Peak Width of Skeletonized Mean Diffusivity as a Marker of Diffuse Cerebrovascular Damage.

The peak width of skeletonized mean diffusivity (PSMD) has been proposed as a fully automated imaging marker of relevance to cerebral small vessel disease (SVD). We assessed PSMD in relation to conventional SVD markers, global measures of neurodegeneration, and cognition. 145 participants underwent 3T brain MRI and cognitive assessment. 112 were patients with mild cognitive impairment, Alzheimer's disease, progressive supranuclear palsy, dementia with Lewy bodies, or frontotemporal dementia. PSMD, SVD burden [white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), microbleeds, lacunes], average mean diffusivity (MD), gray matter (GM), white matter (WM), and total intracranial volume were quantified. Robust linear regression was conducted to examine associations between variables. Dominance analysis assessed the relative importance of markers in predicting various outcomes. Regional analyses examined spatial overlap between PSMD and WMH. PSMD was associated with global and regional SVD measures, especially WMH and microbleeds. Dominance analysis demonstrated that among SVD markers, WMH was the strongest predictor of PSMD. Furthermore, PSMD was more closely associated to WMH than with GM and WM volumes. PSMD was associated with WMH across all regions, and correlations were not significantly stronger in corresponding regions (e.g., frontal PSMD and frontal WMH) compared to non-corresponding regions. PSMD outperformed all four conventional SVD markers and MD in predicting cognition, but was comparable to GM and WM volumes. PSMD was robustly associated with established SVD markers. This new measure appears to be a marker of diffuse brain injury, largely due to vascular pathology, and may be a useful and convenient metric of overall cerebrovascular burden

Efficient and effective assessment of deficits and their neural bases in stroke aphasia

ObjectiveMulti-assessment batteries are necessary for diagnosing and quantifying the multifaceted deficits observed post-stroke. Extensive batteries are thorough but impractically long for clinical settings or large-scale research studies. Clinically-targeted “shallow” batteries superficially cover a wide range of language skills relatively quickly but can struggle to identify mild deficits or quantify the impairment level. Our aim was to compare these batteries across a large group of chronic stroke aphasia and to test a novel data-driven reduced version of an extensive battery that maintained sensitivity to mild impairment, ability to grade deficits and the underlying component structure.MethodsWe tested 75 chronic left-sided stroke participants, spanning global to mild aphasia. The underlying structure of these three batteries was analysed using cross-validation and principal component analysis, in addition to univariate and multivariate lesion-symptom mapping.ResultsThis revealed a four-factor solution for the extensive and data-reduced batteries, identifying phonology, semantic skills, fluency and executive function in contrast to a two-factor solution using the shallow battery (language severity and cognitive severity). Lesion symptom mapping using participants’ factor scores identified convergent neural structures for phonology (superior temporal gyrus), semantics (inferior temporal gyrus), speech fluency (precentral gyrus) and executive function (lateral occipitotemporal cortex). The two shallow battery components converged with the phonology and executive function clusters. In addition, we show that multivariate models could predict the component scores using neural data, however not for every component.ConclusionsOverall, the data-driven battery appears to be an effective way to save time yet retain maintained sensitivity to mild impairment, ability to grade deficits and the underlying component structure observed in post-stroke aphasia

In vivo neuroinflammation and cerebral small vessel disease in mild cognitive impairment and Alzheimer’s disease

Introduction: Associations between cerebral small vessel disease (SVD) and inflammation have been largely examined using peripheral blood markers of inflammation, with few studies measuring inflammation within the brain. We investigated the cross-sectional relationship between SVD and in vivo neuroinflammation using [11C]PK11195 positron emission tomography (PET) imaging. Methods: Forty-two participants were recruited (according to NIA-AA guidelines, 14 healthy controls, 14 mild Alzheimer’s disease, 14 amyloid-positive mild cognitive impairment). Neuroinflammation was assessed using [11C]PK11195 PET imaging, a marker of microglial activation. To quantify SVD, we assessed white matter hyperintensities (WMH), enlarged perivascular spaces, cerebral microbleeds and lacunes. Composite scores were calculated for global SVD burden, and SVD subtypes of hypertensive arteriopathy and cerebral amyloid angiopathy (CAA). General linear models examined associations between SVD and [11C]PK11195, adjusting for sex, age, education, cognition, scan interval, and corrected for multiple comparisons via false discovery rate (FDR). Dominance analysis directly compared the relative importance of hypertensive arteriopathy and CAA scores as predictors of [11C]PK11195. Results: Global [11C]PK11195 binding was associated with SVD markers, particularly in regions typical of hypertensive arteriopathy: deep microbleeds (β=0.63, F(1,35)=35.24, p<0.001), deep WMH (β=0.59, t=4.91, p<0.001). In dominance analysis, hypertensive arteriopathy score outperformed CAA in predicting [11C]PK11195 binding globally and in 28 out of 37 regions of interest, especially the medial temporal lobe (β=0.66–0.76, t=3.90–5.58, FDR-corrected p (pFDR)=<0.001–0.002) and orbitofrontal cortex (β=0.51–0.57, t=3.53–4.30, pFDR=0.001–0.004). Conclusion: Microglial activation is associated with SVD, particularly with the hypertensive arteriopathy subtype of SVD. Although further research is needed to determine causality, our study suggests that targeting neuroinflammation might represent a novel therapeutic strategy for SVD

