Aortic Wall Thickness as a Surrogate for Subclinical Atherosclerosis in Familial and Nonfamilial Hypercholesterolemia: Quantitative 3D Magnetic Resonance Imaging Study and Interrelations with Computed Tomography Calcium Scores, and Carotid Ultrasonography.

We aimed to compare the extent of subclinical atherosclerosis in the ascending and descending aortas by measuring wall area and thickness using 3D cardiovascular magnetic resonance imaging (aAWAI and dAWAI) in patients with asymptomatic familial hypercholesterolemia (FH) and nonfamilial hypercholesterolemia (NFH). We also aimed to establish the interrelations of CMR parameters with other subclinical atherosclerosis measurements, such as calcium scores, obtained using computed tomography in coronary arteries (CCS) and ascending and descending aorta (TCSasc and TCSdsc), as well as the carotid intima-media thicknesses (cIMT) using ultrasonography. A total of 60 patients with FH (29 men and 31 women), with a mean age of 52.3 ± 9.6 years, were analyzed. A subclinical atherosclerosis assessment was also performed on a group consisting of 30 age- and gender-matched patients with NFH, with a mean age of 52.5 ± 7.9 years. We found the ascending and descending aortic wall areas and thicknesses in the FH group to be significantly increased than those of the NFH group. A multivariate logistic regression analysis showed that a positive FH mutation value was a strong predictor of high aAWAI and dAWAI independent of the LDL cholesterol level. Correlations across CMR atherosclerotic parameters, calcium scores, and cIMT in the FH and NFH groups, were significant but low. Most of the atherosclerosis tests with high results belonged to the FH group. We found that patients with documented heterozygous FH had a higher atherosclerosis burden in the aorta compared to patients with severe hypercholesterolemia without FH gene mutation. Atherosclerosis is not severe in asymptomatic patients with FH, but is more pronounced and also more diffuse than in patients with NFH. The etiology of hypercholesterolemia, and not just cholesterol levels, plays a significant role in determining the degree of subclinical atherosclerosis.

Functional Magnetic Resonance Urography in Children-Tips and Pitfalls.

MR urography can be an alternative to other imaging methods of the urinary tract in children. However, this examination may present technical problems influencing further results. Special attention must be paid to the parameters of dynamic sequences to obtain valuable data for further functional analysis. The analysis of methodology for renal function assessment using 3T magnetic resonance in children. A retrospective analysis of MR urography studies was performed in a group of 91 patients. Particular attention was paid to the acquisition parameters of the 3D-Thrive dynamic with contrast medium administration as a basic urography sequence. The authors have evaluated images qualitatively and compared contrast-to-noise ratio (CNR), curves smoothness, and quality of baseline (evaluation signal noise ratio) in every dynamic in each patient in every protocol used in our institution. Quality analysis of the image (ICC = 0.877, p < 0.001) was improved so that we have a statistically significant difference in image quality between protocols (χ2(3) = 20.134, p < 0.001). The results obtained for SNR in the medulla and cortex show that there was a statistically significant difference in SNR in the cortex (χ2(3) = 9.060, p = 0.029). Therefore, the obtained results show that with the newer protocol, we obtain lower values of standard deviation for TTP in the aorta (in ChopfMRU: first protocol SD = 14.560 vs. fourth protocol SD = 5.599; in IntelliSpace Portal: first protocol SD = 15.241 vs. fourth protocol SD = 5.506). Magnetic resonance urography is a promising technique with a few challenges that arise and need to be overcome. New technical opportunities should be introduced for everyday practice to improve MRU results.

The association between white matter tract structural connectivity and information processing speed in relapsing-remitting multiple sclerosis.

