| 1. |
- Janssen, O., et al.
(författare)
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Characteristics of subjective cognitive decline associated with amyloid positivity
- 2022
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:10, s. 1832-1845
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) epsilon 4 carriership, and neuropsychiatric symptoms with amyloid positivity. Results Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE epsilon 4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. Discussion Next to age, setting, and APOE epsilon 4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.
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| 2. |
- Wyborn, C., et al.
(författare)
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An agenda for research and action toward diverse and just futures for life on Earth
- 2021
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Ingår i: Conservation Biology. - : Wiley. - 0888-8892 .- 1523-1739. ; 35:4, s. 1086-1097
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Tidskriftsartikel (refereegranskat)abstract
- Decades of research and policy interventions on biodiversity have insufficiently addressed the dual issues of biodiversity degradation and social justice. New approaches are therefore needed. We devised a research and action agenda that calls for a collective task of revisiting biodiversity toward the goal of sustaining diverse and just futures for life on Earth. Revisiting biodiversity involves critically reflecting on past and present research, policy, and practice concerning biodiversity to inspire creative thinking about the future. The agenda was developed through a 2-year dialogue process that involved close to 300 experts from diverse disciplines and locations. This process was informed by social science insights that show biodiversity research and action is underpinned by choices about how problems are conceptualized. Recognizing knowledge, action, and ethics as inseparable, we synthesized a set of principles that help navigate the task of revisiting biodiversity. The agenda articulates 4 thematic areas for future research. First, researchers need to revisit biodiversity narratives by challenging conceptualizations that exclude diversity and entrench the separation of humans, cultures, economies, and societies from nature. Second, researchers should focus on the relationships between the Anthropocene, biodiversity, and culture by considering humanity and biodiversity as tied together in specific contexts. Third, researchers should focus on nature and economies by better accounting for the interacting structures of economic and financial systems as core drivers of biodiversity loss. Finally, researchers should enable transformative biodiversity research and action by reconfiguring relationships between human and nonhuman communities in and through science, policy, and practice. Revisiting biodiversity necessitates a renewed focus on dialogue among biodiversity communities and beyond that critically reflects on the past to channel research and action toward fostering just and diverse futures for human and nonhuman life on Earth.
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| 3. |
- Fauria, K., et al.
(författare)
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Exploring cognitive and biological correlates of sleep quality and their potential links with Alzheimer's disease (ALFASleep project): protocol for an observational study
- 2022
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The growing worldwide prevalence of Alzheimer's disease (AD) and the lack of effective treatments pose a dire medical challenge. Sleep disruption is also prevalent in the ageing population and is increasingly recognised as a risk factor and an early sign of AD. The ALFASleep project aims to characterise sleep with subjective and objective measurements in cognitively unimpaired middle/late middle-aged adults at increased risk of AD who are phenotyped with fluid and neuroimaging AD biomarkers. This will contribute to a better understanding of the pathophysiological mechanisms linking sleep with AD, thereby paving the way for the development of non-invasive biomarkers and preventive strategies targeting sleep. METHODS AND ANALYSIS: We will invite 200 participants enrolled in the ALFA+ (for ALzheimer and FAmilies) prospective observational study to join the ALFASleep study. ALFA+ participants are cognitively unimpaired middle-aged/late middle-aged adults who are followed up every 3years with a comprehensive set of evaluations including neuropsychological tests, blood and cerebrospinal fluid (CSF) sampling, and MRI and positron emission tomography acquisition. ALFASleep participants will be additionally characterised with actigraphy and CSF-orexin-A measurements, and a subset (n=90) will undergo overnight polysomnography. We will test associations of sleep measurements and CSF-orexin-A with fluid biomarkers of AD and glial activation, neuroimaging outcomes and cognitive performance. In case we found any associations, we will test whether changes in AD and/or glial activation markers mediate the association between sleep and neuroimaging or cognitive outcomes and whether sleep mediates associations between CSF-orexin-A and AD biomarkers. ETHICS AND DISSEMINATION: The ALFASleep study protocol has been approved by the independent Ethics Committee Parc de Salut Mar, Barcelona (2018/8207/I). All participants have signed a written informed consent before their inclusion (approved by the same ethics committee). Study findings will be presented at national and international conferences and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04932473.
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| 4. |
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| 5. |
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| 6. |
- Falgas, N., et al.
