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The Boston Naming Test (BNT) is a neuropsychological tool that is widely utilized in clinical practice to detect naming difficulties (i.e., anomia) in patients with language disorders and to evalua...

Introduction. Prospective memory (PM) is the ability of forming and maintaining an intention in memory over time while performing another task. From previous studies in healthy volunteers the prefrontal regions are deeply involved in PM, although little is known in early Alzheimer's disease (AD). Hence, we investigated the functional neural basis of PM in patients with mild cognitive impairment due to AD (MCI-AD) by assessing brain metabolism (18F-FDG PET). Methods. Eighteen patients (10 males, age:74±4.9; MMSE score:27.7±1.6) with intermediate or high likelihood of MCI-AD and a control group (HC) of 23 healthy subjects (11 males, age:71.5±5.7) underwent FDG-PET, neuropsychological evaluation and the PM-specific Shum and Ungvari paradigm test. Brain metabolism was correlated with the PM score in the two groups separately to find those brain areas correlated with PM performance ('PM cluster'), which were then used as central hub for the subsequent interregional metabolic connectivity analyses (IRCA). Results. In MCI-AD patients PM score positively correlated with metabolic levels in the right anterior prefrontal cortex (aPFC, middle and inferior frontal gyri); no correlation was found in HC. The IRCA showed in MCI-AD patients a loss of the interhemispheric connectivity of the PM cluster. Conclusion. The functioning of the right aPFC and its metabolic interhemispheric connectivity is crucial in early AD to sustain PM performance which deteriorates along with progressive metabolic failure in these regions.

Background Coronavirus disease 2019 (COVID-19) related confinement severely impacted people wellbeing. Many studies focused on general population, although it is reasonable to expect that patients with neurodevelopmental disorders might have been at higher risk. Children/adolescents with Attention Deficit/Hyperactivity Disorder (ADHD) might be potentially more vulnerable, due to their intolerance to forced restrictions that limit stimulating experiences, to obligation to follow instructions and to acceptation of imposed rules We aimed to compare stress-related behavioral changes of the first COVD-19 related confinement among 6-18 years old ADHD and typically developing subjects. Methods Two parent-proxy online surveys have been employed, shared via social media. Symptoms of acute stress related to the pandemic and a question about family members/households' COVID-19 positivity have been listed in 8 yes/no items. Chi-squared tests were applied. Results Final sample consisted of 1078 typically developing subjects and 979 ADHD. Exaggerated startle response, difficulties in waking-up, angry mood as well as COVID-19 related fears were more prevalent among ADHD vs. typically developing subjects. typically developing subjects showed higher prevalence of research for information about COVID-19 and worries about death. Conclusions In conclusion, the COVID-19 experience significantly impacted children and adolescents with ADHD to a great extent, similarly to typically developing subjects. ADHD showed more anxious-phobic responses, while typically developing subjects demonstrate more depressive attitudes. Differences in stress symptoms profiles between ADHD and T typically developing subjects warrant to develop distinct strategies of therapeutic interviews.

Background: Several automatic tools have been implemented for semi-quantitative assessment of brain [ 18 ]F-FDG-PET. Objective: We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e., PALZ), and a volumetric region of interest (VROI-SVM)-based approach, in distinguishing patients with prodromal Alzheimer's disease (pAD) from controls. Methods: Sixty-two pAD patients (MMSE score = 27.0±1.6) and one hundred-nine healthy subjects (CTR) (MMSE score = 29.2±1.2) were enrolled in five centers of the European Alzheimer's Disease Consortium. The three SPM-based methods, based on different rationales, included 1) a cluster identified through the correlation analysis between [ 18 ]F-FDG-PET and a verbal memory test (VROI-1), 2) a VROI derived from the comparison between pAD and CTR (VROI-2), and 3) visual analysis of individual maps obtained by the comparison between each subject and CTR (SPM-Maps). The VROI-SVM approach was based on 6 VROI plus 6 VROI asymmetry values derived from the pAD versus CTR comparison thanks to support vector machine (SVM). Results: The areas under the ROC curves between pAD and CTR were 0.84 for VROI-1, 0.83 for VROI-2, 0.79 for SPM maps, 0.87 for PALZ, and 0.95 for VROI-SVM. Pairwise comparisons of Youden index did not show statistically significant differences in diagnostic performance between VROI-1, VROI-2, SPM-Maps, and PALZ score whereas VROI-SVM performed significantly (p < 0.005) better than any of the other methods. Conclusion: The study confirms the good accuracy of [ 18 ]F-FDG-PET in discriminating healthy subjects from pAD and highlights that a non-linear, automatic VROI classifier based on SVM performs better than the voxel-based methods.

Prader-Willi Syndrome (PWS) is a complex genetic disorder with multiple cognitive, behavioral and endocrine dysfunctions. Sleep alterations and sleep disorders such as Sleep-disordered breathing and Central disorders of hypersomnolence are frequently recognized (either isolated or in comorbidity). The aim of the review is to highlight the pathophysiology and the clinical features of sleep disorders in PWS, providing the basis for early diagnosis and management. We reviewed the genetic features of the syndrome and the possible relationship with sleep alterations in animal models, and we described sleep phenotypes, diagnostic tools and therapeutic approaches in humans. Moreover, we performed a meta-analysis of cerebrospinal fluid orexin levels in patients with PWS; significantly lower levels of orexin were detected in PWS with respect to control subjects (although significantly higher than the ones of narcoleptic patients). Sleep disorders in humans with PWS are multifaceted and are often the result of different mechanisms. Since hypothalamic dysfunction seems to partially influence metabolic, respiratory and sleep/wake characteristics of this syndrome, additional studies are required in this framework.

Objective To investigate clinical and dopaminergic pre-synaptic brain imaging characteristics of subjects with idiopathic rapid eye movement (REM) behavior disorder (iRBD) and mild cognitive impairment (MCI), and to evaluate the combined predictive value of risk factors for short-term conversion to synucleinopathy. Method In sum, 44 polysomnography (PSG)-confirmed iRBD patients (68.5 ± 7.2 years; 38 males) underwent 123I-FP-CIT-SPECT, comprehensive neuropsychological evaluation, clinical examination and clinical follow-up every six months (30.6 ± 21.5 months). Step-wise logistic regression was applied to identify those features discriminating iRBD patients with (iRBD-MCI; n = 14) and without MCI (normal cognition [NC], iRBD-NC; n = 30). The risk of neurodegeneration was estimated with Kaplan–Meier analysis. Predictors of phenoconversion were assessed with Cox proportional-hazards analysis, adjusting for age, gender and education. A generalized linear model (GLM) was applied to define the best combination of risk factors predicting conversion at follow-up. Results At baseline, patients with iRBD-MCI showed reduced striatal dopamine transporter (DAT) specific to non-displaceable binding ratio (SBR) and more constipation compared with iRBD-NC patients (p Conclusions iRBD-MCI patients showed a more severe dopaminergic neuroimaging and clinical phenotype. Combining clinical and neuroimaging markers allowed to achieve excellent ability in identifying iRBD patients at high risk of developing a synucleinopathy within about three years from diagnosis.

