Effects of Nordic walking in Alzheimer's disease: A single-blind randomized controlled clinical trial.

Non-pharmacological approaches, including exercise programs, have been proposed to improve cognitive function and behavioral symptoms, such as depression, agitation, or aggression, in the management of patients with Alzheimer's disease (AD). Indeed, physical inactivity is one of the main modifiable risk factors in patients with AD, as well as in the development of cardiovascular diseases and related pathologies. Although Nordic Walking (NW), a particular type of aerobic exercise, is known to benefit the health of aging populations, there is little evidence that patients with AD may benefit from this non-pharmacological treatment. In this context, we performed a pilot study in 30 patients with mild/moderate AD to evaluate whether NW influences different cognitive domains, including executive functions, visual-spatial abilities, and verbal episodic memory. To this aim, 15 patients (Control group, CG) underwent reality orientation therapy, music therapy, motor, proprioceptive and postural rehabilitation, and 15 patients (experimental group, EG) in addition to the activities performed by the CG also had the NW with a frequency of twice a week. Neuropsychological assessments and evaluations of daily activities and quality of life were performed at baseline and after 24 weeks. Twenty-two patients, including 13 in the CG and nine in the EG completed the activity program after 24 weeks. The EG showed a significant improvement in the Frontal Assessment Battery, Rey's auditory Verbal Learning Test Delayed Recall, Raven's Colored Progressive Matrices, and completion time for the Stroop Word-Color Interference test, compared to the CG. NW was able to improve cognitive domains like visual-spatial reasoning abilities, verbal episodic memory, selective attention, and processing speed in AD patients. These results, if confirmed by further studies with a larger number of patients and a longer training period, may prospect NW as a safe and likely useful strategy to slow down cognitive impairment in mild/moderate AD.

Phenolic Plant Extracts Induce Sirt1 Activity and Increase Antioxidant Levels in the Rabbit's Heart and Liver.

BACKGROUND: Several dietary phytochemicals potentially regulate the equilibrium between oxidant and antioxidant species. The aim of this study was to evaluate the effects of Lippia citriodora, Raphanus sativus, and Solanum lycopersicum on blood parameters, oxidative/antioxidant status, and SIRT1 activity in the rabbit's heart and liver. METHODS: Twenty rabbits were divided into 4 groups of 5 animals each. The control group (CN) received a feed without any additives. One intervention group received a supplement containing verbascoside (VB), another Raphanus sativus extract (RAP), and lastly lycopene (LYC). Oxidant-antioxidant parameters and SIRT1 activity were measured in plasma and in the heart and liver, respectively. RESULTS: The treatment with VB, RAP, and LYC resulted in a marked improvement in the blood lipid and glycaemic profile in respect to CN. VB was the most effective, but all three plant extracts induced a significant reduction in oxidant parameters as well as an increase in antioxidant tissue activity and vitamin A and E levels. SIRT1 activity was significantly increased in both VB and LYC compared to CN, but the increased levels in the VB group were far the highest. The multivariate analysis suggests that the benefits of VB, particularly the antiglycaemic and antioxidant effects, might be mediated by increasing SIRT1 activity.

miR-194-5p/BCLAF1 deregulation in AML tumorigenesis.

This corrects the article DOI: 10.1038/leu.2017.64.

miR-194-5p/BCLAF1 deregulation in AML tumorigenesis.

Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal hematopoietic progenitors. In acute myeloid leukemias this balance is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression of miR-194-5p by treatment with the histone deacetylase inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol. miR-194-5p/BCLAF1 balance was found commonly deregulated in 60 primary acute myeloid leukemia patients and was largely restored by ex vivo SAHA treatment. Our findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance.

Dietary effect of dried bay leaves (Laurus nobilis) meal on some biochemical parameters and on plasma oxidative status in New Zealand white growing rabbit.

Effects of dietary supplementation of Laurus nobilis on selected biochemical parameters and plasma oxidative status in growing rabbits, fed with and without enriched-fat diet, integrated with and without dried bay leaves meal, were investigated. In the test, 120 New Zealand white 35-day-old male rabbits were divided into four homogeneous groups of 30 animals each. A negative control group (CON) received a feed that met the animal nutrient requirement; a positive control group (CG) receiving a supplement of 2.5% pig fat in feed; an experimental group (GA) feeding an integration of 2.5% pig fat and 1 g/kg of dried bay leaves (Laurus nobilis) in feed; an experimental group (CA) with dried bay leaves at the rate of 1 g/kg in feed. The dietary integration with dried bay leaves meal have resulted in a significant decrease in the blood lipid profile, glycemic profile and liver enzymes, with reduced levels of ALT and AST, glucose, total cholesterol, LDL cholesterol, triglycerides and increased HDL cholesterol. Plasma oxidative status markers have statistically improved with an increase in blood total phenols, SOD, ORAC, the FRAP and lipo-vitamin concentration, together with a significant reduction in ROMs and the MDA values. The results of present research underline that the dietary treatment with bay leaves meal, in the extend of 1 g/kg feed, confirms the lowering cholesterol activity and the epato-protective and ipo-glycemic effect in enrich-fat diet, controlling the oxidative status of plasma markers.

