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Please modify the Abstract as follows:Here we tested if the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms from the eye-closed to the eyes-open condition may differ in patients with dementia due to Lewy Bodies (DLB) and Alzheimer's disease (ADD) as a functional probe of the dominant neural synchronization mechanisms regulating the vigilance in posterior visual systems.We used clinical, demographical, and rsEEG datasets in 28 older adults (Healthy), 42 DLB, and 48 ADD participants. The eLORETA freeware was used to estimate cortical rsEEG sources.Results showed a substantial (> -10%) reduction in the posterior alpha activities during the eyes-open condition in 24 Healthy, 26 ADD, and 22 DLB subjects. There were lower reductions in the posterior alpha activities in the ADD and DLB groups than in the Healthy group. That reduction in the occipital region was lower in the DLB than in the ADD group.These results suggest that DLB patients may suffer from a greater alteration in the neural synchronization mechanisms regulating vigilance in occipital cortical systems compared to ADD patients. H2020 Marie S. Curie ITN-ETN project Italian Ministry of Health to the IRCCS SDN of Naples, IRCCS OASI of Troina, and IRCCS San Raffaele Pisana of Rome

To assess internal consistency, validity and test–retest reliability of Italian version of Canadian Occupational Performance Measure (COPM) in Parkinson’s disease (PD) clients.Sixty-one subjects co...

In the present retrospective and exploratory study, we tested the hypothesis that sex may affect cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer’s disease and mild cognitive impairment (ADMCI). Datasets in 69 ADMCI and 57 Nold individuals were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands and fixed beta (14–30 Hz) and gamma (30–40 Hz) bands. Each group was stratified into matched females and males. The sex factor affected the magnitude of rsEEG source activities in the Nold seniors. Compared with the males, the females were characterized by greater alpha source activities in all cortical regions. Similarly, the parietal, temporal, and occipital alpha source activities were greater in the ADMCI-females than the males. Notably, the present sex effects did not depend on core genetic (APOE4), neuropathological (Aβ42/phospho-tau ratio in the cerebrospinal fluid), structural neurodegenerative and cerebrovascular (MRI) variables characterizing sporadic AD-related processes in ADMCI seniors. These results suggest the sex factor may significantly affect neurophysiological brain neural oscillatory synchronization mechanisms underpinning the generation of dominant rsEEG alpha rhythms to regulate cortical arousal during quiet vigilance.

Extending Basar's theory of event-related EEG oscillations, here we hypothesize that even in quiet wakefulness, transient increases in delta rhythms may enhance global cortical arousal as revealed by the desynchronization of alpha rhythms in normal (Nold) seniors with some derangement in Alzheimer's disease dementia (ADD).Clinical and EEG datasets in 100 ADD and 100 Nold individuals matched as demography, education, and gender were taken from an international archive. Standard delta (< 4 Hz) and alpha1 (8-10.5 Hz) bands were used for the main analysis, while alpha2 (10.5-13 Hz), theta (4-8 Hz), beta1 (13-20 Hz), beta2 (20-35 Hz), and gamma (35-40 Hz) served as controls. In the interpretation, the higher the alpha1 power (density), the lower that arousal. As expected, when compared to the Nold group, the ADD group showed higher global (scalp) power density at the delta-theta band and lower global power density at the alpha-beta bands. As novel findings, we observed that: (1) in the Nold group, the global delta and alpha1-2 power were negatively and linearly correlated; (2) in the ADD group, this correlation was just marginal; and (3) in both Nold and AD groups, the EEG epochs with the highest delta power (median value for stratification) were associated with the lowest global alpha1 power. This effect was related to eLORETA freeware solutions showing maximum alpha1 source activations in posterior cortical regions.These results suggest that even in quiet wakefulness, delta and alpha rhythms are related to each other, and ADD partially affects this cross-band neurophysiological mechanism. Ministry of Health, Italy ; Ministry of Health Italy - Ricerca Corrente (MOH-RC) ; H2020 Marie S. Curie ITN-ETN project with the short title "BBDiag" ; H2020-TWINN-2015 project with the short title "SynaNet"