The COVID-19 pandemic has changed individuals' lifestyles to a great extent, particularly in Italy. Although many concerns about it have been highlighted, its impact on children and adolescents has scarcely been examined. The purpose of this study was to explore behavioral consequences and coping strategies related to the pandemic among families in Italy, by focusing on developmental ages from the caregivers' perspective, 3 weeks into quarantine. An exploratory cross-sectional online survey was conducted over 14 days. Google Forms was employed to conduct the survey. Demographic variables and pre-existing Psychological Weaknesses (PsW) were asked. Adults' sleep difficulties (SleepScore) and coping strategies during quarantine were assessed. Behavioral changes related to quarantine of both subjects completing the form (COVIDStress) and their children (when present) were questioned. Of the 6,871 respondents, we selected 6,800 valid questionnaires; 3,245 declared children aged under 18 years of age (caregivers). PsWs were recognizable in 64.9% among non-caregivers and in 61.5% of caregivers, with a mean PsW score of 1.42 ± 1.26 and 1.30 ± 1.25 over 3 points, respectively. The 95.5% of the non-caregivers and the 96.5% of caregivers presented behavioral changes with a mean COVIDStress of 3.85 ± 1.82 and 4.09 ± 1.79 over 8, respectively (pp < 0.001), who showed higher SleepScores (2.41 ± 1.26 against 2.57 ± 1.38 points over 6, p < 0.001). COVIDStress (and SleepScore) strongly correlated with PsW (p < 0.001). Caregivers observed behavioral changes in their children in the 64.3% of the p < 0.001). Presence of caregivers' coping strategies was less associated to behavioral changes in the p = 0.001) but not in the 6–18 (p = 0.06). The COVID-19 pandemic has adversely impacted families in Italy with regard to behavioral changes, especially in high-risk categories with PsWs and caregivers, especially the ones with children aged

Background: Several automatic tools have been implemented for semi-quantitative assessment of brain [ 18 ]F-FDG-PET. Objective: We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e., PALZ), and a volumetric region of interest (VROI-SVM)-based approach, in distinguishing patients with prodromal Alzheimer's disease (pAD) from controls. Methods: Sixty-two pAD patients (MMSE score = 27.0±1.6) and one hundred-nine healthy subjects (CTR) (MMSE score = 29.2±1.2) were enrolled in five centers of the European Alzheimer's Disease Consortium. The three SPM-based methods, based on different rationales, included 1) a cluster identified through the correlation analysis between [ 18 ]F-FDG-PET and a verbal memory test (VROI-1), 2) a VROI derived from the comparison between pAD and CTR (VROI-2), and 3) visual analysis of individual maps obtained by the comparison between each subject and CTR (SPM-Maps). The VROI-SVM approach was based on 6 VROI plus 6 VROI asymmetry values derived from the pAD versus CTR comparison thanks to support vector machine (SVM). Results: The areas under the ROC curves between pAD and CTR were 0.84 for VROI-1, 0.83 for VROI-2, 0.79 for SPM maps, 0.87 for PALZ, and 0.95 for VROI-SVM. Pairwise comparisons of Youden index did not show statistically significant differences in diagnostic performance between VROI-1, VROI-2, SPM-Maps, and PALZ score whereas VROI-SVM performed significantly (p < 0.005) better than any of the other methods. Conclusion: The study confirms the good accuracy of [ 18 ]F-FDG-PET in discriminating healthy subjects from pAD and highlights that a non-linear, automatic VROI classifier based on SVM performs better than the voxel-based methods.

Introduction The reduction of background activity and the increase of low-frequency powers on electroencephalogram (EEG) correlate with cognitive impairment and have been suggested to be underpinned by cholinergic deficit. We aimed to investigate the ratio between α and θ band power (α/θ ratio), as a synoptic index of quantitative EEG (qEEG) slowing-down, in a peculiar group of patients with mild cognitive impairment (MCI) due to an early-stage Lewy body disease (MCI-LBD), as compared to de novo PD patients without cognitive impairment (PD-MOT), to patients with MCI due to Alzheimer's disease (MCI-AD), and to healthy controls (HC). Methods Twelve patients with MCI-LBD (8 males; mean age 74.8 ± 3.6), 11 PD-MOT, 11 MCI-AD and 24 HC subjects undergoing qEEG were matched for gender, age, and education. Following logarithmic transformation, the α/θ ratio was compared among groups and brain regions by repeated measures ANOVA, also exploring group*regions interactions. Results A significant effect of group (p = 0.0003), regions (p = 0.0001), and group*regions interaction (p = 0.0001) on the α/θ ratio was observed. At post-hoc analysis, α/θ ratio was significantly lower in MCI-LBD (p = 0.001) and in PD-MOT (p = 0.02) compared to HC, and in MCI-LBD than MCI-AD (p = 0.05). No significant differences were found between MCI-AD and HC, as well as between MCI-LBD and PD-MOT. Conclusion The α/θ power ratio as a synoptic index of EEG background slowing-down could be a simple and easy-to-use qEEG index which might indirectly mirror a cholinergic failure, useful to pick-up those MCI patients at higher risk of developing a Lewy-body disease.

Trigeminal nerve stimulation (TNS) is a non-invasive neuromodulation method which is increasingly used for its beneficial effects on symptoms of several neuropsychiatric disorders such as drug-resistant epilepsy. Sites and mechanisms of its action are still unknown. The present study was aimed at investigating the physiological effects of acute TNS on rest electroencephalographic (EEG) activity. EEG was recorded with a 19-channel EEG system from 18 healthy adults who underwent 20 min of sham- and real-TNS (cycles of 30 s ON and 30 s OFF) in two separate sessions. EEG was continuously acquired in the 10-min preceding TNS, during TNS in the "OFF" period and throughout 10 min after TNS. Mean frequency, total power over the 0.5-48 Hz frequency range and absolute power for delta, theta, alpha, beta and gamma bands were analyzed by a discrete Fast Fourier Transform algorithm. Interhemispheric and intrahemispheric coherences were also analyzed for each band at different time points. Intra- and interhemispheric coherences were significantly reduced for the beta frequencies only during real-TNS (p = 0.002 and p = 0.006, respectively). No TNS effect on the power spectra of any band was detected. A trend of increase in the mean EEG frequency total power during real-TNS (p = 0.03) and of decrease in interhemispheric gamma coherence after real-TNS (p = 0.01) was observed. Acute TNS may induce a spatially diffuse desynchronization of fast EEG rhythms in healthy adults, this desynchronization may underpin the antiepileptic effect of TNS described by clinical studies.

We investigated the expression of the Alzheimer’s disease-related metabolic brain pattern (ADRP) in 18F-FDG-PET scans of 44 controls, 27 patients with mild cognitive impairment (MCI) who did not convert to Alzheimer’s disease (AD) after five or more years of clinical follow-up, 95 MCI patients who did develop AD dementia on clinical follow-up, and 55 patients with mild-to-moderate AD. The ADRP showed good sensitivity (84%) and specificity (86%) for MCI-converters when compared to controls, but limited specificity when compared to MCI non-converters (66%). Assessment of 18F-FDG-PET scans on a case-by-case basis using the ADRP may be useful for quantifying disease progression.

BACKGROUND Cognitive impairment is a frequent and disabling feature of Parkinson's disease. Identifying the factors able to predict cognitive worsening since the early stage may improve disease management. The objective of this study was to define the best predictors of future cognitive worsening in a group of patients with newly diagnosed PD and to propose cutoff values potentially useful at the individual level. METHODS Fifty-four consecutive drug-naive patients with de novo PD were prospectively evaluated by clinical and neuropsychological assessment, resting EEG, and 123 I-FP-CIT-SPECT and clinically classified into mainly motor, diffuse/malignant, and intermediate PD subtypes; they were then followed up for an average of 5 years. Cognitive outcome was defined by identifying cognitively stable or worsened patients. RESULTS Step-wise logistic regression selected the posterior qEEG mean frequency and 123 I-FP-CIT-SPECT uptake at caudate level (P < 0.0001). The posterior qEEG mean frequency (cut point, 8.3 Hz) and the caudate 123 I-FP-CIT-SPECT uptake (cut point, 2.3, specific to nondisplaceable binding ratio) achieved 82% and 80% of accuracy, respectively, in predicting cognitive outcome. Survival analysis showed decreasing expected time to cognitive worsening associated with scores below the established thresholds for qEEG and 123 I-FP-CIT-SPECT and with the presence of a malignant clinical phenotype. CONCLUSIONS Resting EEG and 123 I-FP-CIT-SPECT are good predictors of future cognitive worsening, in de novo drug-naive PD patients. Wherever available, these biomarkers could add valuable prognostic information to classification into different clinical phenotypes. © 2017 International Parkinson and Movement Disorder Society.