Auditory beat perception is related to speech output fluency in post-stroke aphasia

Aphasia affects at least one third of stroke survivors, and there is increasing awareness that more fundamental deficits in auditory processing might contribute to impaired language performance in such individuals. We performed a comprehensive battery of psychoacoustic tasks assessing the perception of tone pairs and sequences across the domains of pitch, rhythm and timbre in 17 individuals with post-stroke aphasia and 17 controls. At the level of individual differences we demonstrated a correlation between metrical pattern (beat) perception and speech output fluency with strong effect (Spearman’s rho = 0.72). This dissociated from more basic auditory timing perception, which did not correlate with output fluency. This was also specific in terms of the language and cognitive measures, amongst which phonological, semantic and executive function did not correlate with beat detection. We interpret the data in terms of a requirement for the analysis of the metrical structure of sound to construct fluent output, with both being a function of higher-order “temporal scaffolding”. The beat perception task herein allows measurement of timing analysis without any need to account for motor output deficit, and could be a potential clinical tool to examine this. This work suggests strategies to improve fluency after stroke by training in metrical pattern perception

Comparing short and long batteries to assess deficits and their neural bases in stroke aphasia

Multiple language assessments are necessary for diagnosing, characterising and quantifying the multifaceted deficits observed in many patients’ post-stroke. Current language batteries, however, tend to be an imperfect trade-off between time and sensitivity of assessment. There have hitherto been two main types of battery. Extensive batteries provide thorough information but are impractically long for application in clinical settings or large-scale research studies. Clinically-targeted batteries tend to provide superficial information about a large number of language skills in a relatively short period of time by reducing the depth of each test but, consequently, can struggle to identify mild deficits, qualify the level of each impairment or reveal the underlying component structure. In the current study, we compared these batteries across a large group of individuals with chronic stroke aphasia to determine their utility. In addition, we developed a data-driven reduced version of an extensive battery that maintained sensitivity to mild impairment, ability to grade deficits and the component structure. The underlying structure of these three language batteries (extensive, shallow and data-reduced) was analysed using cross-validation analysis and principal component analysis. This revealed a four-factor solution for the extensive and data-reduced batteries, identifying phonology, semantic skills, fluency and executive function in contrast to a two-factor solution using the shallow battery (phonological/language severity and cognitive severity). Lesion symptom mapping using participants’ factor scores identified convergent neural structures based on existing language models for phonology (superior temporal gyrus), semantics (inferior temporal gyrus), speech fluency (precentral gyrus) and executive function (lateral occipitotemporal cortex) based on the extensive and data-reduced batteries. The two components in the shallow battery converged with the phonology and executive function clusters. In addition, we show that multivariate prediction models could be utilised to predict the component scores using neural data, however not for every component score within every test battery. Overall, the data-reduced battery appears to be an effective way to save assessment time yet retain the underlying structure of language and cognitive deficits observed in post stroke aphasia

Report on the 2013 Rapid Assessment Survey of Marine Species at New England Bays and Harbors

Introduced species (i.e., non-native species that have become established in a new location) have increasingly been recognized as a concern as they have become more prevalent in marine and terrestrial environments (Mooney and Cleland 2001; Simberloff et al. 2005). The ability of introduced species to alter population, community, and ecosystem structure and function, as well as cause significant economic damage is well documented (Carlton 1989, 1996b, 2000; Cohen and Carlton 1995; Cohen et al. 1995; Elton 1958; Meinesz et al. 1993; Occhipinti-Ambrogi and Sheppard 2007; Pimentel et al. 2005; Thresher 2000). The annual economic costs incurred from managing the approximately 50,000 introduced species in the United States alone are estimated to be over $120 billion (Pimentel et al. 2005). Having a monitoring network in place to track new introductions and distributional changes of introduced species is critical for effective management, as these efforts may be more successful when species are detected before they have the chance to become established. A rapid assessment survey is one such method for early detection of introduced species. With rapid assessment surveys, a team of taxonomic experts record and monitor marine species–providing a baseline inventory of native, introduced, and cryptogenic (i.e., unknown origin) species (as defined by Carlton 1996a)–and document range expansions of previously identified species. Since 2000, five rapid assessment surveys have been conducted in New England. These surveys focus on recording species at marinas, which often are in close proximity to transportation vectors (i.e., recreational boats). Species are collected from floating docks and piers because these structures are accessible regardless of the tidal cycle. Another reason for sampling floating docks and other floating structures is that marine introduced species are often found to be more prevalent on artificial surfaces than natural surfaces (Glasby and Connell 2001; Paulay et al. 2002). The primary objectives of these surveys are to: (1) identify native, introduced, and cryptogenic marine species, (2) expand on data collected in past surveys, (3) assess the introduction status and range extensions of documented introduced species, and (4) detect new introductions. This report presents the introduced, cryptogenic, and native species recorded during the 2013 survey