The Role Of Physical Activity On The Prevention Of Cognitive Impairment.

Physical exercise is associated with reduced risk of heart disease, type II diabetes mellitus, and overall mortality. However, growing evidence shows that physical activity can also improve cognitive function and may lower the risk of developing dementia, but Randomized Clinical Trials gave mixed results. Aim of this article was to review the knowledge available in literature on the effects of physical activity on cognition and the suggested possible mechanisms involved in these effects. Our group have planned a trial aiming to evaluate the effectiveness of physical activity in preventing or delaying the cognitive decline in individuals at risk of developing dementia. Beside the effects of exercise on cognition are not fully defined, also the mechanisms underlying the benefits of physical activity on cognitive sphere are not completely known. Recently the SIRT1 loss is both closely associated with accumulation of beta amyloid and tau protein in AD patients. Although there is no specific exercise that can be recommended, the available evidence suggests that practicing more types of physical activity is particularly advantageous. It is important to explore further mechanisms involved in the pathogenesis of the AD in order to be able to identify new and effective target treatment, including physical activity.

Non-alcoholic fatty liver disease, metabolic syndrome and patatin-like phospholipase domain-containing protein3 gene variants.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease was traditionally interpreted as a condition which may progress to liver-related complications. However, the increased mortality is primarily a result of cardiovascular diseases. It has been suggested that fatty liver can be considered as the hepatic consequence of the metabolic syndrome. The aim was to describe the different clinical presentations of non-alcoholic fatty liver disease on the basis of the patatin-like phospholipase domain-containing protein3 (PNPLA3) rs738409 gene variant. METHODS: Fatty liver was defined by ultrasonographic Hamaguchi's criteria in 211 consecutive subjects with non-alcoholic fatty liver disease. The rs738409 polymorphism was determined by TaqMan assays. Metabolic syndrome was defined according to ATPIII modified criteria. RESULTS: Prevalence of PNPLA3-148II, PNPLA3-148IM, and PNPLA3-148MM genotypes was 45.0%, 40.7%, and 14.3% respectively. Prevalence of metabolic syndrome progressively increased with the severity of liver steatosis (from 52.5% to 65.2%, and 82.3% respectively, p<0.01). The PNPLA3-148MM group had significantly lower mean serum triglycerides (p<0.001), Framingham cardiovascular risk score (p<0.01) and lower prevalence of metabolic syndrome (p<0.05) and its components. Age and HOMA-IR were positive independent predictors of metabolic syndrome, while a negative independent association was found between metabolic syndrome and the homozygotes PNPLA3 I148M variant. CONCLUSIONS: We suggest a lower prevalence of MetS and reduced cardiovascular risk in NAFLD patients with PNPLA3MM genotype.

Giant dilatations of virchow-robin spaces in the midbrain. MRI aspects and review of the literature.

Virchow-Robin spaces are lesions often seen in the brain parenchyma but their etiopathogenesis remains unsettled. Giant Virchow-Robin spaces placed in the midbrain are extremely rare. We describe three patients with a diagnosis of giant Virchow-Robin spaces in the midbrain, and their clinical and radiologic findings. We reviewed the literature in terms of the etiopathology, anatomic and radiologic appearance and differential diagnosis of the giant Virchow-Robin spaces. The diagno-stic role of the high Tesla magnetic resonance devices and new sequences techniques such as three dimensional isotropic acquisition and diffusion tensor imaging were also evaluated in this case series.

Hippocampal asymmetry with hippocampal sulcus remnants in a patient with mild cognitive impairment. A case report.

A 65-year-old woman underwent MRI for a mild cognitive impairment (MCI) at Mini-Mental State Examination (MMSE). MRI showed hippocampal sulcus remnants bilaterally, although they were larger on the right, and left hippocampal atrophy with increased left fimbriosubicular distance (right side: 1.2 mm; left side: 2.0 mm). The meaning of these findings in relation to clinical aspects is discussed and reviewed according to data from the literature.

Brain atrophy evolution and lesion load accrual in multiple sclerosis: a 2-year follow-up study.