Objective: Here we tested if cortical sources of resting state electroencephalographic (rsEEG) rhythms may differ in sub-groups of patients with prodromal and overt dementia with Lewy bodies (DLB) as a function of relevant clinical symptoms.Methods: We extracted clinical, demographic and rsEEG datasets in matched DLB patients (N = 60) and control Alzheimer's disease (AD, N = 60) and healthy elderly (Nold, N = 60) seniors from our international database. The eLORETA freeware was used to estimate cortical rsEEG sources.Results: As compared to the Nold group, the DLB and AD groups generally exhibited greater spatially distributed delta source activities (DLB > AD) and lower alpha source activities posteriorly (AD > DLB). As compared to the DLB ``controls", the DLB patients with (1) rapid eye movement (REM) sleep behavior disorders showed lower central alpha source activities (p < 0.005); (2) greater cognitive deficits exhibited higher parietal and central theta source activities as well as higher central, parietal, and occipital alpha source activities (p < 0.01); (3) visual hallucinations pointed to greater parietal delta source activities (p < 0.005).Conclusions: Relevant clinical features were associated with abnormalities in spatial and frequency features of rsEEG source activities in DLB patients.Significance: Those features may be used as neurophysiological surrogate endpoints of clinical symptoms in DLB patients in future cross-validation prospective studies. Ministry of Health, Italy; H2020 Marie S. Curie ITN-ETN project; H2020-TWINN-2015 project

Compared with Alzheimer's disease (AD), Parkinson's disease (PD) shows peculiar clinical manifestations related to vigilance (i.e., executive cognitive deficits and visual hallucinations) that may be reflected in resting-state electroencephalographic rhythms. To test this hypothesis, clinical and resting-state electroencephalographic rhythms in age-, sex-, and education-matched PD patients (N = 136) and Alzheimer's disease patients (AD, N = 85), and healthy older participants (Nold, N = 65), were available from an international archive. Electroencephalographic sources were estimated by eLORETA software. The results are as follows: (1) compared to the Nold participants, the AD and PD patients showed higher widespread delta source activities (PD > AD) and lower posterior alpha source activities (AD > PD); (2) the PD patients with the most pronounced motor deficits exhibited very low alpha source activities in widespread cortical regions; (3) the PD patients with the strongest cognitive deficits showed higher alpha source activities in widespread cortical regions; and (4) compared to the PD patients without visual hallucinations, those with visual hallucinations were characterized by higher posterior alpha sources activities. These results suggest that in PD patients resting in quiet wakefulness, abnormalities in cortical neural synchronization at alpha frequencies are differently related to cognitive, motor, and visual hallucinations. Interestingly, parallel PD neuropathological processes may have opposite effects on cortical neural synchronization mechanisms generating cortical alpha rhythms in quiet wakefulness. (C) 2020 Elsevier Inc. All rights reserved.

Orjinal Makale: Functional cortical source connectivity of resting state electroencephalographic alpha rhythms shows similar abnormalities in patients with mild cognitive impairment due to Alzheimer's and Parkinson's diseases. 129(4), 766-782. https://doi.org/10.1016/j.clinph.2018.01.009

WOS: 000465302200012 PubMed ID: 30797169 Previous evidence has shown different resting-state eyes-closed electroencephalographic delta (

WOS: 000450412900002 PubMed ID: 30312790 We hypothesized that dopamine neuromodulation might affect cortical excitability in Parkinson's disease (PD) patients set in quiet wakefulness, as revealed by resting state eyes-closed electroencephalographic (rsEEG) rhythms at alpha frequencies (8-12 Hz). Clinical and rsEEG rhythms in PD with dementia (N = 35), PD with mild cognitive impairment (N = 50), PD with normal cognition (N = 35), and normal (N = 50) older adults were available from an international archive. Cortical rsEEG sources were estimated by exact low-resolution brain electromagnetic tomography. Compared with the normal older group, the PD groups showed reduced occipital alpha sources and increased widespread delta (

AIMS The aims of this study were to assess vascular dysfunction in patients with Alzheimer disease (AD) by investigating cerebral vasomotor reactivity using transcranial Doppler ultrasound (TCD) and to evaluate any correlations between cerebral vasoreactivity and endothelium dysfunction. Moreover, the frequency of circulating progenitor cells (CPCs) and the blood concentration of vascular/inflammatory markers were evaluated. MATERIALS AND METHODS We recruited 35 AD subjects and 17 age-matched, sex-matched, and education-matched healthy control subjects. Cerebral vasomotor reactivity was assessed by means of the TCD-based breath-holding index test (BHI). The level of CPCs was evaluated by means of flow cytometry from venous blood samples, while blood vascular/inflammatory markers were measured by means of enzyme-linked immunosorbent assay. RESULTS Both cerebral assay blood flow velocity in the middle cerebral artery (MCAFV) and BHI values were significantly lower in AD subjects than in healthy controls (P