BACKGROUND: Information processing speed (IPS) deterioration is common in relapsing-remitting multiple sclerosis (RRMS) patients [1] and might severely affect quality of life and occupational activity. However, understanding of its neural substrate is not fully elucidated. We aimed to investigate the associations between MRI-derived metrics of neuroanatomical structures, including the tracts, and IPS. METHODS: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Color Trails Test (CTT) were used to evaluate IPS in 73 RRMS consecutive patients, all undergoing only interferon beta (IFN-ß) therapy during the study. At the same time, 1.5T MRI including diffusion tensor imaging (DTI) data was acquired for each recruited subject. We analyzed volumetric and diffusion MRI measures (FreeSurfer 6.0) including normalized brain volume (NBV), cortical thickness (thk), white matter hypointensities (WMH), volume (vol), diffusion parameters: mean (MD), radial (RD), axial (AD) diffusivities, and fractional anisotropy (FA) of 18 major white-matter (WM) tracts. Multiple linear regression model with interaction resulted in distinguishing the neural substrate of IPS deficit in the IPS impaired subgroup of patients. RESULTS: The most significant tract abnormalities contributing to IPS deficit were right inferior longitudinal fasciculus (R ILF) FA, forceps major (FMAJ) FA, forceps minor (FMIN) FA, R uncinate fasciculus (UNC) AD, R corticospinal tract (CST) FA, and left superior longitudinal fasciculus FA (L SLFT). Among volumetric MRI metrics, IPS deficit was associated with L and R thalamic vol. and cortical thickness of insular regions. CONCLUSION: In this study, we showed that disconnection of the selected WM tracts, in addition to cortical and deep gray matter (GM) atrophy, might underlie IPS deficit in RRMS patients but more extensive studies are needed for precise associations.

Left Ventricular Function and Iron Loading Status in a Tertiary Center Hemochromatosis Cohort-A Cardiac Magnetic Resonance Study.

Background: Haemochromatosis (HCH), a common genetic disorder with variable penetrance, results in progressive but understudied iron overload. We prospectively evaluated organ iron loading and cardiac function in a tertiary center HCH cohort. Methods: 42 HCH patients (47 ± 14 years) and 36 controls underwent laboratory workup and cardiac magnetic resonance (CMR), including T1 and T2* mapping. Results: Myocardial T2* (myoT2*), myocardial T1 (myoT1) and liver T2* (livT2*) were lower in patients compared to controls (33 ± 4 ms vs. 36 ± 3 ms [p = 0.004], 964 ± 33 ms vs. 979 ± 25 ms [p = 0.028] and 21 ± 10 ms vs. 30 ± 5 ms [p < 0.001], respectively). MyoT2* did not reach the threshold of clinically significant iron overload (<20 ms), in any of the patients. In 22 (52.4%) patients, at least one of the tissue parameters was reduced. Reduced myocardial T2* and/or T1 were found in 10 (23.8%) patients, including 4 pts with normal livT2*. LivT2* was reduced in 18 (42.9%) patients. MyoT1 and livT2* inversely correlated with ferritin (rs = −0.351 [p = 0.028] and rs = −0.602 [p < 0.001], respectively). LivT2* by a dedicated sequence and livT2* by cardiac T2* mapping showed good agreement (ICC = 0.876 p < 0.001). Conclusions: In contemporary hemochromatosis, significant myocardial iron overload is rare. Low myocardial T2* and/or T1 values may warrant closer follow-up for accelerated myocardial iron overload even in patients without overt liver overload. Cardiac T2* mapping sequence allows for liver screening at the time of CMR.

Evaluation of Subcortical Structure Volumes in Patients with Non-Specific Digestive Diseases.

(1) Background: To evaluate volume of subcortical structures such as hippocampus, globus pallidus, putamen, thalamus, nucleus accumbens, amygdala, caudate in patients with non-specific digestive diseases (functional dyspepsia-FD, irritable bowel syndrome-IBS) and non-specific inflammatory bowel diseases-IBD (colitis ulcerosa and Crohn's disease) in comparison to healthy control group (CON). (2) Material: The analysis included data obtained from 57 patients (FD-18, IBS-20, IBD-19) and 19 persons in control group. Both groups underwent examination in a 3T scanner (Achieva TX Philips Healthcare). (3) Results: Significant differences between the IBD group and Control group in volume of left thalamus and IBD group vs Control group in volume of right thalamus. (4) Conclusions: The brain-gut axis hypothesis explains connection between biological behavior, emotions and cognitive functions in patients with gastrointestinal disease. We found that there is a difference between volume of thalamus in IBD patients in comparison to both IBS and control group and it occurred to be smaller. Excess inflammation can be linked with psychological disorders like depressive symptoms, sleep difficulties and/or fatigue. Therefore, there is a need for using treatment both for depressive symptoms and IBD to reduce the causes and effects of inflammation.

Skeletonized mean diffusivity and neuropsychological performance in relapsing-remitting multiple sclerosis.