Brain hypometabolism, as evaluated by PET with 18F-fluorodeoxyglucose, is considered a sensitive biomarker of synaptic dysfunction associated with neurodegeneration in Alzheimer disease. Statistical tools for image analysis showed promising capabilities in detecting and evaluating Alzheimer-related hypometabolism. The extended application of such tools requires their consolidation by proving generalizability and reproducibility. The aim of this study was to verify the reliability of an automatic tool for the detection of Alzheimer-related hypometabolic patterns based on a Support-Vector-Machine model. The model processed metabolic data from anatomical volumes of interest also considering interhemispheric asymmetrie. The model was developed and trained on a homogeneous dataset from a memory clinic center and then tested on an independent multicentric dataset drawn from the Alzheimer's Disease Neuroimaging Initiative. The accuracy of the discrimination between patients with Alzheimer disease, in either prodromal or dementia stage, and normal aging subjects was estimated at 95.8%, after cross-validation, in the training set. The accuracy of the same model in the testing set was 86.5%. The role of the two datasets was then reversed and the accuracy in the multicentric training set, after cross-validation, was 89.8% whereas the accuracy of the same model in the independent monocentric testing set was 88.0%. The classification rate was also evaluated in all subgroups in which the samples were partitioned, including non-converter mild cognitive impairment (MCI) patients, subjects with MCI reverted to normal conditions and subjects with significant memory concern (SMC) not confirmed with neuropsychological tests. The percent of positive detections was at the level of healthy controls (around or below 10%) for SMC and reverted MCI patients. An increasing rate of positive tests was found in patients from early prodromal Alzheimer disease (77%) to dementia (91%). A low rate of positivity was found in non-converted MCI patients. The two datasets exhibited similar trends of classification rate and related score through the different subgroups. The present findings show a good level of reproducibility and generalizability of a model for detecting hypometabolic pattern in Alzheimer disease and encourage further training to deepen the characterization of metabolic patterns in the early stage of the disease.

Elderly patients with mild cognitive impairment (MCI) may develop a Lewy body disease; their neuroimaging features at presentation are largely unknown. We present an intriguing group of 13 patients with MCI preceding (2.9 ± 1.9 years) parkinsonism (MCI-P), and eventually dementia 4.6 ± 1.6 years later (6 patients), whereas 7 patients remained dementia free after 4.7 ± 2.7 years. Neuropsychological tests, dopamine transporter (DAT) single photon emission computed tomography, and 18F-fluorodeoxyglucose positron emission tomography were compared with healthy controls and with cognitively normal patients with Parkinson's disease (PD-MOT). Compared to controls, MCI-P but not PD-MOT showed significant posterior temporo-parieto-occipital hypometabolism. Basal ganglia DAT uptake was similar between MCI-P and PD-MOT. Patients who converted to dementia were older, tended to have higher movement disorder society-unified Parkinson's disease rating scale scores and developed at least another clinical core feature fulfilling the criteria for probable dementia with Lewy bodies (DLB). Concurrent impairment of Corsi span and semantic verbal fluency, or of temporal lobe hypometabolism at baseline and reduced putamen-to-caudate ratio on DAT-SPECT at parkinsonism onset, both predicted (p < 0.001) the evolution to dementia. The constructs of Park cognitive subtype and prodromal Lewy body dementia partially overlap; functional imaging and neuropsychology may help in characterizing the patients and in tracking the risk toward dementia.

When dreaming during rapid eye movement (REM) sleep, we can perform complex motor behaviors while remaining motionless. How the motor cortex behaves during this state remains unknown. Here, using intracerebral electrodes sampling the human motor cortex in pharmacoresistant epileptic patients, we report a pattern of electroencephalographic activation during REM sleep similar to that observed during the performance of a voluntary movement during wakefulness. This pattern is present during phasic REM sleep but not during tonic REM sleep, the latter resembling relaxed wakefulness. This finding may help clarify certain phenomenological aspects observed in REM sleep behavior disorder.

Objectives Positron emission tomography (PET) and volume of interest (VOI) analysis have recently shown in amyotrophic lateral sclerosis (ALS) an accuracy of 93% in differentiating patients from controls. The aim of this study was to disclose by spatial independent component analysis (ICA) the brain networks involved in ALS pathological processes and evaluate their discriminative value in separating patients from controls. Experimental design: Two hundred fifty‐nine ALS patients and 40 age‐ and sex‐matched control subjects underwent brain (18)F‐2‐fluoro‐2‐deoxy‐D‐glucose PET (FDG‐PET). Spatial ICA of the preprocessed FDG‐PET images was performed. Intensity values were converted to z‐scores and binary masks were used as data‐driven VOIs. The accuracy of this classifier was tested versus a validated system processing intensity signals in 27 brain meta‐VOIs. A support vector machine was independently applied to both datasets and the ‘leave‐one‐out’ technique verified the general validity of results. Principal observations: The 8 components selected as pathophysiologically meaningful discriminated patients from controls with 99.0% accuracy, the discriminating value of bilateral cerebellum/midbrain alone representing 96.3%. Among the meta‐VOIs, right temporal lobe alone reached an accuracy of 93.7%. Conclusions: Spatial ICA identified in a very large cohort of ALS patients distinct spatial networks showing a high discriminatory value, improving substantially on the previously obtained accuracy. The cerebellar/midbrain component accounted for the highest accuracy in separating ALS patients from controls. Spatial ICA and multivariate analysis perform better than univariate semi‐quantification methods in identifying the neurodegenerative features of ALS and pave the way for inclusion of PET in clinical trials and early diagnosis. Hum Brain Mapp 37:942–953, 2016. © 2015 Wiley Periodicals, Inc.

Background Transcutaneous trigeminal nerve stimulation (TNS) has antiepileptic effects in patients with drug-resistant epilepsy (DRE). However, whether and how TNS is able to modulate the electroencephalogram (EEG) background activity in patients with DRE is still unknown. Objectives To investigate the effect of short-term TNS on EEG background activity in DRE by qualitative and quantitative analyses. Methods Twenty-nine DRE patients participated in the study. Twenty-two were randomly divided into a “sham-TNS” or “real-TNS” group; seven patients underwent stimulation of the median nerve (MNS) at the wrist. Real-TNS was delivered bilaterally to the infraorbital nerve (trains of 1–20 mA, 120 Hz, cyclic modality for 20 min). The sham-TNS protocol mimicked the real-TNS one but at a zero intensity. For MNS, the same parameters as real-TNS were used. EEG was continuously acquired for 40 min: 10′ pre, 20′ during and 10′ post stimulation. EEG was visually inspected for interictal epileptiform discharge (IEDs) changes and processed by spectral analysis for changes in mean frequency and absolute power of each frequency band. Results A significant increase of EEG absolute alpha power was observed during real-TNS compared with the sham-TNS (F34,680 = 1.748; p = 0.006). Conversely, no significant effects were noticed either for quantitative analysis of other frequency bands or for IEDs detection. MNS proved unable to modulate EEG activity. Conclusions Short-term TNS induces an acute and specific effect on background EEG of DRE by increasing the absolute alpha band power. EEG alpha rhythm enhancement may index a cortical functional inhibition and act as a seizure-preventing mechanism.

