Search

Background: Using multi-block methods we combined multimodal neuroimaging metrics of thalamic morphology, thalamic white matter tract diffusion metrics, and cortical thickness to examine changes in behavioural variant frontotemporal dementia. (bvFTD). Method: Twenty-three patients with sporadic bvFTD and 24 healthy controls underwent structural and diffusion MRI scans. Clinical severity was assessed using the Clinical Dementia Rating scale and behavioural severity using the Frontal Behaviour Inventory by patient caregivers. Thalamic volumes were manually segmented. Anterior and posterior thalamic radiation fractional anisotropy and mean diffusivity were extracted using Tract-Based Spatial Statistics. Finally, cortical thickness was assessed using Freesurfer. We used shape analyses, diffusion measures, and cortical thickness as features in sparse multi-block partial least squares (PLS) discriminatory analyses to classify participants within bvFTD or healthy control groups. Sparsity was tuned with five-fold cross-validation repeated 10 times. Final model fit was assessed using permutation testing. Additionally, sparse multi-block PLS was used to examine associations between imaging features and measures of dementia severity. Results: Bilateral anterior-dorsal thalamic atrophy, reduction in mean diffusivity of thalamic projections, and frontotemporal cortical thinning, were the main features predicting bvFTD group membership. The model had a sensitivity of 96%, specificity of 68%, and was statistically significant using permutation testing (p = 0.012). For measures of dementia severity, we found similar involvement of regional thalamic and cortical areas as in discrimination analyses, although more extensive thalamo-cortical white matter metric changes. Conclusions: Using multimodal neuroimaging, we demonstrate combined structural network dysfunction of anterior cortical regions, cortical-thalamic projections, and anterior thalamic regions in sporadic bvFTD.

Family Report: Two rare autosomal recessive neurological disorders, leukoencephalopathy with ataxia and spastic paraplegia 56 (SPG56), were found in members of the same family. Two siblings presented with spastic paraplegia, cognitive impairment, bladder and bowel dysfunction and gait ataxia; their consanguineous parents were unaffected. Ophthalmological examination revealed chorioretinopathy. Brain MRI showed T2 hyperintensities and T1 hypointensities in the internal capsules, cerebral peduncles, pyramidal tracts and middle cerebellar peduncles. Both affected siblings were homozygous for CYP2U1 c.947A > T p.(Asp316Val), a known cause for SPG56. However, they were also homozygous for the novel variant CLCN2 c.607G > T, p.(Gly203Cys), classified as a variant of unknown significance. Testing of additional family members revealed homozygosity for both variants in an additional brother, whom we initially considered unaffected. Both male CLCN2 carriers were infertile, and review of the literature revealed one reported case with azoospermia, however the brother had no overt signs of SPG56. His testicular biopsy revealed incomplete maturation arrest in spermatogenesis; clinically we found mild memory impairment and hand tremor and MRI showed similar changes as his siblings. We consider CLCN2 c.607G > T pathogenic because of the neuroradiological and clinical findings, including azoospermia. Conclusion: Considerable workup may be required to determine the pathogenicity of novel variants, and to unambiguously associate phenotype with genotype. In very rare disorders, highly specific clinical or biomarker combinations provide sufficient evidence for a variant’s pathogenicity. Phenotypic variation of monogenic disorders described in the literature may be attributed to a second co-occurring monogenic disorder, especially in consanguineous families. SPG56 may have reduced penetrance.

Studies of therapy-related AML (t-AML) are usually performed in selected cohorts and reliable incidence rates are lacking. In this study, we characterized, defined the incidence over time and studied prognostic implications in all t-AML patients diagnosed in Sweden between 1997 and 2015. Data were retrieved from nationwide population-based registries. In total, 6,779 AML patients were included in the study, of whom 686 (10%) had t-AML. The median age for t-AML was 71 years and 392 (57%) patients were females. During the study period, the incidence of t-AML almost doubled with a yearly increase in t-AML of 4.5% (95% confidence interval: 2.8%-6.2%), which contributed significantly to the general increase in AML incidence over the study period. t-AML solidly constituted over 10% of all AML cases during the later period of the study. Primary diagnoses with the largest increase in incidence and decrease in mortality rate during the study period (i.e., breast and prostate cancer) contributed significantly to the increased incidence of t-AML. In multivariable analysis, t-AML was associated with poorer outcome in cytogenetically intermediate- and adverse-risk cases but t-AML had no significant impact on outcome in favorable-risk AML, including core binding leukemias, acute promyelocytic leukemia and AML with mutated NPM1 without FLT3-ITD. We conclude that there is a strong increase in incidence in t-AML over time and that t-AML constitutes a successively larger proportion of the AML cases. Furthermore, we conclude that t-AML confers a poor prognosis in cytogenetically intermediate- and adverse-risk, but not in favorable-risk AML.

