Ascertainment bias in dementias: a secondary to tertiary centre analysis in Central Italy and conceptual review.

BACKGROUND AND AIMS: Ascertainment bias (AB) indicates a bias of an evaluation centre in estimating the prevalence/incidence of a disease due to the specific expertise of the centre. The aim of our study was to evaluate classification of different types of dementia in new cases appearing in secondary and tertiary centres, in order to evidence possible occurrence of AB in the various (secondary to tertiary) dementia centres. METHODS: To assess the mechanism of AB, the rates of new cases of the different forms of dementia reported by different centres were compared. The centres involved in the study were 11 hospital-based centres including a tertiary centre, located in the University Department of Clinical Neurology. The tertiary centre is endowed with state-of-the-art diagnostic facilities and its scientific production is prominently focused on dementia with Lewy bodies (DLB) thus suggesting the possible occurrence of a bias. Four main categories of dementia were identified: Alzheimer's disease (AD), DLB, fronto-temporal dementia (FTD), vascular dementia (VaD), with other forms in a category apart. The classification rate of new cases of dementia in the tertiary centre was compared with rates reported by secondary centres and rates of recoding were calculated during a follow-up of 2 years. RESULTS: The study classified 2,042 newly diagnosed cases of dementia in a population of 1,370,000 inhabitants of which 315,000 were older than 65. AD was categorized in 48-52 % of cases, DLB in 25-28 %, FTD in 2-4 % and VaD in 17-28 %. During the 2-year follow-up the diagnosis was re-classified in 40 patients (3 %). The rate of recoding was 5 % in the tertiary centre, 2-8 % in referrals from secondary to tertiary centre, 2-10 % in recodings performed in secondary centres and addressed to tertiary centre. Recoding or percentages of new cases of AD or DLB were not different in the comparison between secondary or between secondary and tertiary centres. FTD and VaD were instead significantly recoded. CONCLUSION: The results of the study suggest that in a homogeneous area, AB is not interfering with diagnosis of AD or DLB.

Electrophysiological traces of visuomotor learning and their renormalization after sleep.

OBJECTIVE: Adapting movements to a visual rotation involves the activation of right posterior parietal areas. Further performance improvement requires an increase of slow wave activity in subsequent sleep in the same areas. Here we ascertained whether a post-learning trace is present in wake EEG and whether such a trace is influenced by sleep slow waves. METHODS: In two separate sessions, we recorded high-density EEG in 17 healthy subjects before and after a visuomotor rotation task, which was performed both before and after sleep. High-density EEG was recorded also during sleep. One session aimed to suppress sleep slow waves, while the other session served as a control. RESULTS: After learning, we found a trace in the eyes-open wake EEG as a local, parietal decrease in alpha power. After the control night, this trace returned to baseline levels, but it failed to do so after slow wave deprivation. The overnight change of the trace correlated with the dissipation of low frequency (<8 Hz) NREM sleep activity only in the control session. CONCLUSIONS: Visuomotor learning leaves a trace in the wake EEG alpha power that appears to be renormalized by sleep slow waves. SIGNIFICANCE: These findings link visuomotor learning to regional changes in wake EEG and sleep homeostasis.

Attention modulation regulates both motor and non-motor performance: a high-density EEG study in Parkinson's disease.

We have previously shown that, in early stages of Parkinson's disease (PD), patients with higher reaction times are also more impaired in visual sequence learning, suggesting that movement preparation shares resources with the learning of visuospatial sequences. Here, we ascertained whether, in patients with PD, the pattern of the neural correlates of attentional processes of movement planning predict sequence learning and working memory abilities. High density Electroencephalography (EEG, 256 electrodes) was recorded in 19 patients with PD performing reaching movements in a choice reaction time paradigm. Patients were also tested with Digit Span and performed a visuomotor sequence learning task that has an important declarative learning component. We found that attenuation of alpha/beta oscillatory activity before the stimulus presentation in frontoparietal regions significantly correlated with reaction time in the choice reaction time task, similarly to what we had previously found in normal subjects. In addition, such activity significantly predicted the declarative indices of sequence learning and the scores in the Digit Span task. These findings suggest that some motor and non motor PD signs might have common neural bases, and thus, might have a similar response to the same behavioral therapy. In addition, these results might help in designing and testing the efficacy of novel rehabilitative approaches to improve specific aspects of motor performance in PD and other neurological disorders.

[Experience in risk assessment in variety type of work: reflection on reliability and judgement in method reference to European accord, 2004]. / Esperienze di valutazioni del rischio stress in realtà lavorative di varia tipologia: riflessioni sull'attendibilità e riproponibilità del metodo anche in riferimento all'accordo europeo del 2004.

Interest in problems of work-related stress has been limited, till now, to its effects on health of workers. The aim of our study, lacking valid literature's instruments, is to experiment and to evaluate a risk's evaluation model to identify and prevent or manage problems of work-related stress also according to indications published in "European Framework Agreement on work-related stress" (08/10/2004). Our evaluation model (even according to art. 28 D.Lgs. 81/2008) has been experimented in a sample composed by 1470 employers in 19 Lomabardia's factories. Valued risk's results have been introduced in the risk assessment and they have been used to sanitary surveillance indications.

Peripheral cytokines profile in Parkinson's disease.