The presence of polysomnography-confirmed REM sleep behavior disorder (RBD) is the stronger risk factor for having prodromal Parkinson disease (PD), followed by abnormal presynaptic dopaminergic radionuclide neuroimaging. Aim of the review is to conduct a meta-analysis of literature data regarding presynaptic dopaminergic neuroimaging in RBD. A literature search was conducted, resulting in 16 papers that met the inclusion criteria. Clinical and neuroimaging data were extracted. The studies are heterogeneous, especially for neuroimaging methodology. Two mathematical transformations were used to allow imaging data to be compared among studies. Tracer uptake progressively decreased from controls to idiopathic RBD and eventually PD patients with RBD at putamen level. Tracer uptake at caudate level overlapped between patients with idiopathic RBD and those with PD without RBD. These results support the hypothesis that idiopathic RBD patients are on the path to developing a synucleinopathy. The receiver operation characteristic analysis found good to excellent discrimination capability between all groups. Presynaptic dopaminergic neuroimaging may be a key feature in the stratification of subjects to be included in neuroprotective trials. However, literature data are heterogeneous. Multicentric, harmonized studies are needed to define the usefulness of presynaptic dopaminergic neuroimaging with the aim of testing neuroprotective trials for idiopathic RBD.

PURPOSE: Mild cognitive impairment (MCI) is a transitional pathological stage between normal ageing (NA) and Alzheimer's disease (AD). Although subjects with MCI show a decline at different rates, some individuals remain stable or even show an improvement in their cognitive level after some years. We assessed the accuracy of FDG PET in discriminating MCI patients who converted to AD from those who did not. METHODS: FDG PET was performed in 42 NA subjects, 27 MCI patients who had not converted to AD at 5 years (nc-MCI; mean follow-up time 7.5 ± 1.5 years), and 95 MCI patients who converted to AD within 5 years (MCI-AD; mean conversion time 1.8 ± 1.1 years). Relative FDG uptake values in 26 meta-volumes of interest were submitted to ANCOVA and support vector machine analyses to evaluate regional differences and discrimination accuracy. RESULTS: The MCI-AD group showed significantly lower FDG uptake values in the temporoparietal cortex than the other two groups. FDG uptake values in the nc-MCI group were similar to those in the NA group. Support vector machine analysis discriminated nc-MCI from MCI-AD patients with an accuracy of 89% (AUC 0.91), correctly detecting 93% of the nc-MCI patients. CONCLUSION: In MCI patients not converting to AD within a minimum follow-up time of 5 years and MCI patients converting within 5 years, baseline FDG PET and volume-based analysis identified those who converted with an accuracy of 89%. However, further analysis is needed in patients with amnestic MCI who convert to a dementia other than AD.

Purpose: We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer's disease (MCI-AD). Methods: We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F-fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia. Results: Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007). Conclusion: The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal metabolism captures speed of conversion to dementia in MCI-AD since baseline. The highlighted prognostic pattern is a further, independent source of heterogeneity in MCI-AD and affects a primary-endpoint on interventional clinical trials (time of conversion to dementia).

Objectives The aim of this study was to develop and validate a questionnaire designed to measure the impact of sleep impairment on emotional distress in patients with various sleep disorders. Methods Five experts created an item data-bank pertaining to sleep-related psychological symptoms and somatic perceptions. Fifty patients in two focus groups examined each item for: a) word clarity (indicating any ambiguity of interpretation) and b) appropriateness for the target population. This process permitted to identify 36 appropriate items. Classical Test Theory and Rasch Analysis were used to further refine the questionnaire, yielding the final 17-item set. Concurrent validation of the new scale was tested with the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and the Anxiety and Depression questionnaires. Results Starting from the initial item data-bank, a 17-item questionnaire, the Maugeri Sleep Quality and Distress Inventory (MaSQuDI–17), was produced. Parallel Analysis on the MaSQuDI–17 confirmed the presence of a single dimension; exploratory factor analysis showed salient loading for each item, explaining 58.7% of total variance. Item-remainder correlation ranged from 0.72 to 0.39 and Cronbach alpha was 0.896. Rasch analysis revealed satisfactory psychometric properties of the new scale: the rating structure performed according to expectations, model fit was good and no item dependencies emerged. The scale presented good convergent validity and scores significantly distinguished healthy subjects from OSAS or Insomnia or BSD (p < 0.001). Conclusions MaSQuDI –17 shows good psychometric qualities, and can be used to assess the impact of sleep disorders such as Insomnia, OSAS, Central Hypersomnia and BSD on emotional stress.

BACKGROUND: Cognitive impairment is a frequent and disabling feature of Parkinson's disease. Identifying the factors able to predict cognitive worsening since the early stage may improve disease management. The objective of this study was to define the best predictors of future cognitive worsening in a group of patients with newly diagnosed PD and to propose cutoff values potentially useful at the individual level. METHODS: Fifty-four consecutive drug-naive patients with de novo PD were prospectively evaluated by clinical and neuropsychological assessment, resting EEG, and 123 I-FP-CIT-SPECT and clinically classified into mainly motor, diffuse/malignant, and intermediate PD subtypes; they were then followed up for an average of 5 years. Cognitive outcome was defined by identifying cognitively stable or worsened patients. RESULTS: Step-wise logistic regression selected the posterior qEEG mean frequency and 123 I-FP-CIT-SPECT uptake at caudate level (P < 0.0001). The posterior qEEG mean frequency (cut point, 8.3 Hz) and the caudate 123 I-FP-CIT-SPECT uptake (cut point, 2.3, specific to nondisplaceable binding ratio) achieved 82% and 80% of accuracy, respectively, in predicting cognitive outcome. Survival analysis showed decreasing expected time to cognitive worsening associated with scores below the established thresholds for qEEG and 123 I-FP-CIT-SPECT and with the presence of a malignant clinical phenotype. CONCLUSIONS: Resting EEG and 123 I-FP-CIT-SPECT are good predictors of future cognitive worsening, in de novo drug-naive PD patients. Wherever available, these biomarkers could add valuable prognostic information to classification into different clinical phenotypes. © 2017 International Parkinson and Movement Disorder Society.

Brain connectivity has been assessed in several neurodegenerative disorders investigating the mutual correlations between predetermined regions or nodes. Selective breakdown of brain networks during progression from normal aging to Alzheimer disease dementia (AD) has also been observed. Methods: We implemented independentcomponent analysis of 18F-FDG PET data in 5 groups of subjects with cognitive states ranging from normal aging to AD--including mild cognitive impairment (MCI) not converting or converting to AD--to disclose the spatial distribution of the independent components in each cognitive state and their accuracy in discriminating the groups. Results: We could identify spatially distinct independent components in each group, with generation of local circuits increasing proportionally to the severity of the disease. AD-specific independent components first appeared in the late-MCI stage and could discriminate converting MCI and AD from nonconverting MCI with an accuracy of 83.5%. Progressive disintegration of the intrinsic networks from normal aging to MCI to AD was inversely proportional to the conversion time. Conclusion: Independent-component analysis of 18F-FDG PET data showed a gradual disruption of functional brain connectivity with progression of cognitive decline in AD. This information might be useful as a prognostic aid for individual patients and as a surrogate biomarker in intervention trials.