Abstract Background Dementia is a syndrome, with a wide range of symptoms. It is important to have a timely diagnosis during the disease course to reduce the risk of medication errors, enable future care planning for the patient and their relatives thereby optimizing quality of life (QoL). For this reason, it is important to avoid a diagnosis of dementia not otherwise specified (DNOS) and instead obtain a diagnosis that reflects the underlying pathology. The aim of this study was to investigate the prevalence and associated factors of DNOS in persons with dementia living at home or in a nursing home. Methods This is a cross-sectional cohort study performed in eight European countries. Persons with dementia aged ≥65 years living at home (n = 1223) or in a nursing home (n = 790) were included. Data were collected through personal interviews with questionnaires based on standardised instruments. Specific factors investigated were sociodemographic factors, cognitive function, and mental health, physical health, QoL, resource utilization and medication. Bivariate and backward stepwise multivariate regression analyses were performed. Results The prevalence of DNOS in the eight participating European countries was 16% (range 1–30%) in persons living at home and 21% (range 1–43%) in persons living in a nursing home. These people are more often older compared to those with a specific dementia diagnosis. In both persons living at home and persons living in a nursing home, DNOS was associated with more severe neuropsychiatric symptoms and less use of anti-dementia medication. In addition, persons with DNOS living at home had more symptoms of depression and less use of antidepressant medication. Conclusions The prevalence of DNOS diagnosis is common and seems to vary between European countries. People with DNOS are more often older with more severe neuropsychiatric symptoms and receive fewer anti-dementia medication, anxiolytics and antidepressants. This would support the suggestion that a proper and specific diagnosis of dementia could help the management of their disease.

Abstract Objective Diagnosis of frontotemporal dementia (FTD) is complicated by the overlap of clinical symptoms with other dementia disorders. Development of robust fluid biomarkers is critical to improve the diagnostic work‐up of FTD. Methods CSF concentrations of placental growth factor (PlGF) were measured in the discovery cohort including patients with FTD (n = 27), Alzheimer disease (AD) dementia (n = 75), DLB or PDD (n = 47), subcortical vascular dementia (VaD, n = 33), mild cognitive impairment that later converted to AD (MCI‐AD, n = 34), stable MCI (sMCI, n = 62), and 50 cognitively healthy controls from the Swedish BioFINDER study. For validation, CSF PlGF was measured in additional independent cohort of FTD patients (n = 22) and controls (n = 18) from the Netherlands. Results In the discovery cohort, MCI, MCI‐AD, AD dementia, DLB‐PDD, VaD, and FTD patients all showed increased CSF levels of PlGF compared with controls (sMCI P = 0.019; MCI‐AD P = 0.005; AD dementia, DLB‐PDD, VaD, and FTD all P

River regulation may filter out riparian plants often resulting in reduced functional diversity, i.e., in the range of functions that organisms have in communities and ecosystems. There is, however, little empirical evidence about the magnitude of such reductions in different regions. We investigated the functional diversity patterns of riparian woody vegetation to streamflow regulation in boreal Sweden and Mediterranean Portugal using nine plant functional traits and field data from 109 sampling sites. We evaluated changes in mean plant functional traits as well as in indices of multidimensional functional traits, i.e., functional richness (FRic) and functional redundancy (FRed) within regions and between free-flowing and regulated river reaches. We found that regulation significantly reduced functional diversity in Sweden but not in Portugal. In Sweden, the increased magnitude of variations in water flow and water level in summer, the prolonged duration of extreme hydrological events, the increased frequency of high-water pulses, and the rate of change in water conditions were the likely main drivers of functional diversity change. Small riparian plant species with tiny leaves, poorly lignified stems, and shallow root systems were consistently associated with regulated sites in the boreal region. In Portugal, the similar functional diversity values for free-flowing and regulated rivers likely stem from the smaller streamflow alterations by regulation combined with the species legacy adaptations to the Mediterranean natural hydrological regimes. We conclude that streamflow regulation may reduce the functional diversity of riparian woody vegetation, but the magnitude of these effects will vary depending on the adaptations of the local flora and the patterns of streamflow disturbances. Our study provides insights into functional diversity patterns of riparian woody vegetation affected by regulation in contrasting biomes and encourages further studies of the functional diversity thresholds for maintaining ecosystems.

Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo, especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process.

Abstract Background Long non-coding RNA (lncRNA) expression has been implicated in a range of molecular mechanisms that are central in cancer. However, lncRNA expression has not yet been comprehensively characterized in acute myeloid leukemia (AML). Here, we assess to what extent lncRNA expression is prognostic of AML patient overall survival (OS) and determine if there are indications of lncRNA-based molecular subtypes of AML. Methods We performed RNA sequencing of 274 intensively treated AML patients in a Swedish cohort and quantified lncRNA expression. Univariate and multivariate time-to-event analysis was applied to determine association between individual lncRNAs with OS. Unsupervised statistical learning was applied to ascertain if lncRNA-based molecular subtypes exist and are prognostic. Results Thirty-three individual lncRNAs were found to be associated with OS (adjusted p value

Abstract Background The challenges of today’s society call for more knowledge about how to maintain all aspects of cognitive health, such as speed/attention, memory/learning, visuospatial ability, language, executive capacity and social cognition during the life course. Main text Medical advances have improved treatments of numerous diseases, but the cognitive implications have not been sufficiently addressed. Disability induced by cognitive dysfunction is also a major issue in groups of patients not suffering from Alzheimer’s disease or related disorders. Recent studies indicate that several negative lifestyle factors can contribute to the development of cognitive impairment, but intervention and prevention strategies have not been implemented. Disability due to cognitive failure among the workforce has become a major challenge. Globally, the changing aging pyramid results in increased prevalence of cognitive disorders, and the diversity of cultures influences the expression, manifestation and consequences of cognitive dysfunction. Conclusions Major tasks in the field of cognitive medicine are basic neuroscience research to uncover diverse disease mechanisms, determinations of the prevalence of cognitive dysfunction, health-economical evaluations, and intervention studies. Raising awareness for cognitive medicine as a clinical topic would also highlight the importance of specialized health care units for an integrative approach to the treatment of cognitive dysfunctions.

Abstract Background The MAPT c.1216C > T (p.Arg406Trp; R406W) mutation is a known cause of frontotemporal dementia with Parkinsonism linked to chromosome 17 tau with Alzheimer’s disease-like clinical features. Methods We compiled clinical data from a new Swedish kindred with R406W mutation. Seven family members were followed longitudinally for up to 22 years. Radiological examinations were performed in six family members and neuropathological examinations in three. We systematically reviewed the literature and compiled clinical, radiological, and neuropathological data on 63 previously described R406W heterozygotes and 3 homozygotes. Results For all cases combined, the median age of onset was 56 years and the median disease duration was 13 years. Memory impairment was the most frequent symptom, behavioral disturbance and language impairment were less common, and Parkinsonism was rare. Disease progression was most often slow. The most frequent clinical diagnosis was Alzheimer’s disease. R406W homozygotes had an earlier age at onset and a higher frequency of behavioral symptoms and Parkinsonism than heterozygotes. In the new Swedish kindred, a consistent imaging finding was ventromedial temporal lobe atrophy, which was evident also in early disease stages as a widening of the collateral sulcus with ensuing atrophy of the parahippocampal gyrus. Unlike previously published R406W carriers, all three autopsied patients from the novel family showed neuropathological similarities with progressive supranuclear palsy, with predominant four-repeat (exon 10+) tau isoform (4R) tauopathy and neurofibrillary tangles accentuated in the basal-medial temporal lobe. Amyloid-β pathology was absent. Conclusions Dominance of 4R over three-repeat (exon 10−) tau isoforms contrasts with earlier reports of R406W patients and was not sufficiently explained by the presence of H1/H2 haplotypes in two of the autopsied patients. R406W patients often show a long course of disease with marked memory deficits. Both our neuropathological results and our imaging findings revealed that the ventromedial temporal lobes were extensively affected in the disease. We suggest that this area may represent the point of origin of tau deposition in this disease with relatively isolated tauopathy.

