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Background: Cognitive impairment is frequent in Parkinson’s disease (PD) and several neurotransmitter changes have been reported since the time of diagnosis, although seldom investigated altogether in the same patient cohort. Objective: Our aim was to evaluate the association between neurotransmitter impairment, brain metabolism, and cognition in a cohort of de novo, drug-naïve PD patients. Methods: We retrospectively selected 95 consecutive drug-naïve PD patients (mean age 71.89±7.53) undergoing at the time of diagnosis a brain [18F]FDG-PET as a marker of brain glucose metabolism and proxy measure of neurodegeneration, [123I]FP-CIT-SPECT as a marker and dopaminergic deafferentation in the striatum and frontal cortex, as well as a marker of serotonergic deafferentation in the thalamus, and quantitative electroencephalography (qEEG) as an indirect measure of cholinergic deafferentation. Patients also underwent a complete neuropsychological battery. Results: Positive correlations were observed between (i) executive functions and left cerebellar cortex metabolism, (ii) prefrontal dopaminergic tone and working memory (r = 0.304, p = 0.003), (iii) qEEG slowing in the posterior leads and both memory (r = 0.299, p = 0.004) and visuo-spatial functions (r = 0.357, p

Background: Neuropsychological assessment is still the basis for the first evaluation of patients with cognitive complaints. The Free and Cued Selective Reminding Test (FCSRT) generates several indices that could have different accuracy in the differential diagnosis between Alzheimer’s disease (AD) and other disorders. Objective: In a consecutive series of naturalistic patients, the accuracy of the FCSRT indices in differentiating patients with either mild cognitive impairment (MCI) due to AD or AD dementia from other competing conditions was evaluated. Methods: We evaluated the accuracy of the seven FCSRT indices in differentiating patients with AD from other competing conditions in 434 consecutive outpatients, either at the MCI or at the early dementia stage. We analyzed these data through the receiver operating characteristics curve, and we then generated the odds-ratio map of the two indices with the best discriminative value between pairs of disorders. Results: The immediate and the delayed free total recall, the immediate total recall, and the index of sensitivity of cueing were the most useful indices and allowed to distinguish AD from dementia with Lewy bodies and psychiatric conditions with very high accuracy. Accuracy was instead moderate in distinguishing AD from behavioral variant frontotemporal dementia, vascular cognitive impairment, and other conditions. Conclusion: By using odd-ratio maps and comparison-customized cut-off scores, we confirmed that the FCSRT represents a useful tool to characterize the memory performance of patients with MCI and thus to assist the clinician in the diagnosis process, though with different accuracy values depending on the clinical hypothesis.

Background: Some authors report steeper slopes of forgetting in early Alzheimer’s disease (AD), while others do not. Contrasting findings are thought to be due to methodological inconsistencies or variety of testing methods, yet they also emerge when people are assessed on the same testing procedure. Objective: We aimed to assess if forgetting slopes of people with mild cognitive impairment due to AD (MCI-AD) are different from age-matched healthy controls (HC) by using a prose paradigm. Methods: Twenty-nine people with MCI-AD and twenty-six HC listened to a short prose passage and were asked to freely recall it after delays of 1 h and 24 h. Results: Generalized linear mixed modelling revealed that, compared to HC, people with MCI-AD showed poorer encoding at immediate recall and steeper forgetting up to 1 h in prose memory as assessed by free recall and with repeated testing of the same material. Forgetting rates between groups did not differ from 1 h to 24 h. Conclusion: The differences observed in MCI-AD could be due to a post-encoding deficit. These findings could be accounted either by a differential benefit from retrieval practice, whereby people with MCI-AD benefit less than HC, or by a working memory deficit in people with MCI-AD, which fails to support their memory performance from immediate recall to 1 h.

Background Sleep disturbances are common non-motor symptoms of Parkinson’s Disease (PD). Methods The aim of this study was to investigate the polysomnographic correlates of sleep changes, as investigated by the Parkinson’s Disease Sleep Scale-2 (PDSS-2), in a cohort of sixty-two consecutive de novo, drug naïve PD patients (71.40 ± 7.84 y/o). Results PDSS-2 total score showed a direct correlation with stage shifts (p = 0.008). Fragmented sleep showed an inverse correlation with sleep efficiency (p = 0.012). Insomnia symptoms showed an inverse correlation with wake after sleep onset (p = 0.005) and direct correlation with periodic leg movements (p = 0.006) and stage shift indices (p = 0.003). Motor Symptoms showed a direct correlation with Apnoea-Hypopnoea (AHI; p = 0.02) and awakenings indices (p = 0.003). Dream distressing showed a direct correlation with REM without atonia (RWA, p = 0.042) and an inverse correlation with AHI (p = 0.012). Sleep quality showed an inverse correlation with RWA (p = 0.008). Conclusion PDSS-2 features are significantly correlated with polysomnography objective findings, thus further supporting its reliability to investigate sleep disturbances in PD patients.