Objective: We investigated a large sample of patients with amyotrophic lateral sclerosis (ALS) at rest in order to assess the value of 18 F-2-fluoro-2-deoxy-d-glucose ( 18 F-FDG) PET as a biomarker to discriminate patients from controls. Methods: A total of 195 patients with ALS and 40 controls underwent brain 18 F-FDG-PET, most within 5 months of diagnosis. Spinal and bulbar subgroups of ALS were also investigated. Twenty-five bilateral cortical and subcortical volumes of interest and cerebellum were taken into account, and 18 F-FDG uptakes were individually normalized by whole-brain values. Group analyses investigated the ALS-related metabolic changes. Discriminant analysis investigating sensitivity and specificity was performed using the 51 volumes of interest as well as age and sex. Metabolic connectivity was explored by voxel-wise interregional correlation analysis. Results: Hypometabolism was found in frontal, motor, and occipital cortex and hypermetabolism in midbrain, temporal pole, and hippocampus in patients with ALS compared to controls. A similar metabolic pattern was also found in the 2 subgroups. Discriminant analysis showed a sensitivity of 95% and a specificity of 83% in separating patients from controls. Connectivity analysis found a highly significant positive correlation between midbrain and white matter in corticospinal tracts in patients with ALS. Conclusions: 18 F-FDG distribution changes in ALS showed a clear pattern of hypometabolism in frontal and occipital cortex and hypermetabolism in midbrain. The latter might be interpreted as the neurobiological correlate of diffuse subcortical gliosis. Discriminant analysis resulted in high sensitivity and specificity in differentiating patients with ALS from controls. Once validated by diseased-control studies, the present methodology might represent a potentially useful biomarker for ALS diagnosis. Classificaton of evidence: This study provides Class III evidence that 18 F-FDG-PET accurately distinguishes patients with ALS from normal controls (sensitivity 95.4%, specificity 82.5%).

Objectives- To investigate common carotid intima-media thickness in a cohort of patients who were vertically infected with human immunodeficiency virus 1 (HIV-1). Methods- We conducted a cross-sectional observational study. Human immunodeficiency virus 1-infected patients were compared with age-, sex-, and body mass index-matched healthy participants. Common carotid intima-media thickness was measured in all participants on both sides of the neck, and the mean intima-media thickness was calculated. Metabolic parameters and markers of inflammation were measured only in HIV-1-infected patients. Statistical analysis was performed by multiple regression and by a matrix of Pearson correlation coefficients. The Student t test was used to compare mean common carotid intima-media thickness values between groups. Results- Forty patients (21 female) with HIV-1 infection acquired from birth with a mean age ± SD of 16.3 ± 4.7 years and 27 healthy participants (11 female) with a mean age of 17.7 ± 4.6 years were included in the study. Mean common carotid intima-media thickness in the HIV-1-infected group (0.450 ± 0.088 mm) was significantly higher (P < .05) than in the control group (0.407 ± 0.079 mm). No significant association was found between intima-media thickness and a specific antiretroviral regimen, exposure to combined antiretroviral agents, and HIV status. In multiple regression analyses, higher levels of insulin (P= .007) and elevated levels of glycated hemoglobin (P= .01) were associated with intima-media thickness changes. Conclusions- Patients perinatally infected with HIV have increased common carotid intima-media thickness compared with healthy individuals. These changes were more pronounced with increasing age and inflammation markers. Interventions that improve cardiovascular risk profiles should be considered in HIV-infected young adults.

PURPOSE: The aim of this study was to assess striatal dopamine transporter (DAT) availability in a large group of normal subjects. METHODS: The study included 122 healthy subjects, aged 18-83 years, recruited in the multicentre 'ENC-DAT' study (promoted by the European Association of Nuclear Medicine). Brain single photon emission computed tomography (SPECT) was acquired by means of dual-head cameras 3 h after [(123)I]FP-CIT administration. Specific to nondisplaceable binding ratios (SBRs) in the basal ganglia were computed using the 'BasGan' software, allowing automatic value extraction with partial volume effect correction. Multicentre camera inhomogeneity was taken into account by calibrating values on basal ganglia phantom data. SBR in each caudate nucleus (C) and putamen (P) were the dependent variables in a repeated measures general linear model analysis; age, gender, handedness and body mass index (BMI) were the independent variables. RESULTS: SBR values in C and P were significantly associated with age (mean rate decrease with age: 0.0306 per year, or 0.57 % of the general mean; p < 0.0001) and gender (women had higher values; p 0.015), while no significant effect was found for handedness and BMI. A significant interaction was found between age and region (p < 0.0001) as the age-related decline was 0.028 for left C, 0.026 for right C and 0.034 for both P. P/C ratio analysis confirmed that age-related SBR decrease was stronger in P than in C (p < 0.0001). No significant effect was found for season or time of the day when the scan was acquired by analysing the residual of SBR values in C and P, after subtraction of age and gender effects. CONCLUSION: This study confirms the dependency of DAT on ageing and highlights the gender differences in a large sample of healthy subjects, while it does not support the dependency of DAT on BMI, handedness, circadian rhythm or season.

Brain connectivity has been assessed in several neurodegenerative disorders investigating the mutual correlations between predetermined regions or nodes. Selective breakdown of brain networks during progression from normal aging to Alzheimer disease dementia (AD) has also been observed.

International audience; Study ObjectivesRigidity is a muscle hypertonia typical of Parkinson disease (PD), whereas rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by abnormally increased muscle tone during REM sleep (REM sleep without atonia) and enacting dream behaviors. Because movements are not bradykinetic during RBD in patients with PD, we investigated whether the background, wake postural rigidity is attenuated during REM sleep without atonia, in absence of movement.MethodsThe amplitude of levator menti (postural muscle) electromyographic activity during relaxed evening wakefulness (considered as reference) and sleep (N2, N3, atonic REM sleep, and quiet REM sleep without atonia) was measured in 20 patients with PD (with and without RBD), 10 patients with idiopathic RBD patients and 10 healthy subjects.ResultsThe chin tone amplitude progressively decreased from wake to N2, N3, and atonic REM sleep in the four groups, but the highest amplitude was observed in PD patients with RBD during atonic REM sleep. Furthermore, chin muscle tone amplitude did not attenuate from wake to REM sleep without atonia in patients with both PD and RBD but dramatically attenuated (by 40% on average) in patients with idiopathic RBD.ConclusionsThe high amplitude of chin muscle tone in PD with RBD (but not in idiopathic RBD) during REM sleep with and without atonia suggests that both PD-related hypertonia and RBD-related enhanced muscle tone coexist during REM sleep, together affecting chin muscle tone. Consequently, some rapid RBD movements likely start against a rigid postural tone.

PURPOSE: To identify both clinical and FDG PET/CT-derived factors predicting the occurrence of relapse, or conversely, the likelihood of false positive findings in surveillance FDG-PET/CT studies (PETsv). METHODS: The study included 149 asymptomatic patients with Hodgkin's lymphoma (HL) (n = 55) or diffuse large B cell lymphoma (DLBCL) (n = 94) in first remission. PETSv studies were performed 12, 18, 24 and 36 months thereafter. Logistic regression analysis was performed to identify clinical and imaging-derived predictors of either PET-detected relapse or false-positive (FP) results. Tested clinical variables were: 1) age, 2) HL vs. DLBCL, 3) stage of disease, 4) bulky disease, 5) previous radiotherapy. PET/CT-derived variables were: 1) maximum standardized uptake value at baseline, 2) size-incorporated maximum standardized uptake value (SIMaxSUV) at baseline, 3) positive interim PET(PET-2), 4) presence of hot spots likely to be unrelated to the disease in final PET, 5) residual non-FDG avid mass. RESULTS: Accuracy was 88 % for PETsv1, 95 % for PETsv2, 95 % for PETsv3 and 91 % for PETsv4. However, PPV was relatively low in all PETsv. Best predictors of relapse were result of interim PET, HL versus NHL type, SIMaxSUV, age >= 60. Best predictors of FP were previous radiotherapy and hot spots unrelated to the disease in final PET. CONCLUSIONS: The present study confirms the need of restricting the use of surveillance PET/CT to patients at high risk of relapse. Information derived from PET/CT performed at baseline (metabolic disease burden), in the course (PET2) and at the end of therapy (unrelated hot spots) can help to select high-risk patients and also to identify patients more likely to present equivocal findings at PETsv.