The computational tool InSTHAn (indicators of short-term hydrological alteration) was developed to summarize data on subdaily stream flows or water levels into manageable, comprehensive and ecologically meaningful metrics, and to qualify and quantify their deviation from unaltered states. The pronunciation of the acronym refers to the recording interval of input data (i.e., instant). We compared InSTHAn with the tool COSH-Tool in a characterization of the subdaily flow variability of the Colorado River downstream from the Glen Canyon dam, and in an evaluation of the effects of the dam on this variability. Both tools captured the hydropeaking caused by a dam operation, but only InSTHAn quantified the alteration of key flow attributes, highlighting significant increases in the range of within-day flow variations and in their rates of change. This information is vital to evaluate the potential ecological consequences of the hydrological alteration, and whether they may be irreversible, making InSTHAn a key tool for river flow management.

Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico-anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information-based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insular-orbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the "prefrontal" syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control.

Many stream restoration projects aim to increase geomorphic complexity, assuming that this increases habitat heterogeneity and, thus, biodiversity. However, empirical data supporting these linkages remain scant. Previous assessments of stream restoration suffer from incomplete quantification of habitat complexity, or a narrow focus on only one organism group and/or one restoration measure, limiting learning. Based on a comprehensive quantification of geomorphic complexity in 20 stream reaches in northern Sweden, ranging from streams channelized for timber floating to restored and reference reaches, we investigated responses of macroinvertebrates, diatoms, and macrophytes to multiple geomorphic metrics. Sediment size heterogeneity, which was generally improved in restored sites, favored macroinvertebrate and diatom diversity and macroinvertebrate abundance. In contrast, macrophyte diversity responded to increased variation along the longitudinal stream profile (e.g., step-pools), which was not consistently improved by the restoration. Our analyses highlight the value of learning across multiple restoration projects, both in identifying which aspects of restoration have succeeded, and pinpointing other measures that might be targeted during adaptive management or future restoration. Given our results, a combination of restoration measures targeting not only sediment size heterogeneity, but also features such as step-pools and instream wood, is most likely to benefit benthic biota in streams.

Behavioural variant frontotemporal dementia (bvFTD) is associated with changes in dorsal striatal parts of the basal ganglia (caudate nucleus and putamen), related to dysfunction in the cortico-striato-thalamic circuits which help mediate executive and motor functions. We aimed to determine whether the size and shape of striatal structures correlated with diagnosis of bvFTD, and measures of clinical severity, behaviour and cognition.Magnetic resonance imaging scans from 28 patients with bvFTD and 26 healthy controls were manually traced using image analysis software (ITK-SNAP). The resulting 3-D objects underwent volumetric analysis and shape analysis, through spherical harmonic description with point distribution models (SPHARM-PDM). Correlations with size and shape were sought with clinical measures in the bvTFD group, including Frontal Behavioural Inventory, Clinical Dementia Rating for bvFTD, Color Word Interference, Hayling part B and Brixton tests, and Trail-Making Test.Caudate nuclei and putamina were significantly smaller in the bvFTD group compared to controls (left caudate 16% smaller, partial eta squared 0.173, p=0.003; right caudate 11% smaller, partial eta squared 0.103, p=0.023; left putamen 18% smaller, partial eta squared 0.179, p=0.002; right putamen 12% smaller, partial eta squared 0.081, p=0.045), with global shape deflation in the caudate bilaterally but no localised shape change in putamen. In the bvFTD group, shape deflations on the left, corresponding to afferent connections from dorsolateral prefrontal mediofrontal/anterior cingulate and orbitofrontal cortex, correlated with worsening disease severity. Global shape deflation in the putamen correlated with Frontal Behavioural Inventory scores-higher scoring on negative symptoms was associated with the left putamen, while positive symptoms were associated with the right. Other cognitive tests had poor completion rates.Behavioural symptoms and severity of bvFTD are correlated with abnormalities in striatal size and shape. This adds to the promise of imaging the striatum as a biomarker in this disease.

