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In contrast to myotonic dystrophy type 1, the cognitive and radiologic profile of myotonic dystrophy type 2 (DM2) is relatively poorly characterized.To conduct a pilot study to systematically evaluate cognitive and radiologic features in a cohort of Greek individuals with DM2.Eleven genetically confirmed individuals with DM2 and 26 age- and education-matched healthy controls were administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) to screen for impairment in multiple cognitive domains. MRI data were evaluated by morphometric analyses to identify disease-specific gray and white matter alterations. The following statistical thresholds were used for cognitive comparisons: PFDR0.05 and Bayes factor (BF 10 )10.The DM2 group exhibited cognitive impairment (ECAS Total score; PFDR = 0.001; BF 10 = 108.887), which was dominated by executive impairment ( PFDR = 0.003; BF 10 = 25.330). A trend toward verbal fluency impairment was also identified. No significant impairments in memory, language, or visuospatial function were captured. The analysis of subscores revealed severe impairments in social cognition and alternation. Voxel-based morphometry identified widespread frontal, occipital, and subcortical gray matter atrophy, including the left superior medial frontal gyrus, right medial orbitofrontal gyrus, right operculum, right precuneus, bilateral fusiform gyri, and bilateral thalami.DM2 may be associated with multifocal cortical and thalamic atrophy, which is likely to underpin the range of cognitive manifestations mostly characterized by executive impairment and specifically by impaired social cognition.

