Publications by authors named "Dario Arnaldi"

92 Publications

Multimodal approach in the pre-surgical evaluation of focal epilepsy surgery candidates: how far are we from a non-invasive ESI-based "sourcectomy"?

Epileptic Disord 2021 Jul 16. Epub 2021 Jul 16.

Unit of Child Neuropsychiatry, Department of Medical and Surgical Neuroscience and Rehabilitation, IRCCS Istituto Giannina Gaslini, Genoa, Italy, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.

The management of drug-resistant patients with focal epilepsy is often challenging. Surgery is recognised as a useful and effective treatment option. The identification of the epileptogenic zone relies on the integration of clinical, neurophysiological, and neuroimaging findings. The role of non-invasive functional neuroimaging techniques has been reported to add diagnostic accuracy to first-line evaluations, avoiding invasive presurgical examinations in selected cases. In this view, we report the case of a 16-year-old male suffering from drug-resistant focal epilepsy with episodes rarely evolving to a bilateral tonic-clonic seizure. Conventional 1.5T and 3T MRI were considered uninformative. Based on electro-clinical data, focal cortical dysplasia was suspected. The epileptogenic zone was identified with the integration of further non-invasive functional neuroimaging techniques ([18F]-fluorodeoxyglucose positron emission tomography and arterial spin labelling), where electrical source imaging played the main role. All techniques pointed towards a cortical region, where a 7T brain MRI identified a signal alteration consistent with focal cortical dysplasia. A tailored resection of the lesion located in the inferior frontal sulcus was performed, guided by intraoperative electrocorticography (strip and depth electrodes). Postoperative seizure freedom was achieved. The histopathology confirmed the suspicion of focal cortical dysplasia type IIa. With this case report, we highlight the importance of a multimodal approach in the presurgical evaluation of candidates for epilepsy surgery, which, in selected cases, may allow invasive procedures, such as stereo-EEG, to be avoided in the investigation of the epileptogenic zone. Moreover, we underline the pivotal role of EEG source imaging, especially when focal cortical dysplasia is suspected.
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http://dx.doi.org/10.1684/epd.2021.1309DOI Listing
July 2021

Resting State Alpha Electroencephalographic Rhythms Are Differently Related to Aging in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment.

J Alzheimers Dis 2021 Jun 12. Epub 2021 Jun 12.

Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy.

Background: In relaxed adults, staying in quiet wakefulness at eyes closed is related to the so-called resting state electroencephalographic (rsEEG) rhythms, showing the highest amplitude in posterior areas at alpha frequencies (8-13 Hz).

Objective: Here we tested the hypothesis that age may affect rsEEG alpha (8-12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with mild cognitive impairment due to Alzheimer's disease (ADMCI).

Methods: Clinical and rsEEG datasets in 63 ADMCI and 60 Nold individuals (matched for demography, education, and gender) were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands, as well as fixed beta (14-30 Hz) and gamma (30-40 Hz) bands. Each group was stratified into three subgroups based on age ranges (i.e., tertiles).

Results: As compared to the younger Nold subgroups, the older one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions. On the contrary, in relation to the younger ADMCI subgroups, the older one displayed a lesser reduction in those rhythms. Notably, the ADMCI subgroups pointed to similar cerebrospinal fluid AD diagnostic biomarkers, gray and white matter brain lesions revealed by neuroimaging, and clinical and neuropsychological scores.

Conclusion: The present results suggest that age may represent a deranging factor for dominant rsEEG alpha rhythms in Nold seniors, while rsEEG alpha rhythms in ADMCI patients may be more affected by the disease variants related to earlier versus later onset of the AD.
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http://dx.doi.org/10.3233/JAD-201271DOI Listing
June 2021

Neurophysiological evaluation of visual function in iRBD: potential role in stratifying RBD conversion risk.

Sleep Med 2021 May 15;84:26-31. Epub 2021 May 15.

Neurology and Stroke Unit, ASST Sette Laghi Ospedale di Circolo, Varese; DMC University of Insubria, Varese, Italy.

Study Objectives: To evaluate neurophysiological alterations of visual function in idiopathic REM sleep Behavior Disorder (iRBD) both as markers and predictors of neurodegenerative disorders.

Methods: In a longitudinal follow-up study of 46 consecutive iRBD patients (follow-up duration 8.4 ± 3.4 years), the baseline parameters in luminance-contrast pattern (VEPp), red-green color (VEPc) and motion-onset (VEPm) Visual Evoked Potentials in iRBD were compared to early (ePD) and advanced (aPD) Parkinson's Disease subjects. Parameters of latency and amplitude of iRBD converters to neurodegenerative disease were compared with those of the non-converters.

Results: The VEP P100 mean latency values for both eyes and for both stimulation checks (30' and 15') were significantly longer in all the three groups of patients as compared to controls; moreover latencies were longer in aPD than in the iRBD group who did not differ from the ePD group. The same held true when we analyzed the number of abnormal subjects belonging to each diagnostic group with a higher number of abnormal subjects in the aPD group compared to both the ePD and in iRBD groups. Chromatic and motion potentials were not different from controls and did not differ in the 3 diagnostic groups. The iRBD subjects who converted to a neurodegenerative disorder showed longer P100 latencies and a higher occurrence of VEPp abnormalities than those who did not convert. Again chromatic and motion VEPs were not different depending on conversion.

