Imaging biomarkers in neurodegeneration: current and future practices

Abstract: There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course “Biomarkers in neurodegenerative diseases”. In this review, we focus on neuroimaging, specifically positron emission tomography (PET) and magnetic resonance imaging (MRI), giving an overview of the current established practices clinically and in research as well as new techniques being developed. We will also discuss the use of machine learning (ML) techniques within these fields to provide additional insights to early diagnosis and multimodal analysis

Multimodal modelling of early neurodegeneration and Alzheimer's disease progression

Alzheimer’s disease (AD) is a heterogeneous condition with a long pre-symptomatic phase. Treatments are likely to be more effective if administered at earlier stages in targeted groups. However, early detection and stratification is challenging, requiring the incorporation of biomarkers that are sensitive to pre-symptomatic disease, and the disentanglement of the different factors that contribute to disease heterogeneity. Two key contributors to AD heterogeneity are temporal heterogeneity (individuals are at a range of underlying stages) and subtype heterogeneity (individuals belong to different subgroups with distinct temporal progression patterns). Whilst a range of clustering methods have been used to characterise AD subtypes, these methods fail to account for temporal heterogeneity, potentially conflating disease subtypes with disease stages and precluding subtyping of individuals at early stages. SuStaIn (Subtype and Stage Inference) extracts both the phenotypical and temporal heterogeneity of AD by using a data-driven combination of clustering and disease progression modelling. However, SuStaIn does not currently account for missing data, often limiting the application of SuStaIn to one type of biomarker and thus excluding key information about the diverse set of early changes that occur in AD. In this thesis, I develop a missing data adaptation of SuStaIn (“missing-data SuStaIn”) and benchmark it against other missing data algorithms. I apply missing-data SuStaIn to a research cohort (ADNI) to characterise the heterogeneity of multi-modal biomarker trajectories in an amyloid-enriched cohort, demonstrating that using multi-modal data significantly improves the prediction of conversion between diagnoses; and unravels a higher number of disease subtypes than when using MRI only. I then apply missing-data SuStaIn to a population cohort (Insight46) to study the heterogeneity of multi-modal biomarker trajectories in an elderly population, uncovering three subgroups with early biomarker changes resembling pre-symptomatic Alzheimer’s disease. The missing-data adaptation to SuStaIn developed in this thesis has wide potential applications to other diseases and developmental processes

L’aprenentatge cooperatiu per a l'elaboració d'un pla d'empresa a Formació Professional

[cat] Els continguts del mòdul d'Empesa i iniciativa Emprenedora (EIE), el qual és impartit en diversos cicles i famílies de Formació Professional, són fonamentals perquè l’alumat es pugui incorporar de forma satisfactòria al mercat laboral un cop finalitzat els seus estudis. Malgrat això, aquest mòdul sovint és considerat per la majoria dels estudiants com un mer tràmit per a l'obtenció del títol amb escassa utilitat pràctica atès que no està relacionat amb el seu perfil professional. Amb l’objectiu d’incrementar l’interès cap al mòdul d’EIE, s’ha desenvolupat una proposta didàctica que consisteix a elaborar un pla d’empresa mitjançant l’aprenentatge cooperatiu. Aquesta metodologia que es basa en el treball en equip i té una finalitat doble: afavorir la motivació per assolir els continguts i les competències del mòdul i aprofitar la interacció simètrica entre els seus membres per participar de forma més activa i col·laborativa. Saber organitzar i planificar les tasques en equip és una de les principals competències que ha de tenir un/a bon emprenedor/a per transformar la seva idea en un negoci d’èxit. En resum, l’aprenentatge cooperatiu facilita la creació d’entorns d'aprenentatge significatiu, els quals proporcionen una retroalimentació constant, tant en la relació amb el professorat com entre iguals. A més, permeten que l’estudiant sigui partícip i responsable del seu procés educatiu i assoleixi els resultats d'aprenentatge, fins i tot quan es tracta d'estudis orientats a la pràctica professional

Propostes d'intervenció per a la revisió de conductes patriarcals en espais mixtos autodenominats feministes

[cat] Atès que es troben tan en auge conceptes tendents a la deconstrucció per referir-nos a la necessitat de desaprendre comportaments, conductes i actituds arrelades en el nostre subconscient, sembla convenient plantejar-se com podem reconstruir-nos, en el sentit d’aprendre comportaments, conductes i actituds noves per a nosaltres i molt menys nocives per al nostre entorn. En aquest sentit, sembla imprescindible, ja que tornam a posar la qüestió sobre les cures sobre la taula en tots els debats, posar en el centre les cures també en els espais d’activisme social i de militància política. Cal tenir cura de tot el nostre entorn per tal que aquest sigui saludable i sostenible. Per aquests motius, les intervencions que es proposen estan destinades a l’espai polític de caire assembleari mixt escollit per dur-les a terme, si bé es consideren extrapolables a altres espais que es valorin similars. L’objectiu de les activitats és triple: en primer lloc, donar eines d’empoderament1 a les dones que participen d’aquests espais; en segon terme, donar eines de revisió de privilegis als homes que en participen; i, per acabar, dotar a l’espai assembleari d’eines i mecanismes per tenir cura de les persones del nostre entorn activista, polític, familiar i social.[eng] Due to the boom of concepts tending to deconstruction to refer us at the necessity of unlearn behaviours and attitudes rooted at our subconscious, seems convenient to consider how can we reconstruct us, in the sense of learning new behaviours and attitudes for us and much less harmful for our surroundings. At this sense, it seems indispensable, since we return at posing the question of cares on the table in all the debates, to pose at the centre the cares also in the spaces of social activism and political militancy. We need to take care of all our surroundings in order to make it healthy. For these reasons, the interventions which are proposed are destined at the political to the political area of a mixed assemblage type to carry them out, although they are extrapolable to other spaces which are considered similar. The purpose of the activities is threefold: in first place, to give empowering tools to women participating in these spaces; in the second place, to give tools to review privileges to the men who participate; and, finally, to equip the assembly space with tools to take care of the people in our activist, political, family and social environment

Neural markers of reduced arousal and consciousness in mild cognitive impairment.