Θεωρητικό υπόβαθρο: Η Πλάγια Μυατροφική Σκλήρυνση (Amyotrophic Lateral Sclerosis – ALS) αποτελεί τη βασικότερη διαγνωστική ομάδα των παθήσεων του κινητικού νευρώνα και χαρακτηρίζεται από προσβολή τόσο του ανώτερου (κεντρικού) κινητικού νευρώνα όσο και του κατώτερου (περιφερικού) κινητικού νευρώνα, με συνέπεια την κατάληξη του ασθενούς τρία έως πέντε -κατά μέσο όρο- έτη μετά τη διάγνωση της νόσου, κυρίως λόγω αναπνευστικής ανεπάρκειας. Η παραδοσιακή θεώρηση της ALS ως μιας αμιγώς κινητικής νόσου, με την όποια μη κινητική προσβολή να αφορά -από δομικής πλευράς- αλλαγές σε μετωπιαίες κυρίως περιοχές και -από λειτουργικής πλευράς- ήπια επιτελική δυσλειτουργία ή συμπεριφορικές μεταβολές στο πλαίσιο του φάσματος ALS – Frontotemporal Dementia (FTD), έχει πλέον αναθεωρηθεί. Η ALS θεωρείται μια πάθηση όπου οι μεταβολές εντοπίζονται εντός και εκτός του πρωτοταγούς κινητικού φλοιού, του φλοιονωτιαίου δεματίου και των μετωπιαίων συνειρμικών περιοχών, σχηματίζοντας ένα χάρτη με πολλές πάσχουσες περιοχές φαιάς (φλοιικώς και υποφλοιωδώς) και λευκής ουσίας. Φαινομενολογικά δε, οι μεταβολές αυτές, πέραν των δεσμιδώσεων, της μυϊκής αδυναμίας και της κινητικής δυσχέρειας, ανιχνεύονται ως ποικίλες νοητικές δυσλειτουργίες, όχι αποκλειστικά επιτελικού τύπου, αλλά και ως συμπεριφορικές μεταβολές ή συναισθηματική ακράτεια (κλαυσίγελος). Σκοπός: Σκοπός της παρούσας διατριβής είναι η δομική και λειτουργική διερεύνηση της κινητικής και μη κινητικής προσβολής στην ALS μέσω σύγχρονων νευροαπεικονιστικών τεχνικών και μεθόδων κλινικής νευροφυσιολογίας και νευροψυχολογίας. Μεθοδολογία: Στη μελέτη συμμετείχαν 75 ασθενείς με σποραδική μορφή της ALS (βάσει των αναθεωρημένων κριτηρίων El Escorial) χωρίς άνοια και όλα τα στοιχεία τους καταγράφηκαν στην ειδική βάση δεδομένων “AMATUM ALS” (Acquisition, Management, Analysis, Therapeutic Unique Monitoring for Amyotrophic Lateral Sclerosis Database). Όλοι ασθενείς εξετάστηκαν με εκτενή νευροψυχολογική συστοιχία (νοητικά πεδία: επιτελικές λειτουργίες, προσοχή & ενεργός μνήμη, μάθηση-μνήμη, εκφραστικός λόγος, οπτικοχωρικές-κατασκευαστικές δεξιότητες, συλλογισμός με μεμαθημένες συμβολικές έννοιες) ενώ αξιολογήθηκε, επίσης, η κατάθλιψη και η συναισθηματική ευμεταβλητότητα. Βάσει τιμών αναφοράς για κάθε νευροψυχολογική δοκιμασία και ευρέως αποδεκτών κριτηρίων ταξινόμησης, οι 75 ασθενείς κατηγοριοποιήθηκαν σε υπο-ομάδες a) ALS-motor (αμιγώς κινητική δυσλειτουργία) και β) ALS-plus (κινητική και νοητική δυσλειτουργία). 25 υγιείς εθελοντές με φυσιολογική νοητική λειτουργία και 50 ασθενείς εκ των 75 υποβλήθηκαν σε νευροαπεικονιστική διερεύνηση με ακολουθίες υψηλής ανάλυσης για τη μετέπειτα διερεύνηση των μεταβολών της φαιάς ουσίας [ακολουθία: HR_3DT1w, ανάλυση: voxel-based morphometry (VBM)] και της λευκής ουσίας [ακολουθία: 30dir-DTI, ανάλυση: tract-based spatial statistics (TBSS), Diffusion Tensor Imaging (DTI) Tractography για συγκεκριμένα δεμάτια λευκής ουσίας]. 17 ασθενείς (με διαθέσιμα νευροψυχολογικά και νευροαπεικονιστικά δεδομένα) υποβλήθηκαν σε νευροφυσιολογικό έλεγχο μέσω διακρανιακού μαγνητικού ερεθισμού (TMS) για τη διερεύνηση της λειτουργικής ακεραιότητας της πυραμιδικής οδού, του μεσολοβίου και του κινητικού φλοιού. Αποτελέσματα: 1. Nευροψυχολογικό πρότυπο: Οι ασθενείς με ALS παρουσιάζουν κινητική και μη κινητική προσβολή που ανιχνεύεται λειτουργικά. Ειδικότερα, >65% των ασθενών με ALS στον ελληνικό πληθυσμό παρουσιάζει νοητική δυσλειτουργία. Οι επιτελικές λειτουργίες είναι αυτές που επηρεάζονται σε μεγαλύτερο βαθμό και ποσοστό 47% των ασθενών παρουσιάζει επιτελική δυσλειτουργία (με ή χωρίς άλλου τύπου νοητική δυσλειτουργία). Ποσοστό 20% των ασθενών παρουσιάζει μόνο μνημονική δυσλειτουργία χωρίς επιτελική ή άλλη νοητική δυσλειτουργία. H επιτελική επίδοση σχετίζεται με τη μνημονική επίδοση στο σύνολο των ασθενών αλλά ερμηνεύει μόνο 9% της συνολικής διακύμανσης της μνημονικής επίδοσης.2. Nευροαπεικονιστικό πρότυπο φαιάς και λευκής ουσίας: Οι ασθενείς με ALS παρουσιάζουν κινητική και μη κινητική προσβολή που ανιχνεύεται με τεχνικές δομικής νευροαπεικόνισης. Προκύπτουν διάχυτες μεταβολές τόσο στη φαιά όσο και στη λευκή ουσία τόσο σε κινητικές (κινητικός φλοιός, αισθητικοκινητικό τμήμα παρεγκεφαλίδας, φλοιονωτιαίο δεμάτιο, σώμα μεσολοβίου) όσο και μη κινητικές περιοχές (έσω, κογχο- και πλαγιοραχιαίες μετωπιαίες περιοχές, κροταφικές και ινιακές περιοχές). Οι ασθενείς χωρίς νοητική δυσλειτουργία (ALS-motor) παρουσιάζουν αύξηση της φαιάς ουσίας στη δεξιά συμπληρωματική κινητική περιοχή. Οι ασθενείς με νοητική δυσλειτουργία (ALS-plus) παρουσιάζουν πιο έντονες μεταβολές σε κινητικές και μη κινητικές περιοχές και συγκριτικά με τους ασθενείς χωρίς νοητική δυσλειτουργία παρουσιάζουν σημαντική ελάττωση στο προσφηνοειδές λόβιο στο αριστερό ημισφαίριο.Η συνδυαστική χρήση σύγχρονων τεχνικών νευροαπεικόνισης και μεθόδων μετεπεξεργασίας των δεδομένων επιτρέπει την ανάδειξη περιοχών ταυτόχρονης προσβολής της φαιάς και λευκής ουσίας.3. Δομική ακεραιότητα του κινητικού φλοιού και του φλοιονωτιαίου δεματίου και βαρύτητα της κινητικής ποοσβολής: Ανιχνεύεται θετική συσχέτιση μεταξύ της βαρύτητας της κινητικής προσβολής (ALSFRS-R) και του όγκου της αριστερής πρόσθιας κεντρικής έλικας. Ανιχνεύεται αρνητική συσχέτιση μεταξύ της ALSFRS-R και του όγκου της αριστερής συμπληρωματικής κινητικής περιοχής. Ανιχνεύεται αρνητική συσχέτιση μεταξύ της κλίμακας ALSFRS-R και του δείκτη διάχυσης Daxial στο αριστερό φλοιονωταίο δεμάτιο.4. Δομική ακεραιότητα του κινητικού φλοιού, του φλοιονωτιαίου δεματίου και των μεσολοβιακών ινών και λειτουργική ακεραιότητα του κινητικού συστήματος, όπως αυτή εξετάζεται μέσω του διακρανιακού μαγνητικού ερεθισμού: Διαπιστώθηκε ότι η λειτουργική ακεραιότητα του φλοιονωτιαίου δεματίου μπορεί να σχετίζεται και με δομικές μεταβολές σε φλοιϊκές αμιγώς κινητικές περιοχές, ανεξάρτητα από τη δομική ακεραιότητα του δεματίου. Βρέθηκε θετική συσχέτιση μεταξύ του όγκου τμήματος της δεξιάς πρόσθιας κεντρικής έλικας και του MEP / M ratio στο δεξί ά.ά., δηλαδή όσο μειώνεται ο λόγος, τόσο μεγαλύτερη η ελάττωση του όγκου στην εν λόγω περιοχή. Βρέθηκε αρνητική συσχέτιση μεταξύ του όγκου τμήματος της δεξιάς συμπληρωματικής κινητικής περιοχής και του MEP / M ratio στο δεξί ά.ά., δηλαδή όσο μειώνεται ο λόγος, τόσο μεγαλύτερος ο όγκος στην εν λόγω περιοχή. Χρησιμοποιώντας τον αλγόριθμο του Brainance DTI Suite που επιτρέπει ιχνηλάτηση τόσο των χιαζόμενων όσο και των μη χιαζόμενων ινών του φλοιονωτιαίου δεματίου, διαπιστώθηκε ότι η διημισφαρική αναστολή μπορεί να είναι παθολογικά αυξημένη στους ασθενείς με ALS λόγω διαφορετικής συμμετοχής του ομόπλευρου και ετερόπλευρου φλοιονωτιαίου δεματίου και των χιαζόμενων και μη χιαζόμενων φλοιονωτιαίων ινών. Βρέθηκε αρνητική συσχέτιση μεταξύ του ΙΗΙ και του FA του αριστερού φλοιονωτιαίου δεματίου, δηλαδή όσο μειώνεται ο δείκτης FA (χειρότερη δομική ακεραιότητα), αυξάνεται ο δείκτης IHI. Βρέθηκε θετική συσχέτιση μεταξύ του IHI και του Dradial του δεξιού φλοιονωτιαίου δεματίου, δηλαδή όσο αυξάνεται ο δείκτης Dradial (χειρότερη δομική ακεραιότητα), αυξάνεται ο δείκτης ΙΗΙ.Βρέθηκε αρνητική συσχέτιση μεταξύ του SP και του FA του αριστερού φλοιονωτιαίου δεματίου, δηλαδή όσο μειώνεται ο δείκτης FA (χειρότερη δομική ακεραιότητα), αυξάνεται ο δείκτης SP. 5. Βαρύτητα των μη κινητικών -δομικών- μεταβολών και νοητική δυσλειτουργία μνημονικού τύπου: Μετά από έλεγχο για πολλαπλές συγκρίσεις, βρέθηκε ότι οι ALS ασθενείς παρουσιάζουν αύξηση του δείκτη Daxial στην αριστερή ζώνη της διατιτραίνουσας οδού του ιπποκάμπου (PPZ) ενώ έχουν ηπιότερες μεταβολές στην μικροδομική ακεραιότητα της ψαλίδας και της αγκιστροειδούς δεσμίδας. Για πρώτη φορά αναδεικνύεται η συνεισφορά του δεματίου PPZ του αριστερού ημισφαιρίου στη λεκτική ακουστική μάθηση των ασθενών με ALS και μαζί με την αριστερή αγκιστροειδή δεσμίδα στην ικανότητα μακροπρόθεσμης ανάκλησης λεκτικών πληροφοριών.6. Βαρύτητα των μη κινητικών -δομικών- μεταβολών και συναισθηματική ευμεταβλητότητα (κλαυσίγελος): Συγκριτικά με τους μάρτυρες, οι ασθενείς με συναισθηματική ευμεταβλητότητα (κλαυσίγελο) παρουσιάζουν διάχυτες περιοχές ατροφίας συγκριτικά με τους μάρτυρες στους μετωπιαίους (κάτω κογχομετωπιαίος, rectus), κροταφικούς (άνω), ινιακούς (σφηνοειδές λόβιο, ατρακτοειδής έλικα, γλωσσική έλικα) λοβούς, στην πρόσθια έλικα του προσαγωγίου και στην παρεγκεφαλίδα αμφοτερόπλευρα. Οι ασθενείς με συναισθηματική ευμεταβλητήτοτα συγκριτικά με τους ασθενείς χωρίς συναισθηματική ευμεταβλητότητα παρουσιάζουν μειωμένο όγκο στο προσφηνοειδές λόβιο/οπίσθια έλικα προσαγωγίου και στη μέση κροταφική έλικα στο δεξί ημισφαίριο, που συνάδει με τη συνεισφορά του δεξιού ημισφαιρίου στη συναισθηματική επεξεργασία και αντίληψη.7. Δομικές (νευροαπεικονιστικές) και λειτουργικές (νευροψυχολογικές) μεταβολές και προγνωστική ικανότητα για το ρυθμό εξέλιξης της νόσου: Η καμπύλη λεκτικής ακουστικής μάθησης αποτελεί αρνητικό προγνωστικό παράγοντα για το ρυθμό εξέλιξης, με βραδύτερη καμπύλη μάθησης να είναι προγνωστική ταχύτητερης εξέλιξης. Η ατροφία στα βασικά γάγγλια (κέλυφος φακοειδούς πυρήνα) αμφοτερόπλευρα και αριστερά στην άνω κροταφική έλικα και στον άνω κροταφικό πόλο σχετίζεται με ταχύτερο ρυθμό εξέλιξης. Η αύξηση του δείκτη Daxial στο σώμα του μεσολοβίου σχετίζεται με ταχύτερο ρυθμό εξέλιξης Συμπερασματικά: Με ιστορία σχεδόν δύο αιώνων από τις πρώτες περιγραφές των Bell και Aran και λίγο λιγότερο του ενάμιση αιώνα από την περιγραφή του Charcot και την καθιέρωση του όρου Amyotrophic Lateral Sclerosis (ALS), η νόσος έχει πολυσυστηματικό χαρακτήρα, με μεγάλη ετερογένεια ως προς το εύρος και τη βαρύτητα της κλινικής και υποκλινικής -κινητικής και μη κινητικής- συμπτωματολογίας και πρόγνωση που δύσκολα μπορεί να προσδιοριστεί με ακρίβεια στατιστικών μοντέλων. Όμως, παράλληλα, συνιστά μία νόσο που επιβεβαιώνει την αλλαγή του κατά Κuhn Παραδείγματος, συνέπεια -στην προκειμένη περίπτωση- τόσο γραμμικής όσο και μη γραμμικής συσσώρευσης νέων γνώσεων από τις μεθόδος κλασσικής νευροφυσιολογίας και νευροψυχολογίας και τις σύγχρονες τεχνικές νευροαπεικόνισης.