Conclusions: In iRBD patients the detection of an abnormal VEPp should be considered as a red flag for possible synnucleinopathy, eventually contributing in stratifying the risk of phenoconversion.
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http://dx.doi.org/10.1016/j.sleep.2021.05.006DOI Listing
May 2021

Dopaminergic and Serotonergic Degeneration and Cortical [ F]Fluorodeoxyglucose Positron Emission Tomography in De Novo Parkinson's Disease.

Mov Disord 2021 May 22. Epub 2021 May 22.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.

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 [ I]ioflupane single-photon emission computed tomography ([ I]FP-CIT-SPECT) and brain [ F]fluorodeoxyglucose positron emission tomography ([ F]FDG-PET). We used a voxel-wise analysis of [ F]FDG-PET images to correlate regional metabolism with striatal DA and thalamic SE innervation as assessed using [ I]FP-CIT-SPECT.

Results: We found that [ 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 [ 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 [ I]FP-CIT SBR values on prefrontal metabolism was fully mediated by thalamus metabolic values (P < 0.001).

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.
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http://dx.doi.org/10.1002/mds.28654DOI Listing
May 2021

Rage and aggressive behaviour in frontal lobe epilepsy: description of a case and review of the mechanisms of aggressive behaviour in epilepsy and dementia.

Epileptic Disord 2021 Apr;23(2):419-425

Epilepsy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, Division of Clinical Neurophysiology and Epilepsy Center, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

The study of dementia and epilepsy may provide particular insight into behavioural alterations. We describe a rare case of ictal aggressive behaviour in a patient with focal epilepsy associated with a non-dominant dorso-lateral prefrontal lesion. During focal seizures, our patient showed intense agitation and anger, for a long time misinterpreted as psychogenic attacks, which disappeared after epilepsy surgery. The defined anatomical origin of such ictal emotional behaviour is not fully understood, however, the dorso-lateral prefrontal area appears to correlate less frequently with aggressiveness compared to the antero-mesial area. We describe the electroclinical data of our patient and provide a brief review of the mechanisms underlying aggressive conduct in epilepsy and dementia. An understanding of this mechanism could help to clarify the neural basis and treatment of violence associated with these and other neurological disorders. [Published with video sequence].
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http://dx.doi.org/10.1684/epd.2021.1277DOI Listing
April 2021

Brain Metabolic Correlates of Persistent Olfactory Dysfunction after SARS-Cov2 Infection.

Biomedicines 2021 Mar 12;9(3). Epub 2021 Mar 12.

IRCCS Ospedale Policlinico San Martino, 16131 Genova, Italy.

We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [F]-FDG PET, including a dedicated brain acquisition at our institution between May and December 2020 following their recovery after SARS-Cov2 infection. Fourteen of these patients presented isolated persistent hyposmia (smell diskettes olfaction test was used). A voxel-wise analysis (using Statistical Parametric Mapping software version 8 (SPM8)) was performed to identify brain regions of relative hypometabolism in patients with hyposmia with respect to controls. Structural connectivity of these regions was assessed (BCB toolkit). Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in patients with respect to controls. Structural connectivity maps highlighted the involvement of bilateral longitudinal fasciculi. This study provides evidence of cortical hypometabolism in patients with isolated persistent hyposmia after SARS-Cov2 infection. [F]-FDG PET may play a role in the identification of long-term brain functional sequelae of COVID-19.
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http://dx.doi.org/10.3390/biomedicines9030287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998481PMC
March 2021

Sleep disorders in Prader-Willi syndrome, evidence from animal models and humans.

Sleep Med Rev 2021 Jun 20;57:101432. Epub 2021 Jan 20.

Unit of Child Neuropsychiatry, Department of Medical and Surgical Neuroscience and Rehabilitation, IRCCS Istituto Giannina Gaslini, Genoa, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.smrv.2021.101432DOI Listing
June 2021

Probing the Role of a Regional Quantitative Assessment of Amyloid PET.

J Alzheimers Dis 2021 ;80(1):383-396

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Child and Maternal Health (DINOGMI), University of Genoa, Genoa, Italy.

Background: In clinical practice, the amy-PET is globally inspected to provide a binary outcome, but the role of a regional assessment has not been fully investigated yet.

Objective: To deepen the role of regional amyloid burden and its implication on clinical-neuropsychological features.

Materials: Amy-PET and a complete neuropsychological assessment (Trail Making Test, Rey Auditory Verbal Learning Test, semantic verbal fluency, Symbol Digit, Stroop, visuoconstruction) were available in 109 patients with clinical suspicion of Alzheimer's disease. By averaging the standardized uptake value ratio and ELBA, a regional quantification was calculated for each scan. Patients were grouped according to their overall amyloid load: correlation maps, based on regional quantification, were calculated and compared. A regression analysis between neuropsychological assessment and the regional amyloid-β (Aβ) load was carried out.

