Cortical Network Topology in Prodromal and Mild Dementia Due to Alzheimer\u2019s Disease: Graph Theory Applied to Resting State EEG

Graph theory analysis on resting state electroencephalographic rhythms disclosed topological properties of cerebral network. In Alzheimer\u2019s disease (AD) patients, this approach showed mixed results. Granger causality matrices were used as input to the graph theory allowing to estimate the strength and the direction of information transfer between electrode pairs. The number of edges (degree), the number of inward edges (in-degree), of outgoing edges (out-degree) were statistically compared among healthy controls, patients with mild cognitive impairment due to AD (AD-MCI) and AD patients with mild dementia (ADD) to evaluate if degree abnormality could involve low and/or high degree vertices, the so called hubs, in both prodromal and over dementia stage. Clustering coefficient and local efficiency were evaluated as measures of network segregation, path length and global efficiency as measures of integration, the assortativity coefficient as a measure of resilience. Degree, in-degree and out-degree values were lower in AD-MCI and ADD than the control group for non-hubs and hubs vertices. The number of edges was preserved for frontal electrodes, where patients\u2019 groups showed an additional hub in F3. Clustering coefficient was lower in ADD compared with AD-MCI in the right occipital electrode, and it was positively correlated with mini mental state examination. Local and global efficiency values were lower in patients\u2019 than control groups. Our results show that the topology of the network is altered in AD patients also in its prodromal stage, begins with the reduction of the number of edges and the loss of the local and global efficiency

Serum osteopontin negatively impacts on intima-media thickness in patients with systemic lupus erythematosus

BACKGROUND Ultrasound evaluation of carotid intima-media thickness (cIMT) has been extensively used for potentially improving cardiovascular (CV) risk stratification in several patients' categories. Subjects with systemic lupus erythematosus (SLE) have been investigated by both imaging and molecular biomarker approaches with contrasting results. Here, we focused on the role of osteopontin (OPN) as biomarker of subclinical atherosclerosis associated with SLE. MATERIALS AND METHODS Eighty females (age 18-65 years) affected by SLE and eighty age-matched healthy female controls without a clinical history of CV disease underwent ultrasound evaluation of cIMT and blood sample assay of high-sensitivity C-reactive protein (hs-CRP) and OPN. RESULTS Healthy controls and SLE patients significantly differed for CV risk factors (ie, waist circumference, hypertension and dyslipidaemia) and the inflammatory status. Noteworthy, an opposite association between cIMT and OPN was observed in the two study groups. Whereas OPN was positively associated with mean cIMT (r = 0.364; P = 0.001) in SLE patients, a negative correlation was found in healthy controls. Furthermore, in SLE patients increased circulating levels of OPN were associated with the use of hydroxychloroquine and the positivity for the anti-dsDNA autoantibodies. At linear regression analysis, only OPN remained independently associated with cIMT also after adjustment for age, smoking pack-year, Heart SCORE, disease length and steroid therapy length. CONCLUSIONS These results indicate that serum OPN levels were strongly associated with subclinical atherosclerosis in patients with LES and it might be a useful CV biomarker that requires additional validation in larger trials

