803 research outputs found

    White matter lesions characterise brain involvement in moderate to severe chronic obstructive pulmonary disease, but cerebral atrophy does not.

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    BACKGROUND: Brain pathology is relatively unexplored in chronic obstructive pulmonary disease (COPD). This study is a comprehensive investigation of grey matter (GM) and white matter (WM) changes and how these relate to disease severity and cognitive function. METHODS: T1-weighted and fluid-attenuated inversion recovery images were acquired for 31 stable COPD patients (FEV1 52.1% pred., PaO2 10.1 kPa) and 24 age, gender-matched controls. T1-weighted images were segmented into GM, WM and cerebrospinal fluid (CSF) tissue classes using a semi-automated procedure optimised for use with this cohort. This procedure allows, cohort-specific anatomical features to be captured, white matter lesions (WMLs) to be identified and includes a tissue repair step to correct for misclassification caused by WMLs. Tissue volumes and cortical thickness were calculated from the resulting segmentations. Additionally, a fully-automated pipeline was used to calculate localised cortical surface and gyrification. WM and GM tissue volumes, the tissue volume ratio (indicator of atrophy), average cortical thickness, and the number, size, and volume of white matter lesions (WMLs) were analysed across the whole-brain and regionally - for each anatomical lobe and the deep-GM. The hippocampus was investigated as a region-of-interest. Localised (voxel-wise and vertex-wise) variations in cortical gyrification, GM density and cortical thickness, were also investigated. Statistical models controlling for age and gender were used to test for between-group differences and within-group correlations. Robust statistical approaches ensured the family-wise error rate was controlled in regional and local analyses. RESULTS: There were no significant differences in global, regional, or local measures of GM between patients and controls, however, patients had an increased volume (p = 0.02) and size (p = 0.04) of WMLs. In patients, greater normalised hippocampal volume positively correlated with exacerbation frequency (p = 0.04), and greater WML volume was associated with worse episodic memory (p = 0.05). A negative relationship between WML and FEV1 % pred. approached significance (p = 0.06). CONCLUSIONS: There was no evidence of cerebral atrophy within this cohort of stable COPD patients, with moderate airflow obstruction. However, there were indications of WM damage consistent with an ischaemic pathology. It cannot be concluded whether this represents a specific COPD, or smoking-related, effect

    The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

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    Objectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). Method: MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. Results: We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Conclusions: Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. Key Points: • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI

    Neuroimaging at 7 Tesla: a pictorial narrative review

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    Neuroimaging using the 7-Tesla (7T) human magnetic resonance (MR) system is rapidly gaining popularity after being approved for clinical use in the European Union and the USA. This trend is the same for functional MR imaging (MRI). The primary advantages of 7T over lower magnetic fields are its higher signal-to-noise and contrast-to-noise ratios, which provide high-resolution acquisitions and better contrast, making it easier to detect lesions and structural changes in brain disorders. Another advantage is the capability to measure a greater number of neurochemicals by virtue of the increased spectral resolution. Many structural and functional studies using 7T have been conducted to visualize details in the white matter and layers of the cortex and hippocampus, the subnucleus or regions of the putamen, the globus pallidus, thalamus and substantia nigra, and in small structures, such as the subthalamic nucleus, habenula, perforating arteries, and the perivascular space, that are difficult to observe at lower magnetic field strengths. The target disorders for 7T neuroimaging range from tumoral diseases to vascular, neurodegenerative, and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, major depressive disorder, and schizophrenia. MR spectroscopy has also been used for research because of its increased chemical shift that separates overlapping peaks and resolves neurochemicals more effectively at 7T than a lower magnetic field. This paper presents a narrative review of these topics and an illustrative presentation of images obtained at 7T. We expect 7T neuroimaging to provide a new imaging biomarker of various brain disorders

    Radiological assessment of dementia: the Italian inter-society consensus for a practical and clinically oriented guide to image acquisition, evaluation, and reporting

