Differential association of cerebral blood flow and anisocytosis in APOE ε4 carriers at midlife.

Cerebral hemodynamic alterations have been observed in apolipoprotein ε4 (APOE4) carriers at midlife, however the physiological underpinnings of this observation are poorly understood. Our goal was to investigate cerebral blood flow (CBF) and its spatial coefficient of variation (CoV) in relation to APOE4 and a measure of erythrocyte anisocytosis (red blood cell distribution width - RDW) in a middle-aged cohort. Data from 563 participants in the PREVENT-Dementia study scanned with 3 T MRI cross-sectionally were analysed. Voxel-wise and region-of-interest analyses within nine vascular regions were run to detect areas of altered perfusion. Within the vascular regions, interaction terms between APOE4 and RDW in predicting CBF were examined. Areas of hyperperfusion in APOE4 carriers were detected mainly in frontotemporal regions. The APOE4 allele differentially moderated the association between RDW and CBF, an association which was more prominent in the distal vascular territories (p - [0.01, 0.05]). The CoV was not different between the considered groups. We provide novel evidence that in midlife, RDW and CBF are differentially associated in APOE4 carriers and non-carriers. This association is consistent with a differential hemodynamic response to hematological alterations in APOE4 carriers.

Factors influencing compliance with Hepatitis C treatment in patients transitioning from prison to community-A summary scoping review.

It is well-established that prevalence of Hepatitis C (HCV) infection in prisoners is disproportionately higher than in the general population. While developments in screening and treatment for HCV have enabled greater detection and treatment in prison, release is a high-risk time for HCV infected prisoners returning to the challenges of community living. A scoping review was conducted to examine the evidence on individual, provider and system level factors that influence compliance with HCV treatment in patients transitioning from prison to community. Retrieved articles were screened and those eligible were selected for data extraction. Quantitative and qualitative studies were included. Electronic peer-reviewed databases were searched in February 2022: 140 articles were initially identified of which seven were included in the final review. Six key themes characterized the literature: education, case management and discharge planning, hepatology in-reach nurses, transition clinics, primary care providers and system wide approach. This summary scoping review highlights the paucity of research in this area. There is a need for experimental research to investigate specific interventions, and to understand HCV care-specific barriers and facilitators. A multi-pronged approach is needed to address barriers to healthcare services in general but also specific barriers relating to HCV. Factors that facilitate compliance should also be recognized and amplified across regional HCV elimination strategies.

Neuronal surface autoantibodies in dementia: a systematic review and meta-analysis.

INTRODUCTION: Neuronal antibodies can cause encephalopathy syndromes often presenting with subacute cognitive impairment, sometimes resembling neurodegenerative dementias. METHODS: We searched Medline and Embase for studies reporting associations between neuronal surface antibodies in all-cause dementia versus controls. Random-effects meta-analysis was used to pool adjusted estimates across studies. RESULTS: Six studies were included, all reporting frequency of serum NMDAR antibodies in dementia with four also reporting frequency in atypical dementias. Both IgG [OR = 8.09 (1.51; 56.85), p = 0.036] and IgA/IgM NMDAR antibodies [OR = 42.48 (11.39; 158.52), p < 0.001] were associated with atypical dementia, but neither were associated with all-cause dementia. DISCUSSION: In the first meta-analysis to explore this literature, serum IgG and IgA/IgM NMDAR antibodies were significantly more common in atypical dementias. However, methodological issues and small-sample sizes necessitate caution interpreting this result. Further studies measuring both serum and CSF antibodies are needed to investigate the role of neuronal antibodies in dementia, since evidence of pathogenicity in even a subset of patients could pave the way for novel treatment options.

Hippocampal Subfield Volumes in Middle-Aged Adults at Risk of Dementia.

BACKGROUND: Alzheimer's disease (AD) begins decades before the onset of dementia. There is a need to investigate biomarkers of early AD for use in clinical trials and to facilitate early intervention. OBJECTIVE: We aimed to determine whether changes in hippocampal subfield volumes in healthy middle-aged adults were associated with risk of future dementia. METHODS: We included 150 participants from the PREVENT-Dementia cohort, which recruited subjects aged 40-59 with or without a family history of dementia (FHD; included here were 81 with FHD and 69 without). Hippocampal subfield volumes were segmented from high resolution T2-weighted 3T MRI images taken at baseline and 2-year follow-up. RESULTS: FHD and greater 20 year-risk of dementia due to cardiovascular risk factors were both associated with lower CA1 volume. FHD was also associated with a relative increase in combined CA3, CA4, and dentate gyrus volume between baseline and follow-up. CONCLUSION: CA1 atrophy may commence as early as middle-age in those with a high risk of future dementia, while increases in CA3, CA4, and dentate gyrus volume may be a response to early AD in the form of inflammation or neurogenesis.

Hydrocephalus as the first presenting symptom of neurosarcoidosis in two patients: a diagnosis more forthcoming in the context of systemic disease.