OBJECTIVES: The study was aimed at estimating the effect of alcohol consumption, time of day, and their interaction on traffic crashes in a real regional context. METHODS: Blood alcohol concentration (BAC) data were collected from drivers involved in traffic accidents during one year in an Italian region and in a control group of drivers over the same road network. Mean circadian sleep propensity was estimated from a previous study as function of time of day. Accident risk was analyzed by logistic regression as function of BAC and circadian sleep propensity. RESULTS: BAC values greater than zero were found in 72.0% of the drivers involved in crashes and in 40.4% of the controls. Among the former 23.6% of the drivers exceeded the BAC legal threshold of 0.05 g/dL, while illegal values were found in 10.4% of the controls. The relative risk showed a significant increase with both BAC and circadian sleep propensity (as estimated from time of day) and their interaction was significant. CONCLUSIONS: Due to the significant interaction, even low BAC levels strongly increased accident risk when associated with high sleep propensity.Copyright © 2016 American Academy of Sleep Medicine. All rights reserved. Language: en

In questo lavoro viene presentato un metodo didattico che si è dimostrato efficace per valutare la resistenza al trattamento dello studente che è uno dei parametri fondamentali per distinguere la difficoltà di apprendimento in matematica dal disturbo di apprendimento noto come discalculia. Il metodo si basa sull'uso dell'applicazione GimmeFive che è stata progettata per sviluppare competenze nel calcolo mentale di addizioni e sottrazioni a più cifre. In questo lavoro vengono presentati risultati di due sperimentazioni condotte con gruppi di studenti rispettivamente con difficoltà di apprendimento e con diagnosi di discalculia. Queste sperimentazioni hanno consentito di mostrare l'efficacia del metodo didattico nella valutazione della resistenza al trattamento e di discutere le caratteristiche che lo rendono adeguato per la valutazione del disturbo di apprendimento.

Introduction The association between Parkinson Disease (PD) and REM sleep behavior disorder (RBD) has been related to a specific, malignant clinical phenotype. Definite RBD diagnosis requires video-polysomnography that is often unfeasible. A malignant clinical PD-RBD phenotype could be expected also in PD patients with probable RBD. Aim of this cross-sectional study was to evaluate whether a more severe neuropsychological and functional neuroimaging phenotype can be identified in PD patients with probable RBD. Methods Thirty-eight de novo , drug naive PD patients underwent a first-line clinical assessment and a second-line multimodal assessment, including neuropsychological evaluation, 123 I-FP-CIT-SPECT and 18 F-FDG-PET, which were compared between PD patients with (PD + RBD+) and without (PD + RBD-) probable RBD. Results On first-line assessment, PD + RBD + patients had significantly more constipation (p = 0.02) and showed worse olfaction (p = 0.01) compared with PD + RBD-while the two groups were similar as for age, presence of orthostatic hypotension, UPDRS-III and MMSE scores. On second-line assessment, PD + RBD + patients showed a worse neuropsychological test profile, more severe nigro-striatal dopaminergic impairment, mainly at caudate level in the less affected hemisphere (p = 0.004) and impaired brain glucose metabolism, with relative hypometabolism in posterior cortical regions and relative hypermetabolism mainly in anterior regions of the more affected hemisphere (p = 0.015). Conclusions PD patients with probable RBD are likely to have a more severe neuropsychological and functional brain-imaging phenotype already at the time of diagnosis.

Sleep disturbances and nocturnal disabilities are common in Parkinson's Disease (PD). The PD sleep scale, second version (PDSS-2), has been proposed as a helpful tool for measuring sleep disorders in PD. We aimed to validate the Italian version of the PDSS-2. One hundred and twenty-three consecutive PD outpatients (76 males) were evaluated by means of PDSS-2, Epworth Sleepiness Scale, Hamilton Depression Rating Scale, Parkinson's Disease Quality of Life Questionnaire (self-administered scales), Unified Parkinson's Disease Rating (motor section) and Hoehn and Yahr Scales, and Mini Mental State Examination. PDSS-2 internal consistency was satisfactory (Cronbach's alpha: 0.77) with significant item to total score correlation and high intra-class correlation coefficient for test-retest reliability (0.943). Total PDSS-2 score was correlated with the scores on all other clinical scales. The factor analysis identified five factors, related to five areas of nocturnal disturbances, similarly as the original PDSS-2. The five factors mainly reflected: (1) nocturnal movement-related problems, (2) quality of sleep, (3) dreaming distress, (4) fragmentation of sleep and (5) insomnia symptoms. The PDSS-2 scale has confirmed its usefulness in evaluating sleep problems in Italian PD patients.

To unveil cognitive-nigrostriatal correlations in Parkinson's disease (PD), 30 de novo, drug-naive PD patients and 15 patients with essential tremor (Controls, CTR) underwent a neuropsychological (NPS) battery and brain SPECT with [I-123]Ioflupane, as a biomarker of nigrostriatal function. Automatic extraction of uptake at caudate and putamen level was conducted through the BasGan software, also allowing partial volume effect correction. Because of the multicollinearity among neuropsychological tests and among SPECT variables, factor analysis was applied to 16 neuropsychological scores; moreover, the four SPECT variables were merged into a mean SPECT value (mSPECT). Factor analysis identified four NPS factors: a dys-executive (NPS-EX), a visuospatial (NPS-VS), a verbal memory (NPS-VM), and a "mixed" (NPD-MIX) factor. In PD group, there were inverse correlations between UPDRS-III score and both NPS-VS (P < 0.01) and mSPECT (P < 0.05), and a direct correlation between mSPECT and NPS-EX (P < 0.05). Post hoc analysis showed a direct correlation between NPS-EX and caudate uptake in both hemispheres (P < 0.05). Moreover, inverse correlations were found between UPDRS-III and, respectively, putamen uptake in the less affected hemisphere (P < 0.01), and putamen and caudate uptake in the more affected hemisphere (P < 0.05). In CTR, no correlation was found between mSPECT and either NPS or GDS values. Nigro-caudate function affects executive capabilities in PD but not in CTR, which appears to be unrelated to the disease motor severity at its onset. Instead, PD motor severity is related to nigro-putaminal impairment and visuospatial dysfunction. The role of these data as predictive features of cognitive decline and eventually dementia remains to be established in longitudinal studies.

Objective This study aimed to evaluate, through polysomnographic analysis, the prognostic value of sleep patterns, compared to other prognostic factors, in patients with disorders of consciousness (DOCs) in the sub-acute phase. Methods Twenty-seven patients underwent 24-h polysomnography and clinical evaluation 3.5 ± 2 months after brain injury. Their clinical outcome was assessed 18.5 ± 9.9 months later. Polysomnographic recordings were evaluated using visual and quantitative indexes. A general linear model was applied to identify features able to predict clinical outcome. Clinical status at follow-up was analysed as a function of the baseline clinical status, the interval between brain injury and follow-up evaluation, patient age and gender, the aetiology of the injury, the lesion site, and visual and quantitative sleep indexes. Results A better clinical outcome was predicted by a visual index indicating the presence of sleep integrity (p = 0.0006), a better baseline clinical status (p = 0.014), and younger age (p = 0.031). Addition of the quantitative sleep index strengthened the prediction. Conclusions More structured sleep emerged as a valuable predictor of a positive clinical outcome in sub-acute DOC patients, even stronger than established predictors (e.g. age and baseline clinical condition). Significance Both visual and quantitative sleep evaluation could be helpful in predicting clinical outcome in sub-acute DOCs.

