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Encephalopathy is part of the clinical triad of Susac syndrome, but a detailed understanding of the neurocognitive and neuropsychiatric profile of this condition is lacking. Existing literature indicates that cognitive deficits range in severity from subtle to profound. Executive function and short-term recall are affected frequently. Psychiatric manifestations may be absent or may include anxiety, mood disorders or psychosis. If psychiatric phenomena develop during the disease course, it can be hard to disentangle whether symptoms directly relate to the pathology of Susac syndrome or are secondary to treatment-related side effects. In this article, we review what is known about the cognitive and psychiatric morbidity of Susac syndrome and identify areas where knowledge is deficient. Importantly, we also provide a framework for future research, arguing that better phenotyping, understanding of pathophysiology, evaluation of treatments on cognitive and psychiatric outcomes, and longitudinal data capture are vital to improving patient outcomes.
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OBJECTIVE: The authors aimed to determine if Project Extension for Community Healthcare Outcomes (ECHO), a health-education model utilising teleconferencing technology, improves the capacity of clinicians in assessing and managing complex psychiatric patients. METHODS: Three pilot Project ECHO programs were evaluated as a prospective waitlist-controlled trial, focusing on Adult Eating Disorders, Adult Intellectual Disability Mental Health, and General Mental Health. Each program comprised 9-10 weekly teleconferencing group sessions. Participants and waitlist-controls completed pre- and post-program surveys. The primary outcomes were self-reported knowledge and confidence in assessing and managing complex patients relevant to each group. Linear mixed models were used to assess the group-by-time interaction, or change over time, as appropriate. RESULTS: Between July 2020 and June 2021, three series of the Adult Intellectual Disability Mental Health program, two series of the Adult Eating Disorders program, and two series of the General Mental Health program were delivered. Compared to waitlist-controls (n = 21), there were statistically significant improvements in self-reported knowledge and confidence for all topics amongst participants of the Adult Eating Disorders program (n = 44). In the Adult Intellectual Disability Mental Health program, there were significant improvements in self-reported knowledge and confidence amongst participants (n = 67) for most topics compared to controls (n = 21). There were no waitlist-controls for the General Mental Health program, but within-group analysis (n = 28) showed significant improvements in participants' knowledge and confidence following program completion, compared to baseline. CONCLUSION: Project ECHO is a feasible and effective model to develop workforce capacity in managing complex psychiatric conditions.
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Personal de Salud , Discapacidad Intelectual , Adulto , Humanos , Personal de Salud/educación , Estudios Prospectivos , Proyectos Piloto , Discapacidad Intelectual/terapia , Encuestas y CuestionariosRESUMEN
BACKGROUND: Cerebral small vessel disease (SVD) and Alzheimer's disease pathology, namely amyloid-ß (Aß) deposition, commonly co-occur. Exactly how they interact remains uncertain. OBJECTIVE: Using participants from the Alzheimer's Disease Neuroimaging Initiative (nâ=â216; mean age 73.29±7.08 years, 91 (42.1%) females), we examined whether the presence of vascular risk factors and/or baseline cerebral SVD was related to a greater burden of Aß cross-sectionally, and at 24 months follow-up. METHOD: Amyloid burden, assessed using 18F-florbetapir PET, was quantified as the global standardized uptake value ratio (SUVR). Multimodal imaging was used to strengthen the quantification of baseline SVD as a composite variable, which included white matter hyperintensity volume using MRI, and peak width of skeletonized mean diffusivity using diffusion tensor imaging. Structural equation modeling was used to analyze the associations between demographic factors, Apolipoprotein E É4 carrier status, vascular risk factors, SVD burden and cerebral amyloid. RESULTS: SVD burden had a direct association with Aß burden cross-sectionally (coeff.â=â0.229, pâ=â0.004), and an indirect effect over time (indirect coeff.â=â0.235, pâ=â0.004). Of the vascular risk factors, a history of hypertension (coeff.â=â0.094, pâ=â0.032) and a lower fasting glucose at baseline (coeff.â=â-0.027, pâ=â0.014) had a direct effect on Aß burden at 24 months, but only the direct effect of glucose persisted after regularization. CONCLUSION: While Aß and SVD burden have an association cross-sectionally, SVD does not appear to directly influence the accumulation of Aß longitudinally. Glucose regulation may be an important modifiable risk factor for Aß accrual over time.