Background: Mild cognitive impairment (MCI) is a heterogeneous condition. Idiopathic REM sleep behavior disorder (iRBD) can be associated with MCI (MCI-RBD). Objective: To investigate neuropsychological and brain metabolism features of patients with MCI-RBD by comparison with matched MCI-AD patients. To explore their predictive value toward conversion to a full-blown neurodegenerative disease. Methods: Seventeen MCI-RBD patients (73.6±6.5 years) were enrolled. Thirty-four patients with MCI-AD were matched for age (74.8±4.4 years), Mini-Mental State Exam score and education with a case-control criterion. All patients underwent a neuropsychological assessment and brain 18F-FDG-PET. Images were compared between groups to identify hypometabolic volumes of interest (MCI-RBD-VOI and MCI-AD-VOI). The dependency of whole-brain scaled metabolism levels in MCI-RBD-VOI and MCI-AD-VOI on neuropsychological test scores was explored with linear regression analyses in both groups, adjusting for age and education. Survival analysis was performed to investigate VOIs phenoconversion prediction power. Results: MCI-RBD group scored lower in executive functions and higher in verbal memory compared to MCI-AD group. Also, compared with MCI-AD, MCI-RBD group showed relative hypometabolism in a posterior brain area including cuneus, precuneus, and occipital regions while the inverse comparison revealed relative hypometabolism in the hippocampus/parahippocampal areas in MCI-AD group. MCI-RBD-VOI metabolism directly correlated with executive functions in MCI-RBD (p = 0.04). MCI-AD-VOI metabolism directly correlated with verbal memory in MCI-AD (p = 0.001). MCI-RBD-VOI metabolism predicted (p = 0.03) phenoconversion to an alpha-synucleinopathy. MCI-AD-VOI metabolism showed a trend (p = 0.07) in predicting phenoconversion to dementia. Conclusion: MCI-RBD and MCI-AD showed distinct neuropsychological and brain metabolism profiles, that may be helpful for both diagnosis and prognosis purposes.

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.

Symptoms referable to central and peripheral nervous system involvement are often evident both during the acute phase of COVID-19 infection and during long-COVID. In this study, we evaluated a population of patients with prior COVID-19 infection who showed signs and symptoms consistent with neurological long-COVID.We prospectively collected demographic and acute phase course data from patients with prior COVID-19 infection who showed symptoms related to neurological involvement in the long-COVID phase. Firstly, we performed a multivariate logistic linear regression analysis to investigate the impact of demographic and clinical data, the severity of the acute COVID-19 infection and hospitalization course, on the post-COVID neurological symptoms at three months follow-up. Secondly, we performed an unsupervised clustering analysis to investigate whether there was evidence of different subtypes of neurological long COVID-19.One hundred and nine patients referred to the neurological post-COVID outpatient clinic. Clustering analysis on the most common neurological symptoms returned two well-separated and well-balanced clusters: long-COVID type 1 contains the subjects with memory disturbances, psychological impairment, headache, anosmia and ageusia, while long-COVID type 2 contains all the subjects with reported symptoms related to PNS involvement. The analysis of potential risk-factors among the demographic, clinical presentation, COVID 19 severity and hospitalization course variables showed that the number of comorbidities at onset, the BMI, the number of COVID-19 symptoms, the number of non-neurological complications and a more severe course of the acute infection were all, on average, higher for the cluster of subjects with reported symptoms related to PNS involvement.We analyzed the characteristics of neurological long-COVID and presented a method to identify well-defined patient groups with distinct symptoms and risk factors. The proposed method could potentially enable treatment deployment by identifying the optimal interventions and services for well-defined patient groups, so alleviating long-COVID and easing recovery.