Higher levels of proinflammatory cytokines are found in Parkinson's disease (PD) patient's brains and inflammation is thought to be a major contributor to the neurodegeneration. During the inflammatory process, microglial release of proinflammatory cytokines act on the endothelium of blood-brain barrier (BBB) cells to stimulate upregulation of adhesion molecules. Consequently, this upregulation leads to the recruitment of passing T cells and monocytes, which express the counter receptors, that then go on to release more cytokines [Whitton, P.S., 2007. Inflammation as a causative factor in the aetiology of Parkinson's disease, Br. J. Pharmacol. 50, 963-976; Kortekaas, R., Leenders, K.L., Van Oostrom, J.C., Vaalburg, W., Bart, J., Willemsen, A.T., Hendrikse, N.H., 2005. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo, Ann. Neurol. 57, 176-179]. In addition, a systemic inflammatory response results in the production of cytokines which circulate in the blood and communicate with neurons within the brain. Thus, a central inflammatory reaction interacts with peripheral blood mononuclear cells (PBMCs) modulating immune activity. The present study investigates levels of production and expression of cyto/chemokines by PBMCs in PD patients. Basal and LPS-induced levels of MCP-1, RANTES, MIP-1alpha, IL-8, IFNgamma, IL-1beta and TNFalpha were significantly higher in PD patients than in HC subjects (p<0.001), as determined by RT-PCR and Elisa methods. Cyto/chemokine levels were significantly correlated with UPDRS III and H/Y stage (p<0.001). The Pearson's correlation coefficient (R) was also used to assess the strength of the relationship between NF-kappaBp65 levels and all studied cyto/chemokines and between NF-kappaBp65, UPDRS III and H/Y score in PD patients. The overall results strengthen and extend the knowledge of the peripheral dysregulation in the cytokine network associated with PD.

New morphologic variants of the hand motor cortex as seen with MR imaging in a large study population.

BACKGROUND AND PURPOSE: The hand motor cortex (HMC) has been classically described as having an omega or epsilon shape in axial-plane images obtained with CT and MR imaging. The aim of this study was to use MR imaging and Talairach normalization in a large sample population that was homogeneous for age and handedness to evaluate in a sex model a new classification with 5 morphologic variants of the HMC in the axial plane (omega, medially asymmetric epsilon, epsilon, laterally asymmetric epsilon, and null). MATERIALS AND METHODS: Structural brain MR images were obtained from 257 right-handed healthy subjects (143 men and 114 women; mean age, 23.1 +/- 1.1 years) via a Talairach space transformed 3D magnetization-prepared rapid acquisition of gradient echo sequence. The frequencies of the different HMC variants were reported for hemisphere and sex. RESULTS: The new variants of the HMC (medially asymmetric epsilon, laterally asymmetric epsilon, and null) were observed in 2.9%, 7.0%, and 1.8% of the hemispheres, respectively. Statistically significant sex differences were observed: The epsilon variant was twice as frequent in men, and an interhemispheric concordance for morphologic variants was observed only for women. CONCLUSION: The large study population permitted the description of a new morphologic classification that included 3 new variants of the HMC. This new morphologic classification should facilitate the identification of the precentral gyrus in subsequent studies and in everyday practice.

Low- and high-frequency evoked responses following pattern reversal stimuli: a MEG study supported by fMRI constraint.

We investigated the neural generators of N1 and P1 components of visual magnetic responses through the concomitant study of low (1-15 Hz)- and high (15-30 Hz)-frequency brain activities phase-locked to stimulus and elicited by pattern reversal visual stimuli. Whole helmet magnetic recordings and dipole modeling technique with support of functional magnetic resonance imaging (fMRI) were used to characterize locations and orientations of N1 and P1 sources as a function of four stimulated visual field quadrants. A comparison between low- and high-frequency activities revealed fundamental differences among orientations of the quadrants dipoles thus suggesting partly distinct neural populations underlying low- and high-frequency responses to transient contrast visual stimuli. Moreover, for both low- and high-frequency bands the specific study of locations and orientations of N1 and P1 sources indicated V1/V2 cortex as the neural substrate generating the two components. In summary, we provided strong support for a cortical genesis of human oscillatory mass activity following transient contrast stimuli with specific neural districts active in the low- and high-frequency bands. The converging results obtained from the concomitant investigation of probably different brain activities provided new evidences for a striate genesis of N1 and P1 components of the broadband visual-evoked responses following pattern reversal.

[Proposal for an evaluation method of the psyco-social risks (stress) and for the orientation of the sanitary surveillance]. / Proposta di un metodo per la valutazione dei rischi psicosociali (stress) e di orientamento per la sorveglianza sanitaria.

The interest for the problematics linked to the stress in work environments has been till now limited to the consideration of its effects on health, even if the D.Lgs 626/94 obliges the employer to evaluate also the psyco-social risk, as has confirmed a sentence of the European Court of Justice. The present survey, lacking valid instruments to be found in literature, aims to experiment and evaluate a principle for the identification of causes, thus creating a model for the evaluation of risk also according to the indications published in the Document for the Consent of SIMLII in 2005, which can be used by Prevention and Protection Services and by Competent Medical Doctors. In the area of risks evaluation and of the attainment deriving from them. The model of evaluation of the risk deriving from work organization (stress), object of the present survey, has been sperimented in a sample composed of 268 employees in 13 municipal administration belonging to biographically known categories for stress risk afferent to 23 homogenuous organizational structures (traffic officers and nursery school teachers). The valued risk has been introduced in the VDR document and the indications for the sanitary surveillance have been formulated.