White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed

Blood-brain barrier (BBB) leakage is considered an important underlying process in both cerebral small vessel disease (cSVD) and Alzheimer's disease (AD). The objective of this study was to examine associations between BBB leakage, cSVD, neurodegeneration, and cognitive performance across the spectrum from normal cognition to dementia. Leakage was measured with dynamic contrast-enhanced magnetic resonance imaging in 80 older participants (normal cognition, n = 32; mild cognitive impairment, n 34; clinical AD-type dementia, n = 14). Associations between leakage and white matter hyperintensity (WMH) volume, hippocampal volume, and cognition (information processing speed and memory performance) were examined with multivariable linear regression and mediation analyses. Leakage within the gray and white matter was positively associated with WMH volume (gray matter, p = 0.03; white matter, p = 0.01). A negative association was found between white matter BBB leakage and information processing speed performance, which was mediated by WMH volume. Leakage was not associated with hippocampal volume. WMH pathology is suggested to form a link between leakage and decline of information processing speed in older individuals with and without cognitive impairment. (C) 2019 Elsevier Inc. All rights reserved

Consensus guidelines for lumbar puncture in patients with neurological diseases

Introduction Cerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize the risk of complications, such as post-LP headache or back pain. Methods We provide consensus guidelines for the LP procedure to minimize the risk of complications. The recommendations are based on (1) data from a large multicenter LP feasibility study (evidence level II-2), (2) systematic literature review on LP needle characteristics and post-LP complications (evidence level II-2), (3) discussion of best practice within the Joint Programme Neurodegenerative Disease Research Biomarkers for Alzheimer's disease and Parkinson's Disease and Biomarkers for Multiple Sclerosis consortia (evidence level III). Results Our consensus guidelines address contraindications, as well as patient-related and procedure-related risk factors that can influence the development of post-LP complications. Discussion When an LP is performed correctly, the procedure is well tolerated and accepted with a low complication rate

Phase Behavior of Aqueous Na-K-Mg-Ca-CI-NO3 Mixtures: Isopiestic Measurements and Thermodynamic Modeling

A comprehensive model has been established for calculating thermodynamic properties of multicomponent aqueous systems containing the Na{sup +}, K{sup +}, Mg{sup 2+}, Ca{sup 2+}, Cl{sup -}, and NO{sub 3}{sup -} ions. The thermodynamic framework is based on a previously developed model for mixed-solvent electrolyte solutions. The framework has been designed to reproduce the properties of salt solutions at temperatures ranging from the freezing point to 300 C and concentrations ranging from infinite dilution to the fused salt limit. The model has been parameterized using a combination of an extensive literature database and new isopiestic measurements for thirteen salt mixtures at 140 C. The measurements have been performed using Oak Ridge National Laboratory's (ORNL) previously designed gravimetric isopiestic apparatus, which makes it possible to detect solid phase precipitation. Water activities are reported for mixtures with a fixed ratio of salts as a function of the total apparent salt mole fraction. The isopiestic measurements reported here simultaneously reflect two fundamental properties of the system, i.e., the activity of water as a function of solution concentration and the occurrence of solid-liquid transitions. The thermodynamic model accurately reproduces the new isopiestic data as well as literature data for binary, ternary and higher-order subsystems. Because of its high accuracy in calculating vapor-liquid and solid-liquid equilibria, the model is suitable for studying deliquescence behavior of multicomponent salt systems

Effects of right-hemisphere cortical infarction and muscarinic acetylcholine receptor blockade on spatial visual attention performance in rats

The syndrome of hemispatial neglect is defined as an inability to report, respond or orient to stimuli contralateral to a cerebral lesion despite intact elementary sensory or motor function. This syndrome is typically observed after lesions of the right cerebral cortex, and has been associated with impairment of attention. We studied whether visual attention performance is impaired after right-hemisphere infarction in rats. Using a behavioural paradigm measuring spatial visual attention, we tested the effects of photothrombotic infarction to either the frontal cortex or the parietal cortex on attention performance. Since the cholinergic system is known to modulate attention performance, we additionally evaluated the role of cholinergic receptor blockade with scopolamine in our task paradigm. Our results show a transient response bias immediately after cortical infarction, with a decrease in contralesional responses and an increase in contralesional omissions after frontal infarction. Parietal infarction and systemic administration of scopolamine also resulted in a decrease in correct responses and an increase in omissions, but without a difference in side responding. In conclusion, right frontal infarction induces a transient impairment in contralesional spatial visual attention that we explain as left-sided neglect. Right parietal infarction and cholinergic blockade shows non-lateralized deficits in spatial visual attention, suggestive of global attentional impairment. We postulate that both effects of cortical infarction on attention performance may be related to cholinergic dysfunction. Our study confirms the role of frontal and parietal cortices in attention performance in rats, and corroborates the theory that attention performance is impaired in hemispatial neglect in human stroke patients

