Alzheimer's disease (AD) and Parkinson's disease (PD), including dementia with Lewy bodies (DLB), account for the majority of dementia cases worldwide. Interestingly, a significant number of patients have clinical and neuropathological features of both AD and PD, i.e., the presence of amyloid deposits and Lewy bodies in the neocortex. The identification of α-synuclein peptides in amyloid plaques in DLB brain led to the hypothesis that both peptides mutually interact with each other to facilitate neurodegeneration. In this article, we report the influence of Aβ(1-42) and pGlu-Aβ(3-42) on the aggregation of α-synuclein in vitro. The aggregation of human recombinant α-synuclein was investigated using thioflavin-T fluorescence assay. Fibrils were investigated by means of antibody conjugated immunogold followed by transmission electron microscopy (TEM). Our data demonstrate a significantly increased aggregation propensity of α-synuclein in the presence of minor concentrations of Aβ(1-42) and pGlu-Aβ(3-42) for the first time, but without effect on toxicity on mouse primary neurons. The analysis of the composition of the fibrils by TEM combined with immunogold labeling of the peptides revealed an interaction of α-synuclein and Aβ in vitro, leading to an accelerated fibril formation. The analysis of kinetic data suggests that significantly enhanced nucleus formation accounts for this effect. Additionally, co-occurrence of α-synuclein and Aβ and pGlu-Aβ, respectively, under pathological conditions was confirmed in vivo by double immunofluorescent labelings in brains of aged transgenic mice with amyloid pathology. These observations imply a cross-talk of the amyloid peptides α-synuclein and Aβ species in neurodegeneration. Such effects might be responsible for the co-occurrence of Lewy bodies and plaques in many dementia cases.

In Parkinson's disease, aggregates of α-synuclein within Lewy bodies and Lewy neurites represent neuropathological hallmarks. However, the cellular and molecular mechanisms triggering oligomeric and fibrillary α-synuclein aggregation are not fully understood. Recent evidence indicates that oxidative stress induced by metal ions and post-translational modifications such as phosphorylation, ubiquitination, nitration, glycation, and SUMOylation affect α-synuclein conformation along with its aggregation propensity and neurotoxic profiles. In addition, proteolytic cleavage of α-synuclein by specific proteases results in the formation of a broad spectrum of fragments with consecutively altered and not fully understood physiological and/or pathological properties. In the present review, we summarize the current knowledge on proteolytical α-synuclein cleavage by neurosin, calpain-1, cathepsin D, and matrix metalloproteinase-3 in health and disease. We also shed light on the contribution of the same enzymes to proteolytical processing of pathogenic proteins in Alzheimer's disease and report potential cross-disease mechanisms of pathogenic protein aggregation.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is neuropathologically characterized by degeneration of dopaminergic neurons of the substantia nigra (SN) and formation of Lewy bodies and Lewy neurites composed of aggregated α-synuclein. Proteolysis of α-synuclein by matrix metalloproteinases was shown to facilitate its aggregation and to affect cell viability. One of the proteolysed fragments, Gln79-α-synuclein, possesses a glutamine residue at its N-terminus. We argue that glutaminyl cyclase (QC) may catalyze the pyroglutamate (pGlu)79-α-synuclein formation and, thereby, contribute to enhanced aggregation and compromised degradation of α-synuclein in human synucleinopathies. Here, the kinetic characteristics of Gln79-α-synuclein conversion into the pGlu-form by QC are shown using enzymatic assays and mass spectrometry. Thioflavin T assays and electron microscopy demonstrated a decreased potential of pGlu79-α-synuclein to form fibrils. However, size exclusion chromatography and cell viability assays revealed an increased propensity of pGlu79- α-synuclein to form oligomeric aggregates with high neurotoxicity. In brains of wild-type mice, QC and α-synuclein were co-expressed by dopaminergic SN neurons. Using a specific antibody against the pGlu-modified neo-epitope of α-synuclein, pGlu79-α-synuclein aggregates were detected in association with QC in brains of two transgenic mouse lines with human α-synuclein overexpression. In human brain samples of PD and dementia with Lewy body subjects, pGlu79-α-synuclein was shown to be present in SN neurons, in a number of Lewy bodies and in dystrophic neurites. Importantly, there was a spatial co-occurrence of pGlu79-α-synuclein with the enzyme QC in the human SN complex and a defined association of QC with neuropathological structures. We conclude that QC catalyzes the formation of oligomer-prone pGlu79-α-synuclein in human synucleinopathies, which may—in analogy to pGlu-Aβ peptides in Alzheimer’s disease—act as a seed for pathogenic protein aggregation.