Results: Significant differences were observed between the correlation maps of patients at increasing levels of Aβ and the overall dataset. The Aβ uptake of the subcortical gray matter resulted not related to other brain regions independently of the global Aβ level. A significant association of semantic verbal fluency was observed with ratios of cortical and subcortical distribution of Aβ which represent a coarse measure of differences in regional distribution of Aβ.

Conclusion: Our observations confirmed the different susceptibility to Aβ accumulation among brain regions. The association between cognition and Aβ distribution deserves further investigations: it is possibly due to a direct local effect or it represents a proxy marker of a more aggressive disease subtype. Regional Aβ assessment represents an available resource on amy-PET scan with possibly clinical and prognostic implications.
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http://dx.doi.org/10.3233/JAD-201156DOI Listing
January 2021

Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European-DLB consortium project.

Alzheimers Dement 2021 Feb 2. Epub 2021 Feb 2.

Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Introduction: We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern.

Methods: Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age).

Results: Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent).

Discussion: These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.
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http://dx.doi.org/10.1002/alz.12294DOI Listing
February 2021

Cuneus/precuneus as a central hub for brain functional connectivity of mild cognitive impairment in idiopathic REM sleep behavior patients.

Eur J Nucl Med Mol Imaging 2021 08 28;48(9):2834-2845. Epub 2021 Jan 28.

Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Largo P. Daneo, 3, 16132, Genoa, Italy.

Purpose: To investigate brain functional correlates of mild cognitive impairment (MCI) in idiopathic REM sleep behavior disorder (iRBD).

Methods: 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, F-FDG-PET, and I-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 F-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 I-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.

Results: The MCI-VOI was characterized by a relative hypometabolism involving precuneus and cuneus (height threshold p<0.0001). IRCA (height threshold p<0.0001) revealed a brain functional network involving regions in frontal, temporal, parietal, and occipital lobes, thalamus, caudate, and red nuclei in iRBD patients. In controls, the network was smaller and involved temporal, occipital, cingulate cortex, and cerebellum. Moreover, MCI-VOI metabolism was correlated with verbal memory (p=0.01), executive functions (p=0.0001), and nigro-putaminal SBR (p=0.005). Finally, MCI-VOI was involved in a white matter network including cingulate fasciculus and corpus callosum.

Conclusion: Our data suggest that cuneus/precuneus is a hub of a large functional network subserving cognitive function in iRBD.
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http://dx.doi.org/10.1007/s00259-021-05205-6DOI Listing
August 2021

Brain Resources: How Semantic Cueing Works in Mild Cognitive Impairment due to Alzheimer's Disease (MCI-AD).

Diagnostics (Basel) 2021 Jan 12;11(1). Epub 2021 Jan 12.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child health (DINOGMI), University of Genoa, 16132 Genova, Italy.

Semantic cues in the Free and Cued Selective Reminding Test (FCRST) play a key role in the neuropsychological diagnosis of Amnesic Mild Cognitive Impairment due to Alzheimer's Disease (MCI-AD); however, the neural bases of their impact of recall abilities are only partially understood. Here, we thus decided to investigate the relationships between brain metabolism and the FCSRT Index of Sensitivity of Cueing (ISC) in patients with MCI-AD and in healthy controls (HC). Thirty MCI-AD patients (age: 74.7 ± 5.7 years; education: 9.6 ± 4.6 years, MMSE score: 24.8 ± 3.3, 23 females) and seventeen HC (age: 66.5 ± 11.1 years; education: 11.53 ± 4.2 years, MMSE score: 28.4 ± 1.14, 10 females) who underwent neuropsychological evaluation and brain F-18 fluorodeoxyglucose Positron Emission Tomography (FDG-PET) were included in the study. ISC was able to differentiate HC from MCI-AD subjects as shown by a ROC analysis (AUC of 0.978, effect size Hedges's g = 2.89). MCI-AD subjects showed significant hypometabolism in posterior cortices, including bilateral inferior Parietal Lobule and Precuneus and Middle Temporal gyrus in the left hemisphere (VOI-1) compared to HC. ISC was positively correlated with brain metabolism in a single cluster (VOI-2) spanning the left prefrontal cortex (superior frontal gyrus) and anterior cingulate cortex (ACC) in the patient group (R = 0.526, < 0.001), but not in HC. Mean uptake values of VOI-2 did not differ between HC and MCI-AD. The structural connectivity analysis showed that VOI-2 is connected with the temporal pole, the cingulate gyrus and the posterior temporal cortices in the left hemisphere. In MCI-AD, the relative preservation of frontal cortex metabolic levels and their correlation with the ISC suggest that the left frontal cortices play a significant role in maintaining a relatively good memory performance despite the presence of posterior hypometabolism in MCI-AD.
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http://dx.doi.org/10.3390/diagnostics11010108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826532PMC
January 2021

Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder.

Brain 2021 02;144(1):278-287

Radiation Physics and Protection Department, Churchill Hospital, Oxford, UK.

