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.

Increase in blood-brain barrier leakage in healthy, older adults.

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.

Associations between pattern separation and hippocampal subfield structure and function vary along the lifespan: A 7 T imaging study.

Pattern separation (PS) describes the process by which the brain discriminates similar stimuli from previously encoded stimuli. This fundamental process requires the intact processing by specific subfields in the hippocampus and can be examined using mnemonic discrimination tasks. Previous studies reported different patterns for younger and older individuals between mnemonic discrimination performance and hippocampal subfield activation.

Contributions of Cerebro-Cerebellar Default Mode Connectivity Patterns to Memory Performance in Mild Cognitive Impairment.

Background: The cerebral default mode network (DMN) can be mapped onto specific regions in the cerebellum, which are specifically vulnerable to atrophy in Alzheimer's disease (AD) patients.

Objective: We set out to determine whether there are specific differences in the interaction between the cerebral and cerebellar DMN in amnestic mild cognitive impairment (aMCI) patients compared to healthy controls using resting-state functional MRI and whether these differences are relevant for memory performance.

Methods: Eighteen patients with aMCI were age and education-matched to eighteen older adults and underwent 3T MR-imaging.

Microvascular Phenotyping in the Maastricht Study: Design and Main Findings, 2010-2018.

Microvascular dysfunction (MVD) is a common pathophysiological change that occurs in various diseases, such as type 2 diabetes mellitus (T2DM), heart failure, dementia, and depression. Recent technical advances have enabled noninvasive measurement and quantification of microvascular changes in humans. In this paper, we describe the protocols of the microvascular measurements applied in the Maastricht Study, an ongoing prospective, population-based cohort study of persons aged 40-75 years being carried out in the southern part of the Netherlands (baseline data assessment, November 2010-January 2020).

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).

Shades of white: diffusion properties of T1- and FLAIR-defined white matter signal abnormalities differ in stages from cognitively normal to dementia.

The underlying pathology of white matter signal abnormalities (WMSAs) is heterogeneous and may vary dependent on the magnetic resonance imaging contrast used to define them. We investigated differences in white matter diffusivity as an indicator for white matter integrity underlying WMSA based on T1-weighted and fluid-attenuated inversion recovery (FLAIR) imaging contrast. In addition, we investigated which white matter region of interest (ROI) could predict clinical diagnosis best using diffusion metrics.

Evidence that reduced gray matter volume in psychotic disorder is associated with exposure to environmental risk factors.

The aim of this study was to examine whether cannabis use, childhood trauma and urban upbringing are associated with total gray matter volume (GMV) in individuals with (risk for) psychotic disorder and whether this is sex-specific. T1-weighted MRI scans were acquired from 89 patients with a psychotic disorder, 95 healthy siblings of patients with psychotic disorder and 87 controls. Multilevel random regression analyses were used to examine main effects and interactions between group, sex and environmental factors in models of GMV.

The details of structural disconnectivity in psychotic disorder: A family-based study of non-FA diffusion weighted imaging measures.

Background: Diffusion tensor imaging (DTI) studies in psychotic disorder have shown reduced FA, often interpreted as disturbed white matter integrity. The observed 'dysintegrity' may be of multifactorial origin, as changes in FA are thought to reflect a combination of changes in myelination, fiber organization and number of axons. Examining the structural substrate of the diffusion tensor in individuals with (risk for) psychotic disorder may provide better understanding of the underlying structural changes.

The Relationship between Cerebral Small Vessel Disease, Hippocampal Volume and Cognitive Functioning in Patients with COPD: An MRI Study.

The neural correlates of cognitive impairment in chronic obstructive pulmonary disease (COPD) are not yet understood. Structural brain abnormalities could possibly be associated with the presence of cognitive impairment through cigarette smoke, inflammation, vascular disease, or hypoxemia in these patients. This study aimed to investigate whether macrostructural brain magnetic resonance imaging (MRI) features of cerebral small vessel disease (SVD) and hippocampal volume (HCV) are related to cognitive performance in patients with COPD.

Serum S100B: A proxy marker for grey and white matter status in the absence and presence of (increased risk of) psychotic disorder?

S100B is a protein with dose-dependent neurotrophic and neurotoxic effects. Whether S100B in psychotic disorder mirrors pathophysiological mechanisms (which elicit exacerbation of disease) or compensatory action is unclear, as is its validity as a proxy marker for brain status. Insight may be gained by examining associations between serum S100B and indices of grey (cortical thickness (CT)) and white matter (fractional anisotropy (FA)), in relation to the absence or presence of (increased risk of) psychotic disorder.

No Evidence of Association between Childhood Urban Environment and Cortical Thinning in Psychotic Disorder.