Report on the 2013: Rapid assessment survey of marine species at New England Bays and Harbors

Introduced species (i.e., non-native species that have become established in\ud a new location) have increasingly been recognized as a concern as they have\ud become more prevalent in marine and terrestrial environments (Mooney and\ud Cleland 2001; Simberloff et al. 2005). The ability of introduced species to alter\ud population, community, and ecosystem structure and function, as well as\ud cause significant economic damage is well documented (Carlton 1989, 1996b,\ud 2000; Cohen and Carlton 1995; Cohen et al. 1995; Elton 1958; Meinesz et al.\ud 1993; Occhipinti-Ambrogi and Sheppard 2007; Pimentel et al. 2005; Thresher\ud 2000). The annual economic costs incurred from managing the approximately\ud 50,000 introduced species in the United States alone are estimated to be over\ud $120 billion (Pimentel et al. 2005).\ud Having a monitoring network in place to track new introductions and\ud distributional changes of introduced species is critical for effective\ud management, as these efforts may be more successful when species are\ud detected before they have the chance to become established. A rapid\ud assessment survey is one such method for early detection of introduced\ud species. With rapid assessment surveys, a team of taxonomic experts\ud record and monitor marine species–providing a baseline inventory of\ud native, introduced, and cryptogenic (i.e., unknown origin) species (as\ud defined by Carlton 1996a)–and document range expansions of previously\ud identified species.\ud Since 2000, five rapid assessment surveys have been conducted in New\ud England. These surveys focus on recording species at marinas, which often\ud are in close proximity to transportation vectors (i.e., recreational boats).\ud Species are collected from floating docks and piers because these structures\ud are accessible regardless of the tidal cycle. Another reason for sampling floating\ud docks and other floating structures is that marine introduced species are often\ud found to be more prevalent on artificial surfaces than natural surfaces (Glasby\ud and Connell 2001; Paulay et al. 2002). The primary objectives of these surveys\ud are to: (1) identify native, introduced, and cryptogenic marine species,\ud (2) expand on data collected in past surveys, (3) assess the introduction status\ud and range extensions of documented introduced species, and (4) detect new\ud introductions. This report presents the introduced, cryptogenic, and native\ud species recorded during the 2013 survey.CZM through NOAA NA13NOS4190040MIT Sea Grant through NOAA NA10OAR4170086

CAIDE dementia risk score relates to severity and progression of cerebral small vessel disease in healthy midlife adults: the PREVENT-Dementia study.