Yes / It is unclear whether people with dementia (PwD) have more negative attitudes toward own aging (ATOA) than people without dementia and what factors influence ATOA among PwD. We investigated whether PwD have more negative ATOA than individuals without dementia and whether cognition and dementia subtype are associated with ATOA in PwD. Data from the IDEAL and PROTECT studies were used to compare ATOA between 1502 PwD (mean (SD) age = 76.3 (8.5)) and 6377 individuals without dementia (mean (SD) age = 66.1 (7.1)). Linear regressions and ANOVA were used. PwD reported slightly more negative ATOA than people without dementia; this relationship disappeared after controlling for depression and self-rated health. In PwD more positive ATOA showed negligible associations with better general cognition, memory performance, verbal fluency, and visuospatial ability. However, after adjusting for covariates only better visuospatial ability predicted more positive ATOA. Additional analyses showed that before and after controlling for covariates, individuals with poorer self-reported visual acuity have more negative ATOA. Amongst dementia subtypes, people with Parkinson's disease dementia and dementia with Lewy bodies reported most negative ATOA. ATOA between PwD and people without dementia do not differ. ATOA in PwD appear to be affected not by cognitive impairment but by other characteristics that vary across dementia subtypes. Among PwD, those with Parkinson's disease dementia and dementia with Lewy bodies may have higher risk of experiencing negative ATOA due to the motor and visual impairments that they experience. / Improving the experience of Dementia and Enhancing Active Life: living well with dementia. The IDEAL study’ was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health and Care Research (NIHR) through grant ES/L001853/2. The IDEAL-2 study’ is funded by Alzheimer’s Society, grant number 348, AS-PR2-16-001

Είναι γνωστό ότι η άνοια σχετίζεται με την απώλεια μνήμης, έκπτωση γλωσσικών ικανοτήτων, έλλειψη αυτονομίας και απώλεια της προσωπικής ταυτότητας του ασθενούς. Στόχος της παρούσας εργασίας είναι να αναδείξει τη σχέση αμφισημίας- άνοιας και να διερευνηθεί η σκοπιμότητα ύπαρξης ενός μεθοδολογικού εργαλείου για την εκτίμηση και τη διερεύνηση της γλωσσικής έκπτωσης στη άνοια μέσα από την γλωσσική επεξεργασία των λεξικών σχέσεων (μεταφορών –ομωνυμίας- μετωνυμιών) και να παρουσιάζει το προφίλ των ασθενών αυτών. Στην πρώτη ενότητα παρουσιάζω γενικά στοιχεία για την νόσο της άνοιας αλλά και στοιχεία για τους κυριότερους τύπους της νόσου όσον αφορά την γλωσσική συμπεριφορά των ασθενών. Στην ενότητα αυτή αναφέρω επίσης βασικά διαγνωστικά εργαλεία που χρησιμοποιούνται ευρέως για τον προσδιορισμό της νόσου, ενώ αναλυτικότερα στοιχεία για τα εργαλεία που χρησιμοποιούνται και τις δομές που εξετάζουν παρατίθενται στο παράρτημα. Κλείνοντας την ενότητα καταλήγω στα οφέλη και την αναγκαιότητα ύπαρξης πρώιμης διάγνωσης. Στην δεύτερη ενότητα αναφέρομαι κυρίως στο νοητικό λεξικό και στην δυσκολία πρόσβασης των ασθενών με πιθανή άνοια σε αυτό. Επιπλέον υπάρχουν στοιχεία για την λεξική κατάκτηση, επιλογή και ανάκτηση των πληροφοριών και φαίνεται η σχέση νοητικού λεξικού – αμφισημίας. Στην τρίτη ενότητα παρουσιάζω το φαινόμενο της αμφισημίας από την θεωρητική άποψη αρχικά της γλωσσολογίας, πως κατακτώνται