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Enfermedad de Alzheimer , Amiloidosis , Enfermedades de los Pequeños Vasos Cerebrales , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Péptidos beta-Amiloides , Proteínas Amiloidogénicas , Amiloidosis/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Imagen de Difusión Tensora/métodos , Femenino , Glucosa , Humanos , Masculino , Factores de RiesgoRESUMEN
OBJECTIVE: To determine the proportional genetic contribution to the variability of cerebral ß-amyloid load in older adults using the classic twin design. METHODS: Participants (n=206) comprising 61 monozygotic (MZ) twin pairs (68 (55.74%) females; mean age (SD): 71.98 (6.43) years), and 42 dizygotic (DZ) twin pairs (56 (66.67%) females; mean age: 71.14 (5.15) years) were drawn from the Older Australian Twins Study. Participants underwent detailed clinical and neuropsychological evaluations, as well as MRI, diffusion tensor imaging (DTI) and amyloid PET scans. Fifty-eight participants (17 MZ pairs, 12 DZ pairs) had PET scans with 11Carbon-Pittsburgh Compound B, and 148 participants (44 MZ pairs, 30 DZ pairs) with 18Fluorine-NAV4694. Cortical amyloid burden was quantified using the centiloid scale globally, as well as the standardised uptake value ratio (SUVR) globally and in specific brain regions. Small vessel disease (SVD) was quantified using total white matter hyperintensity volume on MRI, and peak width of skeletonised mean diffusivity on DTI. Heritability (h2) and genetic correlations were measured with structural equation modelling under the best fit model, controlling for age, sex, tracer and scanner. RESULTS: The heritability of global amyloid burden was moderate (0.41 using SUVR; 0.52 using the centiloid scale) and ranged from 0.20 to 0.54 across different brain regions. There were no significant genetic or environmental correlations between global amyloid burden and markers of SVD. CONCLUSION: Amyloid deposition, the hallmark early feature of Alzheimer's disease, is under moderate genetic influence, suggesting a major environmental contribution that may be amenable to intervention.
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Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/genética , Encéfalo/diagnóstico por imagen , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Australia , Imagen de Difusión Tensora , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Tomografía de Emisión de PositronesRESUMEN
PURPOSE OF REVIEW: The relationship between hypertension and Alzheimer's disease (AD) is complex and varies across the lifespan. Studies have suggested that midlife hypertension is a risk factor for AD, although studies of late life hypertension have suggested that it either has no effect or a weak protective effect. RECENT FINDINGS: Animal models of induced and spontaneous hypertension have found that AD pathological change (ß-amyloid plaques and tau tangles) occurs within weeks of a hypertensive insult. Human imaging and autopsy studies indicate that midlife and late life hypertension are associated with increased AD pathological change. Meta-analyses of longitudinal studies indicate that midlife rather than late life hypertension is a risk factor for AD. New areas of research have suggested that rather than mean blood pressure (BP), it is the negative BP trajectories or the variability of BP that contributes to AD. In a number of meta-analyses of antihypertensive medications and their effect on AD, there were weak associations between improved AD outcomes and treatment. SUMMARY: The combined analysis of animal, human clinical/pathological, epidemiological and drug trial data indicates that hypertension increases the risk of AD and treatment of hypertension may be an appropriate preventive measure.
