Effects of Hysteretic Shape on Dynamic Response

The parameters determined in laboratory tests for use in dynamic analyses are usually the secant modulus and the area of the hysteresis loop. The accuracy of this approach was studied for highly non-linear behavior through analytical solutions and numerical simulations of a single degree of freedom system. Only the effect of the shape of the hysteresis loop was studied, i.e. the stiffness and the area of the loop were kept constant independent of amplitude. The study shows that irregular hysteresis may cause a significant increase in the response of the system in higher frequencies compared to what would be expected from visco-elastic and standard non-linear models. The area of the hysteresis loop provides a good measure of the damping also for high degrees of non-linearity

Biomarkers in subtypes of mild cognitive impairment and subjective cognitive decline

Objectives Preclinical Alzheimers disease (AD) patients may or may not show cognitive impairment on testing. AD biomarkers are central to the identification of those at low, intermediate, or high risk of later dementia due to AD. We investigated biomarker distribution in those identified as subjective cognitive decline (SCD), amnestic (aMCI), and nonamnestic (naMCI) mild cognitive impairment (MCI) subtypes. In addition, the clinical groups were compared with controls on downstream neuroimaging markers. Materials and Methods Cerebrospinal fluid (CSF) amyloid‐β42 (A β42) and total tau (t‐tau), phosphorylated tau (p‐tau), fluorodeoxyglucose (FDG), positron‐emission tomography (PET), and MRI neuroimaging measures were collected from 116 memory clinic patients. They were characterized as SCD, aMCI, and naMCI according to comprehensive neuropsychological criteria. ANOVAs were used to assess differences when biomarkers were treated as continuous variables and chi square analyses were used to assess group differences in distribution of biomarkers. Results We did not find any between group differences in Aβ42, nor in p‐tau, but we observed elevated t‐tau in aMCI and SCD relative to the naMCI group. Significantly lower cortical glucose metabolism (as measured by FDG PET) was found in aMCI relative to SCD and controls, and there was a trend for lower metabolism in naMCI. Significant thinner entorhinal cortex (ERC) was found in aMCI and SCD. As expected biomarkers were significantly more frequently pathological in aMCI than in naMCI and SCD, whereas the naMCI and SCD groups displayed similar pathological biomarker burden. Conclusions aMCI cases show the most pathologic biomarker burden. Interestingly naMCI and SCD subjects show similar levels of pathological biomarkers albeit the former displayed neuropsychological deficits. That the latter group may represent a risk group is supported by our observation of both elevated CSF tau and thinner ERC relative to controls.publishedVersio

Costs of diagnosing early Alzheimer's disease in three European memory clinic settings: Results from the precision medicine in Alzheimer's disease project

Objectives - The implementation of disease-modifying treatments for Alzheimer's Disease (AD) will require cost-effective diagnostic processes. As part of The Precision Medicine In AD consortium (PMI-AD) project, the aim is to analyze the baseline costs of diagnosing early AD at memory clinics in Norway, Slovenia, and the Netherlands. Methods - The costs of cognitive testing and a clinical examination, apolipoprotein E, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), positron emission tomography and blood-based biomarkers (BBM), which are used in different combinations in the three countries, were analyzed. Standardized unit costs, adjusted for GDP per capita and based on Swedish conditions were applied. The costs were expressed in euros (€) as of 2019. A diagnostic set comprising clinical examination, cognitive testing, MRI and CSF was defined as the gold standard, with MRI mainly used as an exclusion filter. Results - Cost data were available for 994 persons in Norway, 169 in Slovenia and 1015 in the Netherlands. The mean diagnostic costs were 1478 (95% confidence interval 1433–1523) € in Norway, 851 (731–970) € in Slovenia and 1184 (1135–1232) € in the Netherlands. Norway had the highest unit costs but also the greatest use of tests. With a uniform diagnostic test set applied, the diagnostic costs were 1264 (1238–1291) €, in Norway, 843 (771–914) € in Slovenia and 1184 (1156–1213) € in the Netherlands. There were no major cost differences between the final set of diagnoses. Conclusions - The total costs for setting a diagnosis of AD varied somewhat in the three countries, depending on unit costs and use of tests. These costs are relatively low in comparison to the societal costs of AD

Stable cerebrospinal fluid neurogranin and β-site amyloid precursor protein cleaving enzyme 1 levels differentiate predementia Alzheimer's disease patients