οι αμφίσημες λέξεις και επεξεργάζονται σε σχέση με την ηλικία και καταλήγω στην νευρική συσχέτιση των λεξικών αμφισημιών με συγκεκριμένες εγκεφαλικές περιοχές. Στο τέλος της παρούσας ενότητας παρουσιάζω ευρήματα/ συμπεράσματα από πλήθος ερευνών που αφορούν την λεξική αμφισημία με διαφορετικές μεθόδους για κάθε τύπο άνοιας. Στην τελευταία ενότητα παρουσιάζω τις βασικές υποθέσεις μου πως η χρήση των λεξικών σχέσεων θα μπορεί να αποτελέσει διαγνωστικό εργαλείο στην άνοια. Επίσης παρουσιάζω την κατασκευή και τα αποτελέσματα της πειραματικής διαδικασίας ανάμεσα σε τέσσερα διαφορετικά υποκείμενα (πασχόντων –υγειών) διαφορετικής παθολογίας και σοβαρότητας. Ακολουθεί τέλος το παράρτημα με στοιχεία που αφορούν την διαφοροδιάγνωση της νόσου βάσει αλγορίθμων με τα γνωστικά ελλείμματα όπως παρουσιάζονται από τους φροντιστές των ασθενών αλλά και παθολογικών συμπτωμάτων που παρουσιάζουν, ενώ σε πίνακα υπάρχουν τα γλωσσικά στοιχεία που βοηθούν επίσης στην διαφοροδιάγνωση των κυριότερων τύπων άνοιας και τα αποτελέσματα της πειραματικής διαδικασίας. / It is well known that dementia is associated with memory loss, impaired language skills, lack of autonomy and loss of patients’ independence. The aim of this paper is to highlight the connection between ambiguity and dementia, and to investigate the feasibility of a methodological tool to assess and investigate the linguistic deduction in dementia through the linguistic processing of lexical relations (metaphor-homonymy-metonymy) and present the profile of such patients. In the first section I present general information as well as the linguistic features of the main types of dementia. In this section there is also a report on the diagnostic tools which are widely used to identify the disease. More detailed information about the use of these diagnostic tools is listed in the Annex. At the end of this section there is evidence about the benefits and the importance of early diagnosis. The second section is mainly referred to the mental lexicon and the difficulty patients with probable dementia face in accessing it. Furthermore there is evidence for lexical acquisition, selection and retrieval of information which shows the mental lexicon – ambiguity connection. In the third section I present the phenomenon of ambiguity, starting from the theoretical linguistic view; how the ambiguous words are conquered and processed in relation to age and lead to neural correlation of lexical ambiguity with specific brain regions. At the end of this section I present findings / conclusions of several researches, using different methods, on the lexical ambiguity on each type of dementia. The last section presents my basic assumptions concerning how the use of lexical relations can be a diagnostic tool in dementia. Furthermore, I present the construction and the results of the experimental process between four different subjects (patient-healthy) with different pathology and severity of the disease. Finally, at the annex, I present data on the differential diagnosis of the disease based on algorithms with cognitive deficits reported by caregivers of patients as well as pathology features. Also there is a board with differential linguistic elements which help distinguish the main types of dementia, along with the experimental material used and the results of the procedure.

