White coat hypertension is associated with increased small vessel disease in the brain

Objective: Small vessel disease, as measured by white matter hyperintensity (WMH) in the brain, is known to be associated with increased stroke risk and cognitive impairment. This study explored the relationship between WMH on computerised tomography (CT) and white coat hypertension/effect (WCH/E) in patients with recent transient ischaemic attack (TIA) or lacunar stroke (LS). Design and method: Ninety-six patients recruited for the ASIST trial (Arterial Stiffness in Lacunar Stroke and TIA) underwent measurement of clinic blood pressure (BP) and ambulatory BP monitoring (APBM) within two weeks of TIA or LS. Twenty-three patients had normotension (clinic BP / = 140/90mmHg and day-time ABPM < 135/85mmHg). Arterial stiffness was measured using carotid-femoral pulse wave velocity (PWV) (Complior®, ALAM Medical) and carotid-ankle vascular index (CAVI) (VaSera VS-1500N®, Fukuda Denshi). CT images were scored for WMH using the four-point Fazekas visual rating scale. Patients were grouped into no-mild WMH (scores 0–1) or moderate-severe (scores 2–3) groups. The relationship between BP, vascular stiffness and WMH was explored with t-tests, chi-square and logistic regression accounting for known cardiovascular risk factors. Results: Forty-four percent of patients with WCH/E had moderate-severe WMH compared to 17% of normotensives (p = 0.047). The regression model with WMH as the dependent factor, and WCH/E and cardiovascular risk factors as independent factors showed WCH/E and either CAVI or PWV to be the only independent significant factor contributing to WMH (CAVI:p = 0.038, PWV:p = 0.043)

P104 White coat hypertension is associated with increased small vessel disease in the brain

Objective: Small vessel disease, measured by brain white matter hyperintensity (WMH), is associated with increased stroke risk and cognitive impairment. This study aimed to explore the relationship between WMH on computerised tomography (CT) and white coat hypertension (WCH) in patients with recent transient ischaemic attack (TIA) or lacunar stroke (LS). Methods: Ninety-six patients recruited for the ASIST trial (Arterial Stiffness in Lacunar Stroke and TIA) underwent measurement of clinic blood pressure (BP) and ambulatory BP monitoring (APBM) within two weeks of TIA or LS. Patients were grouped by BP phenotypes. Twenty-three patients had normotension (clinic BP 140/90 mmHg and day-time ABPM <135/85 mmHg). CT brain images were scored for WMH using the four-point Fazekas visual rating scale. Patients were grouped into no-mild WMH (scores 0–1) or moderate-severe (scores 2–3) groups. The relationship between BP and WMH was explored with chi-square and logistic regression accounting for known cardiovascular risk factors (age, gender, smoking, diabetes and hyperlipidaemia). Results: 44% of WCH patients had moderate-severe WMH compared to 17% of normotensives (p = 0.047). Logistical regression incorporating WCH as the independent factor and cardiovascular risk factors as independent variables showed WCH to be the only independent significant factor contributing to WMH (p = 0.024). Conclusion: Patients with WCH were more likely to have moderate-severe WMH on CT brain than normotensives. WCH was associated with increased WMH, independent of other cardiovascular risk factors. This study suggests that WCH is associated with increased small vessel disease in the brain and may benefit from treatment

C-reactive protein predicts further ischemic events in patients with transient ischemic attack or lacunar stroke

Patients who have experienced a first cerebral ischemic event are at increased risk of recurrent stroke. There is strong evidence that low-level inflammation as measured by high sensitivity C-reactive protein (hs-CRP) is a predictor of further ischemic events. Other mechanisms implicated in the pathogenesis of stroke may play a role in determining the risk of secondary events, including oxidative stress and the adaptive response to it and activation of neuroprotective pathways by hypoxia, for instance through induction of erythropoietin (EPO). This study investigated the association of the levels of CRP, peroxiredoxin 1 (PRDX1, an indicator of the physiological response to oxidative stress) and EPO (a neuroprotective factor produced in response to hypoxia) with the risk of a second ischemic event. Eighty patients with a diagnosis of lacunar stroke or transient ischemic attack (TIA) were included in the study and a blood sample was collected within 14 days from the initial event. Hs-CRP, PRDX1 and EPO were measured by ELISA. Further ischemic events were recorded with a mean follow-up of 42 months (min 24, max 64). Multivariate analysis showed that only CRP was an independent predictor of further events with an observed risk (OR) of 1.14 (P = 0.034, 95% CI 1.01-1.29). No association was observed with the levels of PRDX1 or EPO. A receiver operating curve (ROC) determined a cut-off CRP level of 3.25 μg/ml, with a 46% sensitivity and 81% specificity. Low-level inflammation as detected by hs-CRP is an independent predictor of recurrent cerebrovascular ischemic events

Q351R MAPT mutation is associated with a mixed 3R/4R tauopathy and a slowly progressive cognitive, behavioural and parkinsonian syndrome