This is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent 123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis. 123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed: (i) Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale, motor section score; (ii) Mini-Mental State Examination score; (iii) constipation; and (iv) hyposmia. Kaplan-Meier survival analysis was performed to estimate conversion risk. Hazard ratios for each variable were calculated with Cox regression. A generalized logistic regression model was applied to identify the best combination of risk factors. Bayesian classifier was used to identify the baseline features predicting phenoconversion to parkinsonism or dementia. After quality check of the data, 263 iRBD patients (67.6 ± 7.3 years, 229 males) and 243 control subjects (67.2 ± 10.1 years, 110 males) were analysed. Fifty-two (20%) patients developed a synucleinopathy after average follow-up of 2 years. The best combination of risk factors was putamen dopaminergic dysfunction of the most affected hemisphere on imaging, defined as the lower value between either putamina (P < 0.000001), constipation, (P < 0.000001) and age over 70 years (P = 0.0002). Combined features obtained from the generalized logistic regression achieved a hazard ratio of 5.71 (95% confidence interval 2.85-11.43). Bayesian classifier suggested that patients with higher Mini-Mental State Examination score and lower caudate SBR asymmetry were more likely to develop parkinsonism, while patients with the opposite pattern were more likely to develop dementia. This study shows that iRBD patients older than 70 with constipation and reduced nigro-putaminal dopaminergic function are at high risk of short-term phenoconversion to an overt synucleinopathy, providing an effective stratification approach for future neuroprotective trials. Moreover, we provide cut-off values for the significant predictors of phenoconversion to be used in single subjects.
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http://dx.doi.org/10.1093/brain/awaa365DOI Listing
February 2021

Rapid eye movement sleep behavior disorder: A proof-of-concept neuroprotection study for prodromal synucleinopathies.

Eur J Neurol 2021 Apr 23;28(4):1210-1217. Epub 2020 Dec 23.

Clinical Neurology, Department of Neuroscience (DINOGMI, University of Genoa, Genoa, Italy.

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 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 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 ( 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 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 I-FP-CIT-SPECT as a biomarker of disease progression.
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http://dx.doi.org/10.1111/ene.14664DOI Listing
April 2021

Abnormalities of Cortical Sources of Resting State Alpha Electroencephalographic Rhythms are Related to Education Attainment in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment.

Cereb Cortex 2021 Mar;31(4):2220-2237

Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy.

In normal old (Nold) and Alzheimer's disease (AD) persons, a high cognitive reserve (CR) makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here, we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI). Data in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu-) educational attainment subgroups, were available in an Italian-Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware. As compared to the Nold-Edu- subgroup, the Nold-Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI-Edu- subgroup, the ADMCI-Edu+ subgroup displayed lower alpha source activations topographically widespread. Furthermore, the 2 ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray-white matter measures, and neuropsychological scores. The current findings suggest that a high CR may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients.
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http://dx.doi.org/10.1093/cercor/bhaa356DOI Listing
March 2021

Multicenter Study on Sleep and Circadian Alterations as Objective Markers of Mild Cognitive Impairment and Alzheimer's Disease Reveals Sex Differences.

J Alzheimers Dis 2020 ;78(4):1707-1719

Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: Circadian and sleep disturbances are associated with increased risk of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Wearable activity trackers could provide a new approach in diagnosis and prevention.

Objective: To evaluate sleep and circadian rhythm parameters, through wearable activity trackers, in MCI and AD patients as compared to controls, focusing on sex dissimilarities.

Methods: Based on minute level data from consumer wearable devices, we analyzed actigraphic sleep parameters by applying an electromedical type I registered algorithm, and the corresponding circadian variables in 158 subjects: 86 females and 72 males (42 AD, 28 MCI, and 88 controls). Moreover, we used a confusion-matrix chart method to assess accuracy, precision, sensitivity, and specificity of two decision-tree models based on actigraphic data in predicting disease or health status.

Results: Wake after sleep onset (WASO) was higher (p < 0.001) and sleep efficiency (SE) lower (p = 0.003) in MCI, and Sleep Regularity Index (SRI) was lower in AD patients compared to controls (p = 0.004). SE was lower in male AD compared to female AD (p = 0.038) and SRI lower in male AD compared to male controls (p = 0.008), male MCI (p = 0.047), but also female AD subjects (p = 0.046). Mesor was significantly lower in males in the overall population. Age reduced the dissimilarities for WASO and SE but demonstrated sex differences for amplitude (p = 0.009) in the overall population, controls (p = 0.005), and AD subjects (p = 0.034). The confusion-matrices showed good predictive power of actigraphic data.

Conclusion: Actigraphic data could help identify disease or health status. Sex (possibly gender) differences could impact on neurodegeneration and disease trajectory with potential clinical applications.
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http://dx.doi.org/10.3233/JAD-200632DOI Listing
January 2020

Striatal dopamine transporter SPECT quantification: head-to-head comparison between two three-dimensional automatic tools.

EJNMMI Res 2020 Nov 7;10(1):137. Epub 2020 Nov 7.

IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Purpose: Our aim was to compare a widely distributed commercial tool with an older free software (i) one another, (ii) with a clinical motor score, (iii) versus reading by experts.