Le trouble comportemental en sommeil paradoxal idiopathique (TCSPi) précède de plusieurs années le diagnostic d’une maladie synucléinopathique. Dans cette étude, nous cherchions à déterminer si la puissance spectrale relative, les composantes rythmiques et arythmiques des spectres de puissance, ainsi que la connectivité fonctionnelle permettaient d’identifier à un temps de base les patients ayant un TCSPi qui développerait une synucléinopathie lors des suivis cliniques annuels. Un enregistrement EEG au repos et une évaluation neuropsychologique ont été conduits auprès de quatre-vingt-un participants atteints d’un TCSPi (66.89 ± 6.91 ans, 20 femmes) et des évaluations neurologiques annuelles étaient menées afin de définir si les patients montraient des symptômes d’une maladie synucléinopathique. La puissance spectrale standard ainsi qu’une estimation spectrale des composantes rythmiques et arythmiques ont été calculées. Ensuite, la connectivité fonctionnelle globale et entre chaque paire d’électrodes ont été estimée par le weighted Phase Lag Index. Après une durée de suivi de 5.01 ± 2.76 ans, 34 participants ont été diagnostiqués avec une synucléinopathie et 47 sont restés exempts de maladie. Comparativement aux participants avec un TCSPi n’ayant pas converti, ceux ayant converti montraient, lors de l’évaluation de base, une puissance spectrale relative plus élevée dans la bande thêta, une pente de la composante arythmique plus abrupte ainsi qu'une puissance rythmique plus élevée en thêta dans les régions occipitales et temporales ainsi qu’en en bêta1 dans les régions frontales. De plus, les patients TCSPi ayant converti présentaient une hyperconnectivité globale dans la bande bêta, mais une hypoconnectivité dans la bande alpha entre les régions temporo-occipitales gauches lors de l’évaluation de base comparativement à ceux n’ayant pas converti. Les altérations mesurables en EEG au repos lors de l’évaluation de base chez les participants avec TCSPi ayant converti vers une maladie synucléinopathique suggèrent une perturbation des réseaux à grande échelle affectés par la neurodégénérescence précoce des structures sous-corticales. / Idiopathic REM sleep behavior disorder (iRBD) precedes the diagnosis of synucleinopathies by several years. In this study, we aimed to determine whether relative spectral power, rhythmic and arrhythmic components of power spectra, and functional connectivity at baseline could identify patients with iRBD who will develop a synucleinopathy at follow-up. Resting-state EEG recordings and neuropsychological evaluations were conducted on eighty-one participants with iRBD (66.89 ± 6.91 years; 20 women), and annual neurological assessments were performed to define the emergence of synucleinopathy symptoms. Standard spectral power and spectral estimates of rhythmic and arrhythmic components were calculated. Additionally, global and pairwise functional connectivity were estimated using the weighted Phase Lag Index. After a follow-up period of 5.01 ± 2.76 years, 34 participants were diagnosed with a synucleinopathic disorder, while 47 remained disease-free. Compared to patients who did not convert, patients who converted at follow-up exhibited higher relative spectral power in the theta band, steeper slopes of the arrhythmic component, and increased rhythmic power in theta in posterior regions and beta1 in frontal regions at baseline evaluation. Furthermore, participants who converted showed hyperconnectivity in the beta band and hypoconnectivity in the alpha band between left temporo-occipital regions at baseline compared to participants who did not convert. The measurable alterations in resting-state EEG at baseline in participants with iRBD who phenoconverted towards a synucleinopathy suggest disruption of large-scale networks affected by early neurodegeneration of subcortical structures.

Text in English / The present paper analyses the neuroanatomical and neuropsychological backgrounds of art reception and art creation in modern visual art and creative processes. It critically presents two models of aesthetic experience to provide a comprehensive theoretical basis for the discussion. The research purpose is to show that with increasing experience and expertise the referential frame of the aesthetic judgment is changing and that neural processes involved in object recognition provide a starting point for visual aesthetics. Thus, the investigation focuses on constructing and testing neuropsychological theories that fall in the domain called 'neuroaesthetics'. These theories, in turn, serve as a starting point to formulate neural laws of art and aesthetics and aesthetic experience. Some artistic styles, such as expressionism, reflect specific neural processes. Various studies indicate correlations between hemispheric specialisation and art or creativity and show the right hemisphere plays a particular role in it. However, studies exploring the neural correlates of aesthetic preference have yielded mixed results. Furthermore, neuroimaging studies have proved that different categories of modern artworks are processed in different areas of the brain. These diverging results will be discussed in a critical assessment of the two models of aesthetic experience. Besides, the question of identifying exclusive neural correlates of aesthetic preference will be raised. Comparing amateurs and experts has revealed the more reduced the cortical activation, the more efficiently it works. Biological and neuropsychological factors of creativity point out the meaning of the activation level, cognitive inhibition and prefrontal cortex. Divergent thinking differs from convergent thinking in terms of the neural level. Neurodegenerative processes and brain injuries sometimes influence the artistic output surprisingly or even launch it. Lesion studies contributing to understanding art experience will be explained. / Psychology / M.A. (Psychology)