Theory of mind (ToM) deficit is a frequent finding in subjects with neurological and psychiatric conditions. While a number of brain regions play a role in ToM, to date the contribution of the diffuse projection systems is less understood. Here, we explored the topographical and neurochemical bases of ToM using multi-tracer molecular imaging and quantitative electroencephalography (qEEG) in a group of 30 drug-naive, de novo Parkinson's Disease (PD) patients (mean age 73.39 ± 8.93 years, 11 females). ToM was assessed using the “Reading the Mind in the Eyes Task” (RMET), while general cognition with the MMSE. We acquired FDG-PET images (as a marker of regional neurodegeneration), I-123 Ioflupane Single Photon Emission Computed Tomography (123 I-FP-CIT-SPECT, as a marker of dopaminergic impairment in the basal ganglia and in the cortex and as a proxy marker of serotoninergic deafferentation in the thalamus), and qEEG recordings (using the Theta/Alpha power ratio as marker of cholinergic deafferentation). PD presented with a significantly worse RMET score compared to 60 controls (20.7 ± 5.5 vs 27.5 ± 3.0 p = .001) while there was no difference between the two groups in age, education or MMSE. The voxel-wise analysis of total RMET score and regional metabolism showed a positive correlation in the superior temporal gyrus and in the insula. Among the proxy markers of dopaminergic degeneration, serotoninergic and cholinergic deafferentation, ToM presented only an inverse correlation with 123 I-FP-CIT thalamic specific binding ratio (SBR) values -a proxy serotoninergic marker-which remained significant after correction for FDG metabolism in the areas associated with ToM. On the other hand, MMSE only correlated with qEEG posterior Theta/Alpha power. These findings point to the presence of a specific cortical and neurochemical signature of ToM in PD, to the independence of ToM from general cognition, and suggest possible therapeutic targets to treat social cognition deficits.

BACKGROUND Dopamine transporter single photon-emission computed tomography (DAT-SPECT) is the strongest risk factor for phenoconversion in patients with idiopathic rapid eye movement (REM)-sleep behavior disorder (iRBD). However, it might be used as a second-line stratification tool in clinical trials, because it is expensive and mini-invasive. OBJECTIVE Aim of the study is to investigate whether other cost-effective and non-invasive biomarkers may be proposed as first-line stratification tools. METHODS Forty-seven consecutive iRBD patients (68.53 ± 7.16 years, 40 males) underwent baseline clinical and neuropsychological assessment, olfaction test, resting electroencephalogram (EEG), and DAT-SPECT. All patients underwent 6 month-based clinical follow-up to investigate the emergence of parkinsonism and/or dementia. Survival analysis and Cox regression were used to estimate conversion risk. RESULTS Seventeen patients developed an overt synucleinopathy (eight Parkinsonism and nine dementia) 32.8 ± 22 months after diagnosis. The strongest risk factors were putamen specific to non-displaceable binding ratio (SBR) (hazard ratio [HR], 7.3), attention/working memory cognitive function (NPS-AT/WM) (HR, 5.9), EEG occipital mean frequency (HR, 2.7) and clinical motor assessment (HR, 2.3). On multivariate Cox-regression analysis, only putamen SBR and NPS-AT/WM significantly contributed to the model (HR, 6.2, 95% confidence interval [CI], 1.9-19.8). At post-hoc analysis, the trail-making test B (TMT-B) was the single most efficient first-line stratification tool that allowed to reduce the number of eligible subjects to 76.6% (sensitivity 1, specificity 0.37). Combining TMT-B and DAT-SPECT further reduced the sample to 66% (sensitivity 0.88, specificity 0.47). CONCLUSION The TMT-B seems to be a cost-effective and efficient first-line screening tool, to be used to select patients that deserve DAT-SPECT as second-line screening tool for disease-modifying clinical trials. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Introduction: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts.Methods: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives.Results: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes.Discussion: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

Purpose: FDG-PET is an established supportive biomarker in dementia with Lewy bodies (DLB), but its diagnostic accuracy is unknown at the mild cognitive impairment (MCI-LB) stage when the typical metabolic pattern may be difficultly recognized at the individual level. Semiquantitative analysis of scans could enhance accuracy especially in less skilled readers, but its added role with respect to visual assessment in MCI-LB is still unknown. Methods: We assessed the diagnostic accuracy of visual assessment of FDG-PET by six expert readers, blind to diagnosis, in discriminating two matched groups of patients (40 with prodromal AD (MCI-AD) and 39 with MCI-LB), both confirmed by in vivo biomarkers. Readers were provided in a stepwise fashion with (i) maps obtained by the univariate single-subject voxel-based analysis (VBA) with respect to a control group of 40 age- and sex-matched healthy subjects, and (ii) individual odds ratio (OR) plots obtained by the volumetric regions of interest (VROI) semiquantitative analysis of the two main hypometabolic clusters deriving from the comparison of MCI-AD and MCI-LB groups in the two directions, respectively. Results: Mean diagnostic accuracy of visual assessment was 76.8 ± 5.0% and did not significantly benefit from adding the univariate VBA map reading (77.4 ± 8.3%) whereas VROI-derived OR plot reading significantly increased both accuracy (89.7 ± 2.3%) and inter-rater reliability (ICC 0.97 [0.96-0.98]), regardless of the readers' expertise. Conclusion: Conventional visual reading of FDG-PET is moderately accurate in distinguishing between MCI-LB and MCI-AD, and is not significantly improved by univariate single-subject VBA but by a VROI analysis built on macro-regions, allowing for high accuracy independent of reader skills.