Procedures: We analyzed consecutive scans from one-hundred and fifty-one outpatients submitted to brain DAT SPECT for a suspected parkinsonism. Images were post-processed using a commercial (Datquant®) and a free (BasGanV2) software. Reading by expert was the gold standard. A subset of patients with pathological or borderline scan was evaluated with the clinical Unified Parkinson's Disease Rating Scale, motor part (MDS-UPDRS-III).

Results: SBR, putamen-to-caudate (P/C) ratio, and both P and C asymmetries were highly correlated between the two software with Pearson's 'r' correlation coefficients ranging from .706 to .887. Correlation coefficients with the MDS-UPDRS III score were higher with caudate than with putamen SBR values with both software, and in general higher with BasGanV2 than with Datquant®. Datquant® correspondence with expert reading was 84.1% (94.0% by additionally considering the P/C ratio as a further index). BasGanV2 correspondence with expert reading was 80.8% (86.1% by additionally considering the P/C ratio).

Conclusions: Both Datquant® and BasGanV2 work reasonably well and similarly one another in semi-quantification of DAT SPECT. Both tools have their own strength and pitfalls that must be known in detail by users in order to obtain the best help in visual reading and reporting of DAT SPECT.
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http://dx.doi.org/10.1186/s13550-020-00727-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648825PMC
November 2020

Resting-state electroencephalographic delta rhythms may reflect global cortical arousal in healthy old seniors and patients with Alzheimer's disease dementia.

Int J Psychophysiol 2020 12 17;158:259-270. Epub 2020 Oct 17.

Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy.

Extending Başar's theory of event-related EEG oscillations, here we hypothesize that even in quiet wakefulness, transient increases in delta rhythms may enhance global cortical arousal as revealed by the desynchronization of alpha rhythms in normal (Nold) seniors with some derangement in Alzheimer's disease dementia (ADD). Clinical and EEG datasets in 100 ADD and 100 Nold individuals matched as demography, education, and gender were taken from an international archive. Standard delta (< 4 Hz) and alpha1 (8-10.5 Hz) bands were used for the main analysis, while alpha2 (10.5-13 Hz), theta (4-8 Hz), beta1 (13-20 Hz), beta2 (20-35 Hz), and gamma (35-40 Hz) served as controls. In the interpretation, the higher the alpha1 power (density), the lower that arousal. As expected, when compared to the Nold group, the ADD group showed higher global (scalp) power density at the delta-theta band and lower global power density at the alpha-beta bands. As novel findings, we observed that: (1) in the Nold group, the global delta and alpha1-2 power were negatively and linearly correlated; (2) in the ADD group, this correlation was just marginal; and (3) in both Nold and AD groups, the EEG epochs with the highest delta power (median value for stratification) were associated with the lowest global alpha1 power. This effect was related to eLORETA freeware solutions showing maximum alpha1 source activations in posterior cortical regions. These results suggest that even in quiet wakefulness, delta and alpha rhythms are related to each other, and ADD partially affects this cross-band neurophysiological mechanism.
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http://dx.doi.org/10.1016/j.ijpsycho.2020.08.012DOI Listing
December 2020

Abnormalities of resting-state EEG in patients with prodromal and overt dementia with Lewy bodies: Relation to clinical symptoms.

Clin Neurophysiol 2020 11 23;131(11):2716-2731. Epub 2020 Sep 23.

Department of Neurology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey.

Objective: Here we tested if cortical sources of resting state electroencephalographic (rsEEG) rhythms may differ in sub-groups of patients with prodromal and overt dementia with Lewy bodies (DLB) as a function of relevant clinical symptoms.

Methods: We extracted clinical, demographic and rsEEG datasets in matched DLB patients (N = 60) and control Alzheimer's disease (AD, N = 60) and healthy elderly (Nold, N = 60) seniors from our international database. The eLORETA freeware was used to estimate cortical rsEEG sources.

Results: As compared to the Nold group, the DLB and AD groups generally exhibited greater spatially distributed delta source activities (DLB > AD) and lower alpha source activities posteriorly (AD > DLB). As compared to the DLB "controls", the DLB patients with (1) rapid eye movement (REM) sleep behavior disorders showed lower central alpha source activities (p < 0.005); (2) greater cognitive deficits exhibited higher parietal and central theta source activities as well as higher central, parietal, and occipital alpha source activities (p < 0.01); (3) visual hallucinations pointed to greater parietal delta source activities (p < 0.005).

Conclusions: Relevant clinical features were associated with abnormalities in spatial and frequency features of rsEEG source activities in DLB patients.

Significance: Those features may be used as neurophysiological surrogate endpoints of clinical symptoms in DLB patients in future cross-validation prospective studies.
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http://dx.doi.org/10.1016/j.clinph.2020.09.004DOI Listing
November 2020

NREM sleep arousal-related disorders reflect cognitive impairment in Parkinson's disease.

Sleep Med 2020 11 5;75:491-496. Epub 2020 Sep 5.

Sleep and Epilepsy Unit, IRCCS Mondino Foundation, Pavia, Italy.

Background: Sleep disorders and cognitive impairment are frequently reported in Parkinson's disease (PD) as non-motor disabling symptoms. While it is known that REM sleep Behaviour Disorder (RBD) in PD is associated with motor and cognitive decline, little is known about the neurobiological significance of NREM sleep arousal-related disorders.

