression. Results Loneliness was associated with higher mean diffusivity (MD) in the superior thalamic radiation and the parahippocampal part of the cingulum (standardized mean difference for both tracts: 0.21, 95% CI, 0.09 to 0.34). Better perceived social support was associated with lower MD in the forceps minor (standardized mean difference per point increase in social support: −0.06, 95% CI, −0.09 to −0.03), inferior fronto-occipital fasciculus, and uncinate fasciculus. In male participants, better perceived social support was associated with lower MD in the forceps minor, and not having a partner was associated with lower fractional anisotropy in the forceps minor. Loneliness was associated with higher MD in the superior thalamic radiation in female participants only. Conclusions Social health was associated with tract-specific white matter microstructure. Loneliness was associated with lower integrity of limbic and sensorimotor tracts, whereas better perceived social support was associated with higher integrity of association and commissural tracts, indicating that social health domains involve distinct neural pathways of the brain.

Objectives: The coronavirus disease-2019 (COVID-19) pandemic and accompanying lockdown restrictions impacted social life significantly. We studied associations of sociodemographic factors, mental and social health markers, and brain structure with social health trajectories during the COVID-19 pandemic. Design: Prospective longitudinal population-based cohort study. Setting: Community-dwelling inhabitants of Rotterdam, the Netherlands. Participants: Repeated questionnaires including questions on social health were sent to Rotterdam Study participants from April 2020 onwards. Social health data at study baseline were available for 5017 participants (mean age: 68.7 ± 11.3; 56.9% women). Measurements: Determinants were assessed in routine Rotterdam Study follow-up (1990–2020), including global brain volumes in a subset of participants (N = 1720). We applied linear mixed models and generalized estimating equations to quantify associations between determinants and trajectories of loneliness, perceived social isolation and social connectedness over three time points from April 22nd to July 31st 2020. Results: Loneliness prevalence was 27.9% in April 2020 versus 12.6% prepandemic. Social isolation (baseline mean 4.7 ± 2.4) and loneliness scores (baseline mean 4.9 ± 1.5) decreased over time, whereas social connectedness trajectories remained stable. Depressive symptoms, female sex, prepandemic loneliness, living alone, and not owning a pet were independently associated with lower social connectedness and higher social isolation and loneliness at COVID-19 baseline, but recovery of social health was similar for all determinants. Larger intracranial volume was associated with higher social connectedness. Conclusions: Despite baseline differences for specific determinants, older adults showed similar recovery of loneliness and social isolation alongside stable social connectedness over time during the pandemic. Social health is multidimensional, especially during a global health crisis.

Background Social health markers have been linked to the development of dementia. We hypothesize that social health affects brain structure and consequently influences cognitive function. We aim to elucidate the cross-sectional and longitudinal associations between social health markers and structural brain changes in older adults in the general population. Methods Social health markers (loneliness, perceived social support, marital status) were assessed in the Rotterdam Study from 2002 to 2008. Magnetic resonance imaging of the brain was performed repeatedly between 2005 and 2015 for 3737 participants to obtain brain volumetrics, cerebral small vessel disease markers, and white matter microstructural integrity as measures of brain structure. Cross-sectional associations between social health and brain structure were studied using multivariable linear and logistic regression models. Longitudinal associations between baseline social health and changes in brain structure were examined using linear mixed models and generalized estimating equations. Results Loneliness was associated with smaller white matter volume at baseline (mean difference = −4.63 mL, 95% confidence interval = −8.46 to −0.81). Better perceived social support was associated with larger total brain volume and gray matter volume at baseline and a less steep decrease in total brain volume over time. Better social support was associated with higher global fractional anisotropy and lower mean diffusivity at baseline. Participants who had never been married had a smaller total brain volume (mean difference = −8.27 mL, 95% confidence interval = −13.16 to −3.39) at baseline than married peers. Conclusions Social health is associated with brain structure. Better perceived social support at baseline was associated with better brain structure over time.