Background Late Life Bipolar Disorder (LLBD) is associated with a high prevalence of cognitive impairments, but few studies have examined their risk factors and clinical correlates Methods Participants with bipolar disorder older than 60 ( n = 86) were recruited from psychiatric outpatient and inpatients units. Patients were assessed with various instruments, including the Clinical Dementia Rating scale, the Montreal Cognitive Assessment and the Cumulative Illness Rating Scale. The distribution of disorder-specific and general risk factors was compared between patients with LLBD plus cognitive impairments (mild cognitive impairment or dementia) and those with LLBD but no cognitive impairment. Analyses were first conducted at the bivariate level, then using multiple regression. The association with disability, aggressive behavior and suicidal ideation was also explored. Results Cognitive impairments in LLBD were associated with a diagnosis of type 1 bipolar disorder (OR = 6.40, 95%CI: 1.84 – 22.31, p = 0.004), fewer years of education (OR = 0.79, 95%CI: 0.69 – 0.91, p = 0.001) and higher severity of physical diseases (OR 26.54, 95%CI: 2.07 – 340.37, p = 0.01). Moreover, cognitive impairments were associated with an increased likelihood of disability and recent aggressive behavior, but not suicidal ideation. Limitations retrospective design, conflation of MCI and dementia, not all subjects were in euthymia Conclusions In LLBD, the presence of cognitive impairments was associated with a diagnosis of type I bipolar disorder, lower education and more severe physical comorbidities. In turn, MCI or dementia were associated with increased disability and aggressive behavior. These findings may aid the identification of patients at risk for cognitive deterioration in everyday clinical practice.

Degeneration of the nigrostriatal dopaminergic (DA) and the raphe-thalamic serotonergic (SE) systems is among the earliest changes observed in Parkinson's disease (PD). The consequences of those changes on brain metabolism, especially regarding their impact on the cortex, are poorly understood.Using multi-tracer molecular imaging, we assessed in a cohort of drug-naive PD patients the association between cortical metabolism and DA and SE system deafferentation of either striatum or thalamus, and we explored whether this association was mediated by either striatum or thalamus metabolism.We recruited 96 drug-naive PD patients (aged 71.9 ± 7.5 years) who underwent [We found that [These data suggest that the impact of deep gray matter monoaminergic deafferentation on cortical function is mediated by striatal and thalamic metabolism in drug-naive PD. © 2021 International Parkinson and Movement Disorder Society.

Cognitive decline is a common trait of neurodegenerative diseases of central nervous system and one of the major risk factors associated with faster phenoconversion from prodromal stages. In the transition to full-blown clinical syndromes, increased phase synchronization in the theta, alpha or beta EEG rhythms is thought to reflect the activation of compensatory mechanisms that may counterbalance the cognitive decline of patients affected by Mild Cognitive Impairment (MCI). Patients suffering from idiopathic Rapid eye-movement sleep Behavior Disorder (iRBD) have high risk of developing Parkinson Disease (PD) or Dementia with Lewy Bodies (DLB) and cognitive impairment is among the strongest risk factors together with motor symptoms. Here we wanted to investigate whether altered phase synchronization and amplitude couplings of the brain oscillations could be linked to the balancing of cognitive decline in a longitudinal cohort (N=18) of iRBD patients. We measured high-density Electroencephalographic (HD-EEG) activity at baseline and follow-up and quantified power distribution, orthogonalized amplitude correlation and weighted phase lag index. Despite the overt neurodegenerative progression (three patients converted to PD and one to DLB), cognitive decline was not evident from Mini Mental State Examination (MMSE) or neuropsychological tests. On the other hand, alpha phase synchronization and delta amplitude correlations were significantly different at follow-up compared to baseline. In particular, alpha synchrony was enhanced while delta amplitude coupling was reduced. Those differences were more pronounced among central-posterior channels while frontal channels showed a reduced number of significant edges with respect to surrogates. Both large-scale amplitude and phase coupling significantly correlated with cognitive or neuropsychological scores but not with sleep quality indices. Altogether, these results suggest that increased alpha phase-synchronization and reduced delta amplitude correlation may be considered as electrophysiological signs of an active compensatory mechanism of the cognitive impairment in RDB patients. Large-scale functional modifications could thus be used as significant biomarker in the characterization of prodromal stages of PD.Statement of SignificanceCognitive impairment and RBD emerge much earlier than the better-known motor symptoms distinctive of synucleinopathies. An improved investigation of RBD may constitute an important biomarker for an early diagnosis of the actual neurodegenerative diseases. For the first time, this preliminary study aims to quantify the large-scale network couplings as electrophysiological manifestation of the compensatory mechanism to the cognitive impairment in a longitudinal study of idiopathic RBD patients. Unfortunately, the small number of the subjects limits the generalizability of our observations, but this is only preliminary works in a larger project that aims to investigate advanced electrophysiological markers for an early diagnosis of the synucleinopathies.

