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Background: Allostatic load has been suggested as a pathway through which experiences become biologically embedded to influence health. Research on childhood predictors of allostatic load has focused on socioeconomic and psychosocial exposures, while few studies include prospective measures of biomedical exposures. Further, findings on sex differences in the association of childhood predictors with various health outcomes related to allostatic load are ambiguous. Aims: To examine the influence of early life biomedical and social factors in the first year of life on midlife allostatic load, assessing potential sex differences. Methods: This prospective cohort study includes early life information collected at birth and a one year examination for 1,648 members of the Copenhagen Perinatal Cohort who also participated in the Copenhagen Aging and Midlife Biobank study (aged 49–52 years, 56% women). Allostatic load based on 14 biomarkers was selected as a measure of midlife health status. Early life factors were categorized as predominantly biomedical or social, and their associations with midlife allostatic load were examined in domain-specific and combined sex-stratified multiple regression models. Results: The biomedical factors model explained 6.6% of the variance in midlife allostatic load in men and 6.7% in women, while the social model explained 4.1% of the variance in men and 7.3% in women. For both sexes, parental socioeconomic position at one year and maternal BMI significantly predicted midlife allostatic load in a model containing all early life factors. For women, additional significant predictors were complications at birth, birth weight and not living with parents at one year. Conclusion: The results confirm an association of lower childhood socioeconomic position with higher adult allostatic load while demonstrating the importance of other prenatal and early life exposures and highlighting potential sex differences. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) damages central white matter pathways which has considerable impact on disease-related disability. To identify disease-related alterations in anatomical connectivity, 34 patients (19 with relapsing remitting MS (RR-MS), 15 with secondary progressive MS (SP-MS) and 20 healthy subjects underwent diffusion magnetic resonance imaging (dMRI) of the brain. Based on the dMRI, anatomical connectivity mapping (ACM) yielded a voxel-based metric reflecting the connectivity shared between each individual voxel and all other brain voxels. To avoid biases caused by inter-individual brain-shape differences, they were estimated in a spatially normalized space. Voxel-based statistical analyses using ACM were compared with analyses based on the localized microstructural indices of fractional anisotropy (FA). In both RR-MS and SP-MS patients, considerable portions of the motor-related white matter revealed decreases in ACM and FA when compared with healthy subjects. Patients with SP-MS exhibited reduced ACM values relative to RR-MS in the motor-related tracts, whereas there were no consistent decreases in FA between SP-MS and RR-MS patients. Regional ACM statistics exhibited moderate correlation with clinical disability as reflected by the expanded disability status scale (EDSS). The correlation between these statistics and EDSS was either similar to or stronger than the correlation between FA statistics and the EDSS. Together, the results reveal an improved relationship between ACM, the clinical phenotype, and impairment. This highlights the potential of the ACM connectivity indices to be used as a marker which can identify disease related-alterations due to MS which may not be seen using localized microstructural indices. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) affects the integrity of the blood-brain barrier (BBB). Contrast-enhanced T1 weighted magnetic resonance imaging (MRI) is widely used to characterize location and extent of BBB disruptions in focal MS lesions. We employed quantitative T1 measurements before and after the intravenous injection of a paramagnetic contrast agent to assess BBB permeability in the normal appearing white matter (NAWM) in patients with relapsing-remitting MS (RR-MS). Methodology/Principal Findings: Fifty-nine patients (38 females) with RR-MS undergoing immunomodulatory treatment and nine healthy controls (4 females) underwent quantitative T1 measurements at 3 tesla before and after injection of a paramagnetic contrast agent (0.2 mmol/kg Gd-DTPA). Mean T1 values were calculated for NAWM in patients and total cerebral white matter in healthy subjects for the T1 measurements before and after injection of Gd-DTPA. The pre-injection baseline T1 of NAWM (945±55 [SD] ms) was prolonged in RR-MS relative to healthy controls (903±23 ms, p = 0.028). Gd-DTPA injection shortened T1 to a similar extent in both groups. Mean T1 of NAWM was 866±47 ms in the NAWM of RR-MS patients and 824±13 ms in the white matter of healthy controls. The regional variability of T1 values expressed as the coefficient of variation (CV) was comparable between the two groups at baseline, but not after injection of the contrast agent. After intravenous Gd-DTPA injection, T1 values in NAWM were more variable in RR-MS patients (CV = 0.198±0.046) compared to cerebral white matter of healthy controls (CV = 0.166±0.018, p = 0.046). Conclusions/Significance: We found no evidence of a global BBB disruption within the NAWM of RR-MS patients undergoing immunomodulatory treatment. However, the increased variation of T1 values in NAWM after intravenous Gd-DTPA injection points to an increased regional inhomogeneity of BBB function in NAWM in relapsing-remitting MS. [ABSTRACT FROM AUTHOR]