Blood–brain barrier (BBB) breakdown can disrupt nutrient supply and waste removal, which affects neuronal functioning. Currently, dynamic contrast-enhanced (DCE) MRI is the preferred in-vivo method to quantify BBB leakage. Dedicated DCE MRI studies in normal aging individuals are lacking, which could hamper value estimation and interpretation of leakage rate in pathological conditions. Therefore, we applied DCE MRI to investigate the association between BBB disruption and age in a healthy sample. Fifty-seven cognitively and neurologically healthy, middle-aged to older participants (mean age: 66 years, range: 47–91 years) underwent MRI, including DCE MRI with intravenous injection of a gadolinium-based contrast agent. Pharmacokinetic modeling was applied to contrast concentration time-curves to estimate BBB leakage rate in each voxel. Subsequently, leakage rate was calculated in the white and gray matter, and primary (basic sensory and motor functions), secondary (association areas), and tertiary (higher-order cognition) brain regions. A difference in vulnerability to deterioration was expected between these regions, with especially tertiary regions being affected by age. Higher BBB leakage rate was significantly associated with older age in the white and gray matter, and also in tertiary, but not in primary or secondary brain regions. Even in healthy individuals, BBB disruption was stronger in older persons, which suggests BBB disruption is a normal physiologically aging phenomenon. Age-related increase in BBB disruption occurred especially in brain regions most vulnerable to age-related deterioration, which may indicate that BBB disruption is an underlying mechanism of normal age-related decline. Netherlands Trial Register number: NL6358, date of registration: 2017-03-24.

Background The aim of this systematic review was (1) to identify the brain regions involved in anxiety in Parkinson's disease (PD) based on neuroimaging studies and (2) to interpret the findings against the background of dysfunction of the fear circuit and limbic cortico‐striato‐thalamocortical circuit. Methods Studies assessing anxiety symptoms in PD patients and studies using magnetic resonance imaging, positron emission tomography, or single‐photon emission computed tomography were included. Results The severity of anxiety was associated with changes in the fear circuit and the cortico‐striato‐thalamocortical limbic circuit. In the fear circuit, a reduced gray‐matter volume of the amygdala and the anterior cingulate cortex (ACC); an increased functional connectivity (FC) between the amygdala and orbitofrontal cortex (OFC) and hippocampus and between the striatum and the medial prefrontal cortex (PFC), temporal cortex, and insula; and a reduced FC between the lateral PFC and the OFC, hippocampus, and amygdala were reported. In the cortico‐striato‐thalamocortical limbic circuit, a reduced FC between the striatum and ACC; a reduced dopaminergic and noradrenergic activity in striatum, thalamus, and locus coeruleus; and a reduced serotoninergic activity in the thalamus were reported. Conclusion To conclude, anxiety is associated with structural and functional changes in both the hypothesized fear and the limbic cortico‐striato‐thalamocortical circuits. These circuits overlap and may well constitute parts of a more extensive pathway, of which different parts play different roles in anxiety. The neuropathology of PD may affect these circuits in different ways, explaining the high prevalence of anxiety in PD and also the associated cognitive, motor, and psychiatric symptoms. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

These animal data, together with the view of limited scientifically robust clinical evidence in humans, indicate that physicians consider only short-term administration of COX-2 inhibitors or other drugs in the pain management of patients who are in the phase of fracture or other bone defect healing. COX-2-inhibitors should be considered a potential risk factor for fracture healing, and therefore to be avoided in patients at risk for delayed fracture healing.

In clinical practice, fracture healing is evaluated by clinical judgment in combination with conventional radiography. Due to limited resolution, radiographs don't provide detailed information regarding the bone micro-architecture and bone strength. Recently, assessment of in vivo bone density, architectural and mechanical properties at the microscale became possible using high resolution peripheral quantitative computed tomography (HR-pQCT) in combination with micro finite element analysis (μFEA). So far, such techniques have been used mainly to study intact bone. The aim of this study was to explore whether these techniques can also be used to assess changes in bone density, micro-architecture and bone stiffness during fracture healing. Therefore, the fracture region in eighteen women, aged 50 years or older with a stable distal radius fracture, was scanned using HR-pQCT at 1-2 (baseline), 3-4, 6-8 and 12weeks post-fracture. At 1-2 and 12 weeks post-fracture the distal radius at the contra-lateral side was also scanned as control. Standard bone density, micro-architectural and geometric parameters were calculated and bone stiffness in compression, torsion and bending was assessed using μFEA. A linear mixed effect model with time post-fracture as fixed effect was used to detect significant (p-value ≤0.05) changes from baseline. Wrist pain and function were scored using the patient-rated wrist evaluation (PRWE) questionnaire. Correlations between the bone parameters and the PRWE score were calculated by Spearman's correlation coefficient. At the fracture site, total and trabecular bone density increased by 11% and 20%, respectively, at 6-8 weeks, whereas cortical density was decreased by 4%. Trabecular thickness increased by 23-31% at 6-8 and 12 weeks and the intertrabecular area became blurred, indicating intertrabecular bone formation. Compared to baseline, calculated bone stiffness in compression, torsion and bending was increased by 31% after 12 weeks. A moderate negative correlation was found between the stiffness and the PRWE score. No changes were observed at the contra-lateral side. The results demonstrate that it is feasible to assess clinically relevant and significant longitudinal changes in bone density, micro-architecture and mechanical properties at the fracture region during the healing process of stable distal radius fractures using HR-pQCT.