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    Background: Radiological evaluation of dementia is expected to increase more and more in routine practice due to both the primary role of neuroimaging in the diagnostic pathway and the increasing incidence of the disease. Despite this, radiologists often do not follow a disease-oriented approach to image interpretation, for several reasons, leading to reports of limited value to clinicians. In our work, through an intersocietal consensus on the main mandatory knowledge about dementia, we proposed a disease-oriented protocol to optimize and standardize the acquisition/evaluation/interpretation and reporting of radiological images. Our main purpose is to provide a practical guideline for the radiologist to help increase the effectiveness of interdisciplinary dialogue and diagnostic accuracy in daily practice. Results: We defined key clinical and imaging features of the dementias (A), recommended MRI protocol (B), proposed a disease-oriented imaging evaluation and interpretation (C) and report (D) with a glimpse to future avenues (E). The proposed radiological practice is to systematically evaluate and score atrophy, white matter changes, microbleeds, small vessel disease, consider the use of quantitative measures using commercial software tools critically, and adopt a structured disease-oriented report. In the expanding field of cognitive disorders, the only effective assessment approach is the standardized disease-oriented one, which includes a multidisciplinary integration of the clinical picture, MRI, CSF and blood biomarkers and nuclear medicine

    Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials

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    INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers. DISCUSSION: Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial desig

    The ins and outs of the BCCAo model for chronic hypoperfusion: a multimodal and longitudinal MRI approach

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    Cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAo) in rodents has been proposed as an experimental model of white matter damage and vascular dementia. However, the histopathological and behavioral alterations reported in this model are variable and a full characterization of the dynamic alterations is not available. Here we implemented a longitudinal multimodal magnetic resonance imaging (MRI) design, including time- of-flight angiography, high resolution T1-weighted images, T2 relaxometry mapping, diffusion tensor imaging, and cerebral blood flow measurements up to 12 weeks after BCCAo or sham-operation in Wistar rats. Changes in MRI were related to behavioral performance in executive function tasks and histopathological alterations in the same animals. MRI frequently (70%) showed various degrees of acute ischemic lesions, ranging from very small to large subcortical infarctions. Independently, delayed MRI changes were also apparent. The patterns of MRI alterations were related to either ischemic necrosis or gliosis. Progressive microstructural changes revealed by diffusion tensor imaging in white matter were confirmed by observation of myelinated fiber degeneration, including severe optic tract degeneration. The latter interfered with the visually cued learning paradigms used to test executive functions. Independently of brain damage, BCCAo induced progressive arteriogenesis in the vertebrobasilar tree, a process that was associated with blood flow recovery after 12 weeks. The structural alterations found in the basilar artery were compatible with compensatory adaptive changes driven by shear stress. In summary, BCCAo in rats induces specific signatures in multimodal MRI that are compatible with various types of histological lesion and with marked adaptive arteriogenesis

    Effectiveness of cognitive and physical training in slowing progression to dementia: a clinical and experimental study. Focus on relationship with cardiovascular fitness

