A systematic review of the prevalence of depression, anxiety, and apathy in frontotemporal dementia, atypical and young-onset Alzheimer's disease, and inherited dementia.

OBJECTIVES: Depression, anxiety, and apathy are the most commonly reported neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD). Understanding their prevalence in rarer dementias such as frontotemporal dementia (FTD), primary progressive aphasia (PPA), posterior cortical atrophy (PCA), young-onset AD (YOAD), and inherited dementias has implications for both clinical practice and research. In this study, we aimed to examine the current state of knowledge of the prevalence of these three NPS in less prevalent dementias. DESIGN: We conducted a systematic review based on searches of EMBASE, PsycINFO, and PubMed up to September 2019. RESULTS: 47 articles meeting inclusion criteria were identified. Depression, anxiety, and apathy were commonly reported across the phenotypes studied but their prevalence showed large variation between studies. Apathy showed the highest reported frequency in FTD (50-100% across studies), behavioral variant frontotemporal dementia (bvFTD) (73-100%), and YOAD (44-100%). Anxiety was frequently reported in FTD (0-100%) and bvFTD (19-63%). Depression showed the highest prevalence in FTD (7-69%) and YOAD (11-55%). Among the three variants of PPA, sv-PPA is the one most investigated (seven articles). Three or fewer articles were identified examining NPS in the remaining PPA variants, PCA, familial AD, and familial FTD. Inconsistency in the tools used to measure symptoms and small sample sizes were common methodological limitations. CONCLUSIONS: Future studies should consider the inclusion of larger sample sizes (e.g. through multicenter collaborations) and the use of harmonized protocols that include the combination of caregiver and patient-derived measures and symptom-specific questionnaires. More research is needed on the phenotype-specific barriers and facilitators for people living with dementia to successfully engage in self-reports of NPS

Topology by Design in Magnetic nano-Materials: Artificial Spin Ice

Artificial Spin Ices are two dimensional arrays of magnetic, interacting nano-structures whose geometry can be chosen at will, and whose elementary degrees of freedom can be characterized directly. They were introduced at first to study frustration in a controllable setting, to mimic the behavior of spin ice rare earth pyrochlores, but at more useful temperature and field ranges and with direct characterization, and to provide practical implementation to celebrated, exactly solvable models of statistical mechanics previously devised to gain an understanding of degenerate ensembles with residual entropy. With the evolution of nano--fabrication and of experimental protocols it is now possible to characterize the material in real-time, real-space, and to realize virtually any geometry, for direct control over the collective dynamics. This has recently opened a path toward the deliberate design of novel, exotic states, not found in natural materials, and often characterized by topological properties. Without any pretense of exhaustiveness, we will provide an introduction to the material, the early works, and then, by reporting on more recent results, we will proceed to describe the new direction, which includes the design of desired topological states and their implications to kinetics.Comment: 29 pages, 13 figures, 116 references, Book Chapte

Duffy antigen receptor for chemokines mediates chemokine endocytosis through a macropinocytosis-like process in endothelial cells

Background: The Duffy antigen receptor for chemokines (DARC) shows high affinity binding to multiple inflammatory CC and CXC chemokines and is expressed by erythrocytes and endothelial cells. Recent evidence suggests that endothelial DARC facilitates chemokine transcytosis to promote neutrophil recruitment. However, the mechanism of chemokine endocytosis by DARC remains unclear. Methodology/Principal Findings: We investigated the role of several endocytic pathways in DARC-mediated ligand internalization. Here we report that, although DARC co-localizes with caveolin-1 in endothelial cells, caveolin-1 is dispensable for DARC-mediated 125I-CXCL1 endocytosis as knockdown of caveolin-1 failed to inhibit ligand internalization. 125I-CXCL1 endocytosis by DARC was also independent of clathrin and flotillin-1 but required cholesterol and was, in part, inhibited by silencing Dynamin II expression. 125I-CXCL1 endocytosis was inhibited by amiloride, cytochalasin D, and the PKC inhibitor Gö6976 whereas Platelet Derived Growth Factor (PDGF) enhanced ligand internalization through DARC. The majority of DARC-ligand interactions occurred on the endothelial surface, with DARC identified along plasma membrane extensions with the appearance of ruffles, supporting the concept that DARC provides a high affinity scaffolding function for surface retention of chemokines on endothelial cells. Conclusions/Significance: These results show DARC-mediated chemokine endocytosis occurs through a macropinocytosis-like process in endothelial cells and caveolin-1 is dispensable for CXCL1 internalization. © 2011 Zhao et al