The present paper analyses the neuroanatomical and neuropsychological backgrounds of art reception and art creation in modern visual art and creative processes. It critically presents two models of aesthetic experience to provide a comprehensive theoretical basis for the discussion. The research purpose is to show that with increasing experience and expertise the referential frame of the aesthetic judgment is changing and that neural processes involved in object recognition provide a starting point for visual aesthetics. Thus, the investigation focuses on constructing and testing neuropsychological theories that fall in the domain called 'neuroaesthetics'. These theories, in turn, serve as a starting point to formulate neural laws of art and aesthetics and aesthetic experience. Some artistic styles, such as expressionism, reflect specific neural processes. Various studies indicate correlations between hemispheric specialisation and art or creativity and show the right hemisphere plays a particular role in it. However, studies exploring the neural correlates of aesthetic preference have yielded mixed results. Furthermore, neuroimaging studies have proved that different categories of modern artworks are processed in different areas of the brain. These diverging results will be discussed in a critical assessment of the two models of aesthetic experience. Besides, the question of identifying exclusive neural correlates of aesthetic preference will be raised. Comparing amateurs and experts has revealed the more reduced the cortical activation, the more efficiently it works. Biological and neuropsychological factors of creativity point out the meaning of the activation level, cognitive inhibition and prefrontal cortex. Divergent thinking differs from convergent thinking in terms of the neural level. Neurodegenerative processes and brain injuries sometimes influence the artistic output surprisingly or even launch it. Lesion studies contributing to understanding art experience will be explained. / Psychology / M.A. (Psychology)

Cette thèse de sociologie porte sur les pratiques de sommeil des couples vieillissants confrontés à une maladie neurodégénérative. Elle se fixe comme objectif de saisir les dynamiques temporelles et spatiales de ces pratiques de sommeil, centrales dans la vie du couple, au fil de l'évolution de la maladie en accordant une attention particulière aux relations de genre. Nous avons interviewé 30 couples à domicile, dont 12 concernés par la maladie à corps de Lewy et 18 par la maladie d'Alzheimer et nous avons intégré des dispositifs d'enquête tels que la rédaction de journaux de sommeil, de journaux audio et la constitution d'un ensemble de documentation photographique. L'analyse se déploie selon trois axes. Le premier axe consiste à analyser le rôle du veilleur de nuit assumé par le conjoint aidant. Nous avons constaté le passage du statut de conjoint dormant à celui de "conjoint veilleur". Le rôle de conjoint veilleur est caractérisé par la production d'un travail domestique de soin qui se déroule la nuit et que nous avons appelé "travail domestique nocturne de soin". Nos résultats montrent que ce travail domestique nocturne peut amener le conjoint veilleur à un état d'épuisement qui peut pousser au choix d'institutionnaliser son conjoint malade. Ce travail domestique s'articule avec un état d'inquiétude nocturne du conjoint veilleur qui engendre un sommeil spécifique que l'on peut qualifier de "sommeil en état d'alerte". Il est aussi doublement invisible : il est constitué par des activités se déroulant la nuit et il repose souvent sur les femmes. Le deuxième axe consiste à analyser l'impact de la maladie et des troubles cognitifs sur l'organisation des espaces liés au sommeil en mettant en lumière les négociations qui se font autour de la chambre conjugale. Nous avons dégagé les raisons pour lesquelles une partie des conjoints reste attachée au fait de dormir ensemble. Nous avons aussi analysé les dimensions corporelles liées au partage du lit, contexte où la relation entre les corps trouve son expression privilégiée. Nous avons exploré les expériences de distanciation des conjoints : les significations et les pratiques autour du choix de dormir en couple mais séparés, de faire chambre à part. Le dernier axe porte sur l'analyse des stratégies hétérogènes de la gestion du sommeil telles que l'utilisation des médicaments pour dormir, le recours à la garde nocturne en institution ou au domicile et, enfin, le sommeil diurne. Nous avons analysé les raisons de l'adhésion ou du refus de la part des conjoints aidants et nous avons constaté que la vulnérabilité qui caractérise la nuit et le sommeil peut rendre difficile le recours aux stratégies de gestion du sommeil. / This doctoral dissertation in sociology examines the sleep practices of ageing couples confronted with neuro-degenerative conditions. It aims to understand the time- and space-related aspects of these sleep practices, so central to couples’ lives, throughout