Objective The objective of this study was to analyze the periodicity of leg movement activity emerging during sleep in a group of patients with spinal cord injury and to evaluate their pathophysiological features. Methods Twenty patients (16 males, mean age 34.0 years) with traumatic spinal cord lesions were recruited (5 cervical, 15 thoracic; 16 level A and 4 level B at the American Spinal Injury Association impairment scale). Periodicity of sleep leg movements was analyzed; electroencephalographic spectral analysis and heart rate were evaluated for 20 s preceding and 30 s following the onset of leg movements. Results Periodic leg movements during sleep (PLMS) index >5/h was found in only 4 patients and only 2 of these had PLMS index >15/h. Eleven patients (group I) did not show any increase in heart rate related to the occurrence of leg movements while the remaining 9 did (group II). Two patients in each group had American Spinal Injury Association impairment level B; 5 patients of group I and none of group II had cervical lesions while 6 patients of group I and all 9 of group II had thoracic lesions. Only 2 patients in group I presented clearly periodic leg movements during sleep and PLMS index >15/h. Electroencephalographic delta, alpha and beta bands around leg movements increased clearly in group II while the changes in group I were very limited or absent. Conclusion Leg movements during sleep are recorded in spinal cord injury patients with completely absent volitional activity in their lower limb but they show clear periodicity only in a small subgroup of them. Significance The disconnection from higher nervous structures, in patients with spinal cord injury might favor the appearance of leg movements due to the activity of spinal generators not inhibited by higher influences; correlated autonomic and electroencephalographic changes can be absent. This motor activity might assume the periodic character when a genetic predisposition is present.

PURPOSE: The role of mesocortical dopaminergic pathways in the cognitive function of patients with early Parkinson's disease (PD) needs to be further clarified. METHODS: The study groups comprised 15 drug-naive patients with de novo PD and 10 patients with essential tremor (controls) who underwent (18)F-DOPA PET (static acquisition, normalization on mean cerebellar counts) and an extended neuropsychological test battery. Factor analysis with varimax rotation was applied to the neuropsychological test scores, to yield five factors from 16 original scores, which explained 82 % of the total variance. Correlations between cognitive factors and (18)F-DOPA uptake were assessed with SPM8, taking age and gender as nuisance variables. RESULTS: (18)F-DOPA uptake was significantly lower in PD patients than in controls in the bilateral striatum, mainly in the more affected (right) hemisphere, and in a small right temporal region. Significant positive correlations were found only in PD patients between the executive factor and (18)F-DOPA uptake in the bilateral anterior cingulate cortex (ACC) and the middle frontal gyrus, between the verbal fluency factor and (18)F-DOPA uptake in left BA 46 and the bilateral striatum, and between the visuospatial factor and (18)F-DOPA uptake in the left ACC and bilateral striatum. No correlations were found between (18)F-DOPA uptake and either the verbal memory factor or the abstraction-working memory factor. CONCLUSION: These data clarify the role of the mesocortical dopaminergic pathways in cognitive function in early PD, highlighting the medial frontal lobe, anterior cingulate, and left BA 46 as the main sites of cortical correlation with executive and language functions

We aimed to investigate the accuracy of FDG-PET to detect the Alzheimer's disease (AD) brain glucose hypometabolic pattern in 142 patients with amnestic mild cognitive impairment (aMCI) and 109 healthy controls. aMCI patients were followed for at least two years or until conversion to dementia. Images were evaluated by means of visual read by either moderately-skilled or expert readers, and by means of a summary metric of AD-like hypometabolism (PALZ score). Seventy-seven patients converted to AD-dementia after 28.6 ± 19.3 months of follow-up. Expert reading was the most accurate tool to detect these MCI converters from healthy controls (sensitivity 89.6%, specificity 89.0%, accuracy 89.2%) while two moderately-skilled readers were less (p < 0.05) specific (sensitivity 85.7%, specificity 79.8%, accuracy 82.3%) and PALZ score was less (p < 0.001) sensitive (sensitivity 62.3%, specificity 91.7%, accuracy 79.6%). Among the remaining 67 aMCI patients, 50 were confirmed as aMCI after an average of 42.3 months, 12 developed other dementia, and 3 reverted to normalcy. In 30/50 persistent MCI patients, the expert recognized the AD hypometabolic pattern. In 13/50 aMCI, both the expert and PALZ score were negative while in 7/50, only the PALZ score was positive due to sparse hypometabolic clusters mainly in frontal lobes. Visual FDG-PET reads by an expert is the most accurate method but an automated, validated system may be particularly helpful to moderately-skilled readers because of high specificity, and should be mandatory when even a moderately-skilled reader is unavailable.

Background Sleep disturbances are frequently reported by patients with spinal cord injury (SCI). Studies have shown an increased incidence of sleep-disordered breathing (SDB) and periodic leg movements during sleep (PLMS) in people with stable long-term SCI. Methods This was a prospective observational study in order to evaluate the features and possible predisposing factors of SDB and PLMS in a heterogenic population of consecutive SCI patients admitted at the Spinal Unit of the Niguarda Hospital within the first year after injury. Each patient underwent a clinical assessment, full polysomnography, and arterial blood gas analysis before and immediately after sleep. Multiple logistic regressions were applied in order to evaluate factors associated with SDB and PLMS. Results Thirty-five (15 tetraplegic and 20 paraplegic) patients were enrolled. Nine patients (25.7%) had an obstructive SDB and 10 (28.6%) had PLMS. The frequency of SDB was higher in tetraplegic with respect to paraplegic patients (Wald statistic: 7.71; P = 0.0055), whereas PLMs were significantly more frequent in patients with an incomplete motor lesion than in subjects with a complete motor lesion (Wald statistic: 6.14; P = 0.013). Conclusion This study confirms a high frequency of SDB and PLMS in SCI patients in the first year following injury. Independently from possible sub-acute and chronic clinical variables, the level and the completeness of the spinal cord lesion are the main factors associated respectively with an early development of SDB and PLMS.

STUDY OBJECTIVES: REM sleep behavior disorder (RBD) can be induced by antidepressants, especially serotonin reuptake inhibitors (SSRI), thus a role of the serotonergic system in the pathogenesis of RBD has been proposed. However, the serotonergic system integrity in idiopathic RBD (iRBD) is still unknown. We aimed to study brain stem serotonergic system integrity, by means of (123)I-FP-CIT-SPECT, in a group of iRBD patients as compared to normal subjects. DESIGN: Single-center, prospective observational study. SETTING: University hospital. PATIENTS OR PARTICIPANTS: Twenty iRBD outpatients and 23 age-matched normal controls. MEASUREMENTS AND RESULTS: The diagnosis of RBD was determined clinically and confirmed by means of overnight, laboratory-based video-polysomnography. Both iRBD patients and normal subjects underwent (123)I-FP-CIT-SPECT as a marker of dopamine transporter (DAT) at basal ganglia level and of serotonin transporter (SERT) at brainstem and thalamus levels. (123)I-FP-CIT-SPECT images were analyzed and compared between iRBD patients and controls by means of both region of interest analysis at basal ganglia, midbrain, pons and thalamus levels, and voxel-based analysis, taking into account age and the use of SSRI as confounding factors. No difference in (123)I-FP-CIT-SPECT specific to nondisplaceable binding ratios (SBR) values was found between iRBD and normal subjects at brainstem and thalamus levels while iRBD patients showed lower SBR values in all basal ganglia nuclei (P < 0.0001) compared to controls. CONCLUSIONS: These results suggest that the serotonergic system is not directly involved in RBD pathogenesis while confirming nigro-striatal dopaminergic deafferentation in iRBD.