WOS: 000427485900009 PubMed ID: 29448151 Objective: This study tested the hypothesis that markers of functional cortical source connectivity of resting state eyes-closed electroencephalographic (rsEEG) rhythms may be abnormal in subjects with mild cognitive impairment due to Alzheimer's (ADMCI) and Parkinson's (PDMCI) diseases compared to healthy elderly subjects (Nold). Methods: rsEEG data had been collected in ADMCI, PDMCI, and Nold subjects (N = 75 for any group). eLORETA freeware estimated functional lagged linear connectivity (LLC) from rsEEG cortical sources. Area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification of Nold and MCI individuals. Results: Posterior interhemispheric and widespread intrahemispheric alpha LLC solutions were abnormally lower in both MCI groups compared to the Nold group. At the individual level, AUROC curves of LLC solutions in posterior alpha sources exhibited moderate accuracies (0.70-0.72) in the discrimination of Nold vs. ADMCI-PDMCI individuals. No differences in the LLC solutions were found between the two MCI groups. Conclusions: These findings unveil similar abnormalities in functional cortical connectivity estimated in widespread alpha sources in ADMCI and PDMCI. This was true at both group and individual levels. Significance: The similar abnormality of alpha source connectivity in ADMCI and PDMCI subjects might reflect common cholinergic impairment. (C) 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved. H Marie S. Curie ITN-ETN project The present study was developed based on the data of the informal European Consortium PDWAVES and European Consortium of Dementia with Lewy Body. The members and institutional affiliations of the Consortia are reported in the cover page of this manuscript. Dr. Erol Basar passed away due to health problems on October 28th (November 18th 1938-October 28th 2017) in Istanbul, during the editorial processing of this manuscript. Until the end of his life, he had been working to the development of EEG science and its application in Clinical Neurophysiology. He leaves to all us an invaluable scientific legacy in the Science of Brain Rhythms and Human Cognition. He also leaves a permanent reminder of scientific passion, academic soul, and social responsibility to all fortunate people who met and knew him during his intense life. The research activities of the Unit of University of Rome "La Sapienza" were partially supported by the H2020 Marie S. Curie ITN-ETN project with the short title "BBDiag" (http://bbdiag-ITNetn.eu). We thank Mrs. Jessica Janson and Mrs. Marina Selivanova for their support to those activities in the framework of the BBDiag project.

WOS: 000405068100016 PubMed ID: 28454845 The aim of this retrospective exploratory study was that resting state eyes-closed electroencephalographic (rsEEG) rhythms might reflect brain arousal in patients with dementia due to Alzheimer's disease dementia (ADD), Parkinson's disease dementia (PDD), and dementia with Lewy body (DLB). Clinical and rsEEG data of 42 ADD, 42 PDD, 34 DLB, and 40 healthy elderly (Nold) subjects were available in an international archive. Demography, education, and Mini-Mental State Evaluation score were not different between the patient groups. Individual alpha frequency peak (IAF) determined the delta, theta, alpha 1, alpha 2, and alpha 3 frequency bands. Fixed beta 1, beta 2, and gamma bands were also considered. rsEEG cortical sources were estimated by means of the exact low-resolution brain electromagnetic source tomography and were then classified across individuals, on the basis of the receiver operating characteristic curves. Compared to Nold, IAF showed marked slowing in PDD and DLB and moderate slowing in ADD. Furthermore, all patient groups showed lower posterior alpha 2 source activities. This effect was dramatic in ADD, marked in DLB, and moderate in PDD. These groups also showed higher occipital delta source activities, but this effect was dramatic in PDD, marked in DLB, and moderate in ADD. The posterior delta and alpha sources allowed good classification accuracy (approximately 0.85-0.90) between the Nold subjects and patients, and between ADD and PDD patients. In quiet wakefulness, delta and alpha sources unveiled different spatial and frequency features of the cortical neural synchronization underpinning brain arousal in ADD, PDD, and DLB patients. Future prospective cross-validation studies should test these rsEEG markers for clinical applications and drug discovery. project "GRIDCORE" (Italian Ministry of Health, Finalized Research program) [RF-2010-2319113] The present study was developed based on the data of the informal European Consortium PDWAVES. The members and institutional affiliations of the Consortium are reported in the cover page of this manuscript. The activities for this study of Dr. Claudio Babiloni, Claudio Del Percio, and Roberta Lizio performed in the framework of the project "GRIDCORE" (Italian Ministry of Health, Finalized Research program, prot. RF-2010-2319113).