International audience; Τhe middle longitudinal fasciculus (MdLF) was initially identified in humans as a discrete subcortical pathway connecting the superior temporal gyrus (STG) to the angular gyrus (AG). Further anatomo-imaging studies, however, proposed more sophisticated but conflicting connectivity patterns and have created a vague perception on its functional anatomy. Our aim was, therefore, to investigate the ambiguous structural architecture of this tract through focused cadaveric dissections augmented by a tailored DTI protocol in healthy participants from the Human Connectome dataset. Three segments and connectivity patterns were consistently recorded: the MdLF-I, connecting the dorsolateral Temporal Pole (TP) and STG to the Superior Parietal Lobule/Precuneus, through the Heschl's gyrus; the MdLF-II, connecting the dorsolateral TP and the STG with the Parieto-occipital area through the posterior transverse gyri and the MdLF-III connecting the most anterior part of the TP to the posterior border of the occipital lobe through the AG. The lack of an established termination pattern to the AG and the fact that no significant leftward asymmetry is disclosed tend to shift the paradigm away from language function. Conversely, the theory of "where" and "what" auditory pathways, the essential relationship of the MdLF with the auditory cortex and the functional role of the cortical areas implicated in its connectivity tend to shift the paradigm towards auditory function. Allegedly, the MdLF-I and MdLF-II segments could underpin the perception of auditory representations; whereas, the MdLF-III could potentially subserve the integration of auditory and visual information.

The inconsistency of volumetric results often seen in MR neuroimaging studies can be partially attributed to small sample sizes and variable data analysis approaches. Increased sample size through multi-scanner studies can tackle the former, but combining data across different scanner platforms and field-strengths may introduce a variability factor capable of masking subtle statistical differences. To investigate the sample size effect on regression analysis between depressive symptoms and grey matter volume (GMV) loss in Alzheimer's disease (AD), a retrospective multi-scanner investigation was conducted. A cohort of 172 AD patients, with or without comorbid depressive symptoms, was studied. Patients were scanned with different imaging protocols in four different MRI scanners operating at either 1.5 T or 3.0 T. Acquired data were uniformly analyzed using the computational anatomy toolbox (CAT12) of the statistical parametric mapping (SPM12) software. Single- and multi-scanner regression analyses were applied to identify the anatomical pattern of correlation between GM loss and depression severity. A common anatomical pattern of correlation between GMV loss and increased depression severity, mostly involving sensorimotor areas, was identified in all patient subgroups imaged in different scanners. Analysis of the pooled multi-scanner data confirmed the above finding employing a more conservative statistical criterion. In the retrospective multi-scanner setting, a significant correlation was also exhibited for temporal and frontal areas. Increasing the sample size by retrospectively pooling multi-scanner data, irrespective of the acquisition platform and parameters employed, can facilitate the identification of anatomical areas with a strong correlation between GMV changes and depression symptoms in AD patients.

Objectives: Many people with dementia live in their home and require ongoing care, which is often provided by informal family caregivers. Thus, we examined the effectiveness of a multicomponent home-based intervention by evaluating its impact on a) neuropsychiatric symptoms of people with dementia and b) burden and depression of their caregivers. Methods: During the first 6 months of this prospective single-center study, we applied a home-based multicomponent intervention in 205 dyads of care-recipients and caregivers. In further analyzes, we included only dyads of caregivers and care-recipients with available data both at baseline and 6-month follow-up (N = 144). All assessments were conducted at home and included sociodemographic features, care-recipients’ clinical data, cognitive status (Mini-Mental State Examination), activities of daily living (Instrumental Activities of Daily Living; Katz Index of Independence in Activities of Daily Living), neuropsychiatric symptoms (Neuropsychiatric Inventory), and caregivers’ burden (Zarit Burden Inventory) and depression (Center for Epidemiological Studies-Depression). Results: We found significant decreases in the severity (pFDR = 0.002) and associated distress (pFDR = 0.001) of neuropsychiatric symptoms, as well as caregivers’ burden (pFDR = 0.004) and depressive symptoms (pFDR = 0.001). As expected, there was significant deterioration in care-recipients’ cognitive status (pFDR = 0.005) and measures of activities of daily living (pFDR < 0.005). Conclusion: Despite the progressive course of dementia, the home-based multicomponent intervention was effective in decreasing caregivers’ burden and depression and minimizing care-recipients’ neuropsychiatric symptoms’ severity and associated distress after 6 months. Our study highlights the establishment of home-based care units as an advantageous solution, specifically for family members seen to have a “taken-for-granted” role in dementia caring.

ObjectiveCerebellar disease burden and cerebro-cerebellar connectivity alterations are poorly characterised in amyotrophic lateral sclerosis (ALS) despite the likely contribution of cerebellar pathology to the clinical heterogeneity of the condition.MethodsA prospective imaging study has been undertaken with 271 participants to systematically evaluate cerebellar grey and white matter alterations, cerebellar peduncle integrity and cerebro-cerebellar connectivity in ALS. Participants were stratified into four groups: (1) patients testing positive for GGGGCC repeat expansions inC9orf72, (2) patients carrying an intermediate-length repeat expansion inATXN2, (3) patients without established ALS-associated mutations and (4) healthy controls. Additionally, the cerebellar profile of a single patient with ALS who had anATXN2allele length of 62 was evaluated. Cortical thickness, grey matter and white matter volumes were calculated in each cerebellar lobule complemented by morphometric analyses to characterise genotype-associated atrophy patterns. A Bayesian segmentation algorithm was used for superior cerebellar peduncle volumetry. White matter diffusivity parameters were appraised both within the cerebellum and in the cerebellar peduncles. Cerebro-cerebellar connectivity was assessed using deterministic tractography.ResultsCerebellar pathology was confined to lobules I–V of the anterior lobe in patients with sporadic ALS in contrast to the considerable posterior lobe and vermis disease burden identified inC9orf72mutation carriers. Patients with intermediateATXN2expansions did not exhibit significant cerebellar pathology.ConclusionsFocal rather than global cerebellar degeneration characterises ALS. Pathognomonic ALS symptoms which are typically attributed to other anatomical regions, such as dysarthria, dysphagia, pseudobulbar affect, eye movement abnormalities and cognitive deficits, may be modulated, exacerbated or partially driven by cerebellar changes in ALS.

Objective:This study aimed to adapt the Addenbrooke’s Cognitive Examination-III (ACE-III) and Mini-Addenbrooke’s Cognitive Examination (M-ACE) into Greek and then to examine the convergent validity against their predecessors Addenbrooke’s Cognitive Examination-Revised (ACE-R) and Mini-Mental State Examination (MMSE) in a Greek population. Moreover, a primary aim was to appraise the utility of each screen by conducting a comparison of the psychometric properties of ACE-III, M-ACE, ACE-R, MMSE, and the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS) in detecting Alzheimer’s disease (AD).Methods:Forty patients with AD were recruited and matched with 38 controls. Bayesian Pearson’s correlation analysis was conducted to examine the convergent validity. Receiver operating characteristic curve analysis was implemented to appraise the sensitivity and specificity of the tests in detecting AD.Results:The ACE-III, M-ACE, and the ECAS scores robustly correlated with ACE-R and MMSE. The ACE-III and the ECAS-ALS Non-Specific score were the most sensitive and specific tools in detecting AD, closely followed by ECAS Total score and M-ACE. Only ECAS Total score correlated with the duration of disease. The ECAS scores were more resilient to ceiling effects than the other screens. M-ACE produced fewer ceiling effects than MMSE.Conclusion:The Greek ACE-III and M-ACE were successfully adapted and showed good convergent validity against their predecessors. They showed very good psychometric properties in detecting AD and may be considered in hectic clinical settings. ECAS Total score and ECAS-ALS Non-Specific showed comparable psychometric properties in the detection of AD and may be considered in polypathological clinics where motor impairments are common.