BACKGROUND: Markers of cerebrovascular disease are common in dementia, and may be present before dementia onset. However, their clinical relevance in midlife adults at risk of future dementia remains unclear. We investigated whether the Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score was associated with markers of cerebral small vessel disease (SVD), and if it predicted future progression of SVD. We also determined its relationship to systemic inflammation, which has been additionally implicated in dementia and SVD. METHODS: Cognitively healthy midlife participants were assessed at baseline (n=185) and 2-year follow-up (n=158). To assess SVD, we quantified white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), microbleeds and lacunes. We derived composite scores of SVD burden, and subtypes of hypertensive arteriopathy and cerebral amyloid angiopathy. Inflammation was quantified using serum C-reactive protein (CRP) and fibrinogen. RESULTS: At baseline, higher CAIDE scores were associated with all markers of SVD and inflammation. Longitudinally, CAIDE scores predicted greater total (p<0.001), periventricular (p<0.001) and deep (p=0.012) WMH progression, and increased CRP (p=0.017). Assessment of individual CAIDE components suggested that markers were driven by different risk factors (WMH/EPVS: age/hypertension, lacunes/deep microbleeds: hypertension/obesity). Interaction analyses demonstrated that higher CAIDE scores amplified the effect of age on SVD, and the effect of WMH on poorer memory. CONCLUSION: Higher CAIDE scores, indicating greater risk of dementia, predicts future progression of both WMH and systemic inflammation. Findings highlight the CAIDE score's potential as both a prognostic and predictive marker in the context of cerebrovascular disease, identifying at-risk individuals who might benefit most from managing modifiable risk.Research grants from the UK Alzheimer's Society, the US Alzheimer’s Association and philanthropic donations. This work was funded by a grant for the PREVENT-Dementia programme from the UK Alzheimer’s Society (grant numbers 178 and 264), and the PREVENT-Dementia study is also supported by the US Alzheimer’s Association (grant number TriBEKa-17–519007) and philanthropic donations. AL is supported by the Lee Kuan Yew Fitzwilliam PhD Scholarship and the Tan Kah Kee Postgraduate Scholarship. JDS is a Wellcome clinical PhD fellow funded on grant 203914/Z/16/Z to the Universities of Manchester, Leeds, Newcastle and Sheffield. EM is supported by Alzheimer’s Society Junior Research Fellowship (RG 9611). LS is supported by the Cambridge NIHR Biomedical Research Centre (BRC) and Alzheimer’s Research UK (ARUK-SRF2017B-1). HSM is supported by an NIHR Senior Investigator award. JOB and HSM receive infrastructural support from the Cambridge NIHR Biomedical Research Centre (BRC). This research was supported by the NIHR Cambridge BRC (BRC-1215-20014). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

The Global Burden of Alveolar Echinococcosis

Human alveolar echinococcosis (AE), caused by the larval stage of the fox tapeworm Echinococcus multilocularis, is amongst the world's most dangerous zoonoses. Transmission to humans is by consumption of parasite eggs which are excreted in the faeces of the definitive hosts: foxes and, increasingly, dogs. Transmission can be through contact with the definitive host or indirectly through contamination of food or possibly water with parasite eggs. We made an intensive search of English, Russian, Chinese and other language databases. We targeted data which could give country specific incidence or prevalence of disease and searched for data from every country we believed to be endemic for AE. We also used data from other sources (often unpublished). From this information we were able to make an estimate of the annual global incidence of disease and disease burden using standard techniques for calculation of DALYs. Our studies suggest that AE results in a median of 18,235 cases globally with a burden of 666,433 DALYs per annum. This is the first estimate of the global burden of AE both in terms of global incidence and DALYs and demonstrates the burden of AE is comparable to several diseases in the neglected tropical disease cluster

The multidimensional nature of aphasia recovery post-stroke.

Language is not a single function, but instead results from interactions between neural representations and computations that can be damaged independently of each other. Although there is now clear evidence that the language profile in post-stroke aphasia reflects graded variations along multiple underlying dimensions ('components'), it is still entirely unknown if these distinct language components have different recovery trajectories and rely on the same, or different, neural regions during aphasia recovery. Accordingly, this study examined whether language components in the subacute stage: (i) mirror those observed in the chronic stage; (ii) recover together in a homogeneous manner; and (iii) have recovery trajectories that relate to changing activation in distinct or overlapping underlying brain regions. We analysed longitudinal data from 26 individuals with mild-moderate aphasia following left hemispheric infarct who underwent functional MRI and behavioural testing at ∼2 weeks and ∼4 months post-stroke. The language profiles in early post-stroke aphasia reflected three orthogonal principal components consisting of fluency, semantic/executive function and phonology. These components did not recover in a singular, homogeneous manner; rather, their longitudinal trajectories were uncorrelated, suggesting that aphasia recovery is heterogeneous and multidimensional. Mean regional brain activation during overt speech production in unlesioned areas was compared with patient scores on the three principal components of language at both the early and late time points. In addition, the change in brain activation over time was compared with the change on each of the principal component scores, both before and after controlling for baseline scores. We found that different language components were associated with changing activation in multiple, non-overlapping bilateral brain regions during aphasia recovery. Specifically, fluency recovery was associated with increasing activation in bilateral middle frontal gyri and right temporo-occipital middle temporal gyrus; semantic/executive recovery was associated with reducing activation in bilateral anterior temporal lobes; while phonology recovery was associated with reducing activation in bilateral precentral gyri, dorso-medial frontal poles and the precuneus. Overlapping clusters in the ventromedial prefrontal cortex were positively associated with fluency recovery but negatively associated with semantic/executive and phonology recovery. This combination of detailed behavioural and functional MRI data provides novel insights into the neural basis of aphasia recovery. Because different aspects of language seem to rely on different neural regions for recovery, treatment strategies that target the same neural region in all stroke survivors with aphasia might be entirely ineffective or even impair recovery, depending on the specific language profile of each individual patient