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.

Study Objectives Increased phase synchronization in electroencephalography (EEG) bands might reflect the activation of compensatory mechanisms of cognitive decline in people with neurodegenerative diseases. Here, we investigated whether altered large-scale couplings of brain oscillations could be linked to the balancing of cognitive decline in a longitudinal cohort of people with idiopathic rapid eye-movement sleep behavior disorder (iRBD). Methods We analyzed 18 patients (17 males, 69.7 ± 7.5 years) with iRBD undergoing high-density EEG (HD-EEG), presynaptic dopaminergic imaging, and clinical and neuropsychological (NPS) assessments at two time points (time interval 24.2 ± 5.9 months). We thus quantified the HD-EEG power distribution, orthogonalized amplitude correlation, and weighted phase-lag index at both time points and correlated them with clinical, NPS, and imaging data. Results Four patients phenoconverted at follow-up (three cases of parkinsonism and one of dementia). At the group level, NPS scores decreased over time, without reaching statistical significance. However, alpha phase synchronization increased and delta amplitude correlations decreased significantly at follow-up compared to baseline. Both large-scale network connectivity metrics were significantly correlated with NPS scores but not with sleep quality indices or presynaptic dopaminergic imaging data. Conclusions These results suggest that increased alpha phase synchronization and reduced delta amplitude correlation may be considered electrophysiological signs of an active compensatory mechanism of cognitive impairment in people with iRBD. Large-scale functional modifications may be helpful biomarkers in the characterization of prodromal stages of alpha-synucleinopathies.

Background Degeneration of the nigrostriatal dopaminergic (DA) and the raphe-thalamic serotonergic (SE) systems is among the earliest changes observed in Parkinson's disease (PD). The consequences of those changes on brain metabolism, especially regarding their impact on the cortex, are poorly understood. Objectives Using multi-tracer molecular imaging, we assessed in a cohort of drug-naive PD patients the association between cortical metabolism and DA and SE system deafferentation of either striatum or thalamus, and we explored whether this association was mediated by either striatum or thalamus metabolism. Methods We recruited 96 drug-naive PD patients (aged 71.9 ± 7.5 years) who underwent [123 I]ioflupane single-photon emission computed tomography ([123 I]FP-CIT-SPECT) and brain [18 F]fluorodeoxyglucose positron emission tomography ([18 F]FDG-PET). We used a voxel-wise analysis of [18 F]FDG-PET images to correlate regional metabolism with striatal DA and thalamic SE innervation as assessed using [123 I]FP-CIT-SPECT. Results We found that [123 I]FP-CIT specific to nondisplaceable binding ratio (SBR) and glucose metabolism positively correlated with one another in the deep gray matter (thalamus: P = 0.001, r = 0.541; caudate P = 0.001, r = 0.331; putamen P = 0.001, r = 0.423). We then observed a direct correlation between temporoparietal metabolism and caudate DA innervation, as well as a direct correlation between prefrontal metabolism and thalamus SE innervation. The effect of caudate [123 I]FP-CIT SBR values on temporoparietal metabolism was mediated by caudate metabolic values (percentage mediated: 89%, P-value = 0.008), and the effect of thalamus [123 I]FP-CIT SBR values on prefrontal metabolism was fully mediated by thalamus metabolic values (P Conclusions These data suggest that the impact of deep gray matter monoaminergic deafferentation on cortical function is mediated by striatal and thalamic metabolism in drug-naive PD. © 2021 International Parkinson and Movement Disorder Society.

Bipolar disorder (BD) is a chronic and disabling psychiatric condition that is linked to significant disability and psychosocial impairment. Although current neuropsychological, molecular, and neuroimaging evidence support the existence of neuroprogression and its effects on the course and outcome of this condition, whether and to what extent neuroprogressive changes may impact the illness trajectory is still poorly understood. Thus, this selective review was aimed toward comprehensively and critically investigating the link between BD and neurodegeneration based on the currently available evidence. According to the most relevant findings of the present review, most of the existing neuropsychological, neuroimaging, and molecular evidence demonstrates the existence of neuroprogression, at least in a subgroup of BD patients. These studies mainly focused on the most relevant effects of neuroprogression on the course and outcome of BD. The main implications of this assumption are discussed in light of specific shortcomings/limitations, such as the inability to carry out a meta-analysis, the inclusion of studies with small sample sizes, retrospective study designs, and different longitudinal investigations at various time points.