To evaluate the effectiveness of a structured education program on lifestyle habits, which is also incorporating teaching on deep breathing, progressive muscle relaxation, and guided visualization, in the control of various components of the climacteric symptomatology in peri- and postmenopausal women. Sixty-one women aged 40–65 years with varying climacteric and stress symptoms were included in this study. Women were randomly assigned to the intervention group (31) or the control group (30). The intervention group followed an 8-week stress management program. The following parameters were assessed at baseline and at the end of the 8-week follow-up period in both groups: climacteric symptoms (Green Climacteric Scale (GCS)), sleep quality (Pittsburg Sleep Quality Index (PSQI)), mood status (Depression-Anxiety-Stress Scale), self-esteem (Rosenberg Self-esteem Scale), and health-related control (health locus of control (HLC)). A mixed-model ANOVA showed significant time × group × GCS interaction (within subjects: F = 23.830, p value

Background and purpose : The cerebellum has a pivotal role in regulating human behavior; yet whether this function is mediated only through contralateral cerebro-cerebellar pathways is under-investigated. Thus, we examined feed-backward and feed-forward ipsilateral and contralateral cerebro-cerebellar connections using a detereministic diffusion tensor imaging (DTI) algorithm, the robustness of which was also estimated using phantom DTI data. Materials and methods : Fifty-one healthy controls (22–60 years old; 15 males/36 females) were scanned in a 3T MRI scanner with a 30-direction DTI sequence. Multiple region-of-interest (ROI) method was applied for the reconstruction of the ipsilateral and contralateral (based on cerebellar seed ROI) fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC), occipito-ponto-cerebellar (OPC) and dentate-rubro-thalamo-cortical (DRTC) tract bilaterally using the Brainance DTI Suite. A realistic diffusion MR phantom was used to evaluate the fiber tracking methodology for 16 fibers containing crossing, kissing, splitting and bending configurations. Results Both contralateral and ipsilateral FPC, PPC, OPC and ipsilateral DRTC tracts were successfully reconstructed; the contralateral DRTC tract was not reconstructed in all subjects. Also, the TPC tract was not reproduced in several subjects mostly regarding the contralateral connection. Descriptive DTI measures (number of fibers, fractional anisotropy, radial and axial diffusivity) are presented for each tract. Regarding phantom data, Brainance DTI Suite returned a dataset of 16 fibers that almost perfectly matched the 16 ground truth fibers. Conclusions We identified ipsilateral and contralateral connections using a clinically applicable DTI sequence, a robust deterministic algorithm and an unbiased methodology, which can be applied in daily practice in different brain pathologies.

Cognitive screening measures are widely administered in everyday clinical practice in different geriatric settings. Despite the presence of several extended-like screening tests, Mini-Mental State Examination (MMSE) continues to be largely used not only by neuropsychologists, neurologists, and psychiatrists but also by general practitioners and other health-related specialties.We herein provide normative data for the MMSE in a large sample of community-dwelling healthy participants aged over 50 years old stratified by age and education.The sample included 925 community-dwelling healthy participants (age range: 50-91 years) of both genders (231 males/694 females) with different educational level (range: 1-16 years). Demographic-related effects were examined for the total MMSE score using hierarchical regression analysis; normative data are presented in mean ± standard deviation and percentile ranks and divided into seven overlapping age tables with different midpoints at 55, 60, 65, 70, 75, 80, and 85 years using the overlapping cell procedure.Initial analysis did not show any effect of gender but revealed significant correlation between age, education, and total MMSE. Hierarchical regression analysis revealed that education significantly accounted for 17.3% of the total variance in the MMSE with age adding a significant 7.4% to the final model (adjusted RCurrent normative data for the Greek version of the MMSE are provided as a useful set of norms for clinical and research practice.

The thalamus is a key cerebral hub relaying a multitude of corticoefferent and corticoafferent connections and mediating distinct extrapyramidal, sensory, cognitive and behavioural functions. While the thalamus consists of dozens of anatomically well-defined nuclei with distinctive physiological roles, existing imaging studies in motor neuron diseases typically evaluate the thalamus as a single structure. Based on the unique cortical signatures observed in ALS and PLS, we hypothesised that similarly focal thalamic involvement may be observed if the nuclei are individually evaluated. A prospective imaging study was undertaken with 100 patients with ALS, 33 patients with PLS and 117 healthy controls to characterise the integrity of thalamic nuclei. ALS patients were further stratified for the presence of GGGGCC hexanucleotide repeat expansions in C9orf72. The thalamus was segmented into individual nuclei to examine their volumetric profile. Additionally, thalamic shape deformations were evaluated by vertex analyses and focal density alterations were examined by region-of-interest morphometry. Our data indicate that C9orf72 negative ALS patients and PLS patients exhibit ventral lateral and ventral anterior involvement, consistent with the 'motor' thalamus. Degeneration of the sensory nuclei was also detected in C9orf72 negative ALS and PLS. Both ALS groups and the PLS cohort showed focal changes in the mediodorsal-paratenial-reuniens nuclei, which mediate memory and executive functions. PLS patients exhibited distinctive thalamic changes with marked pulvinar and lateral geniculate atrophy compared to both controls and C9orf72 negative ALS. The considerable ventral lateral and ventral anterior pathology detected in both ALS and PLS support the emerging literature of extrapyramidal dysfunction in MND. The involvement of sensory nuclei is consistent with sporadic reports of sensory impairment in MND. The unique thalamic signature of PLS is in line with the distinctive clinical features of the phenotype. Our data confirm phenotype-specific patterns of thalamus involvement in motor neuron diseases with the preferential involvement of nuclei mediating motor and cognitive functions. Given the selective involvement of thalamic nuclei in ALS and PLS, future biomarker and natural history studies in MND should evaluate individual thalamic regions instead overall thalamic changes.

The increasing evidence for a pure amnestic-like profile in multiple sclerosis (MS) introduces the role of hippocampal formation in MS episodic memory function. The aim of the present study was to investigate structural and functional hippocampal changes in mildly-disabled MS patients with and without memory impairment. Thirty-one MS patients with or without memory impairment and 16 healthy controls (HC) underwent MRI in a 3.0 T MRI scanner. Patients were categorized as memory preserved (MP) and memory impaired (MI) based on verbal and visual memory scores extracted from the Brief Repeatable Neuropsychological Battery. The acquisition protocol included high-resolution 3D-T1-weighted, diffusion weighted imaging and echo-planar imaging sequences for the analysis of hippocampal gray matter (GM) density, perforant pathway area (PPA) tractography, and hippocampal functional connectivity (FC), respectively. Compared to HC, we found decreased left and bilateral hippocampal GM density in MP and MI patients, respectively, decreased fractional anisotropy and increased radial diffusivity on left PPA in MI patients, and reduced FC in MI between left hippocampus and left superior frontal gyrus, precuneus/posterior cingulated cortex and lateral occipital gyrus/angular gyrus. The only differences between MP and MI were found in FC. Specifically, MP patients showed FC changes between left hippocampus and right temporo-occipital fusiform/lingual gyrus (increased FC) as well as supramarginal gyrus (decreased FC). In conclusion, we highlight the early detection of structural hippocampal changes in MS without neuropsychologically-detected memory deficits and decreased hippocampal FC in MS patients with impaired memory performance, when both GM density and PPA integrity are affected.

In the present case study, we investigated possible emotional connectedness between monozygotic twins by means of functional magnetic resonance imaging (fMRI). During the experimental condition, Twin 2 was randomly selected to participate in the neuroimaging protocol while Twin 1 participated in the experimental condition outside the MRI scanner (none of them was aware of the experimental procedure). The experimental condition included two sessions with visual and acoustic stimuli, respectively. Between the two experimental conditions, there was a 2-min break with Twin 1 (i.e., the subject outside the scanner) relaxing with eyes closed. Data analysis revealed significant brain activation in three regions, namely left orbitofrontal gyrus (during visual condition) and left cingulum and precentral gyrus (during the acoustic condition). Our findings denote emotional connectedness between a pair of monozygotic twins using fMRI. Further studies in larger sample sizes are needed to investigate if this is a generalized and systematic phenomenon or an incidental finding.

The changing hormonal milieu during the menopausal transition may contribute to the development of memory disorders. We aimed to assess the association of sex hormones with memory function in a sample of Greek middle-aged women. This pilot study included 44 women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory test (BVMT), and the verbal digits backwards test (VSPAN), to assess verbal, visuospatial, and working memory performance, respectively. Menopausal symptoms were assessed using the Green Climacteric Scale. VSPAN backwards scores were positively associated with log-transformed free androgen index (logFAI), in models adjusted for age, education, log-transformed free estrogen index (logFEI), hypertension, and the intensity of menopausal symptoms. BVMT total scores were predicted by logFAI (b-coefficient = 0.424, p value = 0.002), education, and combined climacteric symptomatology, in a model adjusted for age, logFEI, and hypertension. Women with circulating estradiol above the median value of 10 pg/mL had better total HTLV total scores compared to women with estradiol values below the median (HTLV total scores, estradiol ≤ 10 pg/mL vs. > 10 pg/mL: 24.2 ± 3.6 vs. 30.0 ± 7.9, p value = 0.007 unadjusted). This association was affected by education and remained independent of menopausal symptoms and testosterone levels, education, and hypertension (model R 2 = 22.3%; b-coefficient = 0.318, p value = 0.024). Endogenous total estradiol is associated with verbal episodic memory, while logFAI is associated with working memory performance and visuospatial episodic memory in this sample of postmenopausal women. These associations were not influenced by age, education, or menopausal symptoms. Larger studies are necessary to evaluate the significance of our findings.