A major difference in the revised diagnostic criteria for Alzheimer's disease (AD) is the incorporation of biomarkers to support a clinical diagnosis and allow the identification of preclinical AD due to AD neuropathological processes. However, AD-specific fluid biomarkers which specifically distinguish clinical AD dementia from other dementia disorders are still missing. Here we aimed to evaluate the disease-specificity of increased YKL-40 levels in cerebrospinal fluid (CSF) from AD patients with mild to moderate dementia (n = 49) versus Parkinson's disease (PD) (n = 61) and dementia with Lewy bodies (DLB) patients (n = 36), and non-demented controls (n = 44). Second we aimed to investigate whether altered YKL-40 levels are associated with CSF levels of other inflammation-associated molecules. When correcting for age, AD patients exhibited 21.3%, 27.7% and 38.8% higher YKL-40 levels compared to non-demented controls (p = 0.0283), DLB (p = 0.0027) and PD patients (p

OBJECTIVES: Frontotemporal dementia (FTD) is considered to be a mainly early-onset neurodegenerative disorder with a strong hereditary component. The aim of the study was to investigate age-related incidence and family history in FTD compared to other dementia disorders, especially Alzheimer's disease (AD). METHODS: The Swedish Dementia Registry (SveDem) registers all new cases of dementia diagnosed by the participating centres, including data on demographics, diagnosis, and investigations used. Data for the period 2008-2011 were extracted and compared with age-related population data on a regional and national level. RESULTS: There were 20 305 patients registered in SveDem during 2008-2011, whereof 352 received a diagnosis of FTD. Mean age at diagnosis for FTD was 69.6 years and almost 70% of FTD cases were 65 years or older at the time of diagnosis. Both FTD and AD showed an increased incidence with age, which reached a maximum in the age group 80-84 years at 6.04 and 202 cases per 100 000 person-years, respectively. The proportion of cases with a positive family history was significantly lower in FTD than in AD. CONCLUSIONS: Contrary to general opinion within the field, data from SveDem show that the incidence of FTD increases with age, and that the majority of cases are diagnosed after the age of 65 years. In addition, data from SveDem might suggest that the importance of hereditary factors in general is similar in FTD and AD. The recognition of these findings has important consequences for the diagnosis, treatment and care of patients with FTD.

MRI diffusion tensor imaging (DTI) studies of white matter integrity in behavioral variant frontotemporal dementia have consistently shown involvement of frontal and temporal white matter, corresponding to regional loss of cortical volume. Volumetric imaging has a suboptimal sensitivity as a diagnostic tool and thus we wanted to explore if DTI is a better method to discriminate patients and controls than volumetric imaging. We examined the anterior cingulum bundle in 14 patients with behavioral variant frontotemporal dementia and 22 healthy controls using deterministic manual diffusion tensor tractography, and compared DTI parameters with two measures of cortical atrophy, VBM and cortical thickness, of the anterior cingulate cortex (ACC). Statistically significant changes between patients and controls were detected in all DTI parameters, with large effect sizes. ROC-AUC was for the best DTI parameters: 0.92 (fractional anisotropy) to 0.97 (radial diffusivity), 0.82 for the best cortical parameter, VBM of the ACC. Results from the AUC were confirmed with binary logistic regression analysis including demographic variables, but only for fractional anisotropy and mean diffusivity. Ability to classify patient/nonpatient status was significantly better for mean diffusivity vs. VBM (p=0.031), and borderline significant for fractional anisotropy vs. VBM (p=0.062). The results indicate that DTI could offer advantages in comparison with the assessment of cortical volume in differentiating patients with behavioral variant frontotemporal dementia and controls.