Lifetime Sport Practice and Brain Metabolism in Amyotrophic Lateral Sclerosis

Objective: To evaluate the metabolic correlates of lifetime sport practice in ALS through brain 18F-FDG-PET. Methods: 131 patients completed a questionnaire about lifetime exposures, including physical activity related to sports, hobbies and occupations, and underwent brain 18F-FDG-PET. Exposure to sports was expressed as MET (Metabolic Equivalent of Task). We considered only regular practice (at least 2 h/week, for at least three months). We compared brain metabolism between two groups: subjects who did not report regular sport practice during life (N-group) and patients who did (Y-group). The resulting significant clusters were used in each group as seed regions in an interregional correlation analysis (IRCA) to evaluate the impact of lifetime sport practice on brain networks typically involved by the neurodegenerative process of ALS. Each group was compared to healthy controls (HC, n = 40). Results: We found a significant, relative cerebellar hypermetabolism in the N-group compared to the Y-group. The metabolism of such cerebellar cluster resulted correlated to more significant and widespread metabolic changes in areas known to be affected by ALS (i.e. frontotemporal regions and corticospinal tracts) in the N-group as compared to the Y-group, despite the same level of disability as expressed by the ALS FRS-R. Such findings resulted independent of age, sex, site of onset (bulbar/spinal), presence/absence of C9ORF72 expansion, cognitive status and physical activity related to hobbies and occupations. When compared to HC, the N-group showed more widespread metabolic changes than the Y-group in cortical regions known to be relatively hypometabolic in ALS patients as compared to HC. Conclusions: We hypothesize that patients of the N-group might cope better with the neurodegenerative process, since they show more widespread metabolic changes as compared to the Y-group, despite the same level of disability. Nevertheless, further studies are necessary to corroborate this hypothesis

Different abnormalities of electroencephalographic (EEG) markers in quiet wakefulness are related to motor visual hallucinations in patients with Parkinson's and Lewy body diseases

AbstractBackgroundParkinson's disease (PD) is the second‐most common neurodegenerative disorder that affects 2–3% of the population ≥ 65 years of age and may belong to cognitive deficits and dementia in 50% of cases. Disease with Lewy Bodies (DLB) is emerging as another important cause of dementia in pathological aging. PD and DLB are both due to intra‐neuronal Lewy bodies and are characterized not only by motor dysfunctions but also by cognitive and/or psychiatric symptoms. An open issue is the extent to which these diseases are distinct entities. In this respect, here we compared cortical sources of resting state eyes‐closed electroencephalographic (rsEEG) rhythms in PD and DLB patients having visual hallucinations.MethodClinical and rsEEG rhythms in demographic matched PD (N = 93), DLB (N = 46), Alzheimer's disease dementia (AD, N= 70) and healthy elderly (Nold, N = 60) subjects were available from an international archive. Pathological groups were matched for cognitive status. Individual alpha frequency peak was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were considered. The eLORETA freeware estimated rsEEG cortical sources.ResultAs a confirmation of previous studies, compared to the Nold subjects, the AD, LBD, and PD patients showed higher widespread delta source activities and lower posterior alpha source activities. Specifically, posterior alpha source activities were more abnormal in the AD than the LBD and PD groups, while widespread delta source activities were more abnormal in the PD and DLB than the AD group. As novel results, in relation to the LBD and PD patients without visual hallucinations and the control groups (Nold, AD), those with visual hallucinations were characterized by higher parietal delta source activities (LBD, Figure 1) and parieto‐occipital alpha sources activities (PD, Figure 2).ConclusionThese novel results suggest that in LBD and PD patients resting in the quiet wakefulness, abnormalities in cortical neural synchronization at delta and alpha frequencies in parietal cortex are differently related to visual hallucinations despite the essence of alpha‐synucleinopathy

New tracers and new perspectives for molecular imaging in Lewy body diseases

The term Lewy body diseases (LBDs) refers to a subset of neurodegenerative disorders that share the accumulation of the so-called Lewy bodies (LB) including: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD later characterized by the occurrence of dementia (PDD). Moreover, multiple system atrophy (MSA) and idiopatic Rem Sleeping behaviour disorders (RBD) complete the group of synucleinopathies and have also common symptoms with respect to LBDs. The clinical diagnosis of LBDs can be challenging for physicians, particularly in the early stages of disease. Given the growing number of individuals affected by these neurodegenerative disorders, early and accurate diagnosis can lead to improved clinical management of patients. For this reason, information obtained from molecular imaging biomarkers is playing an increasingly important role in this framework. The present narrative review discusses both established milestones and new evidence on the use of molecular imaging tracers already part of the clinical practice as well as available evidence on new molecular imaging approaches in PD, PDD and DLB

Principal component analysis in mild and moderate Alzheimer's disease - a novel approach to clinical diagnosis