Alzheimer's Research UK; Alzheimer's Society; Brain Research UK; The Wolfson Foundation; UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK; Miriam Marks Brain Research UK Senior Fellowship; MRC Clinician Scientist Fellowship (MR/M008525/1); NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH); Alzheimer’s Society and by the NIHR UCLH Biomedical Research Centre; NIHR UCL/H Biomedical Research Centre; UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK

Las áreas marinas protegidas como asunto de política internacional: el escenario de la Comisión para la Conservación de los Recursos Vivos Marinos Antárticos

In 2016, the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) created a Marine Protected Area (MPA) in the Ross Sea. The purpose of this article is to know the United Kingdom, the United States and New Zealand stance on this decision, regarding the impacts global warming on the Antarctic geopolitics and the discussions on the establishment of new MPAs in the CCAMLR’s scope. A qualitative methodology was used for this purpose through an inductive approach. Documents and materials published by the CCAMLR and by the three countries were analyzed. Everything was supplemented by performing semi-structured interviews with key actors. The paper concludes that the stance of the United Kingdom, the United States and New Zealand on the CCAMLR, when a MPA was designated in the Ross Sea, requires understanding the context of the political impact of global warming on Antarctic geopolitics and the debates to designate new MPAs. It is also necessary to consider the strategic interests of these countries in the CCAMLR’s area of application, their views on the MPA debate, the geopolitical component of their relevant strategies for marine conservation of biodiversity and, finally, the impacts of changes in international policy on existing environmental commitments.Em 2016, a Comissão para a Conservação dos Recursos Vivos Marinhos Antárticos (CCRVMA), criou uma área marinha protegida (AMP) no Mar de Ross. Este artigo tem como objetivo conhecer o posicionamento do Reino Unido, Estados Unidos e Nova Zelândia diante dessa decisão, no contexto dos efeitos do aquecimento global na geopolítica antártica, e as discussões em torno do estabelecimento de novas AMPs no campo da CCRVMA. Por isso, foi utilizada uma metodologia qualitativa sob uma perspectiva indutiva. Os documentos e materiais publicados pela CCRVMA e pelos três Estados foram analisados. Tudo isso foi complementado por entrevistas semiestruturadas realizadas com os principais atores. O artigo conclui que o comportamento do Reino Unido, Estados Unidos e Nova Zelândia na CCRVMA, quando designaram uma AMP no Mar de Ross, precisa ser entendido no contexto do efeito político do aquecimento global na geopolítica antártica e dos debates para designar novas AMPs. Além disso, é necessário levar em conta nessa situação os interesses estratégicos desses Estados na área de atuação da CCRVMA, suas percepções sobre o debate das AMPs, o componente geopolítico de suas respectivas estratégias de conservação da biodiversidade marinha e, finalmente, os efeitos das mudanças na política internacional sobre os compromissos ambientais existentes.En 2016, la Comisión para la Conservación de los Recursos Vivos Marinos Antárticos creó un área marina protegida en Mar de Ross. Este artículo tiene como objetivo conocer el posicionamiento del Reino Unido, Estados Unidos y Nueva Zelanda ante esta decisión, en el contexto de los efectos del calentamiento global en la geopolítica antártica, y las discusiones en torno del establecimiento de nuevas AMP en el ámbito de la CCRVMA. Para tal efecto, se utilizó una metodología cualitativa a través de una perspectiva inductiva. Se analizaron documentos y materiales publicados por la CCRVMA y esto tres Estados. Se consideraron también entrevistas semi-estructuradas realizadas a actores claves. El trabajo concluye que el comportamiento estos tres Estados en la CCRVMA, cuando se designó una AMP en el Mar de Ross, requiere ser comprendido en el contexto del efecto político del calentamiento global sobre la geopolítica antártica y los debates para designar nuevas AMP. También es necesario tener en cuenta en esta situación los intereses estratégicos de estos Estados, sus percepciones sobre el debate acerca de las AMP, el componente geopolítico de sus estrategias de conservación marina de la biodiversidad y, por último, los efectos en política internacional sobre los compromisos ambientales existentes

Neural markers of category-based selective working memory in aging

Working memory (WM) is essential for normal cognitive function, but shows marked decline in aging. The importance of selective attention in guiding WM performance is increasingly recognized. Studies so far are inconclusive about the ability to use selective attention during WM in aging. To investigate the neural mechanisms supporting selective attention in WM in aging, we tested a large group of older adults using functional magnetic resonance imaging whilst they performed a category-based (faces/houses) selective-WM task. Older adults were able to use attention to encode targets and suppress distractors to reach high levels of task performance. A subsequent, surprise recognition-memory task showed strong consequences of selective attention. Attended items in the relevant category were recognized significantly better than items in the ignored category. Neural measures also showed reliable markers of selective attention during WM. Purported control regions including the dorsolateral and inferior prefrontal and anterior cingulate cortex were reliably recruited for attention to both categories. Activation levels in category-sensitive visual cortex showed reliable modulation according to attentional demands, and positively correlated with subsequent memory measures of attention and WM span. Psychophysiological interaction analyses showed that activity in category-sensitive areas were coupled with non-sensory cortex known to be involved in cognitive control and memory processing, including regions in the prefrontal cortex and hippocampus. In summary, we found that older adults were able to recruit a network of brain regions involved in top-down attention during selective WM, and individual differences in attentional control corresponded to the degree of attention-related modulation in the brain