PurposeThe aim of the study was to determine the usefulness of diffusion tensor tractography (DTT) in parkinsonian disorders using a recently developed method for normalization of diffusion data and tract size along white matter tracts. Furthermore, the use of DTT in selected white matter tracts for differential diagnosis was assessed.MethodsWe quantified global and regional diffusion parameters in major white matter tracts in patients with multiple system atrophy (MSA), progressive nuclear palsy (PSP), idiopathic Parkinson's disease (IPD) and healthy controls). Diffusion tensor imaging data sets with whole brain coverage were acquired at 3 T using 48 diffusion encoding directions and a voxel size of 2×2×2 mm(3). DTT of the corpus callosum (CC), cingulum (CG), corticospinal tract (CST) and middle cerebellar peduncles (MCP) was performed using multiple regions of interest. Regional evaluation comprised projection of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and the apparent area coefficient (AAC) onto a calculated mean tract and extraction of their values along each structure.ResultsThere were significant changes of global DTT parameters in the CST (MSA and PSP), CC (PSP) and CG (PSP). Consistent tract-specific variations in DTT parameters could be seen along each tract in the different patient groups and controls. Regional analysis demonstrated significant changes in the anterior CC (MD, RD and FA), CST (MD) and CG (AAC) of patients with PSP compared to controls. Increased MD in CC and CST, as well as decreased AAC in CG, was correlated with a diagnosis of PSP compared to IPD.ConclusionsDTT can be used for demonstrating disease-specific regional white matter changes in parkinsonian disorders. The anterior portion of the CC was identified as a promising region for detection of neurodegenerative changes in patients with PSP, as well as for differential diagnosis between PSP and IPD.

Neurosin is a protease that in vitro degrades α-synuclein, the main constituent of Lewy bodies found in brains of patients with synucleinopathy including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Several studies have reported reduced cerebrospinal fluid (CSF) levels of α-synuclein in synucleinopathy patients and recent data also proposes a significant role of α-synuclein in the pathophysiology of Alzheimer's disease (AD). To investigate potential links between neurosin and its substrate α-synuclein in vivo we used a commercially available sandwich ELISA and an in-house developed direct ELISA to quantify CSF levels of α-synuclein and neurosin in patients diagnosed with DLB, PD and PD dementia (PDD) versus AD patients and non-demented controls. We found that patients with synucleinopathy displayed lower CSF levels of neurosin and α-synuclein compared to controls and AD patients. In contrast, AD patients demonstrated significantly increased CSF α-synuclein but similar neurosin levels compared to non-demented controls. Further, CSF neurosin and α-synuclein concentrations were positively associated in controls, PD and PDD patients and both proteins were highly correlated to CSF levels of phosphorylated tau in all investigated groups. We observed no effect of gender or presence of the apolipoprotein Eε4 allele on neither neurosin or α-synuclein CSF levels. In concordance with the current literature our study demonstrates decreased CSF levels of α-synuclein in synucleinopathy patients versus AD patients and controls. Importantly, decreased α-synuclein levels in patients with synucleinopathy appear linked to low levels of the α-synuclein cleaving enzyme neurosin. In contrast, elevated levels of α-synuclein in AD patients were not related to any altered CSF neurosin levels. Thus, altered CSF levels of α-synuclein and neurosin in patients with synucleinopathy versus AD may not only mirror disease-specific neuropathological mechanisms but may also serve as fit candidates for future biomarker studies aiming at identifying specific markers of synucleinopathy.

We developed a conceptual framework for evaluating the process of ecological restoration and applied it to 10 examples of restoration projects in the northern hemisphere. We identified three major phases, planning, implementation, and monitoring, in the restoration process. We found that evaluation occurred both within and between the three phases, that it included both formal and informal components, and that it often had an impact on the performance of the projects. Most evaluations were short-term and only some parts of them were properly documented. Poor or short-term evaluation of the restoration process creates a risk that inefficient methods will continue to be used, which reduces the efficiency and effectiveness of restoration. To improve the restoration process and to transfer the knowledge to future projects, we argue for more formal, sustained evaluation procedures, involving all relevant stakeholders, and increased and improved documentation and dissemination of the results.

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.