Sarcoidosis is a multisystem disorder, characterised histologically by the presence of non-caseating epithelioid granulomas with exclusion of other granulomatous diseases. While the lungs and lymph nodes are affected in 90%, approximately 5% of patients have neurological involvement. The clinical manifestations of neurosarcoidosis (NS) are diverse, making diagnosis especially difficult in patients without known systemic disease. Hydrocephalus occurs in only 9% of patients with NS and although uncommon, is an important manifestation because it is associated with high morbidity and mortality. We report two cases of NS presenting with hydrocephalus, one as the first presentation of sarcoidosis and one in a patient with known multisystem sarcoidosis. The patient without systemic sarcoidosis posed the greater diagnostic challenge and followed a protracted course with multiple surgical interventions, progression of central nervous system inflammation and significant physical disability.

Dementia risk assessment and risk reduction using cardiovascular risk factors.

Given the poor efficacy of disease modifying treatments and evidence that Alzheimer's Disease (AD) pathophysiology begins in middle-age, efforts to reduce the substantial disease burden have shifted towards preventative intervention in midlife. Up to a third of all AD (the commonest cause of dementia) is attributable to modifiable cardiovascular risk factors. A tool for predicting risk of future dementia using only cardiovascular risk factors has been validated and the effect of lifestyle modification on future cognitive decline is under investigation. In the UK, the QRISK3 risk calculator is used to quantify 10-year risk of cardiovascular disease. Lifestyle changes and lipid modifying therapy are recommended to patients based on their risk score. We will compare the emerging evidence for dementia risk assessment and risk reduction using cardiovascular risk factors with the evidence used to support the implementation of QRISK3 for cardiovascular disease risk assessment and intervention. This will guide future research to determine whether cardiovascular risk assessment can also be used to inform patients of risk of future dementia and advise on risk reduction strategies, in a primary care setting.

A Review of the Epidemiology of Major Depressive Disorder and of its consequences for Society and the individual.

Depression is a common and debilitating disease that affects people from adolescence to old age. The impact of depression extends beyond the individual with depressive symptoms. Depression adversely affects the mental and physical health, and the social and financial welfare of the individual and society. We will address how factors including sex, age, ethnicity and societal changes affect the prevalence of depression, consider common co-morbid conditions and highlight the lessons learned from treating depression.

Charity, Hospitality, and the Human Person.

We believe that in order to properly interpret all aspects of human scientific enquiry in terms of its impact on human beings it is necessary to have an adequate all encompassing model of the human person. We began this presentation by discussing the differences between the 'Cartesian' Dualistic model of the human Person and that of Aquinas and Augustine (which depend on Aristotle and Plato respectively). While the 'Cartesian' describes a completely separate 'soul' or 'mind' from the physical body, the Thomistic model of the Human Person is that of an Embodied Spirit, in which every aspect of the human spirit is reflected in an aspect or function of the physical body. We argued that the 'Cartesian view', in the modern age of 'Evidence Based Science' is inadequate, because the absence of evidence of a separate Mind allows the existence if this to be challenged by the application of 'Ockham's Razor', whereas the Thomistic or Augustinian view need not be so challenged, since every aspect of the human spirit is reflected in an aspect or function of the physical body. Thus we argued that the 'embodied spirit' model of the Human Person can be an appropriate model in understanding the relationship of modern neuroscience to the reality of the human person. We were able to observe numerous examples from Neuroscience, at the level of organs, neural systems and also at the molecular level in which a dualistic model was inadequate to explain experimental observations. We then related these ideas to the idea of Empathy, the neural system for which appears to be the same as the system for establishing a sense of self for the person. We argued that therefore since the Concept of Charity, that is caring for others, related to the concept of Empathy, then the same neural system existed to promote Charity, as a function of the Human Person. We used anthropological data on the confraternities of 'Our Lady of Charity' to describe how humans had, since Roman Times at least given expression to thin imperative for Charity , and took this further to show how paintings of the Roman story see Pero, who secretly breastfeeds her father, Cimon, after he is incarcerated and sentenced to death by starvation, expresses the need for Charity as a 'giving of self' to others which can be explained by the embedded of the neural network for empathy in the human brain, closely linked with the sense of self. Finally, we moved to hospitality, most easily expressed among humans by the sharing of a meal. We showed the Confraternities of 'Our Lady of Charity' used paintings of the feast of the Marriage of Cana to express hospitality and their charitable work. We took the metaphor of sharing a meal further, and suggested that in paintings of the Trinity by Andrei Rublëv and the Supper of Emmeus by Caravaggio expressed that hospitality, as in sharing a meal, can link the human person to the Transendent ... perhaps through the mediation of the Neural system which expresses both sense of self and empathy. We concluded that 'In the consultation we should treat people as embodied spirits', and that 'Treating people as an embodied spirit - demands charity, in which we give of our own embodied spirit'.