Principal component analysis (PCA) provides a method to explore functional brain connectivity. The aim of this study was to identify regional cerebral blood flow (rCBF) distribution differences between Alzheimer's disease (AD) patients and controls (CTR) by means of volume of interest (VOI) analysis and PCA. Thirty-seven CTR, 30 mild AD (mildAD) and 27 moderate AD (modAD) subjects were investigated using single photon emission computed tomography with (99m)Tc-hexamethylpropylene amine oxime. Analysis of covariance (ANCOVA), PCA, and discriminant analysis (DA) were performed on 54 VOIs. VOI analysis identified in both mildAD and modAD subjects a decreased rCBF in six regions. PCA in mildAD subjects identified four principal components (PCs) in which the correlated VOIs showed a decreased level of rCBF, including regions that are typically affected early in the disease. In five PCs, including parietal-temporal-limbic cortex, and hippocampus, a significantly lower rCBF in correlated VOIs was found in modAD subjects. DA significantly discriminated the groups. The percentage of subjects correctly classified was 95, 70, and 81 for CTR, mildAD and modAD groups, respectively. PCA highlighted, in mildAD and modAD, relationships not evident when brain regions are considered as independent of each other, and it was effective in discriminating groups. These findings may allow neurophysiological inferences to be drawn regarding brain functional connectivity in AD that might not be possible with univariate analysis

Volume properties of the hippocampal regions as predictors of DAT development

In this work we look at the statistical distribution of geometrical observables computed in volumes centered on the right and left hippocampus in MR images. The observable distributions are then correlated with the clinical diagnosis in patients potentially affected by the Alzheimer disease. We then evaluate the discrimination ability of the geometrical observables combined with the MMSE test results

Brain Aging, Cardiovascular Diseases, Mixed Dementia, and Frailty in the Oldest\ua0Old: From Brain Phenotype to\ua0Clinical\ua0Expression

Dementia is an age-related clinical condition, with higher incidence rates in older ages. However, there is some evidence that a reverse epidemiology is also observed. Namely, the cohort analysis of dementia incidence rates by birth in selected populations demonstrated a decreased incidence of dementia in late life across the last twenty years, possibly due to decreased incidence of cardiovascular disorders and increased education and cognitive reserve. In line with that, age is probably a proxy for other pathophysiological processes rather than a strictly causative factor for the onset of dementia, especially in oldest old persons. The present narrative review provides an update on the clinical interplay between the spectrum of brain aging, cardiovascular morbidity, dementia pathologies, and their clinical expression in the oldest old patients. Available evidence suggests that vascular prevention in the perspective of dementia largely involve middle ages, with an apparent reverse epidemiology in oldest old. Similarly, the present findings underline how cognitive resilience and frailty may be key relevant mediators in the modulation of the clinical expression of brain mixed neuropathologies in persons over 85 years old, providing a new integrated conceptual framework

A Survey of FDG- and Amyloid-PET Imaging in Dementia and GRADE Analysis

PET based tools can improve the early diagnosis of Alzheimer’s disease (AD) and differential diagnosis of dementia. The importance of identifying individuals at risk of developing dementia among people with subjective cognitive complaints or mild cognitive impairment has clinical, social, and therapeutic implications. Within the two major classes of AD biomarkers currently identified, that is, markers of pathology and neurodegeneration, amyloid- and FDG-PET imaging represent decisive tools for their measurement. As a consequence, the PET tools have been recognized to be of crucial value in the recent guidelines for the early diagnosis of AD and other dementia conditions. The references based recommendations, however, include large PET imaging literature based on visual methods that greatly reduces sensitivity and specificity and lacks a clear cut-off between normal and pathological findings. PET imaging can be assessed using parametric or voxel-wise analyses by comparing the subject’s scan with a normative data set, significantly increasing the diagnostic accuracy. This paper is a survey of the relevant literature on FDG and amyloid-PET imaging aimed at providing the value of quantification for the early and differential diagnosis of AD. This allowed a meta-analysis and GRADE analysis revealing high values for PET imaging that might be useful in considering recommendations