BACKGROUND: Peak width of Skeletonized Mean Diffusivity (PSMD), as a novel marker of white matter (WM) microstructure damage, is associated with cognitive decline in several WM pathologies (i.e., small vessel disorders). We hypothesized that markers combining alterations in whole WM could be associated with cognitive dysfunction in relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: We used PSMD based on tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) magnetic resonance (MR) scans. We investigated RRMS patients (n = 73) undergoing interferon beta (IFN-ß) therapy. In this cross-sectional study, we investigated the association between neuropsychological data and clinical and MRI variables: PSMD, WM hypointensities, and normalized brain volume (NBV). RESULTS: In our cohort, 37 (50.7%) patients were recognized as cognitively impaired (CI) and 36 (49.3%) patients were cognitively normal (CN). In regression analysis, PSMD was a statistically significant contributor in the California Verbal Learning Test (CVLT) list A (p = 0.04) and semantic fluency (p = 0.036). PSMD (p < 0.001, r2  = 0.35), NBV (p = 0.002, r2  = 2.6) and WM hypointensities (p < 0.001, r2  = 0.40) were major contributors to upper extremity disability (9HPT) in the CN subgroup. A significant contributor in the majority of neuropsychological measures was education attainment. CONCLUSION: We investigated PSMD as a new parameter of WM microstructure damage that is a contributor in complex cognitive tasks, CVLT performance, and semantic fluency. PSMD was a statistically significant contributor to upper extremity disability (9HPT) together with WM hypointensities and NBV. Education attainment proved to be relevant in the majority of cognitive domains. Further studies are needed to estimate PSMD relevance as a marker of CI in MS.

Retinal nerve fiber and ganglion cell complex layer thicknesses mirror brain atrophy in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is associated with progressive brain atrophy, which in turn correlates with disability, depression, and cognitive impairment. Relapsing-remitting multiple sclerosis (RRMS) is a type of MS in which relapses of the disease are followed by remission periods. This is the most common type of the disease. There is a significant need for easy and low-cost methods to these cerebral changes. Changes in retinal layer thickness may reflect alterations in brain white and gray matter volumes. Therefore, this paper aims to determine whether retinal layer thickness, measured using optical coherence tomography (OCT), correlates with volumetric brain assessments obtained by magnetic resonance imaging (MRI). METHODS: This retrospective cohort study recruited 53 patients with relapsing-remitting MS who underwent MRI and OCT examinations for evaluation of brain compartment volumes and thickness of retinal layers, respectively. OCT parameters, including central retinal thickness; retinal nerve fiber layer thickness (RNFL, peripapillary thickness); ganglion cell complex thickness (GCC, macular thickness); and Expanded Disability Status Scale (EDSS) results were compared with MRI parameters (cerebral cortex; cerebral cortex and basal ganglia combined; brain hemispheres without the ventricular system; and white matter plaques). We also checked whether there is a correlation between the number of RRMS and OCT parameters. OBJECTIVE: Our primary objective was to identify whether these patients had retinal thickness changes, and our secondary objective was to check if those changes correlated with the MRI brain anatomical changes. RESULTS: RNFL and GCC thicknesses were strongly (p-value < 0.05) associated with (i) cerebral cortex volume, (ii) combination of brain cortex and basal ganglia volumes, and (iii) the hemispheres but without the ventricular system. White matter plaques (combined) showed only weak or no correlation with RNFL and GCC. There was no correlation between central retinal thickness and brain compartment volumes, and there were weak or no correlations between the summary EDSS scores and OCT results. CONCLUSIONS: Retinal layer thickness measured by OCT correlates with select volumetric brain assessments on MRI. During the course of RRMS, the anatomo-pathological structure of the retina might serve as a surrogate marker of brain atrophy and clinical progression within selected domains.

Respiratory Motion-Registered Isotropic Whole-Heart T2 Mapping in Patients With Acute Non-ischemic Myocardial Injury.