To investigate brain functional correlates of mild cognitive impairment (MCI) in idiopathic REM sleep behavior disorder (iRBD). Thirty-nine consecutive iRBD patients, 17 with (RBD-MCI, 73.6±6.5 years), and 22 without (RBD-NC, 69.6±6.1 years) MCI underwent neuropsychological assessment, 18F-FDG-PET, and 123I-FP-CIT-SPECT as a marker of nigro-striatal dopaminergic function. Forty-two healthy subjects (69.6±8.5 years) were used as control for 18F-FDG-PET analysis. Brain metabolism was compared between the three groups by univariate analysis of variance. Post hoc comparison between RBD-MCI and RBD-NC was performed to investigate the presence of an MCI-related volume of interest (MCI-VOI). Brain functional connectivity was explored by interregional correlation analysis (IRCA), using the whole-brain normalized MCI-VOI uptake as the independent variable. Moreover, the MCI-VOI uptake was correlated with 123I-FP-CIT-SPECT specific-to-non displaceable binding ratios (SBR) and neuropsychological variables. Finally, the MCI-VOI white matter structural connectivity was analyzed by using a MRI-derived human atlas. The MCI-VOI was characterized by a relative hypometabolism involving precuneus and cuneus (height threshold p

BACKGROUND AND PURPOSE To explore the feasibility of a neuroprotection trial in prodromal synucleinopathy, using idiopathic rapid eye movement sleep behavior disorder (iRBD) as the target population and 123 I-FP-CIT-SPECT as a biomarker of disease progression. METHODS Consecutive iRBD patients were randomly assigned to a treatment arm receiving selegiline and symptomatic rapid eye movement sleep behavior disorder treatment, or to a control arm receiving symptomatic treatment only. Selegiline was chosen because of a demonstrated neuroprotection effect in animal models. Patients underwent 123 I-FP-CIT-SPECT at baseline and after 30 months on average. The clinical outcome was the emergence of parkinsonism and/or dementia. A repeated-measures general linear model (GLM) was applied using group (control and treatment) as "between" factor, and both time (baseline and follow-up) and regions (123 I-FP-CIT-SPECT putamen and caudate uptake) as the "within" factors, adjusting for age. RESULTS Thirty iRBD patients completed the study (68.2 ± 6.9 years; 29 males; 21% dropout rate), 13 in the treatment arm, and 17 in the control arm. At follow-up (29.8 ± 9.0 months), three patients in the control arm developed dementia and one parkinsonism, whereas two patients in the treatment arm developed parkinsonism. Both putamen and caudate uptake decreased over time in the control arm. In the treatment arm, only the putamen uptake decreased over time, whereas caudate uptake remained stable. GLM analysis demonstrated an effect of treatment on the 123 I-FP-CIT-SPECT uptake change, with a significant interaction between the effect of group, time, and regions (p = 0.004). CONCLUSIONS A 30-months neuroprotection study for prodromal synucleinopathy is feasible, using iRBD as the target population and 123 I-FP-CIT-SPECT as a biomarker of disease progression.

Background Seizures are common in patients with dementia but precise epidemiologic data of epilepsy in neurodegenerative dementia is lacking. Objective The first aim of the study was to investigate prevalence and clinical characteristics of epilepsy in a large cohort of patients with neurodegenerative dementias. Subsequently, we explored clinical, neuropsychological, and quantitative electroencephalogram (qEEG) data of Alzheimer's disease (AD) patients with epilepsy (AD-EPI) as compared to AD patients without epilepsy (AD-CTR). Methods We retrospectively evaluated consecutive patients with a diagnosis of a neurodegenerative dementia and a clinically diagnosed epilepsy that required antiepileptic drugs (AED). All patients underwent baseline comprehensive neuropsychological assessment. A follow-up of at least one year was requested to confirm the dementia diagnosis. In AD patients, qEEG power band analysis was performed. AD-CTR and AD-EPI patients were matched for age, Mini-Mental State Examination score, and gender. Results Thirty-eight out of 2,054 neurodegenerative dementia patients had epilepsy requiring AED. The prevalence of epilepsy was 1.82% for AD, 1.28% for the behavioral variant of frontotemporal dementia (bvFTD), 2.47% for dementia with Lewy bodies (DLB), and 12% for primary progressive aphasia. Epilepsy were more drug-responsive in AD than in non-AD dementias. Finally, no significant differences were found in neuropsychological and qEEG data between AD-EPI and AD-CTR patients. Conclusion In our cohort, AD, FTD, and DLB dementias have similar prevalence of epilepsy, even if AD patients were more responsive to AED. Moreover, AD-EPI patients did not have significant clinical, neuropsychological qEEG differences compared with AD-CTR patients.

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.