BACKGROUND: To investigate in a large cohort of patients with multiple sclerosis (MS), lesion load and atrophy evolution, and the relationship between clinical and magnetic resonance imaging (MRI) correlates of disease progression. METHODS: Two hundred and sixty-seven patients with MS were studied at baseline and two years later using the same MRI protocol. Abnormal white matter fraction, normal appearing white matter fraction, global white matter fraction, gray matter fraction and whole brain fraction, T2-hyperintense, and T1-hypointense lesions were measured at both time points. RESULTS: The majority of patients were clinically stable, whereas MRI-derived brain tissue fractions were significantly different after 2 years. The correlation between MRI data at baseline and their variation during the follow-up showed that lower basal gray matter atrophy was significantly related with higher progression of gray matter atrophy during follow-up. The correlation between MRI parameters and disease duration showed that gray matter atrophy rate decreased with increasing disease duration, whereas the rate of white matter atrophy had a constant pattern. Lower basal gray matter atrophy was associated with increased probability of developing gray matter atrophy at follow-up, whereas gray matter atrophy progression over 2 years and new T2 lesion load were risk factors for whole brain atrophy progression. CONCLUSIONS: In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression.

Role of advanced MR imaging modalities in diagnosing cerebral gliomas.

The objective of this study was to evaluate the potential role of newly developed, advanced magnetic resonance (MR) imaging techniques (spectroscopy, diffusion and perfusion imaging) in diagnosing brain gliomas, with special reference to histological typing and grading, treatment planning and posttreatment follow-up. Conventional MR imaging enables the detection and localisation of neoplastic lesions, as well as providing, in typical cases, some indication about their nature. However, it has limited sensitivity and specificity in evaluating histological type and grade, delineating margins and differentiating oedema, tumour and treatment side-effects. These limitations can be overcome by supplementing the morphological data obtained with conventional MR imaging with the metabolic, structural and perfusional information provided by new MR techniques that are increasingly becoming an integral part of routine MR studies. Incorporation of such new MR techniques can lead to more comprehensive and precise diagnoses that can better assist surgeons in determining prognosis and planning treatment strategies. In addition, the recent development of new, more effective, treatments for cerebral glioma strongly relies on morphofunctional MR imaging with its ability to provide a biological interpretation of these characteristically heterogeneous tumours.

Lung cancer single intramedullary metastasis vs delayed radionecrosis. A case report.

Intramedullary metastases are rare, accounting for 0.9-5% of spinal metastases. Radiation myelopathy is considered one of the most distressing complications of radiotherapy. In both cases symptoms are aspecific, and there are no characteristic neuroradiologic findings. We describe a case of single intramedullary metastasis from lung microcytoma in a 55-year-old man with a history of malignancy, treated by radiotherapy five years previously. The patient returned to our observation complaining of pain and paraesthesia in the left C7 area. Spinal MRI and rachicentesis findings were aspecific. Ten days later a new MRI showed that the lesion size had increased, and neoplastic cells were found in CSF. Intramedullary metastases are extremely rare, accounting for 0.1-0.4% of all CNS tumors. The risk of developing delayed radionecrosis varies with the total dose administered. In both cases diagnosis is histological, while contrast-enhanced MRI is highly sensitive and specific in identifying and characterizing the lesion. In case of metastatic lesions the prognosis is unfavorable. Differential diagnosis is important because it has a strong effect on patient management.

Role of perfusion-weighted imaging at 3 Tesla in the assessment of malignancy of cerebral gliomas.

PURPOSE: This study was performed to clarify the role of perfusion-weighted imaging (PWI) at 3 Tesla in the characterisation of haemodynamic heterogeneity within gliomas and surrounding tissues and in the differentiation of high-grade from low-grade gliomas. MATERIALS AND METHODS: We examined 36 patients with histologically verified gliomas (25 with high-grade and 11 with low-grade gliomas). PWI was performed by first-pass gadopentetate dimeglumine T2*-weighted echo-planar images, and cerebral blood volume (CBV) maps were computed with a nondiffusible tracer model. Relative CBV (rCBV) was calculated by dividing CBV in pathological areas by that in contralateral white matter. RESULTS: In high-grade gliomas, rCBV were markedly increased in mass [mean+/-standard deviation (SD), 4.3+/-1.2] and margins (4.0+/-1.1) and reduced in necrotic areas (0.3+/-0.3). Oedematous-appearing areas were divided in two groups according to signal intensity on T2-weighted images: tumour with lower (nearly isointense to grey matter) and oedema with higher (scarcely isointense to cerebrospinal fluid) signal intensity. Tumour showed significantly higher rCBV than did oedema (1.8+/-0.5 vs. 0.5+/-0.2; p<0.001) areas. In low-grade gliomas, mass (2.0+/-1.5) and margin (2.2+/-1.2) rCBV were significantly lower than in high-grade gliomas (p<0.001). CONCLUSIONS: Three-Tesla PWI helps to distinguish necrosis from tumour mass, infiltrating tumour from oedema and high-grade from low-grade gliomas. It enhances the magnetic resonance (MR) assessment of cerebral gliomas and provides useful information for planning surgical and radiation treatment.