A cross-sectional study of memory and executive functions in patients with sporadic inclusion body myositis

INTRODUCTION: Sporadic inclusion body myositis (IBM) is a degenerative and inflammatory acquired myopathy characterised by muscle deposition of various proteins typically associated with Alzheimer's disease and other neurodegenerative diseases. While cognitive impairment is not noted as a clinical feature of IBM, evidence is lacking. We aimed to investigate whether cognitive performance of patients with IBM differs from population norms, focussing on cognitive domains affected in early Alzheimer's disease (memory, executive function), and to test whether disease duration and the level of disability of IBM are associated with cognitive function. METHODS: Twenty-four patients with IBM (mean [SD] age 62.0 [7.2] years; disease duration 9.6 [4.8] years) were assessed cross-sectionally on neuropsychological tests covering multiple cognitive domains, including the Preclinical Alzheimer Cognitive Composite (PACC). Performance was compared to published normative data adjusted for age, sex and education (National Alzheimer's Coordinating Center; N = 3268). Associations were examined between PACC score, disease duration and level of disability (assessed using the IBM Functional Rating Scale [IBMFRS]). RESULTS: Across all cognitive tests, group performance was within ±1SD of the normative mean. There was no evidence of associations between PACC score and either disease duration (ρ = -0.04, p = 0.87) or IBMFRS total score (ρ = 0.14, p = 0.52). DISCUSSION: Memory and executive function in patients with IBM did not differ from normative data, and we observed no evidence of associations between the cognitive composite and disease duration or level of disability. This addresses a question frequently asked by patients, and will be of value for clinicians and patients alike. This article is protected by copyright. All rights reserved

Cervical lymph node metastasis in high-grade transformation of head and neck adenoid cystic carcinoma: a collective international review

Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation

Biology and conservation of freshwater bivalves : past, present and future perspectives

Freshwater bivalves have been highly threatened by human activities, and recently their global decline has been causing conservational and social concern. In this paper, we review the most important research events in freshwater bivalve biology calling attention to the main scientific achievements. A great bias exists in the research effort, with much more information available for bivalve species belonging to the Unionida in comparison to other groups. The same is true for the origin of these studies, since the publishing pattern does not always correspond to the hotspots of biodiversity but is concentrated in the northern hemisphere mainly in North America, Europe and Russia, with regions such as Africa and Southeast Asia being quite understudied. We also summarize information about past, present and future perspectives concerning the most important research topics that include taxonomy, systematics, anatomy, physiology, ecology and conservation of freshwater bivalves. Finally, we introduce the articles published in this Hydrobiologia special issue related with the International Meeting on Biology and Conservation of Freshwater Bivalves held in 2012 in Braganc¸a, Portugal.We would like to express our gratitude to our sponsors and institutions, especially to the Polytechnic Institute of Braganca for all the logistic support. We acknowledge all keynote speakers, authors, session chairpersons and especially to all attendees whose contributions were fundamental for the success of this meeting. We would also like to thank all referees of this special issue and to Koen Martens, Editor-in-Chief of Hydrobiologia, for all the valuable comments and suggestions. The chronogram was built with the help of the expert opinion of fellow colleagues Rafael Araujo, Arthur Bogan, Kevin Cummings, Dan Graf, Wendell Haag, Karl-Otto Nagel and David Strayer to whom we are very grateful. The authors acknowledge the support provided by Portuguese Foundation for Science and Technology (FCT) and COMPETE funds-projects CONBI (Contract: PTDC/AAC-AMB/117688/2010) and ECO-IAS (Contract: PTDC/AAC-AMB/116685/2010), and by the European Regional Development Fund (ERDF) through the COMPETE, under the project "PEst-C/MAR/LA0015/2011"

Views and Perceptions of Amyloid Imaging in a Preclinical Alzheimer’s Disease Trial