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Enfermedad de Alzheimer/epidemiología , Hipertensión/epidemiología , Edad de Inicio , Enfermedad de Alzheimer/prevención & control , Animales , Humanos , Hipertensión/tratamiento farmacológico , Estudios Longitudinales , Factores de RiesgoRESUMEN
As a part of a larger Affectome Project (http://neuroqualia.org/background.php) with an overarching goal of mapping and redefining biological substrates of feelings and emotions, we explored the neural underpinnings for the functions of motivation and emotion. Historically emotion and motivation have been placed into distinct neural circuits and examined separately. We propose a novel view of significant neural convergence of emotion and motivation, in contrast to conventional neural-based frameworks emphasizing segregation. Evidence from diverse research areas in emotion and motivation was reviewed, pinpointing key neural regions of overlap. The findings support important neural sharing between emotion and motivation, suggesting that these two functions are tightly intertwined with one another in the brain. Neural overlap does not necessarily imply continuous functional overlap. Even if identical brain regions/systems are activated for motivation and emotion, this activation may involve distinct and unique patterns of connection and information flow as the network shifts functionality. This review highlights the crucial importance of further research to explicate the patterns and modes of responding of these overlapping systems.
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Emociones , Motivación , Encéfalo , Mapeo Encefálico , HumanosRESUMEN
We present 'UBO Detector', a cluster-based, fully automated pipeline for extracting and calculating variables for regions of white matter hyperintensities (WMH) (available for download at https://cheba.unsw.edu.au/group/neuroimaging-pipeline). It takes T1-weighted and fluid attenuated inversion recovery (FLAIR) scans as input, and SPM12 and FSL functions are utilised for pre-processing. The candidate clusters are then generated by FMRIB's Automated Segmentation Tool (FAST). A supervised machine learning algorithm, k-nearest neighbor (k-NN), is applied to determine whether the candidate clusters are WMH or non-WMH. UBO Detector generates both image and text (volumes and the number of WMH clusters) outputs for whole brain, periventricular, deep, and lobar WMH, as well as WMH in arterial territories. The computation time for each brain is approximately 15â¯min. We validated the performance of UBO Detector by showing a) high segmentation (similarity index (SI)â¯=â¯0.848) and volumetric (intraclass correlation coefficient (ICC)â¯=â¯0.985) agreement between the UBO Detector-derived and manually traced WMH; b) highly correlated (r2â¯>â¯0.9) and a steady increase of WMH volumes over time; and c) significant associations of periventricular (tâ¯=â¯22.591, pâ¯<â¯0.001) and deep (tâ¯=â¯14.523, pâ¯<â¯0.001) WMH volumes generated by UBO Detector with Fazekas rating scores. With parallel computing enabled in UBO Detector, the processing can take advantage of multi-core CPU's that are commonly available on workstations. In conclusion, UBO Detector is a reliable, efficient and fully automated WMH segmentation pipeline.
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Encéfalo/diagnóstico por imagen , Encéfalo/patología , Procesamiento de Imagen Asistido por Computador/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Anciano , Algoritmos , Análisis por Conglomerados , Estudios Transversales , Femenino , Humanos , Aprendizaje Automático , Imagen por Resonancia Magnética/métodos , Masculino , Programas InformáticosRESUMEN
Incidental findings on structural cerebral magnetic resonance imaging (MRI) are common in healthy subjects, and the prevalence increases with age. There is a paucity of data regarding incidental cerebral findings in twins. We examined brain MRI data acquired from community-dwelling older twins to determine the prevalence and concordance of incidental cerebral findings, as well as the associated clinical implications. Participants (n = 400) were drawn from the Older Australian Twins Study. T1-weighted and T2-weighted fluid-attenuated inversion recovery (FLAIR) cerebral MRI scans were systematically reviewed by a trained, blinded clinician. Incidental findings were recorded according to pre-determined categories, and the diagnosis confirmed by an experienced neuroradiologist. Periventricular and deep white matter hyperintensities (WMH) were scored visually. WMH heritability was calculated for those with the twin pair included in the study (n = 320 individuals; monozygotic (MZ) = 92 twin pairs, dizygotic (DZ) = 68 twin pairs). Excluding infarcts and WMH, a total of 47 (11.75%) incidental abnormalities were detected. The most common findings were hyperostosis frontalis interna (8 participants; 2%), meningiomas, (6 participants; 1.5%), and intracranial lipomas (5 participants; 1.25%). Only 3% of participants were referred for follow-up. Four twin pairs, all monozygotic, had lesions concordant with their twin. Periventricular WMH was moderately heritable (0.61, CI 0.43-0.75, p = 7.21E-08) and deep WMH highly heritable (0.80, CI 0.66-0.88, p = 1.76E-13). As in the general population, incidental findings on cerebral MRI in older twins are common, although concordance rates are low. Such findings can alter the clinical outcome of participants, and should be anticipated by researchers when designing trials involving cerebral imaging.