the different stages of illness, and places particular emphasis on gender-based relations. Thirty couples were interviewed in their homes, 12 of whom were affected by Lewy Body Dementia and 18 by Alzheimer’s Disease. Empirical methods such as sleep journals, audio journals, and photographic documentation were incorporated into the study’s methodology. The study is divided into three branches. The first branch examines the role of “night-time guardian” assumed by the caregiving partner. The author was able to observe that a shift takes place from the status of sleeping partner to that of night-time caregiver. The role of the “night-time guardian” is characterized by domestic labor that takes the form of caregiving provided at night, a phenomenon the author calls “nocturnal domestic caregiving work”. The findings of the study show that this domestic night-time work can bring about a state of exhaustion in caregiving partners that can drive them to institutionalize the partner suffering from a medical condition. In addition to this domestic work, caregiving partners are prone to a state of night-time worry that results in a specific variety of sleep that can be described as “alert sleep”. This domestic work also goes largely unseen for two reasons: it is made up of activities that take place at night, and it often falls to women. The study's second branch offers an analysis of the impact of illness and cognitive disorders on the way areas of the home associated with sleep are organized, bringing to light the give-and-take that occurs where the marital bedroom is concerned. The author examined the reasons some sleep partners continue to insist on sleeping together. Also addressed are the bodily aspects of shared beds, a special context in which the bonds shared between bodies can be expressed in a unique way. The dissertation further explores the experience of placing distance between sleep partners: the meanings and practices surrounding the decision to sleep as a couple but in separate rooms. The final branch of the study examines a range of strategies used to manage sleep, such as taking sleeping medication, turning to in-home or institutional night-time caretaking, and day-time sleep. The author surveyed the reasons that caregiving partners accepted or refused to utilize these strategies, and the study’s findings show that the vulnerability represented by night and sleep can render it difficult to decide to use strategies to manage sleep.

Le rôle que pourrait jouer l’interaction des systèmes cholinergiques (ACh) et dopaminergiques (DA) semble crucial dans la physiopathologie de certaines maladies neurodégénératives, en particulier dans la démence à corps de Lewy (DCL). Ce travail de thèse se propose de valider un protocole d’imagerie moléculaire en tomographie d’émission monophotonique, consistant en un marquage de l’ACh et de la DA chez un même individu, afin de pouvoir étudier in vivo les interactions ACh/DA.Après avoir mis au point chez des sujets âgés et des patients atteints de maladie d’Alzheimer une méthode d’imagerie cérébrale quantitative des neurones ACh utilisant un radioligand sélectif du transporteur vésiculaire de l’ACh, le [123I]-IBVM, et basée sur une modélisation pharmacocinétique, nous avons montré le potentiel de cette méthode à mettre en évidence une atteinte différentielle des circuits ACh dans la Paralysie Supranucléaire Progressive et l’Atrophie Multisystématisée. Dans la dernière partie de ce travail de thèse, nous avons pour la première fois réalisé un double marquage des systèmes ACh et DA dans la DCL, en utilisant, en plus du [123I]-IBVM, un radioligand sélectif du transporteur de la dopamine et validé en routine clinique, le [123I]-FP-CIT. En parallèle, une étude comportementale évaluant la présence d’hallucinations, de fluctuations cognitives, d’altérations des rythmes circadiens ainsi qu’un bilan des performances neuropsychologiques, ont été menés. Cette étude est actuellement en cours de réalisation. Les tous premiers résultats montrent l’existence de liens cohérents entre les données d’imagerie moléculaire et les données cliniques. / The question of how acetylcholine (ACh) and dopamine (DA) could be involved together in the pathophysiology of some neurodegenerative disorders is essential, particularly in dementia with Lewy bodies (DLB). The present study aims at assessing an in vivo molecular imaging method of both ACh and DA brain systems using single photon emission computed tomography. In the first part of the present study, a method based on pharmacokinetic analysis making it possible to quantify ACh neurons in vivo, using [123I]-IBVM, a specific radioligand of vesicular acetylcholine transporter, was developed and validated in healthy subjects and Alzheimer’s disease patients. Then, we showed the ability of our method to demonstrate a differential alteration of ACh pathways in Progressive Supranuclear Palsy and Multiple System Atrophy patients. In the last part of this study, we imaged for the first time both ACh and DA systems in DLB patients, using not only [123I]-IBVM, but also [123I]-FP-CIT, a specific radioligand of dopamine transporter. Concomitantly, a behavioral exploration of hallucinations, fluctuating cognition and disturbances of circadian rhythms was achieved in these patients, as well as a neuropsychological examination. This study is currently in progress. The first results show consistent links between imaging and clinical data.