Publication status: PublishedFunder: Wellcome TrustFunder: Wellcome Clinical Research Career Development FellowshipOBJECTIVES: People with Alzheimer's Disease (AD) experience changes in their level and content of consciousness, but there is little research on biomarkers of consciousness in pre-clinical AD and Mild Cognitive Impairment (MCI). This study investigated whether levels of consciousness are decreased in people with MCI. METHODS: A multi-site site magnetoencephalography (MEG) dataset, BIOFIND, comprising 83 people with MCI and 83 age matched controls, was analysed. Arousal (and drowsiness) was assessed by computing the theta-alpha ratio (TAR). The Lempel-Ziv algorithm (LZ) was used to quantify the information content of brain activity, with higher LZ values indicating greater complexity and potentially a higher level of consciousness. RESULTS: LZ was lower in the MCI group versus controls, indicating a reduced level of consciousness in MCI. TAR was higher in the MCI group versus controls, indicating a reduced level of arousal (i.e. increased drowsiness) in MCI. LZ was also found to be correlated with mini-mental state examination (MMSE) scores, suggesting an association between cognitive impairment and level of consciousness in people with MCI. CONCLUSIONS: A decline in consciousness and arousal can be seen in MCI. As cognitive impairment worsens, measured by MMSE scores, levels of consciousness and arousal decrease. These findings highlight how monitoring consciousness using biomarkers could help understand and manage impairments found at the preclinical stages of AD. Further research is needed to explore markers of consciousness between people who progress from MCI to dementia and those who do not, and in people with moderate and severe AD, to promote person-centred care

Systematic Review on Resting-State EEG for Alzheimer’s Disease Diagnosis and Progression Assessment

Alzheimer’s disease (AD) is a neurodegenerative disorder that accounts for nearly 70% of the more than 46 million dementia cases estimated worldwide. Although there is no cure for AD, early diagnosis and an accurate characterization of the disease progression can improve the quality of life of AD patients and their caregivers. Currently, AD diagnosis is carried out using standardized mental status examinations, which are commonly assisted by expensive neuroimaging scans and invasive laboratory tests, thus rendering the diagnosis time consuming and costly. Notwithstanding, over the last decade, electroencephalography (EEG) has emerged as a noninvasive alternative technique for the study of AD, competing with more expensive neuroimaging tools, such as MRI and PET. This paper reports on the results of a systematic review on the utilization of resting-state EEG signals for AD diagnosis and progression assessment. Recent journal articles obtained from four major bibliographic databases were analyzed. A total of 112 journal articles published from January 2010 to February 2018 were meticulously reviewed, and relevant aspects of these papers were compared across articles to provide a general overview of the research on this noninvasive AD diagnosis technique. Finally, recommendations for future studies with resting-state EEG were presented to improve and facilitate the knowledge transfer among research groups

The Forensic Medical Council's protocol for urgent assessment of the risk of gender violence

La violencia contra las mujeres es una violación grave de los derechos humanos y las libertades fundamentales que genera un daño multidimensional que afecta a todos los órdenes y aspectos de su vida. Todos los datos existentes hasta la fecha no hacen sino mostrarnos la gravedad y la magnitud de este problema. Hasta la fecha, la cifra de víctimas mortales por violencia de género (VG) en España asciende a 1.079 víctimas desde el 1 de enero de 20031. La predicción del riesgo en el contexto forense

The Forensic Medical Council's protocol for urgent assessment of the risk of gender violence

La violencia contra las mujeres es una violación grave de los derechos humanos y las libertades fundamentales que genera un daño multidimensional que afecta a todos los órdenes y aspectos de su vida. Todos los datos existentes hasta la fecha no hacen sino mostrarnos la gravedad y la magnitud de este problema. Hasta la fecha, la cifra de víctimas mortales por violencia de género (VG) en España asciende a 1.079 víctimas desde el 1 de enero de 2003. La predicción del riesgo en el contexto forense tiene interés para la adopción de estrategias de gestión del riesgo, relacionadas con la supervisión y control del potencial agresor y con la adopción de medidas de protección sobre la potencial víctima. La evaluación del riesgo de VG supone un reto en distintos contextos, principalmente policiales, judiciales y forenses. La formación en el uso de los protocolos y la revisión de los mismos es una constante necesidad

Imaging biomarkers in neurodegeneration: current and future practices

Abstract: There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course “Biomarkers in neurodegenerative diseases”. In this review, we focus on neuroimaging, specifically positron emission tomography (PET) and magnetic resonance imaging (MRI), giving an overview of the current established practices clinically and in research as well as new techniques being developed. We will also discuss the use of machine learning (ML) techniques within these fields to provide additional insights to early diagnosis and multimodal analysis