WOS: 000404876400029 PubMed ID: 28621693 The aim of this retrospective and exploratory study was that the cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms might reveal different abnormalities in cortical neural synchronization in groups of patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) and Parkinson's disease (PDMCI) as compared to healthy subjects. Clinical and rsEEG data of 75 ADMCI, 75 PDMCI, and 75 cognitively normal elderly (Nold) subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini-Mental State Evaluation (MMSE) was matched between the ADMCI and PDMCI groups. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Receiver operating characteristic curve (ROC) classified these sources across individuals. Results showed that compared to the Nold group, the posterior alpha2 and alpha3 source activities were more abnormal in the ADMCI than the PDMCI group, while the parietal delta source activities were more abnormal in the PDMCI than the ADMCI group. The parietal delta and alpha sources correlated with MMSE score and correctly classified the Nold and diseased individuals (area under the ROC=0.77-0.79). In conclusion, the PDMCI and ADMCI patients showed different features of cortical neural synchronization at delta and alpha frequencies underpinning brain arousal and vigilance in the quiet wakefulness. Future prospective cross-validation studies will have to test these rsEEG markers for clinical applications and drug discovery. Italian Ministry of Health [RF-2010-2319113] The present study was developed based on the data of the informal European Consortium PDWAVES. The members and institutional affiliations of the Consortium are reported in the cover page of this manuscript. The activities for this study of Dr. Claudio Babiloni, Claudio Del Percio, and Roberta Lizio were performed in the framework of the project "GRIDCORE" (Italian Ministry of Health, Finalized Research program, prot. RF-2010-2319113).

Although a large number of studies have examined possible differences in cognitive performance between Alzheimer's disease (AD) and vascular dementia (VaD), the data in the literature are conflicting. The aims of this study were to analyze the neuropsychological pattern of subjects affected by degenerative dementia without evidence of small vessel pathology (DD) and small vessel VaD subjects in the early stages and to investigate differences in the progression of cognitive impairment. Seventy-five patients with probable VaD and 75 patients with probable DD were included. All the subjects underwent a standard neuropsychological evaluation, including the following test: Visual Search, Attentional matrices, Story Recall, Raven's Coloured Progressive Matrices, Phonological and Semantic Verbal Fluency, Token, and Copying Drawings. The severity of cognitive impairment was stratified according to the MMSE score. Fifteen subjects with probable DD and 10 subjects with probable VaD underwent a 12-month cognitive re-evaluation. No significant difference was found between DD and VaD subjects in any of the neuropsychological tests except Story Recall in the mild cognitive impairment (P

Inflammation is a common response of an individual against either exogenous or endogenous damage. The role of inflammation and of inflammatory cells recently emerged also in the pathogenesis of neurodegenerative disorders. Experimental evidences show how neurotransmitters, besides their role in the synapses, play a modulatory role during immune response. Drugs used for treatment of dementia symptoms are able to increase neurotransmitters levels, and likely to have a modulatory role during immune response. Aim of this review is to discuss the most recent advances on inflammation role during neurodegeneration and also to individuate the potential anti-inflammatory role played by drugs currently used for Alzheimer's disease treatment.

Previous evidence showed a 75.5% best accuracy in the classification of 120 Alzheimer's disease (AD) patients with dementia and 100 matched normal elderly (Nold) subjects based on cortical source current density and linear lagged connectivity estimated by eLORETA freeware from resting state eyes-closed electroencephalographic (rsEEG) rhythms (Babiloni et al., 2016a). Specifically, that accuracy was reached using the ratio between occipital delta and alpha1 current density for a linear univariate classifier (receiver operating characteristic curves). Here we tested an innovative approach based on an artificial neural network (ANN) classifier from the same database of rsEEG markers. Frequency bands of interest were delta (2–4 Hz), theta (4–8 Hz Hz), alpha1 (8–10.5 Hz), and alpha2 (10.5–13 Hz). ANN classification showed an accuracy of 77% using the most 4 discriminative rsEEG markers of source current density (parietal theta/alpha 1, temporal theta/alpha 1, occipital theta/alpha 1, and occipital delta/alpha 1). It also showed an accuracy of 72% using the most 4 discriminative rsEEG markers of source lagged linear connectivity (inter-hemispherical occipital delta/alpha 2, intra-hemispherical right parietal-limbic alpha 1, intra-hemispherical left occipital-temporal theta/alpha 1, intra-hemispherical right occipital-temporal theta/alpha 1). With these 8 markers combined, an accuracy of at least 76% was reached. Interestingly, this accuracy based on 8 (linear) rsEEG markers as inputs to ANN was similar to that obtained with a single rsEEG marker (Babiloni et al., 2016a), thus unveiling their information redundancy for classification purposes. In future AD studies, inputs to ANNs should include other classes of independent linear (i.e., directed transfer function) and non-linear (i.e., entropy) rsEEG markers to improve the classification.