Purpose Psychosocial health problems, such as social isolation, loneliness, depression and anxiety, have gained attention during the COVID-19 pandemic and are commonly co-occurring. We investigated the network of psychosocial health constructs during the COVID-19 pandemic. Methods This study included 4553 participants (mean age: 68.6 ± 11.2 years, 56% women) from the prospective Rotterdam Study, who filled out a questionnaire between April and July 2020, the time of the first COVID-19 wave in the Netherlands. Psychosocial health constructs included were depressive symptoms (Center for Epidemiological Studies Depression scale), anxiety symptoms (Hospital Anxiety and Depression scale), loneliness (University of California, Los Angeles loneliness scale), social connectedness (five items) and pandemic-related worry (five items). We estimated mixed graphical models to assess the network of items of these constructs and whether age and sex affected the network structure. Results Within the network of psychosocial constructs, a higher depressive symptoms score was particularly associated with items of loneliness and social connectedness, whereas overall anxiety was particularly associated with items of pandemic-related worry. Between people from different sex and age, the network structure significantly altered. Conclusion This study demonstrates that within the same network of psychosocial health constructs, depressive symptom score is particularly associated with loneliness and social connectedness, whereas anxiety symptom score is associated with pandemic-related worry during the first COVID-19 lockdown. Our results support that psychosocial constructs should be considered in conjunction with one another in prevention and treatment efforts in clinical care, and that these efforts need to be tailored to specific demographic groups.

Alzheimer’s disease (AD) is a complex, multicausal disorder involving several spatiotemporal scales and scientific domains. While many studies focus on specific parts of this system, the complexity of AD is rarely studied as a whole. In this work, we apply systems thinking to map out known causal mechanisms and risk factors ranging from intracellular to psychosocial scales in sporadic AD. We report on the first systemic causal loop diagram (CLD) for AD, which is the result of an interdisciplinary group model building (GMB) process. The GMB was based on the input of experts from multiple domains and all proposed mechanisms were supported by scientific literature. The CLD elucidates interaction and feedback mechanisms that contribute to cognitive decline from midlife onward as described by the experts. As an immediate outcome, we observed several non-trivial reinforcing feedback loops involving factors at multiple spatial scales, which are rarely considered within the same theoretical framework. We also observed high centrality for modifiable risk factors such as social relationships and physical activity, which suggests they may be promising leverage points for interventions. This illustrates how a CLD from an interdisciplinary GMB process may lead to novel insights into complex disorders. Furthermore, the CLD is the first step in the development of a computational model for simulating the effects of risk factors on AD. Electronic supplementary material The online version of this article (10.1007/s11357-020-00228-7) contains supplementary material, which is available to authorized users.

Introduction Cardiac function is a key player in maintaining energy homeostasis in the brain. Heart failure is closely related to higher risk of neurocognitive disorders. Recent evidence shows that this relationship might not be limited to patients with advanced heart failure, and even suboptimal cardiac functioning is associated with accelerated brain aging. Hence, hemodynamic and serum cardiac markers may provide valuable information about the risk of dementia. Methods We provide an overview on the link between cardiac markers and cognitive function by a systematic search in five databases. Furthermore, we discuss the pathophysiological aspects of this link and highlight the pertinent clinical and public health implications. Results Increasing evidence supports the associations of hemodynamic and serum cardiac markers with accelerated cognitive decline. Discussion Hemodynamic and serum cardiac markers are closely linked with risk of cognitive impairment. This highlights the significance of the heart–brain connection in reducing the burden of dementia.

It is well established that patients with heart failure are at a greater risk for dementia. Recent evidence suggests that the heart-brain link goes beyond advanced heart failure, and even suboptimal cardiac function is associated with brain structural and functional changes leading to cognitive impairment. In this review, we address several pathophysiological mechanisms underlying this association, including hemodynamic stress and cerebral hypoperfusion, neuroinflammation, cardiac arrhythmias, and hypercoagulation. The close link between cardiac function and brain health has numerous clinical and public health implications. Cardiac dysfunction and cognitive impairment are both common in older adults. However, in our current clinical practice, these medical conditions are generally evaluated and treated in isolation. Emerging evidence on the significance of the heart-brain link calls for comprehensive cardiovascular risk assessment in patients with cognitive impairment and a neurocognitive workup in patients with impaired cardiac function. A multidisciplinary approach by cardiologists, neurologists, and geriatricians would benefit the diagnostic process and disease management and ultimately improve the quality of life for patients with cardiac and cognitive dysfunction.