Background: T2 mapping is a magnetic resonance imaging technique that can be used to detect myocardial edema and inflammation. However, the focal nature of myocardial inflammation may render conventional 2D approaches suboptimal and make whole-heart isotropic 3D mapping desirable. While self-navigated 3D radial T2 mapping has been demonstrated to work well at a magnetic field strength of 3T, it results in too noisy maps at 1.5T. We therefore implemented a novel respiratory motion-resolved compressed-sensing reconstruction in order to improve the 3D T2 mapping precision and accuracy at 1.5T, and tested this in a heterogeneous patient cohort. Materials and Methods: Nine healthy volunteers and 25 consecutive patients with suspected acute non-ischemic myocardial injury (sarcoidosis, n = 19; systemic sclerosis, n = 2; acute graft rejection, n = 2, and myocarditis, n = 2) were included. The free-breathing T2 maps were acquired as three ECG-triggered T2-prepared 3D radial volumes. A respiratory motion-resolved reconstruction was followed by image registration of the respiratory states and pixel-wise T2 mapping. The resulting 3D maps were compared to routine 2D T2 maps. The T2 values of segments with and without late gadolinium enhancement (LGE) were compared in patients. Results: In the healthy volunteers, the myocardial T2 values obtained with the 2D and 3D techniques were similar (45.8 ± 1.8 vs. 46.8 ± 2.9 ms, respectively; P = 0.33). Conversely, in patients, T2 values did differ between 2D (46.7 ± 3.6 ms) and 3D techniques (50.1 ± 4.2 ms, P = 0.004). Moreover, with the 2D technique, T2 values of the LGE-positive segments were similar to those of the LGE-negative segments (T2LGE-= 46.2 ± 3.7 vs. T2LGE+ = 47.6 ± 4.1 ms; P = 0.49), whereas the 3D technique did show a significant difference (T2LGE- = 49.3 ± 6.7 vs. T2LGE+ = 52.6 ± 8.7 ms, P = 0.006). Conclusion: Respiratory motion-registered 3D radial imaging at 1.5T led to accurate isotropic 3D whole-heart T2 maps, both in the healthy volunteers and in a small patient cohort with suspected non-ischemic myocardial injury. Significantly higher T2 values were found in patients as compared to controls in 3D but not in 2D, suggestive of the technique's potential to increase the sensitivity of CMR at earlier stages of disease. Further study will be needed to demonstrate its accuracy.

Imaging of Morphological Background in Selected Functional and Inflammatory Gastrointestinal Diseases in fMRI.

The study focuses on evaluation of the Default Mode Network (DMN) activity in functional magnetic resonance imaging (fMRI) in resting state in patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS), Crohn's disease and colitis ulcerosa (IBD) in comparison to healthy volunteers. We assume that etiology of both functional and non-specific inflammatory bowel diseases is correlated with disrupted structure of axonal connections. We would like to identify the network of neuronal connections responsible for presentation of symptoms in these diseases. 56 patients (functional dyspepsia, 18; Crohn's disease and colitis ulcerosa, 18; irritable bowel syndrome, 20) and 18 healthy volunteers underwent examination in MRI of the brain with assessment of brain morphology and central nervous system activity in functional imaging in resting state performed in 3T scanner. Compared to healthy controls' DMN in patients with non-specific digestive tract diseases comprised additional areas in superior frontal gyrus of left hemisphere, in left cingulum and in the left supplementary motor area. Discovered differences in the DMNs can be interpreted as altered processing of homeostatic stimuli. Our study group involved patients suffering from both functional and non-specific inflammatory bowel diseases. Nevertheless a spectrum of changes in the study group (superior frontal gyrus of the left hemisphere, in the left cingulum and in the left supplementary motor area) we were able to find common features, differentiating the whole study group from the healthy controls.

Nanodiamond phantoms mimicking human liver: perspective to calibration of T1 relaxation time in magnetic resonance imaging.

Phantoms of biological tissues are materials that mimic the properties of real tissues. This study shows the development of phantoms with nanodiamond particles for calibration of T1 relaxation time in magnetic resonance imaging. Magnetic resonance imaging (MRI) is a commonly used and non-invasive method of detecting pathological changes inside the human body. Nevertheless, before a new MRI device is approved for use, it is necessary to calibrate it properly and to check its technical parameters. In this article, we present phantoms of tissue with diamond nanoparticles dedicated to magnetic resonance calibration. The method of producing phantoms has been described. As a result of our research, we obtained phantoms that were characterized by the relaxation time T1 the same as the relaxation time of the human tissue T1 = 810.5 ms. Furthermore, the use of diamond nanoparticles in phantoms allowed us to tune the T1 value of the phantoms which open the way to elaborated phantoms of other tissues in the future.

Reliability of diffusion tensor tractography of facial nerve in cerebello-pontine angle tumours.