Cognitive alterations accompany or follow motor disorders in subjects with Parkinsonism. The canonical phenotypeof the Parkinson's disease Dementia (PD-D) or Lewy Body Dementia (LBD) includes deficit of attention, executiveand visuospatial functions, and presents often with apathy, hallucinations, delusions, excessive daytime sleepiness,or sleep disorders. However, the clinical expression may overlap with other neurodegenerative diseases associatedwith cognitive disorders. Thus, while clinicians rely on phenomenological patterns to infer the disease causing thecognitive impairment, the inference is weakened by the heterogeneous clinical expression of the disease. In addition,recent post-mortem studies seem to undermine the supposed pathology-phenotype coherence, making it moreand more unreliable the diagnosis based on symptoms. The lack of coherence between phenotype and pathologymay support the speculation about a common mechanism underlying the progression of the disease. While it is verylikely that a distinct, specific causal event determines the disease itself, the progression might well follow commonpatterns. A number of observations suggest that progressive diseases, which cause cognitive impairment, share aprion-like mechanism. A seeding process is supposed to account for the spreading of the lesion.

Here we investigated the effect of the rivastigmine patch alone on depression in 50 mild Alzheimer's Disease (AD) patients with comorbid major depressive episode (MDE). First diagnosis acetyl-cholinesterase inhibitor and psychoactive drug-free outpatients (n = 50) were recruited in memory clinics and reassessed after 3 and 6 months. Global cognitive functioning, depressive symptoms and MDE frequency were evaluated with the Mini Mental State Exami- nation, the CERAD Dysphoria scale and the modified DSM-IV criteria for MDE in AD. MDE frequency reduced significantly from the first diagnostic visit (100%) to the 6-month follow-up (62%). We also found a significant reduction in CERAD Dysphoria scores that decreased from 6.2 ± 3.9 mean ± standard deviation to 4.9 ± 4.5 at the 6-month follow-up. In AD patients with MDE rivastigmine alone can have a positive impact on depressive phenomena. Thus, future controlled study are justified to definitively verify if rivastigmine alone may improve depression in AD.

Cortical gray matter volume and resting state cortical electroencephalographic rhythms are typically abnormal in subjects with amnesic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Here we tested the hypothesis that in amnesic MCI and AD subjects, abnormalities of EEG rhythms are a functional reflection of cortical atrophy across the disease. Eyes‐closed resting state EEG data were recorded in 57 healthy elderly (Nold), 102 amnesic MCI, and 108 AD patients. Cortical gray matter volume was indexed by magnetic resonance imaging recorded in the MCI and AD subjects according to Alzheimer's disease neuroimaging initiative project (http://www.adni-info.org/). EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha1 (8–10.5 Hz), alpha2 (10.5–13 Hz), beta1 (13–20 Hz), beta2 (20–30 Hz), and gamma (30–40 Hz). These rhythms were indexed by LORETA. Compared with the Nold, the MCI showed a decrease in amplitude of alpha 1 sources. With respect to the Nold and MCI, the AD showed an amplitude increase of delta sources, along with a strong amplitude reduction of alpha 1 sources. In the MCI and AD subjects as a whole group, the lower the cortical gray matter volume, the higher the delta sources, the lower the alpha 1 sources. The better the score to cognitive tests the higher the gray matter volume, the lower the pathological delta sources, and the higher the alpha sources. These results suggest that in amnesic MCI and AD subjects, abnormalities of resting state cortical EEG rhythms are not epiphenomena but are strictly related to neurodegeneration (atrophy of cortical gray matter) and cognition. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.

Preliminary studies, based on a region-of-interest approach, suggest that quantitative magnetization transfer (qMT), an extension of magnetization transfer imaging, provides complementary information to conventional magnetic resonance imaging (MRI) in the characterisation of Alzheimer's disease (AD). The aim of this study was to extend these findings to the whole brain, using a voxel-wise approach. We recruited 19AD patients and 11 healthy subjects (HS). All subjects had an MRI acquisition at 3.0T including a T(1)-weighted volume, 12 MT-weighted volumes for qMT, and data for computing T(1) and B(1) maps. The T(1)-weighted volumes were processed to yield grey matter (GM) volumetric maps, while the other sequences were used to compute qMT parametric maps of the whole brain. qMT maps were warped to standard space and smoothed, and subsequently compared between groups. Of all the qMT parameters considered, only the forward exchange rate, RM(0)(B), showed significant group differences. These images were therefore retained for the multimodal statistical analysis, designed to locate brain regions of RM(0)(B) differences between AD and HS groups, adjusting for local GM atrophy. Widespread areas of reduced RM(0)(B) were found in AD patients, mainly located in the hippocampus, in the temporal lobe, in the posterior cingulate and in the parietal cortex. These results indicate that, among qMT parameters, RM(0)(B) is the most sensitive to AD pathology. This quantity is altered in the hippocampus of patients with AD (as found by previous works) but also in other brain areas, that PET studies have highlighted as involved with both, reduced glucose metabolism and amyloid β deposition. RM(0)(B) might reflect, through the measurement of the efficiency of MT exchange, some information with a specific pathological counterpart. Given previous evidence of a strict relationship between RM(0)(B) and intracellular pH, an intriguing speculation is that our findings might reflect metabolic changes related to mitochondrial dysfunction, which has been proposed as a contributor to neurodegeneration in AD.