Dissociable effects in reaction time performance after unilateral cerebral infarction: a comparison between the left and right frontal cortices in rats

Reaction time performance reflects the speed of information processing, both in humans and lower vertebrates like the rat. The present study compared reaction time performance in rats following unilateral infarction to the frontal cortex. The objective was to model cognitive impairment as it is seen in humans after stroke. Rats were trained in a reaction time paradigm, after which unilateral cortical infarction was induced photochemically. Reaction time performance was differentially affected after unilateral infarction to either the left or right frontal cortex, whereas sham operation did not result in a significant alteration in reactivity. An overall increase in reaction time of about 10% was present at 4 weeks after frontal infarction. In addition, a lateralized reaction time deficit occurred very early after right frontal infarction as an increase of 10-15% in trials directed towards the contralesional side. Additional analyses showed that these reaction time deficits can be explained differently: the former as a gradual and general decrease in the speed of information processing, whereas the latter shows specific impairment to initiate a contralateral motor response. The former matches well with the mental slowing observed in stroke patients, whereas the latter resembles a neglect phenomenon. We conclude that measuring reaction time performance after frontal cortical infarction in rats could offer a useful tool to model particular human cognitive impairments following cerebral infarction

Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer's Disease

Background: Though mediotemporal lobe volume changes are well-known features of Alzheimer's disease (AD), grey matter volume changes may be distributed throughout the brain. These distributed changes are not independent due to the underlying network structure and can be described in terms of a structural covariance network (SCN).Objective: To investigate how the cortical brain organization is altered in AD we studied the mutual connectivity of hubs in the SCN, i.e., the rich-club.Methods: To construct the SCNs, cortical thickness was obtained from structural MRI for 97 participants (normal cognition, n = 37; mild cognitive impairment, n = 41; Alzheimer-type dementia, n = 19). Subsequently, rich-club coefficients were calculated from the SCN, and related to memory performance and hippocampal volume using linear regression.Results: Lower rich-club connectivity was related to lower memory performance as well as lower hippocampal volume.Conclusion: Therefore, this study provides novel evidence of reduced connectivity in hub areas in relation to AD-related cognitive impairments and atrophy.Radiolog

Rich-Club Connectivity of the Structural Covariance Network Relates to Memory Processes in Mild Cognitive Impairment and Alzheimer's Disease

Background: Though mediotemporal lobe volume changes are well-known features of Alzheimer's disease (AD), grey matter volume changes may be distributed throughout the brain. These distributed changes are not independent due to the underlying network structure and can be described in terms of a structural covariance network (SCN).Objective: To investigate how the cortical brain organization is altered in AD we studied the mutual connectivity of hubs in the SCN, i.e., the rich-club.Methods: To construct the SCNs, cortical thickness was obtained from structural MRI for 97 participants (normal cognition, n = 37; mild cognitive impairment, n = 41; Alzheimer-type dementia, n = 19). Subsequently, rich-club coefficients were calculated from the SCN, and related to memory performance and hippocampal volume using linear regression.Results: Lower rich-club connectivity was related to lower memory performance as well as lower hippocampal volume.Conclusion: Therefore, this study provides novel evidence of reduced connectivity in hub areas in relation to AD-related cognitive impairments and atrophy

Associations of increased interstitial fluid with vascular and neurodegenerative abnormalities in a memory clinic sample

The vascular and neurodegenerative processes related to clinical dementia cause cell loss which induces, amongst others, an increase in interstitial fluid (ISF).We assessed microvascular, parenchymal integrity, and a proxy of ISF volume alterations with intravoxel incoherent motion imaging in 21 healthy controls and 53 memory clinic patients - mainly affected by neurodegeneration (mild cognitive impairment, Alzheimer's disease dementia), vascular pathology (vascular cognitive impairment), and presumed to be without significant pathology (subjective cognitive decline).The microstructural components were quantified with spectral analysis using a non-negative least squares method. Linear regression was employed to investigate associations of these components with hippocampal and white matter hyperintensity (WMH) volumes. In the normal appearing white matter, a large f(int )(a proxy of ISF volume) was associated with a large WMH volume and low hippocampal volume. Likewise, a large f(int) value was associated with a lower hippocampal volume in the hippocampi.Large ISF volume (f(int)) was shown to be a prominent factor associated with both WMHs and neurodegenerative abnormalities in memory clinic patients and is argued to play a potential role in impaired glymphatic functioning. (C) 2021 The Author(s). Published by Elsevier Inc.Neuro Imaging Researc