PURPOSE: The role of mesocortical dopaminergic pathways in the cognitive function of patients with early Parkinson's disease (PD) needs to be further clarified. METHODS: The study groups comprised 15 drug-naive patients with de novo PD and 10 patients with essential tremor (controls) who underwent 18F-DOPA PET (static acquisition, normalization on mean cerebellar counts) and an extended neuropsychological test battery. Factor analysis with varimax rotation was applied to the neuropsychological test scores, to yield five factors from 16 original scores, which explained 82 % of the total variance. Correlations between cognitive factors and 18F-DOPA uptake were assessed with SPM8, taking age and gender as nuisance variables. RESULTS: 18F-DOPA uptake was significantly lower in PD patients than in controls in the bilateral striatum, mainly in the more affected (right) hemisphere, and in a small right temporal region. Significant positive correlations were found only in PD patients between the executive factor and 18F-DOPA uptake in the bilateral anterior cingulate cortex (ACC) and the middle frontal gyrus, between the verbal fluency factor and 18F-DOPA uptake in left BA 46 and the bilateral striatum, and between the visuospatial factor and 18F-DOPA uptake in the left ACC and bilateral striatum. No correlations were found between 18F-DOPA uptake and either the verbal memory factor or the abstraction-working memory factor. CONCLUSION: These data clarify the role of the mesocortical dopaminergic pathways in cognitive function in early PD, highlighting the medial frontal lobe, anterior cingulate, and left BA 46 as the main sites of cortical correlation with executive and language functions.

A number of phasic events influence sleep quality and sleep macrostructure. The detection of arousals and the analysis of cyclic alternating patterns (CAP) support the evaluation of sleep fragmentation and instability. Sixteen polygraphic overnight recordings were visually inspected for conventional Rechtscaffen and Kales scoring, while arousals were detected following the criteria of the American Sleep Disorders Association (ASDA). Three electroencephalograph (EEG) segments were associated to each event, corresponding to background activity, pre-arousal period and arousal. The study was supplemented by the analysis of time-frequency distribution of EEG within each subtype of phase A in the CAP. The arousals were characterized by the increase of alpha and beta power with regard to background. Within NREM sleep most of the arousals were preceded by a transient increase of delta power. The time-frequency evolution of the phase A of the CAP sequence showed a strong prevalence of delta activity during the whole A1, but high amplitude delta waves were found also in the first 2/3 s of A2 and A3, followed by desynchronization. Our results underline the strict relationship between the ASDA arousals, and the subtype A2 and A3 within the CAP: in both the association between a short sequence of transient slow waves and the successive increase of frequency and decrease of amplitude characterizes the arousal response.

Study Objectives: Under particular conditions, a patent foramen ovale (PFO) can potentially give rise to ischemic stroke by means of paradoxical embolization, due to right-to-left shunt. Our study aimed to evaluate the presence of right-to-left shunt in patients with obstructive sleep apnea syndrome (OSAS) and diagnosed PFO during sleep. Design and Setting: Assessment of provocative-only PFO and concomitant OSAS. Evaluation of right-to-left shunting during sleep by means of transcranial doppler with contrast medium injected in the cubital vein. Participants: 10 consecutive patients affected by PFO detectable only under Valsalva maneuver during wakefulness and affected by OSAS (mean age 52.8 ± 10.7 years). Interventions: Patients underwent transcranial doppler with injection of agitated saline solution mixed with air during normal breathing and during periods of apnea/hypopnea in nocturnal sleep. Measurements and Results: Right-to-left shunt was present in 9 patients out of 10 and appeared during obstructive apneas longer than 17 seconds. In 1 out of 10 patients, only hypopneas occurred and no right-to-left shunt could be shown. The number of microembolic signals detected during periods of nocturnal apnea was positively correlated with the number detected during Valsalva maneuver in wakefulness (p

Forty-nine consecutive, drug naive outpatients with de novo Parkinson's disease (PD) and 12 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) underwent clinical examination and dopamine transporter single photon emission computed tomography with [(123)I]-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane as a biomarker of nigro-striatal function. PD patients were grouped into rapid eye movement sleep behavior disorder (RBD) negative (PD-RBD-) and RBD positive (PD-RBD+). Repeated measures and univariate analysis of variance were used to compare dopaminergic and clinical impairment among groups. The variations of dopamine transporter-single photon emission computed tomography specific binding ratios (SBR) as a function of group belonging were significantly different (p = 0.0013) at caudate with respect to putamen level. Indeed, putamen SBR progressively decreased from iRBD to PD-RBD- and PD-RBD+ groups while caudate SBR were higher in PD-RBD- group than in PD-RBD+ and even than in iRBD group. Motor impairment was more severe in PD patients with RBD than in those without RBD. Our data suggest that a more severe nigro-caudate dopaminergic deafferentation is related to RBD, both in its idiopathic form and in PD patients.

Objectives : Fatal familial insomnia (FFI) is linked to a mutation at codon 178 (C178) of the prion protein gene (PRNP). FFI is pathologically characterized by selective atrophy of the anteroventral and mediodorsal thalamic nuclei and clinically by loss of sleep, dysautonomia and motor signs. A key early polysomnographic sign of the disease onset is the loss of sleep spindling (sigma activity, SA). In FFI the loss of SA leads to the spectral representation of a sudden slow wave activity (SWA) increase from an awake state, the reaching of a stable plateau without oscillations, followed by abrupt fall down to REM sleep. We evaluated the presence of differences in the spectral sleep EEG pattern in FFI relatives carriers (C178 pos ) or non-carriers (C178 neg ) of the C178 mutation. Methods : Seventeen healthy relatives of FFI patients, 8 carriers of the C178 FFI mutation in a preclinical condition and 9 non carriers, underwent two-night polysomnography. The absolute and relative EEG power of the 4 main bands (delta: SWA, 0.5–4.0 Hz; theta: TB, 4.5–8 Hz; alpha: AB, 8.5–12 Hz; sigma: SA, 12.5–16 Hz) has been studied for the total sleep time, the period of delta increase after sleep onset, and the period of delta plateau. Multiple regression has been applied to investigate relations between the power of the bands studied and 3 parameters: age, the gender of the subjects and the C178 genotype. Results : Our study could not show evidence of differences in the sleep EEG composition between carriers and non-carriers of the C178 FFI mutation. Conclusions : The spectral analysis techniques we used were not able to disclose sleep EEG markers linked to the FFI C178 pos in the preclinical condition. Key sleep EEG alteration become evident only at the clinical onset of the disease.

Objective : The hypothesis that the two main synchronizing mechanisms (spindle and delta oscillations) acting during non-rapid eye movement sleep show opposite relationship with the distribution of generalized epileptiform discharges (GEDs) during sleep was evaluated. Methods : We studied the temporal relationship between the distribution of sleep GEDs and the dynamics of Sigma Activity (SA, 12–16 Hz) and Delta Activity (DA, 0.5–4.5 Hz) in 5 children affected by childhood absence epilepsy. Results : Using correlation techniques, we found a high and positive correlation between GEDs and SA, while DA resulted negatively correlated with GEDs. Conclusion : Sleep generalized spike-and-slow-waves seems to be produced when spindle synchronizing mechanisms are active while DA production seem to exert an inhibiting role. Such a feature seems to be common to other childhood partial and undetermined epileptic syndromes.