To investigate, in a group of subjects with cognitive impairment, the relationship between anosognosia, in each dimension of insight, and neuropsychological domains.Two hundred and seventy-one subjects affected by cognitive impairment were consecutively enrolled. Anosognosia was evaluated by means of the Clinical Insight Rating Scale (CIRS). The general level of cognitive impairment was evaluated by means of the Mini-Mental State Examination, while 8 cognitive domains were examined by means of neuropsychological tests.The number of subjects with anosognosia evaluated by means of the CIRS total score as well as those with anosognosia divided according to the reason for visit was higher in moderately cognitively impaired subjects than in mildly cognitively impaired subjects (p0.001). A relationship between anosognosia and neuropsychological scores was only found in mild cognitive impairment, with subjects with anosognosia displaying significantly lower Raven's Colored Progressive Matrices Test and Rey Auditory Verbal Learning Test-delayed recall scores than subjects without anosognosia.Our study suggests that the relationship between the severity of cognitive deficits and anosognosia in subjects with cognitive impairment is partial and depends on the specific domain of unawareness. Furthermore, in the early phase of cognitive impairment, the presence of specific cognitive deficits suggests that the nature of anosognosia is domain-specific.

This study investigates the differential contribution of gray matter (GM) atrophy and deafferentation through white matter (WM) damage in the clinical progression of Alzheimer's disease (AD). Thirty‐one patients with probable AD, 23 with amnestic mild cognitive impairment (a‐MCI), and 14 healthy subjects underwent MRI scanning at 3T. Voxel‐based morphometry was used to assess regional GM atrophy in AD and a‐MCI patients. Diffusion tensor‐MRI tractography was used to reconstruct the cingulum bilaterally, and to quantify, voxel‐by‐voxel, its fractional anisotropy (FA) and mean diffusivity (MD) (measures of microscopic WM integrity). Atrophy of the cinguli was also assessed by means of jacobian determinants (JD) of local transformations. In AD patients, four clusters of reduced GM were found nearby the cinguli, in the posterior (PCC) and anterior cingulate cortex, and in the hippocampal/parahippocampal areas. Widespread areas of reduced FA and increased MD were found in the cinguli of both, AD and a‐MCI patients. A region of macroscopic atrophy was detectable in AD patients only. Strong associations were found between local GM densities in the four identified clusters, and measures of micro‐ and (to a lesser extent) macroscopic damage of patients' cinguli. Linear regression analyses revealed that MD in the cinguli predicts patients' measures of episodic memory in combination with GM density of hippocampal/parahippocampal areas, and measures of global cognition in combination with GM density of the PCC. This study indicates that brain deafferentation though the cingulum is likely to play a remarkable role in progressive development of cognitive impairment in AD. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.

The subventricular zone (SVZ) is a region that lies immediately beneath the ependymal layer on the lateral wall of the lateral ventricles, and is separated from the caudate nucleus by a layer of myelin. It contains multipotent neural stem cells. The aim of this study was to investigate the tissue around the SVZ, with the hypothesis that multimodal MRI is able to highlight the progressive disruption of tissue caused by the neurodegenerative disease in this area. We combined volumetric and diffusion tensor (DTI) imaging using a 3 T imager in a cross-sectional study including 30 patients with amnestic-mild cognitive impairment (a-MCI), 30 patients with Alzheimer's disease (AD) and 30 age- and gender-matched healthy controls (HC). Our data indicate that mean diffusivity (MD) values increase continuously from HC through a-MCI to AD in the bilateral SVZ, where most of the proliferating stem cells in the adult brain are located. This result was specific for the SVZ and could not be observed in other periventricular areas. Multimodal MRI, being able to highlight structural changes of microscopic tissue in humans in vivo, could represent a precious tool to complement histological studies of neurogenesis.

JO N 2912 and personal life of these patients. Hypothesizing that impotence may be an intrinsic characteristic in DM1, we performed a study to assess its frequency and characteristics. The complete series of male patients (aged 18-60 years) with genetically-confirmed DM1, under clinical surveillance in our Neuromuscular Unit in January 2005, was clinically evaluated for any disease or medication and tested with both the Mini-Mental State Examination and Hamilton Depression Rating Scale. Subjects with physical or mental diseases known to interfere with sexual activity [4] and those with congenital DM1, or cognitive dysfunction or HAM-D “severe” or “very severe” scores, were excluded. Patients are shown in Fig. 1. A total of 31 patients and 31 age-matched healthy controls filled out the questionnaire of the Internationally Validated Index of ErecGiovanni Antonini Alessandro Clemenzi Elisabetta Bucci Stefania Morino Matteo Garibaldi Micaela Sepe-Monti Franco Giubilei Giuseppe Novelli