3.0-T functional brain imaging: a 5-year experience.

The aim of this paper is to illustrate the technical, methodological and diagnostic features of functional imaging (comprising spectroscopy, diffusion, perfusion and cortical activation techniques) and its principal neuroradiological applications on the basis of the experience gained by the authors in the 5 years since the installation of a high-field magnetic resonance (MR) magnet. These MR techniques are particularly effective at 3.0 Tesla (T) owing to their high signal, resolution and sensitivity, reduced scanning times and overall improved diagnostic ability. In particular, the high-field strength enhances spectroscopic analysis due to a greater signal-to-noise ratio (SNR) and improved spectral, space and time resolution, resulting in the ability to obtain high-resolution spectroscopic studies not only of the more common metabolites, but also--and especially--of those which, due to their smaller concentrations, are difficult to detect using 1.5-T systems. All of these advantages can be obtained with reduced acquisition times. In diffusion studies, the high-field strength results in greater SNR, because 3.0-T magnets enable increased spatial resolution, which enhances accuracy. They also allow exploration in greater detail of more complex phenomena (such as diffusion tensor and tractography), which are not clearly depicted on 1.5-T systems. The most common perfusion study (with intravenous injection of a contrast agent) benefits from the greater SNR and higher magnetic susceptibility by achieving dramatically improved signal changes, and thus greater reliability, using smaller doses of contrast agent. Functional MR imaging (fMRI) is without doubt the modality in which high-field strength has had the greatest impact. Images acquired with the blood-oxygen-level-dependent (BOLD) technique benefit from the greater SNR afforded by 3.0-T magnets and from their stronger magnetic susceptibility effects, providing higher signal and spatial resolution. This enhances reliability of the localisation of brain functions, making it possible to map additional areas, even in the millimetre and submillimetre scale. The data presented and results obtained to date show that 3.0-T morphofunctional imaging can become the standard for high-resolution investigation of brain disease.

Spectroscopic, diffusion and perfusion magnetic resonance imaging at 3.0 Tesla in the delineation of glioblastomas: preliminary results.

Recent advances in magnetic resonance imaging (MRI) have allowed the evaluation of metabolic, diffusion and hemodynamic features of malignant gliomas. The aim of this study was to evaluate whether such information provided useful, complementary information to conventional MRI for improving the evaluation of glioblastoma extent. Ten patients with glioblastoma multiforme underwent conventional MRI, proton MR spectroscopic imaging (1H-MRSI), perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI). Metabolite signals, including normalized choline, N-acetylaspartate, creatine and lactate/lipids, were obtained by 1H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. In edematous-appearing areas, 3 multiparametric patterns were identified: infiltrating tumor, with abnormal metabolite ratios, lower ADC and higher rCBV; pure edema, with normal metabolite ratios, higher ADC and lower rCBV; and tumor-infiltrated edema, with abnormal metabolite ratios and intermediate ADC and rCBV. In normal-appearing areas, 2 multiparametric patterns were identified: tumor-infiltrated tissue, with abnormal metabolite ratios and higher rCBV; and normal tissue, with normal MR parameters. The combination of 1H-MRSI, DWI and PWI features contributed to delineation of glioblastomas, offering information not available with conventional MRI. This approach may enhance the assessment of brain gliomas, providing useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Treatment of multiple sclerosis with interferon beta in clinical practice: 2-year follow-up data from the South Italy Mobile MRI Project.

This follow-up study assessed the 2-year clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) originally enrolled in an MRI study conducted at eight centres in south Italy (the South Italy Mobile MRI Project). Of the 597 MS patients recruited at baseline, 391 returned for the follow-up study. Of these, 363 provided 2-year clinical and MRI follow-up data, and 215 were still undergoing treatment with one of four interferon beta regimens: Avonex, 30 mcg intramuscularly once weekly; Betaferon, 250 mcg subcutaneously (sc) every other day; Rebif 22 mcg sc three times weekly (tiw; Rebif 22); or Rebif 44 mcg sc tiw (Rebif 44). Over the 2-year follow-up period, patients receiving the higher dose of Rebif were more likely to remain free from relapses [odds ratio (OR) = 2.23] and from developing both new T2 (OR = 0.15) and new T1 black hole lesions (OR = 0.22), when compared with patients in the Avonex group. Despite some limitations in the trial design, the results from this follow-up study provide helpful clinical and MRI data on the efficacy of interferon beta regimens in MS patients treated in the clinical setting.