(författare)
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Contribution of CSF biomarkers to early-onset Alzheimer's disease and frontotemporal dementia neuroimaging signatures
- 2020
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 41:8, s. 2004-2013
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Tidskriftsartikel (refereegranskat)abstract
- Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early‐onset AD (EOAD) and FTLD structural alterations and CSF biomarker levels. We included 138 subjects (64 EOAD, 26 FTLD, and 48 controls), all of them with a 3T MRI brain scan and CSF biomarkers available (the 42 amino acid‐long form of the amyloid‐beta protein [Aβ42], total‐tau protein [T‐tau], neurofilament light chain [NfL], neurogranin [Ng], and 14‐3‐3 levels). We used FreeSurfer and FSL to obtain cortical thickness (CTh) and fraction anisotropy (FA) maps. We studied group differences in CTh and FA and described the “AD signature” and “FTLD signature.” We tested multiple regression models to find which CSF‐biomarkers better explained each disease neuroimaging signature. CTh and FA maps corresponding to the AD and FTLD signatures were in accordance with previous literature. Multiple regression analyses showed that the biomarkers that better explained CTh values within the AD signature were Aβ and 14‐3‐3; whereas NfL and 14‐3‐3 levels explained CTh values within the FTLD signature. Similarly, NfL levels explained FA values in the FTLD signature. Ng levels were not predictive in any of the models. Biochemical markers contribute differently to structural (CTh and FA) changes typical of AD and FTLD.
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| 7. |
- Siwani, Samer, et al.
(författare)
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Hippocampal OLMα2 cells gate basolateral amygdala inputs for threat processing
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- It is becoming increasingly clear that the hippocampus is functionally diverse across its longitudinal axis. The ventral hippocampus is known to participate anxiety-related behaviors and may, together with the basolateral amygdala (BLA), facilitate threat aversion. Nevertheless, studies of mechanisms and circuit organization for processing value related cues are scarce. Here we investigate a microcircuit involving a subgroup of interneurons, referred to as Oriens lacunosum-moleculare cells, defined by their expression of the nicotinic receptor alpha2 subunit (OLMα2). Such cells can bidirectionally affect the response to predator odor as well as the encoding of object memories. In tracing experiments, we found that the basolateral amygdala mainly projects to the ventral hippocampus, whereas the medial amygdala and claustrum projects to the intermediate hippocampus. Moreover, we found that BLA inputs inhibit intrinsic hippocampal slow oscillation. Optogenetic stimulation of OLMα2 cells in the intermediate hippocampus caused an increase in approach of objects. Inhibition of ventrally located OLMα2 cells cause an increased avoidance to natural aversive stimuli and could entrain aversion to value neutral odors. In contrast, theta II oscillations, which predominantly appear in the ventral hippocampus during anxiety related behaviors, were absent during object recognition. Theta II oscillations only appeared when the animal was naïve to the arena setting. We conclude that there are functional differences between the intermediate and ventral hippocampus and that OLMα2 cells, in addition to sensory inputs, process emotional value signals from the amygdala.
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| 8. |
- Siwani, Samer, et al.
(författare)
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Inhibition of hippocampal OLMα2 cells rescue nicotine induced memory impairment
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Nicotine is a commonly used drug that has been extensively studied for decades. Some of these studies have found cognitive enhancing effects; however, they were usually based on moderate and not the higher doses to which the regular consumer might be accustomed. Here we investigate how higher doses of nicotine may influence the performance of mice in object recognition and in the Y-maze. Further, we examined specific circuits underlying the hippocampal-dependent effects by targeting a subgroup of inhibitory interneurons, referred to as OLMα2 cells. We subjected mice to nicotine during an object recognition task and a working memory task. We found that a high dose of 1.5 mg/kg nicotine impaired memory performance in the object recognition task but not in the working memory task. It was previously demonstrated that OLMα2 cells bidirectionally affect learning in the object recognition task and that these cells respond to nicotine. Subsequently, we subjected mice to nicotine while optogenetically inhibiting OLMα2 cells and found that this intervention reversed the nicotine-induced memory impairment. We conclude that some learning and memory effects from nicotine are hippocampus dependent and are probably mediated by OLMα2 cells.
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| 9. |
- Siwani, Samer, et al.
(författare)
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OLM alpha 2 Cells Bidirectionally Modulate Learning
- 2018
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Ingår i: Neuron. - : CELL PRESS. - 0896-6273 .- 1097-4199. ; 99:2, s. 404-412
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitory interneurons participate in mnemonic processes. However, defined roles for identified interneuron populations are scarce. A subpopulation of oriens lacunosum-moleculare (OLM) interneurons genetically defined by the expression of the nicotinic receptor alpha 2 subunit has been shown to gate information carried by either the temporoammonic pathway or Schaffer collaterals in vitro. Here we set out to determine whether selective modulation of OLM alpha 2 cells in the intermediate CA1 affects learning and memory in vivo. Our data show that intermediate OLM alpha 2 cells can either enhance (upon their inhibition) or impair (upon their activation) object memory encoding in freely moving mice, thus exerting bidirectional control. Moreover, we find that OLM alpha 2 cell activation inhibits fear-related memories and that OLM alpha 2 cells respond differently to nicotine in the dorsoventral axis. These results suggest that intermediate OLM alpha 2 cells are an important component in the CA1 microcircuit regulating learning and memory processes.
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