Pathological laughing and crying (PLC) is common in several neurological and psychiatric diseases and is associated with a distributed network involving the frontal cortex, the brainstem and cortico-pontine-cerebellar circuits. By applying multimodal neuroimaging approach, we examined the neuroanatomical substrate of PLC in a sample of patients with amyotrophic lateral sclerosis (ALS).We studied 56 non-demented ALS patients and 25 healthy controls (HC). PLC was measured in ALS using the Center of Neurologic Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based morphometry and tract-based spatial-statistics analysis was used to examine gray matter (GM) and white matter (WM) differences between ALS patients with and without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted to regions with detected differences between ALS and HC, controlling for age, gender, total intracranial volume and depressive symptoms.In regions with significant differences between ALS and HC, ALS-PLC patients showed decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased fractional anisotropy in left cingulum bundle and posterior corona radiata. WM abnormalities were additionally detected in WM associative and ponto-cerebellar tracts (using a more liberal threshold).PLC in ALS is driven by both GM and WM abnormalities which highlight the role of circuits rather than isolated centers in the emergence of this condition. ALS is suggested as a useful natural experimental model to study PLC.

Considering genetic influence on brain structure and function, including motor control, we report a case of right-handed monozygotic twins with atypical organization of fine motor movement control that might imply genetic influence. Structural and functional organization of the twins' motor function was assessed using transcranial magnetic stimulation (TMS), fMRI with a motor-task paradigm, and diffusion tensor imaging (DTI) tractography. TMS revealed that both twins presented the same unexpected activation and inhibition of both motor cortices during volitional unilateral fine hand movement. The right ipsilateral corticospinal tract was weaker than the left contralateral one. The motor-task fMRI identified activation in the left primary motor cortex and bilateral secondary motor areas during right-hand (dominant) movement and activation in the bilateral primary motor cortex and secondary motor areas during left-hand movement. Based on DTI tractography, both twins showed a significantly lower streamline count (number of fibers) in the right corticospinal tract compared with a control group, which was not the case for the left corticospinal tract. Neither twin reported any difficulty in conducting fine motor movements during their activities of daily living. The combination of TMS and advanced neuroimaging techniques identified an atypical motor control organization that might be influenced by genetic factors. This combination emphasizes that activation of the unilateral uncrossed pyramidal tract represents an alternative scheme to a "failure" of building a standard pattern but may not necessarily lead to disability.

Objectives: 1) Adapt the ECAS into Greek, validate it in ALS patients and compare with the ALS-CBS 2) Determine the sensitivity and specificity of ECAS in the differentiation between AD and non-demented ALS patients as compared with the ACE-III and mini-ACE. Methods: ALS patients (n=28) were recruited. and AD patients (n=26) matched in age, sex, and education with ALS patients (n=24). The normative data was derived from a random sample of controls (n=52). Bayes correlation analysis was conducted to examine convergent validity. Bayes t-test was performed to assess between groups’ differences. Receiver operating characteristics (ROC) curve analyses and area under the curve (AUC) were implemented to appraise the sensitivity and specificity in the differentiation between AD and non-demented ALS patients. Results: The ECAS and its sub-scores in addition to the behaviour interview demonstrated robust correlations with the ALS-CBS. Impairment in language and verbal fluency were the most prominent deficits in the ALS patients. The most frequently reported change was apathy. The ROC analysis demonstrated that the ECAS-ALS Non-Specific score (comprising memory and visuospatial domains) is the most sensitive and specific in differentiating AD from ALS patients. The other measures expressed high sensitivity, yet a poor specificity. Conclusions: The ECAS is a multi-purpose screening tool. The ECAS-ALS Specific appraises the whole spectrum of the highly prevalent cognitive impairments in ALS. The ECAS-ALS Non-Specific (memory and visuospatial) is a sensitive score to detect AD related deficits and is able to differentiate AD from non-demented ALS patients better than the ACE-III and mini-ACE

Background: Cognitive screening measures are widely administered in everyday clinical practice in different geriatric settings. Despite the presence of several extended-like screening tests, Mini-Mental State Examination (MMSE) continues to be largely used not only by neuropsychologists, neurologists, and psychiatrists but also by general practitioners and other health-related specialties.

Background Several factors may account for inter- and intra-individual variability in cognitive functions, including age, gender, education level, information processing speed, and mood. Objective To evaluate the combined contribution of demographic factors, information processing speed, and depressive symptoms to scores on several diagnostic cognitive measures that are commonly used in geriatric neuropsychological practice in Greece. Methods Using a cross-sectional study, we established a multivariate general linear model and analyzed the predictive role of age, gender, education, information processing speed (Trail Making Test-Part A), and depressive symptoms (Geriatric Depression Scale-15 Items) on measures of general cognitive status (Mini-Mental State Examination), verbal memory (Rey Auditory Verbal Learning Test), language (Confrontation Naming), and executive functions (Category and Phonemic Fluency, Trail Making Test-Part B) for a sample of 755 healthy, community-dwelling Greek individuals aged 50 to 90 years. Results Participant factors significantly but differentially contributed to cognitive measures. Demographic factors and information processing speed emerged as the significant predictors for the majority of the cognitive measures (Mini-Mental State Examination; Rey Auditory Verbal Learning Test; Confrontation Naming; Category and Phonemic Fluency; Trail Making Test-Part B), whereas depressive symptoms significantly predicted verbal memory and semantic fluency measures (Rey Auditory Verbal Learning Test and Category Fluency). Conclusions Clinicians should consider participant demographics, underlying slowing of processing speed, and depressive symptoms as potential confounding factors in cognitive measures. Our findings may explain the observed inter- and intra-individual variability in cognitive functions in the elderly population.

A prospective, standardised neuroimaging protocol was implemented to characterise mesial temporal lobe pathology in amyotrophic lateral sclerosis, Alzheimer's disease and healthy controls focusing on the evaluation of interconnected white and grey matter structures. “Hippocampal pathology in Amyotrophic Lateral Sclerosis: selective vulnerability of subfields and their associated projections” [1]. High-resolution diffusion tensor and structural imaging data were acquired on a 3 T MRI platform using standardised sequence parameters. The integrity of the fornix and the perforant pathway was assessed by tractography, to provide fractional anisotropy, axial diffusivity and radial diffusivity measures. Quantitative structural imaging was used to estimate the total intracranial volume, total hippocampal volumes and hippocampal subfield volumes for each participant. Raw white- and grey-matter measures, demographic and clinical data are available online at ‘Mendeley Data’. Amyotrophic lateral sclerosis and Alzheimer's disease exhibit divergent hippocampal profiles.

Myotonic dystrophies (DMs) are hereditary, multisystem, slowly progressive myopathies. One of the systems they affect is the CNS. In contrast to the well-established cognitive profile of myotonic dystrophy type 1 (DM1), only a few studies have investigated cognitive dysfunction in individuals with myotonic dystrophy type 2 (DM2), and their findings have been inconsistent. To identify the most commonly affected cognitive domains in individuals with DM2, we performed a formal comprehensive review of published DM2 studies. Using the terms "myotonic dystrophy type 2" AND "cognitive deficits," "cognitive," "cognition," "neuropsychological," "neurocognitive," and "neurobehavioral" in all fields, we conducted an advanced search on PubMed. We read and evaluated all of the available original research articles (13) and one case study, 14 in total, and included them in our review. Most of the research studies of DM2 reported primary cognitive deficits in executive functions (dysexecutive syndrome), memory (short-term nonverbal, verbal episodic memory), visuospatial/constructive-motor functions, and attention and processing speed; language was rarely reported to be affected. Based on the few neuroimaging and/or multimodal DM2 studies we could find, the cognitive profile of DM2 is associated with brain abnormalities in several secondary and high-order cortical and subcortical regions and associative white matter tracts. The limited sample size of individuals with DM2 was the most prominent limitation of these studies. The multifaceted profile of cognitive deficits found in individuals with DM2 highlights the need for routine neuropsychological assessment at both baseline and follow-up, which could unveil these individuals' cognitive strengths and deficits.