Arctic and subarctic (i.e., [sub]arctic) ecosystems are predicted to be particularly susceptible to climate change. The area of tundra is expected to decrease and temperate climates will extend further north, affecting species inhabiting northern environments. Consequently, species at high latitudes should be especially susceptible to climate change, likely experiencing significant range contractions. Contrary to these expectations, our modelling of species distributions suggests that predicted climate change up to 2080 will favour most mammals presently inhabiting (sub)arctic Europe. Assuming full dispersal ability, most species will benefit from climate change, except for a few cold-climate specialists. However, most resident species will contract their ranges if they are not able to track their climatic niches, but no species is predicted to go extinct. If climate would change far beyond current predictions, however, species might disappear. The reason for the relative stability of mammalian presence might be that arctic regions have experienced large climatic shifts in the past, filtering out sensitive and range-restricted taxa. We also provide evidence that for most (sub)arctic mammals it is not climate change per se that will threaten them, but possible constraints on their dispersal ability and changes in community composition. Such impacts of future changes in species communities should receive more attention in literature.

Humans depend on services provided by ecosystems, and how services are affected by climate change is increasingly studied. Few studies, however, address changes likely to affect services from seminatural ecosystems. We analyzed ecosystem goods and services in natural and seminatural systems, specifically how they are expected to change as a result of projected climate change during the 21st century. We selected terrestrial and freshwater systems in northernmost Europe, where climate is anticipated to change more than the global average, and identified likely changes in ecosystem services and their societal consequences. We did this by assembling experts from ecology, social science, and cultural geography in workshops, and we also performed a literature review. Results show that most ecosystem services are affected by multiple factors, often acting in opposite directions. Out of 14 services considered, 8 are expected to increase or remain relatively unchanged in supply, and 6 are expected to decrease. Although we do not predict collapse or disappearance of any of the investigated services, the effects of climate change in conjunction with potential economical and societal changes may exceed the adaptive capacity of societies. This may result in societal reorganization and changes in ways that ecosystems are used. Significant uncertainties and knowledge gaps in the forecast make specific conclusions about societal responses to safeguard human well-being questionable. Adapting to changes in ecosystem services will therefore require consideration of uncertainties and complexities in both social and ecological responses. The scenarios presented here provide a framework for future studies exploring such issues.

An international overview of the extent and type of ecological restoration can offer new perspectives for understanding, planning, and implementation. The Nordic countries, with a great range of natural conditions but historically similar social and political structures, provide an opportunity to compare restoration approaches and efforts across borders. The aim of this study was to explore variation in ecological restoration using the Nordic countries as an example. We used recent national assessments and expert evaluations of ecological restoration. Restoration efforts differed among countries: forest and peatland restoration was most common in Finland, freshwater restoration was most common in Sweden, restoration of natural heathlands and grasslands was most common in Iceland, restoration of natural and semi-cultural heathlands was most common in Norway, and restoration of cultural ecosystems, mainly abandoned agricultural land, was most common in Denmark. Ecological restoration currently does not occur on the Faroe Islands. Economic incentives influence ecological restoration and depend on laws and policies in each country. Our analyses suggest that habitat types determine the methods of ecological restoration, whereas socio-economic drivers are more important for the decisions concerning the timing and location of restoration. To improve the understanding, planning, and implementation of ecological restoration, we advocate increased cooperation and knowledge sharing across disciplines and among countries, both in the Nordic countries and internationally. An obvious advantage of such cooperation is that a wider range of experiences from different habitats and different socio-economic conditions becomes available and thus provides a more solid basis for developing practical solutions for restoration methods and policies.

Interest in ecological restoration has recently intensified as scientists, policymakers, and stakeholders use restoration in management strategies to address and mitigate global climate change and biodiversity loss. Northern ecosystems offer special challenges to restoration managers because of their short growing seasons and long recovery periods. This special feature of Ecology and Society on ecological restoration in northern regions draws together 11 papers based on presentations from the conference "Restoring the North", convened in October 2011 in Selfoss, Iceland. We summarize two themes of this conference: (1) setting objectives and evaluating success in restoration, and (2) legislation, policy, and implementation of restoration. We conclude that northern countries altogether comprise a significant knowledge base and suggest five actions to enhance restoration practices within them: (1) improved documentation of restoration actions, including objectives, measures and results, (2) regular evaluation of restoration progress and outcome, (3) coordination of conservation actions among northern countries, including location of restoration actions to sites where they are most useful in a global context, (4) formation of a common platform to strengthen development of research about ecological, political, social, and technical aspects of ecological restoration, and (5) education of new generations of restoration actors who can work in diverse biogeographic settings and cultures.