AIM OF THE STUDY: This study aimed to verify the accuracy of preoperative visualisation of the facial nerve (FN) by magnetic resonance-based (MR) diffusion tensor imaging-fibre tracking (DTI-FT) with neuronavigation system integration in patients with cerebello-pontine angle (CPA) tumours. CLINICAL RATIONALE FOR THE STUDY: Complete excision with preservation of the FN remains the critical goal of today's vestibular schwannoma (VS) surgery. DTI-FT of the FN with neuronavigation is yet to be fully evaluated, and could make surgery safer. MATERIALS AND METHODS: This was a prospective cohort study in which 38 consecutive patients with a CPA tumour (32 VSs, five meningiomas and one epidermoid cyst) were operated on via the retrosigmoid route from 2013 to 2019. The course of the FN was simulated before surgery using StealthViz and the images were transferred to the Medtronic S7 neuronavigation system. The FN location reconstructed by DTI-FT was verified during the surgery. RESULTS: MR acquisition was inappropriate in three patients (7.9%). DTI-FT correctly predicted the course of the FN in 31 of the 38 patients; the discordance rate was 18.4%. The accuracy of DTI-FT was 81.6% (95% CI: 65.67-92.26), sensitivity 88.57% (95% CI: 73.26-96.80) and positive predictive value was 91.18% (95% CI: 90.17-92.09). The reliability of the neuronavigation-integrated visualisation of the FN did not depend on the tumour size (p = 0.85), but the method was more accurate when the nerve was compact in shape (p = 0.03, area under curve (AUC) 0.87, 95% CI: 0.60-1.00) and in females (p = 0.04, AUC 0.78, 95% CI: 0.56-1.00). Following surgery, 86.5% of the patients presented with useful facial function (House-Brackmann grades I-III). Correct simulation of the FN did not prevent postoperative facial palsy (p = 0.35). CONCLUSIONS: The accuracy of DTI-FT of the FN integrated with neuronavigation remains unsatisfactory. This method does not provide any clinical benefit over non-integrated DTI-FT in terms of nerve function preservation. CLINICAL IMPLICATIONS: Due to the low reliability of the predictions, further technical advances in predicting the course of the FN are awaited by clinicians. However, DTI-FT images in the operating theatre would make tumour excision more comfortable for the surgeon.

Use of functional magnetic resonance imaging in patients with irritable bowel syndrome and functional dyspepsia.

Functional brain imaging (positron emission tomography - PET, functional magnetic resonance imaging - fMRI), allowing in vivo analysis of the brain-digestive tract interaction and the neurological mechanisms underlying visceral hypersensitivity, significantly advanced research and helped in the understanding of the interrelations in this field. Differences in this parameter can result from alterations in task-related cognitive states or from resting state processes. Nowadays, advanced imaging techniques such as fMRI are more frequently used and are acknowledged among both clinicians and radiologists in the diagnostic algorithm of digestive tract diseases. Functional dyspepsia is a condition in which neuroimaging allows for analysis of dysfunctions within the brain-gut axis (BGA) engaged in processing of visceral discomfort and pain. The results of studies in patient groups with irritable bowel syndrome prove that psychosocial factors significantly affect the mechanisms regulating visceral sensitivity within the brain. The BGA includes neuronal pathways (autonomic nervous system), neuroendocrine (hypothalamo-pituitary-adrenal axis), and neuroimmunological ones. Psychological processes affect the functioning of the digestive system and can cause dyspeptic symptoms. A patient's mental condition associated with stress can affect processes taking place in the central nervous system and trigger somatic reactions in the digestive tract through the autonomic visceral system.

Computed tomography indicators of cerebral microperfusion improve long term after carotid stenting in symptomatic patients.

OBJECTIVES: We tested the hypothesis that computed tomography (CT) perfusion markers of cerebral microcirculation would improve 36 months after internal carotid artery stenting for symptomatic carotid stenosis while results obtained 6-8 weeks after the stenting procedure would yield a predictive value. METHODS: We recruited consecutive eligible patients with >70% symptomatic carotid stenosis with a complete circle of Willis and normal vertebral arteries to the observational cohort study. We detected changes in the cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and permeability surface area-product (PS) before and after carotid stenting. We have also compared the absolute differences in the ipsilateral and contralateral CT perfusion markers before and after stenting. The search for regression models of "36 months after stenting" results was based on a stepwise analysis with bidirectional elimination method. RESULTS: A total of 34 patients completed the 36 months follow-up (15 females, mean age of 69.68±S.D. 7.61 years). At 36 months after stenting, the absolute values for CT perfusion markers had improved: CBF (ipsilateral: +7.76%, contralateral: +0.95%); CBV (ipsilateral: +5.13%, contralateral: +3.00%); MTT (ipsilateral: -12.90%; contralateral: -5.63%); TTP (ipsilateral: -2.10%, contralateral: -4.73%) and PS (ipsilateral: -35.21%, contralateral: -35.45%). MTT assessed 6-8 weeks after stenting predicted the MTT value 36 months after stenting (ipsilateral: R2=0.867, contralateral R2=0.688). CONCLUSIONS: We have demonstrated improvements in CT perfusion markers of cerebral microcirculation health that persist for at least 3 years after carotid artery stenting in symptomatic patients. MTT assessed 6-8 weeks after stenting yields a predictive value.