Objectives: to evaluate the cognitive and clinical correlates of arousal-related disorders in PD.

Methods: Clinical data and video-polysomnography were analysed from one hundred-seventy consecutive subjects with PD. Based on the neuropsychological assessment, the subjects were divided into three groups: no cognitive impairment (PD; n = 58), mild cognitive impairment (PD-MCI; n = 58) and overt dementia (PDD; n = 54).

Results: Arousal-related disorders by history were reported in 32.9% of the subjects: 10.3% PD, 31.6% PD-MCI and 59.3% PDD (p = 0.001). Video-PSG captured arousal-related disorders in 1.7% PD, 21.2% MCI-PD and 35.6% PDD (p = 0.001). Arousal-related disorders and RBD were recorded in the same night in 7.7% PD, 9.8% MCI-PD and 15.6% PDD (p = 0.04). Patients with arousal-related disorders captured at V-PSG have a longer disease duration (p = 0.003), higher UPDRS score (p = 0.039), longer duration of treatment with levodopa (p = 0.017) and dopamine agonists (p = 0.018), worse H&Y staging (p = 0.001), lower MMSE score (p = 0.019) and more frequently hallucinations (p = 0.004). In multivariate analysis, cognitive impairment significantly increases the risk of arousal-related disorders (OR 3.387-95% CI 1.395-8.220, p = 0.007).

Conclusion: Arousal-related disorders appear to be a marker of cognitive decline in PD. Recognizing arousal-related disorders should make clinicians aware of a possible cognitive decline in PD and eventually modify the therapeutic approach.
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http://dx.doi.org/10.1016/j.sleep.2020.08.029DOI Listing
November 2020

The role of anterior prefrontal cortex in prospective memory: an exploratory FDG-PET study in early Alzheimer's disease.

Neurobiol Aging 2020 12 8;96:117-127. Epub 2020 Sep 8.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

From previous studies in healthy volunteers the prefrontal regions are deeply involved in prospective memory (PM), although little is known about the functional neural basis of PM in prodromal Alzheimer's disease (AD). To this end, we retrospectively recruited 18 patients with mild cognitive impairment caused by AD and 23 matched healthy control subjects who had undergone F-fluorodeoxyglucose positron emission tomography and the PM-specific paradigm test. Brain metabolism was correlated with the PM score in the 2 groups separately to find those brain areas correlated with PM performance, which were then used as a hub for an inter-regional metabolic connectivity analyses (inter-regional correlation analysis). Of note, in mild cognitive impairment caused by AD, but not in healthy control subjects, PM score positively correlated with metabolic levels in the right anterior prefrontal cortex (middle and inferior frontal gyri), which disclosed a loss of interhemispheric connectivity in the inter-regional correlation analysis. According to our findings, the functioning of the right anterior prefrontal cortex and its interhemispheric metabolic connectivity is crucial in early AD to sustain PM performance, which deteriorates along with progressive metabolic failure of the interconnected areas.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.09.003DOI Listing
December 2020

An application of generalized matrix learning vector quantization in neuroimaging.

Comput Methods Programs Biomed 2020 Dec 22;197:105708. Epub 2020 Aug 22.

Bernoulli Institute for Mathematics, Computer Science and Artificial Intelligence, University of Groningen, the Netherlands.

Background And Objective: Neurodegenerative diseases like Parkinson's disease often take several years before they can be diagnosed reliably based on clinical grounds. Imaging techniques such as MRI are used to detect anatomical (structural) pathological changes. However, these kinds of changes are usually seen only late in the development. The measurement of functional brain activity by means of [F]fluorodeoxyglucose positron emission tomography (FDG-PET) can provide useful information, but its interpretation is more difficult. The scaled sub-profile model principal component analysis (SSM/PCA) was shown to provide more useful information than other statistical techniques. Our objective is to improve the performance further by combining SSM/PCA and prototype-based generalized matrix learning vector quantization (GMLVQ).

Methods: We apply a combination of SSM/PCA and GMLVQ as a classifier. In order to demonstrate the combination's validity, we analyze FDG-PET data of Parkinson's disease (PD) patients collected at three different neuroimaging centers in Europe. We determine the diagnostic performance by performing a ten times repeated ten fold cross validation. Additionally, discriminant visualizations of the data are included. The prototypes and relevance of GMLVQ are transformed back to the original voxel space by exploiting the linearity of SSM/PCA. The resulting prototypes and relevance profiles have then been assessed by three neurologists.

Results: One important finding is that discriminative visualization can help to identify disease-related properties as well as differences which are due to center-specific factors. Secondly, the neurologist assessed the interpretability of the method and confirmed that prototypes are similar to known activity profiles of PD patients.

Conclusion: We have shown that the presented combination of SSM/PCA and GMLVQ can provide useful means to assess and better understand characteristic differences in FDG-PET data from PD patients and HCs. Based on the assessments by medical experts and the results of our computational analysis we conclude that the first steps towards a diagnostic support system have been taken successfully.
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http://dx.doi.org/10.1016/j.cmpb.2020.105708DOI Listing
December 2020

Epilepsy course during COVID-19 pandemic in three Italian epilepsy centers.