Purpose: To investigate the bleeding complications associated with endovascular therapy (EVT) for peripheral artery disease (PAD) and develop a dedicated peripheral bleeding score (PBS). Materials and Methods: This prospective, single-center study enrolled 530 patients (mean age 67.6±9.8 years; 396 men) undergoing endovascular procedures between August 2016 and July 2018 for chronic PAD. Primary endpoints were the incidence of 30-day bleeding complications [minor and major (prolonging hospitalization, causing permanent sequelae, or resulting in death)], the identification of factors associated with bleeding events, and the development of a dedicated PBS based on univariate and multivariate analysis. Hazard ratios (HR) and 95% confidence intervals (CI) are reported. The HAS-BLED score was compared with the PBS. Results: The overall peripheral bleeding complication rate was 3.8% (20/530), of which 3.2% (17/530) were major and included 4 (0.7%) active retroperitoneal bleeding events and 13 (2.4%) pseudoaneurysms. The annualized incidences of overall bleeding and major bleeding complications were 1.9% and 1.6%, respectively. Multivariable regression analysis identified age ≥75 as a correlate of significantly increased bleeding risk (HR 3.32, 95% CI 1.12 to 9.80, p

Background Neuroimaging studies revealed structural and functional changes in medication-overuse headache (MOH), but it remains unclear whether similar changes could be observed in other chronic pain disorders. Methods In this cross-sectional study, we investigated functional connectivity (FC) with resting-state functional magnetic resonance imaging (fMRI) and white matter integrity using diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) and mean diffusivity (MD) in patients with MOH ( N = 12) relative to two control groups: patients with chronic myofascial pain (MYO; N = 11) and healthy controls (CN; N = 16). Results In a data-driven approach we found hypoconnectivity in the fronto-parietal attention network in both pain groups relative to CN (i.e. MOH Conclusions Hyperconnectivity within the SN along with associated white matter changes therein suggest a particular role of this network in MOH. In addition, abnormal connectivity between the PAG and other pain modulatory (frontal) regions in MOH are consistent with dysfunctional central pain control.

Gerstmann's syndrome is a syndrome caused by lesions of the dominant parietal lobe. It has historically been a subject of dispute as it is often accompanied by other neuropsychological deficits such as aphasia. Novel neuropsychological tests and neuroimaging techniques have lately changed the perspective allowing to decode a conjunction of symptoms like Gerstmann's. In our case, we present Diffusion Tensor Imaging Tractography findings of a patient who acutely exhibited Gerstmann's tetrad. Using advanced structural neuroimaging we tested a hypothesis that up until recently could only be challenged post mortem. Our study offers much needed patient neuroimaging data helping to establish Gerstmann's as a disconnection syndrome. More reports of Gerstmann's syndrome patients including high resolution tractography and fMRI data are needed.

Background The cerebellum has a crucial role in mood regulation. While cerebellar grey matter (GM) alterations have been previously reported in bipolar disorder (BD), cerebro-cerebellar white matter (WM) connectivity alterations and cerebellar GM profiles have not been characterised in the context of predominant polarity (PP) and onset polarity (OP) subphenotypes of BD patients which is the aim of the present study. Methods Forty-two euthymic BD patients stratified for PP and OP and 42 healthy controls (HC) were included in this quantitative neuroimaging study to evaluate cerebellar GM patterns and cerebro-cerebellar WM connections. Diffusion tensor tractography was used to characterise afferent and efferent cerebro-cerebellar tract integrity. False discovery rate corrections were applied in post-hoc comparisons. Results BD patients exhibited higher fractional anisotropy (FA) in fronto-ponto-cerebellar tracts bilaterally compared to HC. Subphenotype-specific FA profiles were identified within the BD cohort. Regarding PP subgroups, we found FA changes in a) left contralateral fronto-ponto-cerebellar tract (depressive-PP > HC) and b) contralateral/ipsilateral fronto-ponto-cerebellar tracts bilaterally (manic-PP > HC). Regarding OP subgroups, we observed FA changes in a) left/right contralateral fronto-ponto-cerebellar tracts (depressive-OP > HC) and b) all fronto-ponto-cerebellar, most parieto-ponto-cerebellar and right contralateral occipito-ponto-cerebellar tracts (manic-OP>HC). In general, greater and more widespread cerebro-cerebellar changes were observed in manic-OP patients than in depressive-OP patients compared to HC. Manic-OP showed higher FA compared to depressive-OP patients in several afferent WM tracts. No GM differences were identified between BD and HC and across BD subgroups. Conclusions Our findings highlight fronto-ponto-cerebellar connectivity alterations in euthymic BD. Polarity-related subphenotypes have distinctive cerebro-cerebellar WM signatures with potential clinical and pathobiological implications.

Temporal lobe studies in motor neuron disease overwhelmingly focus on white matter alterations and cortical grey matter atrophy. Reports on amygdala involvement are conflicting and the amygdala is typically evaluated as single structure despite consisting of several functionally and cytologically distinct nuclei. A prospective, single-centre, neuroimaging study was undertaken to comprehensively characterise amygdala pathology in 100 genetically-stratified ALS patients, 33 patients with PLS and 117 healthy controls. The amygdala was segmented into groups of nuclei using a Bayesian parcellation algorithm based on a probabilistic atlas and shape deformations were additionally assessed by vertex analyses. The accessory basal nucleus (p = .021) and the cortical nucleus (p = .022) showed significant volume reductions in C9orf72 negative ALS patients compared to controls. The lateral nucleus (p = .043) and the cortico-amygdaloid transition (p = .024) were preferentially affected in C9orf72 hexanucleotide carriers. A trend of total volume reduction was identified in C9orf72 positive ALS patients (p = .055) which was also captured in inferior-medial shape deformations on vertex analyses. Our findings highlight that the amygdala is affected in ALS and our study demonstrates the selective involvement of specific nuclei as opposed to global atrophy. The genotype-specific patterns of amygdala involvement identified by this study are consistent with the growing literature of extra-motor clinical features. Mesial temporal lobe pathology in ALS is not limited to hippocampal pathology but, as a key hub of the limbic system, the amygdala is also affected in ALS.

Objectives: We examined the neuroanatomical substrate of different pain catastrophizing (PC) dimensions (i.e. rumination; magnification; helplessness) in patients with medication-overuse headache (MOH). Methods: We included 18 MOH patients who were administered the Pain Catastrophizing Scale (PCS) and scanned in a 3T-MRI. We conducted whole-brain volumetric and resting-state functional connectivity (FC) analysis to examine the association between gray matter (GM) density and FC strength and PCS dimensions controlling for depression and anxiety. Results: Higher total PCS score was associated with decreased GM density in precentral and inferior temporal gyrus, increased FC between middle temporal gyrus and cerebellum and reduced FC between precuneus and inferior temporal gyrus, as well as between frontal pole and temporal fusiform cortex. Regarding PCS dimensions, we mainly observed the involvement of a) somatosensory cortex, supramarginal gyrus, basal ganglia, core default-mode network (DMN) in rumination; b) somatosensory cortex, core DMN, dorsal medial prefrontal cortex (DMPFC)-DMN subsystem and cerebellum in magnification; and c) temporal regions, DMN and basal ganglia in helplessness. Conclusion: PC dimensions are associated with a specific structural and functional neuroanatomical pattern, which is different from the pattern observed when PC is considered as a single score. The involvement of basal ganglia and cerebellum needs further investigation.

Amyotrophic lateral sclerosis (ALS) is now universally recognized as a complex multisystem disorder with considerable extra-motor involvement. The neuropsychological manifestations of frontotemporal, parietal, and basal ganglia involvement in ALS have important implications for compliance with assistive devices, survival, participation in clinical trials, caregiver burden, and the management of individual care needs. Recent advances in neuroimaging have been instrumental in characterizing the biological substrate of heterogeneous cognitive and behavioral deficits in ALS. In this review we discuss the clinical and radiological aspects of cognitive and behavioral impairment in ALS focusing on the recognition, assessment, and monitoring of these symptoms.

Hippocampal pathology in Amyotrophic Lateral Sclerosis (ALS) remains surprisingly under recognized despite compelling evidence from neuropsychology, neuroimaging and neuropathology studies. Hippocampal dysfunction contributes significantly to the clinical heterogeneity of ALS and requires structure-specific cognitive and neuroimaging tools for accurate in vivo evaluation. Recent imaging studies have generated unprecedented insights into the presymptomatic and longitudinal processes affecting this structure and have contributed to the characterisation of both focal and network-level changes. Emerging neuropsychology data suggest that memory deficits in ALS may be independent from executive dysfunction. In the era of precision medicine, where the development of individualized care strategies and patient stratification for clinical trials are key priorities, the comprehensive review of hippocampal dysfunction in ALS is particularly timely.