Some ecological restoration projects include elements of trial and error where new measures are repeatedly tried, evaluated, and modified until satisfactory results are achieved. Thereafter, the resulting methods may be applied on larger scales. A difficult step is judging whether developed "best-practice" methods have become reasonably ecologically functional or whether further experimentation "demonstration" methods can lead to yet better results. Here, we use a stream restoration project as a case study for evaluating methods and abiotic effects and outlining stakeholder support for demonstration restoration measures, rather than only using best-practice methods. Our work was located in the Vindel River system, a free-flowing river that is part of the Natura 2000 network. The river was exploited for timber floating from 1850-1976, and rapids in the main channel and tributaries below timberline were channelized to increase timber transport capacity. Several side channels in multi-channeled rapids were blocked and the flow was concentrated to a single channel from which boulders and large wood were removed. Hence, previously heterogeneous environments were replaced by more homogeneous systems with limited habitat for riverine species. The restoration project strives to alleviate the effects of fragmentation and channelization in affected rapids by returning coarse sediment from channel margins to the main channel. However, only smaller, angular sediment is available given blasting of large boulders, and large (old-growth) wood is largely absent; therefore, original levels of large boulders and large wood in channels cannot be achieved with standard restoration practices. In 10 demonstration sites, we compensated for this by adding large boulders and large wood (i.e., entire trees) from adjacent upland areas to previously best-practice restored reaches and compared their hydraulic characteristics with 10 other best-practice sites. The demonstration sites exhibited significantly reduced and more variable current velocities, and wider channels, but with less variation than pre-restoration. The ecological response to this restoration has not yet been studied, but potential outcomes are discussed.

The increasing number of deteriorating old dams that need renovation or have lost their function make dam removal a viable management option. There are at least four major reasons for dam removal: safety, law and policy, economy, and ecology. Here we discuss 17 Swedish dams that were recently considered for removal. Because dam removal usually causes controversy, dam removal initiatives may succeed, fail, or result in a compromise such as a bypass channel for migrating fish. We identify and discuss three major obstructions to dam removal: funding, cultural-historical values, and threatened species. To facilitate dam removal, the reasons for, and the effects of, dam removal must be carefully explained, and the public and stakeholders must be kept informed. In complicated cases in which compromise solutions may be the most feasible outcome, the integration of the knowledge of different stakeholders is crucial. The involvement of diverse stakeholders increases their willingness to find compromises, thus avoiding conflicts and failures.

Water quality describes the physicochemical characteristics of the water body. These vary naturally with the weather and with the spatiotemporal variation of the water flow, i.e., the flow regime. Worldwide, biota have adapted to the variation in these variables. River channels and their riparian zones contain a rich selection of adapted species and have been able to offer goods and services for sustaining human civilizations. Many human impacts on natural riverine environments have been destructive and present opportunities for rehabilitation. It is a big challenge to satisfy the needs of both humans and nature, without sacrificing one or the other. New ways of thinking, new policies, and institutional commitment are needed to make improvements, both in the ways water flow is modified in rivers by dam operations and direct extractions, and in the ways runoff from adjacent land is affected by land-use practices. Originally, prescribed flows were relatively static, but precepts have been developed to encompass variation, specifically on how water could be shared over the year to become most useful to ecosystems and humans. A key aspect is how allocations of water interact with physicochemical variation of water. An important applied question is how waste releases and discharge can be managed to reduce ecological and sanitary problems that might arise from inappropriate combinations of flow variation and physicochemical characteristics of water. We review knowledge in this field, provide examples on how the flow regime and the water quality can impact ecosystem processes, and conclude that most problems are associated with low-flow conditions. Given that reduced flows represent an escalating problem in an increasing number of rivers worldwide, managers are facing enormous challenges.

This special issue of Ecology and Society on restoring riverine landscapes draws together nine presentations from the Second International Symposium on Riverine Landscapes, convened in August 2004 in Storforsen, Sweden. We summarize three themes related to river restoration: (1) setting priorities, (2) identifying relevant reference conditions, and (3) choosing appropriate techniques. We discuss ways of developing river restoration and provide examples of future needs in sustaining functioning river ecosystems that can support human societies.