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.

Where is VALDO? VAscular Lesions Detection and segmentatiOn challenge at MICCAI 2021.

Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. Here, we present the results of the VAscular Lesions DetectiOn and Segmentation (Where is VALDO?) challenge that was run as a satellite event at the international conference on Medical Image Computing and Computer Aided Intervention (MICCAI) 2021. This challenge aimed to promote the development of methods for automated detection and segmentation of small and sparse imaging markers of cerebral small vessel disease, namely enlarged perivascular spaces (EPVS) (Task 1), cerebral microbleeds (Task 2) and lacunes of presumed vascular origin (Task 3) while leveraging weak and noisy labels. Overall, 12 teams participated in the challenge proposing solutions for one or more tasks (4 for Task 1-EPVS, 9 for Task 2-Microbleeds and 6 for Task 3-Lacunes). Multi-cohort data was used in both training and evaluation. Results showed a large variability in performance both across teams and across tasks, with promising results notably for Task 1-EPVS and Task 2-Microbleeds and not practically useful results yet for Task 3-Lacunes. It also highlighted the performance inconsistency across cases that may deter use at an individual level, while still proving useful at a population level.