Regular practice of sport activities yields psychophysical benefits for both the general population and persons affected by physical or intellectual impairments. Practicing competitive sport may add further value to these benefits. The objective of this observational cross-sectional study was to investigate the role of competitive sport practice in enhancing self-perceived psychophysical well-being of some select participants, using the Psychological General Well-Being Index and the Short Form-12 indices. We recruited at national events 100 young Italian competitive swimmers affected by physical or intellectual impairment. These respondents' results were compared with those of a control group of 100 Italian participants who did not practice competitive sport but who were also affected by physical or intellectual impairment, randomly selected from rehabilitation clinics and communities of young people with disabilities. Scores of psychological and emotional well-being were higher by 40% or more for the practitioners of competitive sport ( p

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.

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).

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.

Few studies have examined the relationship between CSF and structural biomarkers, and cognitive function in MCI. We examined the relationship between cognitive function, hippocampal volume and cerebrospinal fluid (CSF) Aβ42 and tau in 145 patients with MCI. Patients were assessed on cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), the Geriatric Depression Scale and the Functional Activities Questionnaire. Hippocampal volume was measured using magnetic resonance imaging (MRI), and CSF markers of Aβ42, tau and p-tau181 were also measured. Worse performance on a wide range of memory and sustained attention tasks were associated with reduced hippocampal volume, higher CSF tau and p-tau181 and increased tau/Aβ42 ratio. Memory tasks were also associated with lower ability to conduct functional activities of daily living, providing a link between AD biomarkers, memory performance and functional outcome. These results suggest that biomarkers of Aβ and tau are strongly related to cognitive performance as assessed by the CANTAB, and have implications for the early detection and characterization of incipient AD.

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.

Background In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. Objective To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). Methods A total of 147 aMCI patients were enrolled in 13 European memory clinics. Patients underwent clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG) and lumbar puncture to assess the levels of amyloid β peptide 1–42 (Aβ42), tau and p‐tau, and blood samples were collected. Genetic (APOE), neuroimaging (3T morphometry and diffusion MRI) and EEG (with resting‐state and auditory oddball event‐related potential (AO‐ERP) paradigm) biomarkers were evaluated. Results Prodromal AD was found in 55 aMCI patients defined by low Aβ42 in the cerebrospinal fluid (Aβ positive). Compared to the aMCI group with high Aβ42 levels (Aβ negative), Aβ positive patients showed poorer visual (P = 0.001), spatial recognition (P < 0.0005) and working (P = 0.024) memory, as well as a higher frequency of APOE4 (P < 0.0005), lower hippocampal volume (P = 0.04), reduced thickness of the parietal cortex (P < 0.009) and structural connectivity of the corpus callosum (P < 0.05), higher amplitude of delta rhythms at rest (P = 0.03) and lower amplitude of posterior cingulate sources of AO‐ERP (P = 0.03). Conclusion These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.

The Stroop color and word test (SCWT) is widely used to evaluate attention, information processing speed, selective attention, and cognitive flexibility. Normative values for the Italian population are available only for selected age groups, or for the short version of the test. The aim of this study was to provide updated normal values for the full version, balancing groups across gender, age decades, and education. Two kinds of indexes were derived from the performance of 192 normal subjects, divided by decade (from 20 to 90) and level of education (4 levels: 3-5; 6-8; 9-13; >13 years). They were (i) the correct answers achieved for each table in the first 30 s (word items, WI; color items, CI; color word items, CWI) and (ii) the total time required for reading the three tables (word time, WT; color time, CT; color word time, CWT). For each index, the regression model was evaluated using age, education, and gender as independent variables. The normative data were then computed following the equivalent scores method. In the regression model, age and education significantly influenced the performance in each of the 6 indexes, whereas gender had no significant effect. This study confirms the effect of age and education on the main indexes of the Stroop test and provides updated normative data for an Italian healthy population, well balanced across age, education, and gender. It will be useful to Italian researchers studying attentional functions in health and disease.

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.

Purpose The diagnosis of behavioural variant frontotemporal dementia (bvFTD) is challenging during the predementia stage when symptoms are subtle and confounding. Morphological and functional neuroimaging can be particularly helpful during this stage but few data are available. Methods We retrospectively selected 25 patients with lateonset probable bvFTD. Brain structural MRI and FDG PET were performed during the predementia stage (mean MMSE score 27.1± 2.5) on average 2 years before. The findings with the two imaging modalities were compared (SPM8) with those in a group of 20 healthy subjects. The bvFTD patients were divided into two subgroups: those with predominant disinhibition (bvFTD+) and those with apathy (bvFTD-). Results Hypometabolism exceeded grey matter (GM) density reduction in terms of both extension and statistical significance in all comparisons. In the whole bvFTD group, hypometabolism involved the bilateral medial, inferior and superior lateral frontal cortex, anterior cingulate, left temporal and right parietal cortices and the caudate nuclei. GM density reduction was limited to the right frontal cortex and the left medial temporal lobe. In bvFTD+ patients hypometabolism was found in the bilateral medial and basal frontal cortex, while GM reduction involved the left anterior cingulate and left inferior frontal cortices, and the right insula. In bvFTD- patients, atrophy and mainly hypometabolism involved the lateral frontal cortex and the inferior parietal lobule. Conclusion These findings suggest that hypometabolism is more extensive than, and thus probably precedes, atrophy in predementia late-onset bvFTD, underscoring different topographic involvement in disinhibited and apathetic presentations. If confirmed in a larger series, these results should prompt biomarker operationalization in bvFTD, especially for patient selection in therapeutic clinical trials.