A body of evidence indicates that inflammation plays a pivotal role in AD pathogenesis. IL-18 is a pro-inflammatory cytokine produced in the brain, emerging to be implicated in AD. Although no differences in circulating IL-18 levels were measured between AD patients and controls, a significant increased production of IL-18 was obtained from stimulated blood mononuclear cells of AD patients. This was true particularly in AD subjects carrying the C/C genotype at the -607 position of IL-18 gene promoter. Furthermore, a significant correlation between IL-18 production and cognitive decline was observed in AD patients. Overall, these data indicate that IL-18-related inflammatory pathways, probably also in virtue of polymorphic IL-18 gene influence, are exacerbated in AD patients, and that this cytokine may indeed participate in pathogenic processes leading to dementia.

We present the case of a man affected by amnestic mild cognitive impairment (aMCI) who showed bilateral hippocampal sclerosis at magnetic resonance imaging (MRI). We argue the concept that aMCI is heterogeneous syndrome and suggested the utility of coronal T2-weighted MRI images in the routine dementia workup.

There is a growing interest to evaluate metals in biological fluids in Alzheimer's disease (AD). There are numerous studies on this theme, but just few papers analyzed the relationship between haematic metal concentrations and the clinical features of the disease. In this study, possible associations between clinical features of AD and the variations in serum and blood concentration of some metals, as well as the serum oxidative status and the antioxidant capacity have been investigated. Sixty subjects with AD were enrolled. Some elements correlated with gender, depression and duration of the disease. However, the most significant result was the relationship between blood Ca and Fe levels and the severity of cognitive impairment. We hypothesize that Ca and Fe might play an important role in the pathogenetic mechanisms of AD.

Brain involvement in myotonic dystrophy type 1 (DM1) is characterised by cortical atrophy and white matter lesions. We compared the magnetic resonance imaging derived grey matter maps of 22 DM1 patients with those of matched, healthy controls using voxel based morphometry to evaluate the extension of global and regional cortical atrophy in DM1, as well as its relationships with clinical and genetic features. Patients had significantly reduced brain tissue volumes. Grey matter volume was inversely correlated with age; this inverse correlation was significantly stronger in DM1 than in controls. Neither the clinical and genetic characteristics nor white matter lesions were correlated with cortical atrophy. Grey matter atrophy was located mainly in the bilateral frontal and parietal lobes, in the bilateral middle temporal gyrus, and in the left superior temporal and occipital gyrus.

The cause of downbeat nystagmus (DBN) remains undiagnosed in about 40% of patients. This paper reports the presence of antiglutamic acid decarboxylase antibodies (GAD-Ab) in a patient with DBN. Antibodies against GABAergic neurons located in the vestibular complex may induce chemical denervation of the floccular neurons, which normally suppress the peripheral imbalance between vertical semicircular canal systems, thereby causing DBN. Testing for GAD-Ab may be indicated in DBN patients without an identifiable anatomical brain lesion.

Despite the vast amount of literature on non-specific immune mechanisms in Alzheimer’s disease (AD), little is known about the role of antigen-specific immune responses. We investigated T cell reactivity to fragment 1–42 of amyloid-β (Aβ) and to N-terminal peptides of human mitochondrial and control microbial proteins. Thirty subjects with a diagnosis of probable AD according to NINCDS-ADRDA criteria and 30 sex- and age-matched healthy controls were enrolled. T cell responses to Aβ fragment showed no significant differences between AD patients and controls. By contrast, the mean number of positive T cell responses to both human mitochondrial and microbial peptides was significantly decreased in AD patients compared to control subjects. No significant correlation was found between T cell responses and both the severity of cognitive impairment and duration of the disease. Our results suggest that antigen-specific immune responses are impaired in AD. Protective immune responses to harmful amyloidogenic substances may also be impaired, thus favoring their accumulation in the brain.

Two distinct pathways are thought to connect the striatum to the basal ganglia output nuclei: a direct pathway, originating from neurons bearing dopamine, D 1 receptors and an indirect pathway, originating from neurons expressing D 2 receptors. It has been recently suggested, however, that dopamine receptor sub-types may co-localize and co-operate in the striatum. We sought to verify the functional segregation of the two pathways by measuring cerebral glucose utilization following intrastriatal injection of selective D 1 (SKF 38393), D 2 (quinpirole), or non-selective indirect (amphetamine) and direct (apomorphine) dopamine agonists, in freely-moving rats. All drugs – regardless of receptor selectivity – reduced glucose utilization in nuclei of both the direct and indirect pathways, thus lending further support to the existence of a functional co-operation of striatal D 1 and D 2 receptors.