Background: The alterations in cortical morphology, such as cortical thinning, observed in psychotic disorder, may be the outcome of interacting genetic and environmental effects. It has been suggested that urban upbringing may represent a proxy environmental effect impacting cortical thickness (CT). Therefore, the current study examined whether the association between group as a proxy genetic variable (patients with psychotic disorder [high genetic risk], healthy siblings of patients [intermediate risk] and healthy control subjects [average risk]) and CT was conditional on different levels of the childhood urban environment and whether this was sex-dependent.

Reduced specialized processing in psychotic disorder: a graph theoretical analysis of cerebral functional connectivity.

Background: Previous research has shown that the human brain can be represented as a complex functional network that is characterized by specific topological properties, such as clustering coefficient, characteristic path length, and global/local efficiency. Patients with psychotic disorder may have alterations in these properties with respect to controls, indicating altered efficiency of network organization. This study examined graph theoretical changes in relation to differential genetic risk for the disorder and aimed to identify clinical correlates.

White Matter Hyperintensities Potentiate Hippocampal Volume Reduction in Non-Demented Older Individuals with Abnormal Amyloid-β.

Cerebral small vessel disease (cSVD) and amyloid-β (Aβ) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Aβ have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37).

Physical Activity Is Associated With Glucose Tolerance Independent of Microvascular Function: The Maastricht Study.

Context And Objective: Moderate-to-vigorous physical activity (MVPA) and physical fitness (PF) are positively associated with glucose tolerance. Such associations may be partly conditioned by microvascular function, which is a common correlate to MVPA, PF, and glucose tolerance. To test this hypothesis, the present study sought to investigate independent associations of MVPA and PF with glucose tolerance and to what extent these associations are mediated by microvascular function.

Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study.

Background: Although widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of level of psychosis liability.

Methods: Two DTI scans with a 3-year time interval were acquired from 159 participants (55 patients with a psychotic disorder, 55 nonpsychotic siblings and 49 healthy controls) and processed with tract-based spatial statistics.

Capillary Rarefaction Associates with Albuminuria: The Maastricht Study.

Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction.

Semi-metric analysis of the functional brain network: Relationship with familial risk for psychotic disorder.

Background: Dysconnectivity in schizophrenia can be understood in terms of dysfunctional integration of a distributed network of brain regions. Here we propose a new methodology to analyze complex networks based on semi-metric behavior, whereby higher levels of semi-metricity may represent a higher level of redundancy and dispersed communication. It was hypothesized that individuals with (increased risk for) psychotic disorder would have more semi-metric paths compared to controls and that this would be associated with symptoms.

Cognitive correlates of frontoparietal network connectivity 'at rest' in individuals with differential risk for psychotic disorder.

Altered frontoparietal network functional connectivity (FPN-fc) has been associated with neurocognitive dysfunction in individuals with (risk for) psychotic disorder. Cannabis use is associated with cognitive and FPN-fc alterations in healthy individuals, but it is not known whether cannabis exposure moderates the FPN-fc-cognition association. We studied FPN-fc in relation to psychosis risk, as well as the moderating effects of psychosis risk and cannabis use on the association between FPN-fc and (social) cognition.

Can FreeSurfer Compete with Manual Volumetric Measurements in Alzheimer's Disease?

Alzheimer's disease-related pathology results in tremendous structural and functional changes in the brain. These morphological changes might lead to a less precise performance of automated brain segmentation techniques in AD-patients, which in turn could possibly lead to false allocations of gray matter, white matter or cerebrospinal fluid. FreeSurfer has been shown to operate as an accurate and reliable instrument to measure cortical thickness and volume of neuroanatomical structures.

Altered mesocorticolimbic functional connectivity in psychotic disorder: an analysis of proxy genetic and environmental effects.

Background: Altered dopaminergic neurotransmission in the mesocorticolimbic (MCL) system may mediate psychotic symptoms. In addition, pharmacological dopaminergic manipulation may coincide with altered functional connectivity (fc) 'in rest'. We set out to test whether MCL-fc is conditional on (familial risk for) psychotic disorder and/or interactions with environmental exposures.

Default mode network connectivity as a function of familial and environmental risk for psychotic disorder.

Background: Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.

Methods: Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls.

Relevance of parahippocampal-locus coeruleus connectivity to memory in early dementia.

Neuropathology suggests an important role for the locus coeruleus (LC) in Alzheimer's disease (AD) pathophysiology. Neuropathology and structural damage in the LC appears to be one of the earliest changes. We hypothesize that reduced functional integration of the LC reflected by lower brain functional connectivity contributes to early memory dysfunction.

Subjective cognitive failures in patients with hypertension are related to cognitive performance and cerebral microbleeds.

Previous studies on the relationship between subjective cognitive failures (SCF) and objective cognitive function have shown inconsistent results. In addition, research on the association between SCF and imaging markers of cerebral small vessel disease is limited. We investigated whether SCF in patients with essential hypertension, who are at high risk of cerebral small vessel disease, are associated with objective cognitive function and magnetic resonance imaging manifestations of cerebral small vessel disease.