Epilepsy Behav 2020 11 25;112:107375. Epub 2020 Aug 25.

Division of Clinical Neurophysiology and Epilepsy Center, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, Genova, Italy.

During epidemic outbreaks, epilepsy course can be modified by different physical and psychological stressors and, most importantly, by irregular therapy intake. The effect of COVID-19 and quarantine isolation on the course of epilepsy and on incidence of new-onset seizures is still unclear. With the aim of managing epilepsy in quarantined patients, three Italian Epilepsy Centers set up telephone consultations using a semistructured interview, allowing a prospective collection of data on seizure course and other seizure-related problems during pandemic. The collected data on seizure course were compared with the analogous period of 2019. The level of patients' concern relating to the COVID-19 pandemic was also assessed using a numeric rating scale. To address the effect of COVID-19 pandemic on seizure incidence, data collection included the number of consultations for first seizures, relapse seizures, and status epilepticus (SE) in the emergency department of one of the participating centers. Clinical telephone interviews suggest the absence of quarantine effect on epilepsy course in our cohort. No differences in incidence of emergency consultations for seizures over a two-month period were also observed compared with a control period. As demonstrated in other infective outbreaks, good antiepileptic drug (AED) supplying, precise information, and reassurance are the most important factors in chronic conditions to minimize psychological and physical stress, and to avoid unplanned treatment interruptions.
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http://dx.doi.org/10.1016/j.yebeh.2020.107375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445187PMC
November 2020

Hyperconnectivity in Dementia Is Early and Focal and Wanes with Progression.

Cereb Cortex 2021 Jan;31(1):97-105

Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, 66100 Chieti, Italy.

We investigated in a longitudinal multicenter cohort study functional cortical connectivity changes along the course of frontotemporal dementia (FTD) and Alzheimer's disease (AD) from the prodromal stage of the diseases. Electroencephalography (EEG) was recorded in 18 FTD and 18 AD patients at the prodromal stage of dementia, at dementia onset, and 3 years after dementia onset. Twenty healthy controls (HC) underwent EEG recordings at the same time interval as the patients. Mutual information (MI) analysis measured the strength of functional network connectivity. FTD and AD patients showed greater MI at the prodromal stage of dementia (FTD vs. HC P = 2 × 10-8; AD vs. HC P = 4 × 10-3). Local connectivity was higher in left and right frontal areas of FTD (P = 7 × 10-5 and 0.03) and in left and right posterior areas in AD (P = 3 × 10-5 and 5 × 10-5) versus HC. We showed cortical hyperconnectivity at the prodromal stage of dementia in areas involved in the specific pathological process of FTD (frontal regions) and AD (posterior regions). Hyperconnectivity disappeared during follow-up, thus suggesting that it is an early electrophysiological feature of dementia, potentially useful to identify prodromal FTD and AD.
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http://dx.doi.org/10.1093/cercor/bhaa209DOI Listing
January 2021

Anatomical and neurochemical bases of theory of mind in de novo Parkinson's Disease.

Cortex 2020 09 10;130:401-412. Epub 2020 Jul 10.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico S. Martino, Genoa, Italy. Electronic address:

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-naïve, 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.
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http://dx.doi.org/10.1016/j.cortex.2020.06.012DOI Listing
September 2020

Utility of quantitative EEG in early Lewy body disease.

Parkinsonism Relat Disord 2020 06 24;75:70-75. Epub 2020 May 24.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI, Department of Excellence of the Italian Ministry of University and Research), University of Genoa, Largo Daneo 3, 16132, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Largo Benzi 10, 16132, Genoa, Italy.

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.
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http://dx.doi.org/10.1016/j.parkreldis.2020.05.007DOI Listing
June 2020

The fate of patients with REM sleep behavior disorder and mild cognitive impairment.

Sleep Med 2021 03 29;79:205-210. Epub 2020 Feb 29.

Clinical Neurology, Dept. of Neuroscience (DINOGMI), University of Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

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 I-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 < 0.0001). During the follow-up, 10 patients (22.7%) develop an overt synucleinopathy. GLM analysis showed that patients with orthostatic hypotension, non-motor experiences of daily living, reduced putaminal DAT-SPECT SBR, and cognitive impairment in verbal memory/visuoconstruction abilities were at higher risk of phenoconversion (Hazard Ratio [HR] 26.05; Sensitivity 90%; Specificity 100%; Accuracy 97.73%; Positive Predictive Value 100%; Negative Predictive Value 97.14%).

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.
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http://dx.doi.org/10.1016/j.sleep.2020.02.011DOI Listing
March 2021

Anterior EEG slowing in dementia with Lewy bodies: a multicenter European cohort study.

Neurobiol Aging 2020 09 29;93:55-60. Epub 2020 Apr 29.