To detect signs of axonal damage in MS, the authors investigated the occurrence in EMG of motor unit action potentials with satellite potentials (SP-MUAP) in the upper limb muscles in 10 consecutive patients with MS with cervical spinal cord demyelinating lesions and 10 control subjects. Subjects' SP-MUAP rate was 0 to 2.5% (median 0%) in the control group, and 0 to 17.5% (median 7.5%) in the MS group (p < 0.01). Motor unit remodeling secondary to axonal transection of spinal motor neurons traversing cervical demyelinating lesions may be hypothesized.

Contrasting data on reading ability in Alzheimer's disease patients have been reported in the literature. Recently Patterson, Graham and Hodges (1994) found that irregular words were misread by demented subjects, while regular words were read correctly. The present study hypothesizes that reading latency may be a sensitive measure of Alzheimer's patients reading impairment. Fifteen Alzheimer's patients were compared with 17 elderly normal subjects on three tasks that used the same set of concrete, regular words: a picture naming task, a word-picture matching task and a word-nonword reading task. The results of the study indicate that reading latency is longer in Alzheimer's patients than in normal subjects, and that misnamed and mismatched words are read with the same mechanism as nonwords.

Summary Alzheimer's disease (AD) has a significant social and economic impact on patients, their families and society as a whole. The diagnosis is difficult at the onset of symptoms, when the memory decline or a behavioral changes are easily explained with stress or general age-related asthenia, slowing down the correct diagnosis and often requires very expensive diagnostical examinations. The aim of this work was at evaluating the global price sustained by each patient before reaching the diagnosis of probable AD, paid for examination, drugs and specialists consultations because of the progressive cognitive and/or behavioral diseases. Twenty patients were interviewed by a semi-structured method, in order to evaluate the clinical onset of the disease, the number of specialists consulted before diagnosis of probable AD, the list of examinations performed, the costs of examinations and drugs administered in this period. The mean delay between clinical onset and diagnosis of probable AD was 30.7 ± 32.7 months (SD). The clinical picture at onset was dominated by behavioral disease in 66 % of cases and by cognitive symptoms in 34 % of cases. The patients consulted on average 2 specialists before diagnosis. Five patients were affected also by other concomitant pathologies at the onset of cognitive decline and, for this reason, these patients were visited and treated also by other specialists who made hypothesis or reaffirm the diagnostical course for a cognitive decline. The examinations performed, suggested by the specialist, were: blood chemistry, computed tomography (CT) scans, ultrasonography of cervical arteries, magnetic resonance imagin electroencephalography, single photon positron emission tomography. The meancost sustained by each patient for examinations performed by the public health service was about 112 US Dollars, while the mean cost sustained by each patient for examinations performed by private health service was about 402 Dollars. The specialists prescribed more often vitamins, nootropics and benzodiazepines. The most expensive drugs were the psychiatric drugs. The main price sustained for drugs was 505 + 233 Dollars. AD is a strongly devastating and expensive illness, and the magnitude of the economic burden imposed by the disease on society will increase in the coming years. Moreover, some examinations prescribed are often not helpful for the diagnosis. It is possible that the costs in the future may be influenced, among other things, by demographic changes, new therapies and diagnostical examinations.

Patients with myotonic dystrophy frequently complain of hypersomnolence, a symptom which seriously restricts their social life. The pathogenesis of this symptom is a matter of debate: it has been attributed to both alveolar hypoventilation and pathological changes in the brainstem. As selegiline has been shown to reduce the number of sleep attacks in narcolepsy, we tested whether hypersomnolence in myotonic dystrophy would respond to the same treatment. Ten patients with myotonic dystrophy received selegiline/placebo (20 mg daily) in a double-blind crossover trial. We monitored daytime sleepiness by means of a multiple sleep latency test. Treatment appeared to be well tolerated but did not alter hypersomnolence in myotonic dystrophy. Further studies to assess the effect of higher doses of selegiline are warranted.

Blood levels of triglycerides, total cholesterol, isolated lipoprotein fractions (VLDL- LDL- and HDL-cholesterol) and apoproteins (Apo-A1 and Apo-B) were examined in multi-infarct dementia, senile dementia of the Alzheimer type, ischemic stroke associated with carotid atherosclerosis and in control subjects. Forty patients divided into 10 consecutive patients for each group were studied. Alzheimer patients showed mean total cholesterol and Apo-B values significantly higher than control subjects. Apo-B was significantly higher in stroke patients than in controls. The mean lowest HDL-cholesterol (HDL-c) value was observed in stroke patients. No significant differences in mean HDL-c levels were found between patients with multi-infarct and Alzheimer dementia.