Aim: To unveil a brain single photon emission computed tomography (SPECT) pattern in Alzheimer’s disease (AD) patients, showing a reversed clock drawing test (CDT) phenomenon. Patients and Methods: Among 1,005 consecutive subjects, 9 AD patients who drew a reversed CDT (AD-R) underwent SPECT, which was analysed (SPM2) versus a group of 10 AD patients performing the CDT correctly (AD+) and versus 15 controls (CTR). Brain SPECT in 11 AD patients who mistook the CDT in a common way (AD–) was compared with AD+ and CTR groups. Results: Relative hypoperfusion was found in AD-R versus CTR in right medial frontal, parahippocampal and subcallosal gyri, and in left insula and superior temporal gyrus. Hypoperfusion was found in AD-R versus AD+ in the right uncus, superior temporal and parahippocampal gyri. In the AD– versus CTR comparison, hypoperfusion was found in left hippocampus, parahippocampal gyrus and superior parietal lobule. In AD-R versus AD+ and CTR merged together, the analysis showed hypoperfusion in the right parahippocampus, medial frontal gyrus, superior temporal gyrus and uncus, in the left insula and superior temporal gyrus. Conclusion: Fronto-temporal dysfunction, especially in the right hemisphere, plays a role in the reversed CDT phenomenon in AD patients, whereas matched AD patients mistaking the CDT in a common way show left posterior temporo-parietal hypoperfusion.

The purpose of this study was to investigate cortical dysfunction in Parkinson's disease (PD) patients with amnestic deficit (PD-MCI). Perfusion single photon emission computed tomography was performed in 15 PD-MCI patients and compared (statistical parametric mapping [SPM2]) with three groups, i.e., healthy subjects (CTR), cognitively intact PD patients (PD), and common amnestic MCI patients (aMCI). Age, depression, and UPDRS-III scores were considered as confounding variables. PD-MCI group (P < 0.05, false discovery rate-corrected for multiple comparisons) showed relative hypoperfusion in bilateral posterior parietal lobe and in right occipital lobe in comparison to CTR. As compared to aMCI, MCI-PD demonstrated hypoperfusion in bilateral posterior parietal and occipital areas, mainly right cuneus and angular gyrus, and left precuneus and middle occipital gyrus. With a less conservative threshold (uncorrected P < 0.01), MCI-PD showed hypoperfusion in a left parietal region, mainly including precuneus and inferior parietal lobule, and in a right temporal-parietal-occipital region, including middle occipital and superior temporal gyri, and cuneus-precuneus, as compared to PD. aMCI versus PD-MCI showed hypoperfusion in bilateral medial temporal lobe, anterior cingulate, and left orbitofrontal cortex. PD-MCI patients with amnestic deficit showed cortical dysfunction in bilateral posterior parietal and occipital lobes, a pattern that can be especially recognized versus both controls and common aMCI patients, and to a lesser extent versus cognitively intact PD. The relevance of this pattern in predicting dementia should be evaluated in longitudinal studies.

Objective: To investigate quantitative EEG (qEEG) in anorexia nervosa (AN) and bulimia nervosa (BN) in comparison with healthy controls. Methods: Resting EEG was recorded in 30 healthy females (age: 27.1 ± 5.5), 16-AN females (age: 26.4 ± 9.5) and 12-BN females (age: 27.0 ± 6.3). Cortical EEG sources (delta, theta, alpha 1, alpha 2, beta 1, beta 2) were modeled by LORETA solutions. The statistical analysis was performed considering the factors Group, power Band, and region of interest (central, frontal, parietal, occipital, temporal, limbic). Results: Alpha 1 sources in central, parietal, occipital and limbic areas showed a greater amplitude in Controls versus AN and BN groups. Alpha 2 sources in parietal, occipital and limbic areas showed a greater amplitude in Controls than in both AN and BN groups. Alpha 1 sources in temporal area showed a greater amplitude in Controls compared to both the BN and AN groups as well as in the BN group compared to AN group. Central alpha 1 source correlated significantly with BMI in patients. Conclusions: These results support the hypothesis that eating disorders are related to altered mechanisms of cortical neural synchronization, especially in rolandic alpha rhythms. Significance: To our knowledge this is the first study by LORETA able to detect modifications of cortical EEG activity in eating disorders.