Deep brain stimulation of the internal globus pallidus does not affect the limbic circuit in patients with Parkinson's disease: a PET study.

INTRODUCTION: Internal globus pallidus (GPi) deep brain stimulation (DBS) is a safe and effective alternative treatment in Parkinson's disease (PD) for patients with cognitive impairment. However, no study has yet investigated metabolic changes within a large series of patients undergoing GPi stimulation. OBJECTIVE: We assessed motor, cognitive and psychiatric changes, as well as modifications in brain glucose metabolism measured with FDG-PET, before and after bilateral GPi-DBS. METHODS: In the same week, 32 patients with PD underwent a motor, cognitive and psychiatric assessment and a resting-state FDG-PET scan, 4 months before and 4 months after GPi-DBS surgery. For the voxelwise metabolic change assessment, the p value was controlled for multiple comparisons using the family wise error rate. RESULTS: After GPi-DBS surgery, patients showed a significant overall improvement in motor status. No cognitive or psychiatric changes were observed after surgery. Nor were any clusters with significantly relative metabolic changes found in the limbic circuit after surgery. Clusters with significantly relative metabolic changes were observed in the left and right Brodmann area (BA) 6, the right BA 9, the right and left BA 39 and the left BA 17. CONCLUSION: The present study confirmed that GPi-DBS is an effective treatment in patients with advanced PD, owing to metabolic changes in the areas involved in motor execution. The absence of relative metabolic decrease in the limbic circuit and the few changes affecting the associative circuit could explain why GPi-DBS is cognitively safe.

HIV infection and cerebral small vessel disease are independently associated with brain atrophy and cognitive impairment.

OBJECTIVE: The objective of this study is to investigate whether cerebral small vessel disease (CSVD) is more common in virologically suppressed HIV-positive participants compared with HIV-negative controls and examine the potential synergistic effects of HIV and CSVD on brain structure and cognition. DESIGN: Cross-sectional analysis of 119 treated, virologically suppressed HIV-positive and 55 HIV-negative participants. Forty-six HIV-positive and 30 HIV-negative participants had follow-up 2 years later. All participants underwent MRI and neuropsychological testing. METHODS: Volume of white matter hyperintensities (WMH) was used as a surrogate measure of CSVD severity. Tensor-based morphometry and cortical modeling estimated brain volumes and cortical thickness, respectively. Rasch measurement theory was applied to neuropsychological test scores to estimate overall cognition. Linear models compared WMH loads, brain volumes, and cognition between groups; evaluated the association of WMH loads with brain volumes and cognition; and tested the interaction between HIV and WMH loads on brain volumes and cognition. Mixed-effects models compared the change in WMH loads between groups. RESULTS: WMH loads and change in WMH loads were similar between the groups. HIV-positive participants had poorer cognition, thinner cortex and reduced subcortical volumes compared with HIV-negative controls. Higher WMH loads were associated with reduced cortical thickness and subcortical volumes and worse cognition, regardless of HIV serostatus. No significant interactions were observed between HIV and WMH loads with regards to brain volumes or cognition. CONCLUSION: These findings suggest that the contributions of HIV and CSVD on brain atrophy and cognitive impairment are independent but additive processes. This argues that optimizing vascular health may mitigate brain injury and cognitive decline, especially in treated, virologically suppressed HIV-positive individuals.

Synthesis and Biological Assessment of Racemic Benzochromenopyrimidinimines as Antioxidant, Cholinesterase, and Aß1-42 Aggregation Inhibitors for Alzheimer's Disease Therapy.

Given the complex nature of Alzheimer's disease (AD), compounds that are able to simultaneously address two or more AD-associated targets show greater promise for development into drugs for AD therapy. Herein we report an efficient two-step synthesis and biological evaluation of new racemic benzochromene derivatives as antioxidants, inhibitors of cholinesterase and ß-amyloid (Aß1-42 ) aggregation. Based on the results of the primary screening, we identified 15-(3-methoxyphenyl)-9,11,12,15-tetrahydro-10H,14H-benzo[5,6]chromeno[2,3-d]pyrido[1,2-a]pyrimidin-14-imine (3 e) and 16-(3-methoxyphenyl)-9,10,11,12,13,16-hexahydro-15H-benzo[5',6']chromeno[2',3':4,5]pyrimido[1,2-a]azepin-15-imine (3 f) as new potential multitarget-directed ligands for AD therapy. Further in-depth biological analysis showed that compound 3 f is a good human acetylcholinesterase inhibitor [IC50 =(0.36±0.02) µm], has strong antioxidant activity (3.61 µmol Trolox equivalents), and moderate Aß1-42 antiaggregating power (40.3 %).

Hemodynamic impact of anastomosis size and angle in side-to-end arteriovenous fistulae: a computer analysis.

PURPOSE: An arteriovenous fistula (AVF) is the first choice vascular access for hemodialysis. The AVF pathway can be seen as consisting of seven segments: proximal artery, distal artery, arterial collaterals, proximal vein, distal vein, venous collaterals, and the anastomosis. While most studies describe access complications without considering the impact of the anastomosis (7th segment), the present mathematical study investigated the hemodynamic impact of anastomosis size and angle on pressure drop and flow distribution. METHODS: A side-to-end AVF model was developed, consisting of an anastomosis with a given cross-sectional area (substudy 1) and angle (substudy 2). Starting from two reference cases (one for each substudy) with fixed flow distribution, pressure drop over the anastomosis was calculated for an arterial inflow in the range 600 to 1200 mL/min. The same reference cases, subsequently with fixed pressure boundary conditions, were further used to assess flow distribution over the proximal vein and distal artery. RESULTS: Pressure drop decreased with a larger anastomosis cross-sectional area and an angle wider than 43 degrees , while it was almost stable for smaller angles. Although proximal arterial inflow increased for larger anastomosis areas, the overall flow distribution shifted almost totally to the proximal vein. When the anastomosis angle exceeded 58 degrees , the proximal arterial inflow was not sufficient to deliver enough flow, leading to distal arterial flow reversal. CONCLUSION: Despite the underestimation of the hemodynamic impact of the anastomosis size and angle in the literature, this study showed major influences on the pressure drop over the anastomosis and, with it, on flow distribution towards the arterial and venous outflow.