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Encefalopatías/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Hallazgos Incidentales , Imagen por Resonancia Magnética , Anciano , Australia , Encefalopatías/epidemiología , Encefalopatías/genética , Encefalopatías/terapia , Femenino , Humanos , Estudios Longitudinales , Masculino , Derivación y Consulta , Gemelos Dicigóticos , Gemelos MonocigóticosRESUMEN
PURPOSE OF REVIEW: Alzheimer's disease and cerebrovascular disease (CVD) commonly co-occur. Whether CVD promotes the progression of Alzheimer's disease pathology remains a source of great interest. Recent technological developments have enabled us to examine their inter-relationship using quantifiable, biomarker-based approaches. We provide an overview of advances in understanding the relationship between vascular and Alzheimer's disease pathologies, with particular emphasis on ß-amyloid and tau as measured by positron emission tomography and cerebrospinal fluid (CSF) concentration, and magnetic resonance imaging markers of small vessel disease (SVD). RECENT FINDINGS: The relationship between cerebral ß-amyloid and various markers of SVD has been widely studied, albeit with somewhat mixed results. Significant associations have been elucidated, particularly between ß-amyloid burden and white matter hyperintensities (WMH), as well as lobar cerebral microbleeds (CMB), with additive effects on cognition. There is preliminary evidence for an association between SVD and tau burden in vivo, although compared with ß-amyloid, fewer studies have examined this relationship. SUMMARY: The overlap between Alzheimer's disease and cerebrovascular pathologies is now being increasingly supported by imaging and CSF biomarkers, indicating a synergistic effect of these co-pathologies on cognition. The association of WMH and CMB with Alzheimer's disease pathology does not establish direction of causality, for which long-term longitudinal studies are needed.
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Enfermedad de Alzheimer/patología , Trastornos Cerebrovasculares/patología , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/metabolismo , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/metabolismo , Encéfalo/patología , Trastornos Cerebrovasculares/líquido cefalorraquídeo , Trastornos Cerebrovasculares/metabolismo , Cognición/fisiología , Trastornos del Conocimiento/etiología , Comorbilidad , Progresión de la Enfermedad , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Sustancia Blanca/patología , Proteínas tau/líquido cefalorraquídeo , Proteínas tau/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to evaluate the effectiveness of a 6-week mindfulness-based stress release program (SRP) on stress and work engagement in fulltime university employees. METHODS: Perceived stress, workplace wellbeing, and engagement were measured at baseline and within 1 week of the SRP completion, and contemporaneously 6 weeks apart for a waitlist control group. A second program was implemented to examine reproducibility of results. RESULTS: Fifty participants undertook the SRPs, and 29 participants were waitlisted. A significant improvement in distress, workplace wellbeing, and vigor was observed within the first SRP group, when compared with the control group. The improvement in distress and wellbeing was reproduced in the second SRP group. CONCLUSIONS: This study adds to the growing body of research that mindfulness may be an effective method for reducing workplace stress, improving employee wellbeing, and enhancing work engagement.