Aging and Hypertension - Independent or Intertwined White Matter Impairing Factors? Insights From the Quantitative Diffusion Tensor Imaging.

Aging disrupts white matter integrity, and so does continuous elevated blood pressure that accompanies hypertension (HTN). Yet, our understanding of the interrelationship between these factors is still limited. The study aimed at evaluating patterns of changes in diffusion parameters (as assessed by quantitative diffusion fiber tracking - qDTI) following both aging, and hypertension, as well as the nature of their linkage. 146 participants took part in the study: the control group (N = 61) and the patients with hypertension (N = 85), and were divided into three age subgroups (25-47, 48-56, 57-71 years). qDTI was used to calculate the values of fractional anisotropy, mean, radial and axial diffusivity in 20 main tracts of the brain. The effects of factors (aging and hypertension) on diffusion parameters of tracts were tested with a two-way ANOVA. In the right hemisphere there was no clear effect of the HTN, nor an interaction between the factors, though some age-related effects were observed. Contrary, in the left hemisphere both aging and hypertension contributed to the white matter decline, following a functional pattern. In the projection pathways and the fornix, HTN and aging played part independent of each other, whereas in association fibers and the corpus callosum if the hypertension effect was significant, an interaction was observed. HTN patients manifested faster decline of diffusion parameters but also reached a plateau earlier, with highest between-group differences noted in the middle-aged subgroup. Healthy and hypertensive participants have different brain aging patterns. The HTN is associated with acceleration of white matter integrity decline, observed mainly in association fibers of the left hemisphere.

Cognitive Dysfunction in Type 1 Diabetes Mellitus.

CONTEXT: We have summarized key studies assessing the epidemiology, mechanisms, and consequences of cognitive dysfunction (CD) in type 1 diabetes. EVIDENCE SYNTHESIS: In a number of studies, the severity of CD in type 1 diabetes was affected by the age of onset and duration, and the presence of proliferative retinopathy and autonomic neuropathy. Diabetes-related CD has been observed, not only in adults, but also in children and adolescents. Most neuroimaging studies of patients with type 1 diabetes did not show any differences in whole brain volumes; however, they did reveal selective deficits in gray matter volume or density within the frontal, posterior, and temporal cortex and subcortical gray matter. Studies of middle-age adults with long-standing type 1 diabetes using diffusion tensor imaging have demonstrated partial lesions in the white matter and decreased fractional anisotropy in posterior brain regions. The mechanisms underlying diabetes-related CD are very complex and include factors related to diabetes per se and to diabetes-related cardiovascular disease and microvascular dysfunction, including chronic hyperglycemia, hypoglycemia, macro- and microvascular disease, and increased inflammatory cytokine expression. These mechanisms might contribute to the development and progression of both vascular dementia and Alzheimer disease. CONCLUSIONS: Higher rates of CD and faster progression in type 1 diabetes can be explained by both the direct effects of altered glucose metabolism on the brain and diabetes-related cardiovascular disease. Because the presence and progression of CD significantly worsens the quality of life of patients with diabetes, further multidisciplinary studies incorporating the recent progress in both neuroimaging and type 1 diabetes management are warranted to investigate this problem.

Blood-brain barrier permeability and physical exercise.

In this narrative review, a theoretical framework on the crosstalk between physical exercise and blood-brain barrier (BBB) permeability is presented. We discuss the influence of physical activity on the factors affecting BBB permeability such as systemic inflammation, the brain renin-angiotensin and noradrenergic systems, central autonomic function and the kynurenine pathway. The positive role of exercise in multiple sclerosis and Alzheimer's disease is described. Finally, the potential role of conditioning as well as the effect of exercise on BBB tight junctions is outlined. There is a body of evidence that regular physical exercise diminishes BBB permeability as it reinforces antioxidative capacity, reduces oxidative stress and has anti-inflammatory effects. It improves endothelial function and might increase the density of brain capillaries. Thus, physical training can be emphasised as a component of prevention programs developed for patients to minimise the risk of the onset of neuroinflammatory diseases as well as an augmentation of existing treatment. Unfortunately, despite a sound theoretical background, it remains unclear as to whether exercise training is effective in modulating BBB permeability in several specific diseases. Further research is needed as the impact of exercise is yet to be fully elucidated.