BackgroundMany cognitively unimpaired older adults are interested in learning their Alzheimer's disease (AD) biomarker status, but little is known about motivations to undergo biomarker testing and result disclosure in the setting of preclinical AD trials.ObjectivesExamine whether motivations to undergo AD biomarker testing and disclosure differ for individuals who have elevated amyloid compared to those with not elevated amyloid, and whether disclosure of amyloid results impacts participants' motivations.Design, setting, participantsWe conducted post-hoc analyses using data from the EARLY study, a preclinical AD trial of the beta-secretase inhibitor atabecestat. As part of the screening process of the trial, participants underwent biomarker testing and disclosure. We analyzed data from n=2241 participants.MeasurementsWe analyzed data from the Views and Perceptions of Amyloid Imaging (VPAI), a 9-item questionnaire assessing how strongly participants agreed with motivating factors for undergoing amyloid testing. The VPAI was administered at the first screening visit and again after amyloid disclosure.ResultsPrior to amyloid disclosure, a greater proportion of participants in the elevated amyloid group responded at the two highest levels of endorsement for the items, "to confirm the feeling that I might already be developing symptoms of AD dementia" (p<0.001) and "to prepare my family for my possible illness in the future" (p=0.008), compared to participants in the not elevated amyloid group. Following disclosure, the not elevated amyloid group had higher odds of positive change in categorical VPAI item level scores for the items "to put mind at ease" (OR: 0.54; p<0.001), "to confirm the feeling that I might already be developing symptoms of AD dementia" (OR: 0.79; p=0.049), and "to prepare my family for my possible illness in the future" (OR: 0.67; p=<0.001), while the elevated amyloid group had higher odds of positive change for the item "curiosity" (OR:1.32; p=0.014).ConclusionsInvestigators might consider adjusting recruitment strategies for future trials to align with the motivations to undergo biomarker testing and disclosure most strongly endorsed by participants with elevated amyloid

Spatiotemporal scaling of North American continental interior wetlands: implications for shorebird conservation

Within interior North America, erratic weather patterns and heterogeneous wetland complexes cause wide spatio-temporal variation in the resources available to migrating shorebirds. Identifying the pattern-generating components of landscape-level resources and the scales at which shorebirds respond to these patterns will better facilitate conservation efforts for these species. We constructed descriptive models that identified weather variables associated with creating the spatio-temporal patterns of shorebird habitat in ten landscapes in north-central Oklahoma. We developed a metric capable of measuring the dynamic composition and configuration of shorebird habitat in the region and used field data to empirically estimate the spatial scale at which shorebirds respond to the amount and configuration of habitat. Precipitation, temperature, solar radiation and wind speed best explained the incidence of wetland habitat, but relationships varied among wetland types. Shorebird occurrence patterns were best explained by habitat density estimates at a 1.5 km scale. This model correctly classified 86 % of shorebird observations. At this scale, when habitat density was low, shorebirds occurred in 5 % of surveyed habitat patches but occurrence reached 60 % when habitat density was high. Our results suggest scale dependence in the habitat-use patterns of migratory shorebirds. We discuss potential implications of our results and how integrating this information into conservation efforts may improve conservation strategies and management practices

Cognition at age 70: Life course predictors and associations with brain pathologies

Objective: To investigate predictors of performance on a range of cognitive measures including the Preclinical Alzheimer Cognitive Composite (PACC) and test for associations between cognition and dementia biomarkers in Insight 46, a substudy of the Medical Research Council National Survey of Health and Development. // Methods: A total of 502 individuals born in the same week in 1946 underwent cognitive assessment at age 69–71 years, including an adapted version of the PACC and a test of nonverbal reasoning. Performance was characterized with respect to sex, childhood cognitive ability, education, and socioeconomic position (SEP). In a subsample of 406 cognitively normal participants, associations were investigated between cognition and β-amyloid (Aβ) positivity (determined from Aβ-PET imaging), whole brain volumes, white matter hyperintensity volumes (WMHV), and APOE ε4. // Results: Childhood cognitive ability was strongly associated with cognitive scores including the PACC more than 60 years later, and there were independent effects of education and SEP. Sex differences were observed on every PACC subtest. In cognitively normal participants, Aβ positivity and WMHV were independently associated with lower PACC scores, and Aβ positivity was associated with poorer nonverbal reasoning. Aβ positivity and WMHV were not associated with sex, childhood cognitive ability, education, or SEP. Normative data for 339 cognitively normal Aβ-negative participants are provided. // Conclusions: This study adds to emerging evidence that subtle cognitive differences associated with Aβ deposition are detectable in older adults, at an age when dementia prevalence is very low. The independent associations of childhood cognitive ability, education, and SEP with cognitive performance at age 70 have implications for interpretation of cognitive data in later life