Neuroanatomy of impaired self-awareness in Alzheimer's disease and mild cognitive impairment

Introduction: Patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) may be unaware of their cognitive impairment. The neuroanatomical mechanisms underlying this symptom, termed anosognosia or impaired self-awareness, are still poorly understood. In the present study we aimed to explore the functional correlates of self-awareness in patients with MCI and AD. Methods: Fifty-one participants (17 healthy elderly, 17 patients with MCI, and 17 patients with AD), each accompanied by a study partner, took part in a functional magnetic resonance imaging (fMRI) study, in which they were presented with questions regarding themselves (Self condition) or their study partner (Other condition). The study partner was asked to complete a paper questionnaire answering the same questions so the responses of participant and study partner could be compared and "discrepancy" scores calculated for each of the 2 conditions (Self and Other). Results: Behavioural results showed that AD patients had significantly higher "Self discrepancy scores" than controls and MCI patients, whereas there were no significant differences between groups for "Other discrepancy scores" Imaging results showed a significant group-by-condition interaction in brain activation in medial prefrontal and anterior temporal regions, with AD patients showing significantly decreased activation in these regions only for the Self condition. There were no significant differences between Self and Other conditions in either control or MCI groups, suggesting that, in these groups, Self- and Other-appraisal share similar neuroanatomical substrates. Conclusions: Decreased functional activation of medial prefrontal and anterior temporal cortices is associated with impaired self-awareness in AD patients. This dysfunction, which is specific for Self- but not for Other-appraisal, may be a contributing factor to anosognosia in AD. © 2012 Elsevier Ltd

Resting functional connectivity reveals residual functional activity in Alzheimer's disease.

Functional MRI (fMRI) has great potential for unravelling mechanisms of functional decline in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI), but task-fMRI studies have produced conflicting results, partly due to failure to account for underlying morphological changes, and to variations in ability to perform the tasks. Resting-fMRI is promising because it does not require a task. We aimed to improve the understanding of how resting-fMRI relates to brain function

Resting functional connectivity reveals residual functional activity in Alzheimer's disease.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has great potential for measuring mechanisms of functional changes in Alzheimer's disease (AD) and mild cognitive impairment, but task fMRI studies have produced conflicting results, partly due to failure to account for underlying morphological changes and to variations in patients' ability to perform the tasks. Resting fMRI has potential for assessing brain function independently from a task, but greater understanding of how networks of resting functional connectivity relate to the functioning of the brain is needed. We combined resting fMRI and task fMRI to examine the correspondence between these methods in individuals with cognitive impairment. METHODS: Eighty elderly (25 control subjects, 25 mild cognitive impairment, 30 AD) underwent a combined multimodal magnetic resonance imaging protocol including task fMRI and resting fMRI. Task fMRI data were acquired during the execution of a memory paradigm designed to account for differences in task performance. Structural and physiological confounds were modeled for both fMRI modalities. RESULTS: Successful recognition was associated with increased task fMRI activation in lateral prefrontal regions in AD relative to control subjects; this overlapped with increased resting fMRI functional connectivity in the same regions. CONCLUSIONS: Our results show that task fMRI and resting fMRI are sensitive markers of residual ability over the known changes in brain morphology and cognition occurring in AD and suggest that resting fMRI has a potential to measure the effect of new treatments

Structural and functional bases of visuospatial associative memory in older adults.

Impaired visuospatial associative memory may be one of the earliest changes predicting cognitive impairment and Alzheimer's disease. We explored the relationship between performance on a visuospatial associative memory task (the Placing Test) and brain structure and function in cognitively healthy older adults. First, we performed a voxel-based morphometry correlational analysis on structural magnetic resonance imaging (MRI) data from 144 healthy older adults with their scores on the Placing Test. Second, we carried out a functional MRI study on another group of 28 healthy older adults who performed a similar task during functional MRI. Decreased performance on the Placing Test was associated with increased atrophy in medial-temporal regions. Functional activation of the same regions-controlling for the effect of atrophy-occurred during successful performance of the same task. The colocalization of structural and functional MRI correspondents of visuospatial associative test performance within medial-temporal regions validates multimodal imaging in describing behaviorally relevant variability in the aging brain and suggests that the Placing Test has the potential for detecting early cognitive changes occurring in preclinical phases of Alzheimer's disease