The sledge runner fasciculus (SRF) has been recently identified as a discrete fiber tract of the occipital lobe and has been allegedly implicated in the axonal connectivity of cortical areas conveying spatial navigation and visuospatial imagery. However, detailed knowledge regarding its anatomic and tractographic morphology is lacking. We thus opted to investigate the anatomy and connectivity of the SRF through cadaveric dissections and DTI studies. Twenty normal, adult, cerebral, cadaveric hemispheres treated with the Klingler’s method were dissected through the fiber microdissection technique and 35 healthy participants from the MGH-USC Adult Diffusion Dataset (Human Connectome available dataset) underwent a tailored DTI protocol aiming to investigate the structural architecture of the SRF. SR was identified as a discrete fiber pathway, just under the U fibers of the medial occipital lobe, exhibiting a dorsomedial–ventrolateral trajectory and connecting the cortical areas of the anterior cuneus, anterior lingula, isthmus of the cingulum and posterior parahippocampal gyrus. The topography of the SR in relation to adjacent fiber pathways such as the cingulum, major forceps and stratum calcarinum is clearly delineated. Dissection and tractographic findings showed a good correspondence regarding SR topography, morphology and axonal connectivity. Our results support the hypothesis that the SRF is involved in the structural axonal connectivity of cerebral areas that strongly activate during spatial navigation and visuospatial imagery. Furthermore detailed anatomo-imaging evidence is provided on the microanatomic architecture of this newly discovered fiber tract.

We examined the contribution of demographics and cognitive background variables (processing speed, visuospatial skill, working memory, and interference control) on derived Trail Making Test (TMT) scores in a large sample of Greek healthy participants. We included 775 participants and administered the TMT (TMT-A and TMT-B) and the Wechsler Intelligence Adult Scale (WAIS). Direct (TMT-A & TMT-B time-to-completion) and derived [difference TMT-(B - A) & ratio TMT-(B/A)] scores were calculated. Demographics (age, age(2), education, and gender) and WAIS Full Intelligence Quotient significantly predicted the direct TMT-A (R(2) = 0.426) and TMT-B (R(2) = 0.593) scores and to a lesser extent, the derived TMT-(B - A) (R(2) = 0.343) and TMT-(B/A) (R(2) = 0.088) scores. In a subsample of 537 healthy participants who also completed the Stroop Neuropsychological Screening Test (SNST), demographics (age and education), WAIS Digit Symbol, Block Design, Arithmetic, and SNST accounted for 44.8% and 59.7% of the variance on TMT-A and TMT-B, and 32.5% and 9.6% of the variance on TMT-(B - A) and TMT-(B/A), respectively. We found minimal influence of Block Design and Arithmetic on TMT-(B - A) and an absence of significant influence of any cognitive variable on TMT-(B/A) score. Concluding, derived TMT scores are suggested as indices to detect impairment in cognitive flexibility across the adult life span, since they minimize the effect of demographics and other cognitive background variables.

The association between gray matter (GM) density and neurophysiologic changes is still unclear in amyotrophic lateral sclerosis (ALS). We evaluated the relationship between GM density and motor system integrity combining voxel-based morphometry (VBM) and transcranial magnetic stimulation (TMS) in ALS. We included 17 ALS patients and 22 healthy controls (HC) who underwent 3D-T1-weighted imaging. Among the ALS group, we applied left motor cortex single-pulse TMS. We used whole-brain VBM comparing ALS and HC in GM density. We also conducted regression analysis to examine correlations between GM density and the following TMS parameters: motor evoked potential (MEP)/M ratio and central motor conduction time (CMCT). We found significantly decreased GM density in ALS patients in several frontal, temporal, parietal/occipital and cerebellar regions (p

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients’ management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson’s and Alzheimer’s diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients’ well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits.

Background. Informant-based rating scales are widely used in dementia but patients’ and caregivers’ features influence the final scoring. We aimed to evaluate the role of patient- and caregiver-related factors in a caregiver rated Global Deterioration Scale (GDS) score in a sample of Greek patients with dementia. Methods. We included 194 patients with dementia and 194 caregivers/family relatives; Mini-Mental State Examination (MMSE); Neuropsychiatric Inventory (NPI); Katz Index of Activities of Daily Living (K-IADL) were administered to (a) patients and Center for Epidemiologic Studies-Depression (CES-D) Scale; Zarit Burden Interview (ZBI) to (b) caregivers. Participants’ demographics and patients’ and caregivers’ characteristics were entered into a 3-block regression analysis. Results. The final model explained 55% of the total variance of the caregiver assessed GDS score. The following variables significantly contributed to the final model: MMSE (β=-0.524); K-IADL (β=-0.264); ZBI (β=0.145). Conclusion. We herein confirm the contribution of patients’ cognitive and functional status and caregivers’ burden in caregiver rated GDS scoring irrespective of demographic-related characteristics.

Background and objectives Clinicians commonly use verbal and nonverbal measures to test fluency in patients with epilepsy, either during routine cognitive assessment or as part of pre- and postsurgical evaluation. We hypothesized that patients with mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis would perform worse than patients with lateral TLE in both verbal and design fluency. Methods We assessed semantic, phonemic, and nonverbal fluency in 49 patients with TLE: 31 with lateral TLE and 18 with mesial TLE plus hippocampal sclerosis. We also gave non-fluency cognitive measures: psychomotor speed, attentional set shifting, selective attention, abstract reasoning, verbal and visual episodic memory, and incidental memory. Results Patients with mesial TLE performed significantly worse on figural fluency than patients with lateral TLE. Even though group differences on verbal fluency measures were not significant, the patients with mesial TLE had a pattern of poorer performance. The patients with mesial TLE scored significantly worse on measures of selective attention, verbal episodic memory, and incidental memory. Conclusions Our study underlines differences in cognitive function between patients with mesial and lateral TLE, particularly in figural fluency. Although we cannot directly assess the role of the hippocampus in cognitive aspects of creative and divergent thinking related to figural fluency, the cognitive discrepancies between these two TLE groups could be ascribed to the mesial TLE hippocampal pathology shown in our study and addressed in the literature on hippocampal involvement in divergent thinking. Our findings could benefit cognitive rehabilitation programs tailored to the needs of patients with TLE.

The phenotypic heterogeneity in amyotrophic lateral sclerosis (ALS) implies that patients show structural changes within but also beyond the motor cortex and corticospinal tract and furthermore outside the frontal lobes, even if frank dementia is not detected. The aim of the present study was to investigate both gray matter (GM) and white matter (WM) changes in non-demented amyotrophic lateral sclerosis (ALS) patients with or without cognitive impairment (ALS-motor and ALS-plus, respectively). Nineteen ALS-motor, 31 ALS-plus and 25 healthy controls (HC) underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging on a 3 T MRI scanner. Voxel-based morphometry and tract-based spatial-statistics analysis were performed to examine GM volume (GMV) changes and WM differences in fractional anisotropy (FA), axial and radial diffusivity (AD, RD, respectively). Compared to HC, ALS-motor patients showed decreased GMV in frontal and cerebellar areas and increased GMV in right supplementary motor area, while ALS-plus patients showed diffuse GMV reduction in primary motor cortex bilaterally, frontotemporal areas, cerebellum and basal ganglia. ALS-motor patients had increased GMV in left precuneus compared to ALS-plus patients. We also found decreased FA and increased RD in the corticospinal tract bilaterally, the corpus callosum and extra-motor tracts in ALS-motor patients, and decreased FA and increased AD and RD in motor and several WM tracts in ALS-plus patients, compared to HC. Multimodal neuroimaging confirms motor and extra-motor GM and WM abnormalities in non-demented cognitively-impaired ALS patients (ALS-plus) and identifies early extra-motor brain pathology in ALS patients without cognitive impairment (ALS-motor).

Young-onset dementias pose a major challenge to both clinicians and researchers. Cognitive decline may be accompanied by systemic features, leading to a diagnosis of "dementia plus" syndromes. Whipple disease is a rare systemic illness characterized by arthralgias, chronic diarrhea, weight loss, fever, and abdominal pain. Central nervous system involvement, including severe cognitive deterioration, may precede systemic manifestations, appear during the course of the disease, or even be the only symptom. We report a previously highly functional 48-year-old man whom we first suspected of having early-onset neurodegenerative dementia but then diagnosed with Whipple disease based on a detailed clinical and laboratory evaluation. Initial neuropsychological evaluation revealed marked impairment in the patient's fluid intelligence and severe cognitive deficits in his information processing speed, complex attention, memory, visuomotor and construction dexterities, problem solving, and executive functions. At neuropsychological follow-up 21 months later, his information processing speed had improved only slightly and deficits persisted in his other cognitive functions. Repeat brain magnetic resonance imaging at that time showed that he had responded to antibiotic treatment. Because Whipple disease can cause young-onset "dementia plus" syndromes that may leave patients with neurocognitive deficits even after apparently successful treatment, we recommend comprehensive neuropsychological assessment for early detection of residual and reversible cognitive processes and evaluation of treatment response.