Brain atrophy and lesion load in a large population of patients with multiple sclerosis.

OBJECTIVE: To measure white matter (WM) and gray matter (GM) atrophy and lesion load in a large population of patients with multiple sclerosis (MS) using a fully automated, operator-independent, multiparametric segmentation method. METHODS: The study population consisted of 597 patients with MS and 104 control subjects. The MRI parameters were abnormal WM fraction (AWM-f), global WM-f (gWM-f), and GM fraction (GM-f). RESULTS: Significant differences between patients with MS and control subjects included higher AWM-f and reduced gWM-f and GM-f. MRI data showed significant differences between patients with relapsing-remitting and secondary progressive forms of MS. Significant correlations between MRI parameters and between MRI and clinical data were found. CONCLUSIONS: Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability.

GABA(B) receptor 1 polymorphism (G1465A) is associated with temporal lobe epilepsy.

BACKGROUND: Dysfunction of gamma-aminobutyric acid (GABA) (B) receptors has been implicated in the pathogenesis of temporal lobe epilepsy (TLE). OBJECTIVE: To evaluate the genetic contribution of cloned human GABA(B) receptors to TLE. METHODS: The authors genotyped 141 patients (78 women and 63 men; mean age = 49.1 +/- 18.0 years) with nonlesional TLE and 372 age- and sex-matched normal individuals for the known polymorphism G1465A in the human GABA(B) receptor 1 [GABA(B[1])] gene. RESULTS: There was a highly significant overrepresentation of the G1465A heterozygote in patients with TLE compared with controls. The A/G genotype was found in 17% of the 141 patients with TLE and in only 0.5% of the 372 controls (p < 0.0001). The authors also found that patients carrying the A allele had a significantly higher risk (p = 0.003, OR = 6.47, 95% CI = 2.02 to 20.76) of developing drug-resistant TLE. Furthermore, the age at onset of seizures tended to be lower in patients with A/G genotype, but the difference was not significant. CONCLUSIONS: The results of this study indicate that the GABA(B[1]) polymorphism (G1465A) confers a highly increased susceptibility to TLE. Moreover, it seems to influence the severity of this common epileptic disorder.

Anti-GM1 ganglioside antibodies in Parkinson's disease.

OBJECTIVES: To determine whether anti-GM1 antibodies are increased in Parkinson's disease (PD). METHODS: Serum immunoglobulin M (IgM) and IgG anti-GM1 antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in 147 patients with PD and in 186 age-matched normal control subjects. Sera were assayed at initial dilution of 1:800 for IgM and 1:200 for IgG and were considered positive at absorbance values exceeding the value of 0.05 for IgM and 0.1 for IgG. RESULTS: Forty patients with PD (27.2%) had sera positive for IgM anti-GM1 antibodies, whereas only five normal controls (2.7%) resulted positive (P < 0.0001). Most of patients (75%) with positive sera had a tremor-dominant form of PD. Only two patients with PD (1.4%) and none of normal controls had sera positive for IgG anti-GM1 antibodies. CONCLUSION: A consistent portion of parkinsonians, mainly with a tremor-dominant form of PD, may have increased circulating IgM anti-GM1 antibodies.

Dilated Virchow-Robin spaces in myotonic dystrophy: frequency, extent and significance.

To study the frequency, extent and significance of dilated Virchow-Robin spaces (VRSs) in dystrophia myotonica (DM), we evaluated the cranial magnetic resonance imaging (MRI) of 41 patients with the adult form of DM and 41 healthy controls. Dilated VRSs and white matter lesions (WMLs) were rated according to semiquantitative methods. Convexity VRSs were more frequent (68 vs. 34%; p < 0.01) and severer (median scores: 4 vs. 0; p < 0.01) in DM patients than in controls, while lenticulostriate VRSs did not show significant differences in frequency (83 vs. 70%; p > 0.05) and severity (median scores: 4 vs. 3; p > 0.05). WMLs were more frequent (66 vs. 22%; p < 0.01) and severer (median scores: 5 vs. 0; p < 0.01) in patients. Disease duration was negatively correlated with convexity VRSs and positively with lobar (centrum semiovale) WML scores. Dilated convexity VRSs might be one of the initial findings in cranial MRI of DM, preceding the appearance of lobar WMLs.