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    Physical activity is beneficial to vascular health; on the other hand, vascular damage is associated with cognitive impairment. Both physical activity and a cognitively stimulating environment are known to delay the onset of dementia. The Train The Brain study evaluated the effectiveness of a comprehensive program of physical training and mental activity in delaying cognitive decline in elderly people with initial cognitive impairment, at the same time investigating the relationship between physical, vascular, neurological, and cognitive fitness. Elders age 65-89 with were recruited with the help of family physicians and territorial services. All participants underwent a neurological and cardiologic evaluation. Carotid-femoral pulse wave velocity and carotid pressure were measured with the SphygmoCor system (AtCor, Australia). Longitudinal ultrasound scans of the common carotid were performed and 10-second video clips were recorded to be analysed offline through the Cardiovascular Suite software (Quipu srl, Italy), with the computation of diameter, intima-media thickness, wall cross-sectional area, distensibility coefficient, and elastic modulus. The latter software was used also to measure endothelial function through flow mediated dilation (FMD) of the brachial artery. Subjects classified as mild cognitive impairment at the neurological examination were randomized either to standard care, or a 7-month program of physical training and environmental stimulation (lectures, games, music, social activities) three hours a week. The evaluation was then repeated. Data were obtained for 54 patients who underwent training and 36 controls. The intervention was successful in improving cognitive function as measured through the ADAS-Cog score: 11.95 (3.86) to 13.00 (4.73) for no training, 14.32 (4.27) to 12.85 (4.03) for training, time x treatment p<0.001. Pulse wave velocity showed no significant effect (p=0.5). FMD improved with intervention (no training: 3.20 (2.03) to 2.50 (1.77) %; training: from 2.82 (2.19) to 3.42 (1.82); p=0.014). All selected carotid parameters were influenced by the combination of time and treatment, in a diverging trend, at a statistically significant level, with intervention determining less dilated, less thick and less stiff vessels. None of the parameters measured analysing the vessels showed a correlation The proposed 7-months program improved cognitive function in elders with initial cognitive impairment. There was a significant difference in behaviour in time of the two groups as for endothelial function and carotid enlargement, wall thickening and arterial stiffening. The intervention seems to oppose the typical harmful effects of aging on vessels; at the same time, the positive effects on cognition and vascular health do not appear as directly correlated

    Effectiveness of cognitive and physical training in slowing progression to dementia: a clinical and experimental study. Focus on relationship with cardiovascular fitness

    Get PDF
    Physical activity is beneficial to vascular health; on the other hand, vascular damage is associated with cognitive impairment. Both physical activity and a cognitively stimulating environment are known to delay the onset of dementia. The Train The Brain study evaluated the effectiveness of a comprehensive program of physical training and mental activity in delaying cognitive decline in elderly people with initial cognitive impairment, at the same time investigating the relationship between physical, vascular, neurological, and cognitive fitness. Elders age 65-89 with were recruited with the help of family physicians and territorial services. All participants underwent a neurological and cardiologic evaluation. Carotid-femoral pulse wave velocity and carotid pressure were measured with the SphygmoCor system (AtCor, Australia). Longitudinal ultrasound scans of the common carotid were performed and 10-second video clips were recorded to be analysed offline through the Cardiovascular Suite software (Quipu srl, Italy), with the computation of diameter, intima-media thickness, wall cross-sectional area, distensibility coefficient, and elastic modulus. The latter software was used also to measure endothelial function through flow mediated dilation (FMD) of the brachial artery. Subjects classified as mild cognitive impairment at the neurological examination were randomized either to standard care, or a 7-month program of physical training and environmental stimulation (lectures, games, music, social activities) three hours a week. The evaluation was then repeated. Data were obtained for 54 patients who underwent training and 36 controls. The intervention was successful in improving cognitive function as measured through the ADAS-Cog score: 11.95 (3.86) to 13.00 (4.73) for no training, 14.32 (4.27) to 12.85 (4.03) for training, time x treatment p<0.001. Pulse wave velocity showed no significant effect (p=0.5). FMD improved with intervention (no training: 3.20 (2.03) to 2.50 (1.77) %; training: from 2.82 (2.19) to 3.42 (1.82); p=0.014). All selected carotid parameters were influenced by the combination of time and treatment, in a diverging trend, at a statistically significant level, with intervention determining less dilated, less thick and less stiff vessels. None of the parameters measured analysing the vessels showed a correlation The proposed 7-months program improved cognitive function in elders with initial cognitive impairment. There was a significant difference in behaviour in time of the two groups as for endothelial function and carotid enlargement, wall thickening and arterial stiffening. The intervention seems to oppose the typical harmful effects of aging on vessels; at the same time, the positive effects on cognition and vascular health do not appear as directly correlated

    What can imaging tell us about cognitive impairment and dementia?

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