Whipple’s disease (WD) is a rare systemic disease caused by the gram-positive bacillusTropheryma Whippleiand mostly characterized by arthralgias, chronic diarrhea, weight loss, fever and abdominal pain. Central Nervous System involvement is not uncommon and it may precede other disease manifestations, appear after treatment and improvement of gastrointestinal signs or rarely be the only WD symptom. We report a case in a middle-aged male with unexplained neurological signs and symptoms which were presented as relapse of previously undiagnosed WD with atypical symptoms at onset. After diagnosis confirmation, the patient was appropriately treated which resulted in improvement of major symptoms.

The present study evaluates the integrity of uncinate fasciculus (UF) and the association between UF microstructure and verbal episodic memory (as one of the cognitive functions linked to UF) in non-demented patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). We studied 21 patients with ALS and 11 healthy, demographically-comparable volunteers. Fractional anisotropy, apparent diffusion coefficient, axial and radial diffusivity were the DTI metrics examined. Episodic memory was evaluated with Babcock Story Recall Test and Rey Auditory Verbal Learning Test (RAVLT) for patients; measures of immediate and delayed recall and retention for both tests and sum of words recalled through five learning trials for RAVLT were considered. Patients with ALS showed significant bilateral reduction of axial diffusivity in the UF as compared to controls. Furthermore, there were several significant relations between various DTI metrics (mostly in left hemisphere) and memory measures (specifically for the RAVLT). UF microstructural changes may contribute to ALS-related memory impairment, with word-list learning performance relying more upon the integrity of frontal and temporal connections than memory components associated with story recall.

The present study investigates selective attention and verbal free recall in amyotrophic lateral sclerosis (ALS) and examines the contribution of selective attention, encoding, consolidation, and retrieval memory processes to patients’ verbal free recall. We examined 22 non-demented patients with sporadic ALS and 22 demographically related controls using Stroop Neuropsychological Screening Test (SNST; selective attention) and Rey Auditory Verbal Learning Test (RAVLT; immediate & delayed verbal free recall). The item-specific deficit approach (ISDA) was applied to RAVLT to evaluate encoding, consolidation, and retrieval difficulties. ALS patients performed worse than controls on SNST (p < .001) and RAVLT immediate and delayed recall (p < .001) and showed deficient encoding (p = .001) and consolidation (p = .002) but not retrieval (p = .405). Hierarchical regression analysis revealed that SNST and ISDA indices accounted for: (a) 91.1% of the variance in RAVLT immediate recall, with encoding (p = .016), consolidation (p < .001), and retrieval (p = .032) significantly contributing to the overall model and the SNST alone accounting for 41.6%; and (b) 85.2% of the variance in RAVLT delayed recall, with consolidation (p < .001) and retrieval (p = .008) significantly contributing to the overall model and the SNST alone accounting for 39.8%. Thus, selective attention, encoding, and consolidation, and to a lesser extent of retrieval, influenced both immediate and delayed verbal free recall. Concluding, selective attention and the memory processes of encoding, consolidation, and retrieval should be considered while interpreting patients’ impaired free recall. (JINS, 2012, 18, 1–10)

Based on the importance of the perforant pathway (PP) for normal hippocampal function, the vulnerability of temporal structures, and significant memory impairment in patients with traumatic brain injury (TBI), we investigated in vivo changes in the PP zone, hippocampus, and temporal lobe white and gray matter using diffusion tensor imaging (DTI) and volumetric analysis, and any specific relations with memory performance (Verbal Selective Reminding Test, Rey-Osterrieth Complex Figure Test), in 14 patients with severe TBI. Compared to a demographically-similar control group, our patients had significantly decreased fractional anisotropy (FA) and higher apparent diffusion coefficient (ADC) for the PP zone bilaterally, and higher ADC bilaterally in the hippocampus. Volumetric analysis revealed significantly decreased volumes in both hippocampi and temporal gray matter bilaterally. Consistent long-term retrieval (CLTR) and delayed recall were significantly related to (1) right and left PP zone ADC, (2) left hippocampus ADC, and (3) left hippocampal volume. Nonverbal memory (immediate and delayed recall) was significantly associated with (1) right and left PP zone ADC, (2) left hippocampal volume, and (3) gray (immediate recall) and white (immediate recall, bilaterally; delayed recall, left) matter temporal volumes. Advanced neuroimaging analysis can detect in vivo changes in the PP zone and temporal structures in patients with severe TBI, with these changes being highly associated with memory impairment.

The presence of cerebrospinal fluid oligoclonal bands (CSF-OCB) in Caucasian patients with multiple sclerosis (MS) is supportive of diagnosis, though the relation with patients’ clinical and specifically cognitive features has never been established or thoroughly examined. Thus, we investigated the clinical and for the first time the cognitive profile of MS patients in relation to CSF-OCB. We studied 108 patients with and without OCB and recorded demographic characteristics and detailed clinical data. A comprehensive neuropsychological battery covering different cognitive domains (attention/processing speed, memory, perception/constructions, reasoning, executive functions) was administered to MS patients and 142 demographically related healthy controls (HC). We did not find any significant differences between patients with and without OCB on demographic and clinical parameters (p > 0.05), including subtype and brain neuroimaging findings. Results revealed significantly higher cognitive scores in HC compared to both OCB subgroups, with more widespread cognitive changes in patients with OCB. Analysis between OCB subgroups showed significantly worse performance in patients with OCB on visual memory (Rey’s complex figure test-recall; p = 0.006). Concluding, the presence of CSF-OCB in our MS patients tends to be related to more widespread cognitive changes, specifically worse visual memory. Future longitudinal studies in different populations are warranted to better clarify the clinical and cognitive characteristics related to CSF-OCB which could serve as early biomarker in disease monitoring.

The applications of diffusion tensor imaging (DTI) have increased considerably among both normal and diverse neuropsychiatric populations in recent years. In this chapter, the authors examine the contributions of DTI in identifying profiles of trait-specific connectivity in several groups defined in terms of gender, age, handedness, and general intelligence. Additionally, the DTI literature is reviewed across a range of neurodegenerative disorders including Alzheimer’s disease, mild cognitive impairment, frontotemporal dementia, Parkinson disease, multiple sclerosis, and acquired neurological disorders resulting from neuronal injury such as traumatic brain injury, aphasia, agnosia, amnesia, and apraxia. DTI metrics sensitive to psychiatric disorders encompassing obsessive-compulsive disorder, depression, bipolar disorder, schizophrenia, and alcoholism are reviewed. Future uses of DTI as a promising means of confirming diagnoses and identifying in vivo early microstructural changes of patients’ clinical symptoms are discussed.

The use of non-traditional scores in neuropsychological assessment allows for pattern analysis of test performance, commonly referred to as Quantified Process Approach (QPA). In the present study, the QPA was taken to study error rates on the Trail Making Test (TMT) in 26 non-demented patients with classic motor neuron disease (cMND), who commonly present with impaired cognitive flexibility, and 26 matched healthy controls. Between-group comparisons revealed that cMND patients exhibited higher total error rates on the TMT Part B (TMT-B) relative to controls (p < 0.001), though no significant associations were noted between TMT errors and measures of attention and executive function obtained using the Stroop Neuropsychological Screening Test, the Wechsler Adult Intelligence Scale Digit Symbol and Digit Span subtests and the Wisconsin Card Sorting Test. Moreover, the percentage of cMND patients with normal TMT-B time-to-completion who committed at least one error (either sequential or perseverative errors) in TMT-B was significantly higher compared to controls (p = 0.005). These findings suggest that error analysis using the QPA may increase the clinical utility of TMT and should be considered in addition to time-to-completion scores, in the neuropsychological assessment of patients with cMND.

Although executive functions in sporadic non-demented amyotrophic lateral sclerosis (ALS) patients are mostly affected, it remains unclear whether executive measures can differentiate between patients with bulbar and spinal ALS forms. Thirty spinal and 18 bulbar-onset ALS patients (ALS-s and ALS-b, respectively) as well as 47 demographically related healthy controls were examined in executive processes (Trail Making Test-part B [TMT-(B-A)]; Stroop Neuropsychological Screening Test [SNST]; Similarities subtest of the Wechsler Adult Intelligence Scale [WAIS Similarities]; Wisconsin Card Sorting Test [WCST]). ALS subgroups were similar with regard to demographic characteristics and disease duration; yet, ALS-b showed greater disease severity compared with ALS-s patients (p = .006). Both ALS-s and ALS-b patients were significantly inferior to healthy controls on TMT-(B-A) (p.001), SNST (p = .009 and p = .02, respectively) and WAIS Similarities (p = .031 and p = .021, respectively), whereas ALS-s performed significantly worse than controls on the WCST perseverative responses (p = .005). However, neuropsychological measures did not significantly differ between ALS subgroups (p.05). Despite the fact that ALS-b patients may present greater disease severity, specific executive impairments that are present early in the course of ALS seems to be independent of the site of onset.