Department of Neuroscience, Imaging and Clinical Science, and Aging Research Centre, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy. Electronic address:

Electroencephalography (EEG) slowing with prealpha dominant frequency (DF) in posterior derivations is a biomarker for dementia with Lewy bodies (DLB) diagnosis, in contrast with Alzheimer's disease (AD). However, an intrasubject re-evaluation of the original data, which contributed to the identification of EEG DLB biomarker, showed that DF was slower in anterior than posterior derivations. We suppose this anterior-posterior gradient of DF slowing could arise in DLB from a thalamocortical dysrhythmia, differently involving the anterior and posterior cortical areas, and correlating with cognitive impairment (Mini-Mental State Examination). EEG was recorded in 144 DLB, 116 AD, and 65 controls from 7 Centers of the European DLB Consortium. Spectra were divided into delta, theta, prealpha, alpha frequency bands. In DLB, mean DF was prealpha both anteriorly and posteriorly, but lower anteriorly (p < 0.001). In 14% of DLB, DF was prealpha anteriorly, whereas alpha posteriorly. In AD and controls, DF was constantly alpha. EEG slowing in DLB correlated with cognitive impairment. Thalamocortical dysrhythmia gives rise to prealpha rhythm with an anterior-posterior gradient and correlates with impaired cognition.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.04.023DOI Listing
September 2020

I-FP-CIT SPECT validation of nigro-putaminal MRI tractography in dementia with Lewy bodies.

Eur Radiol Exp 2020 05 4;4(1):27. Epub 2020 May 4.

Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.

Background: Assessment of nigrostriatal degeneration is a key element to discriminate between dementia with Lewy bodies (DLB) and Alzheimer disease (AD), and it is often evaluated using ioflupane (I-FP-CIT) single-photon emission computed tomography (SPECT). Given the limited availability of I-FP-CIT SPECT, we evaluated if a mask-based approach to nigroputaminal magnetic resonance imaging (MRI) diffusion-weighted tractography could be able to capture microstructural changes reflecting nigroputaminal degeneration in DLB.

Methods: A nigroputaminal bundle mask was delineated on 12 healthy volunteers (HV) and applied to MRI diffusion-weighted data of 18 subjects with DLB, 21 subjects with AD and another group of 12 HV. The correlation between nigroputaminal fractional anisotropy (FA) values and I-FP-CIT SPECT findings was investigated. Shapiro-Wilk, ANOVA, ANCOVA, and parametric correlation statistics as well as receiver operating characteristic (ROC) analysis were used.

Results: DLB patients showed a higher nigroputaminal FA values compared with both AD and HV-controls groups (p = 0.001 for both comparisons), while no difference was observed between HV-controls and AD groups (p = 0.450); at ROC analysis, the area under the curve for the discriminating DLB and AD subjects was 0.820; FA values correlated with I-FP-CIT values (on the left, r = -0.670; on the right, r = -720). No significant differences were observed for the FA of the corticospinal tract across the three groups (p = 0.740).

Conclusions: In DLB, nigroputaminal degeneration could be reliably assessed on MRI diffusion scans using a mask of nigroputaminal bundle trajectory. Nigroputaminal FA in DLB patients correlated with I-FP-CIT values data may allow to differentiate these patients from AD patients and HV-controls.
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http://dx.doi.org/10.1186/s41747-020-00153-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196565PMC
May 2020

Abnormal cortical neural synchronization mechanisms in quiet wakefulness are related to motor deficits, cognitive symptoms, and visual hallucinations in Parkinson's disease patients: an electroencephalographic study.

Neurobiol Aging 2020 07 12;91:88-111. Epub 2020 Mar 12.

Department of Biophysics, International School of Medicine, Istanbul Medipol University, Istanbul, Turkey.

Compared with Alzheimer's disease (AD), Parkinson's disease (PD) shows peculiar clinical manifestations related to vigilance (i.e., executive cognitive deficits and visual hallucinations) that may be reflected in resting-state electroencephalographic rhythms. To test this hypothesis, clinical and resting-state electroencephalographic rhythms in age-, sex-, and education-matched PD patients (N = 136) and Alzheimer's disease patients (AD, N = 85), and healthy older participants (Nold, N = 65), were available from an international archive. Electroencephalographic sources were estimated by eLORETA software. The results are as follows: (1) compared to the Nold participants, the AD and PD patients showed higher widespread delta source activities (PD > AD) and lower posterior alpha source activities (AD > PD); (2) the PD patients with the most pronounced motor deficits exhibited very low alpha source activities in widespread cortical regions; (3) the PD patients with the strongest cognitive deficits showed higher alpha source activities in widespread cortical regions; and (4) compared to the PD patients without visual hallucinations, those with visual hallucinations were characterized by higher posterior alpha sources activities. These results suggest that in PD patients resting in quiet wakefulness, abnormalities in cortical neural synchronization at alpha frequencies are differently related to cognitive, motor, and visual hallucinations. Interestingly, parallel PD neuropathological processes may have opposite effects on cortical neural synchronization mechanisms generating cortical alpha rhythms in quiet wakefulness.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.02.029DOI Listing
July 2020

Epilepsy in Neurodegenerative Dementias: A Clinical, Epidemiological, and EEG Study.

J Alzheimers Dis 2020 ;74(3):865-874

Department of Neuroscience (DINOGMI), Clinical Neurology, University of Genoa, Genoa, Italy.

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.
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http://dx.doi.org/10.3233/JAD-191315DOI Listing
April 2021
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