Cerebrospinal fluid (CSF) β-site amyloid precursor protein cleaving enzyme 1 (BACE1), neurogranin and the neurogranin/BACE1 ratio are proposed markers for Alzheimer’s disease. BACE1 is also a drug target. However, CSF levels may differ between early-stage amyloid plaque formation (A) and later stage downstream tau-tangle pathology (T) and neurodegeneration (N) and may be expressed as an A/T/N stage (e.g. A+/T−/N or A+/T+/N+). Whether BACE1 and neurogranin levels are persistent traits or change with disease progression is unknown. The aim of this study was to investigate whether CSF neurogranin and BACE1 concentrations differ between A/T/N stages, whether these change over time and correlate with memory decline. This may have implications for patient selection in future trials. We used CSF markers to determine A/T/N stage using amyloid beta42/40 ratio, p-tau181 and total-tau respectively in predementia Alzheimer’s disease cases (n = 176) [including cases that progressed to dementia (n = 10)] and controls (n = 74) from the Norwegian Dementia Disease Initiation cohort. We selected cases at the presumed early (A+/T−/N−, n = 86) and late stages (A+/T+/N+, n = 90) of the Alzheimer’s disease continuum and controlled with normal markers (A−/T−/N−, n = 74). A subset of subjects in all A/T/N groups underwent repeat CSF sampling at approximately 2-year intervals up to 6 years from baseline. Using linear mixed models, longitudinal measurements of CSF BACE1 and neurogranin levels in A+/T−/N− and A+/T+/N+ as compared to A−/T−/N− healthy controls were performed. Next, we measured changes in CSF BACE1 and neurogranin levels in cases that progressed from A−/T−/N− to A+/T−/N− (n = 12), from A+/T−/N− to A+/T or N+ (n = 12), remained stable A+/T−/N− (n = 26), remained stable A+/T+/N+ (n = 28) compared with controls remaining stable A−/T−/N− (n = 33). Lastly, associations between these markers and memory decline were assessed. Compared with A−/T−/N− healthy controls, neurogranin was unaltered in A+/T−/N− (n.s.) but higher in A+/T+/N+ (P < 0.0001). In contrast, BACE1 was lower in A+/T−/N− (P < 0.05) and higher in A+/T+/N+ (P < 0.0001). The neurogranin/BACE1 ratio was increased in both A+/T−/N− (P < 0.05) and A+/T+/N+ (P < 0.0001) groups as compared to A-/T-/N- healthy controls and was more strongly associated with memory decline (b = −0.29, P = 0.0006) than neurogranin (b = −0.20, P = 0.002) and BACE1 (b = −0.13, P = 0.046). Neurogranin and BACE1 level differences remained stable over time not only within A/T/N groups but also in patients progressing to more pathological A/T/N stages (e.g. progressing from A+/T−/N− to A + T or N+) and in cases progressing to dementia. Our results suggest that neurogranin and BACE1 levels may differentiate pathomechanistic Alzheimer’s disease subgroups, putatively with different options for treatment

Medial Temporal Lobe Atrophy in Predementia Alzheimer's Disease: A Longitudinal Multi-Site Study Comparing Staging and A/T/N in a Clinical Research Cohort

Background: Atrophy of the medial temporal lobe (MTL) is a biological characteristic of Alzheimer’s disease (AD) and can be measured by segmentation of magnetic resonance images (MRI). Objective: To assess the clinical utility of automated volumetry in a cognitively well-defined and biomarker-classified multi-center longitudinal predementia cohort. Methods: We used Automatic Segmentation of Hippocampal Subfields (ASHS) to determine MTL morphometry from MRI. We harmonized scanner effects using the recently developed longitudinal ComBat. Subjects were classified according to the A/T/N system, and as normal controls (NC), subjective cognitive decline (SCD), or mild cognitive impairment (MCI). Positive or negative values of A, T, and N were determined by cerebrospinal fluid measurements of the Aβ42/40 ratio, phosphorylated and total tau. From 406 included subjects, longitudinal data was available for 206 subjects by stage, and 212 subjects by A/T/N. Results: Compared to A–/T–/N– at baseline, the entorhinal cortex, anterior and posterior hippocampus were smaller in A+/T+orN+. Compared to NC A– at baseline, these subregions were also smaller in MCI A+. Longitudinally, SCD A+ and MCI A+, and A+/T–/N– and A+/T+orN+, had significantly greater atrophy compared to controls in both anterior and posterior hippocampus. In the entorhinal and parahippocampal cortices, longitudinal atrophy was observed only in MCI A+ compared to NC A–, and in A+/T–/N– and A+/T+orN+ compared to A–/T–/N–. Conclusion: We found MTL neurodegeneration largely consistent with existing models, suggesting that harmonized MRI volumetry may be used under conditions that are common in clinical multi-center cohorts

Associations between changes in levels of phosphorylated tau and severity of cognitive impairment in early Alzheimer’s disease

Background and objectives: Aligning biomarker evidence with clinical presentation in early Alzheimer's disease (AD) is essential for improving diagnosis, prognosis, and interventions. This study evaluates the relationship between cognitive impairment, future decline, and phosphorylated tau levels in plasma and cerebrospinal fluid (CSF) in predementia AD.Methods: This longitudinal observational study included predementia cases and controls from two independent cohorts: the Norwegian DDI, and Canadian PREVENT-AD. In DDI, cognitively normal (CN) and mild cognitive impairment (MCI) cases were classified using CSF Aβ42/40 ratio (A) and p-tau181 (T), while classification in PREVENT-AD (A) was based on amyloid positron emission tomography (PET) scans. In DDI, we assessed CSF-plasma correlations for p-tau181, p-tau217, and p-tau231. Diagnostic accuracies via Receiver Operating Characteristic analyses. Linear mixed models evaluated p-tau associations with future memory decline. Between-group differences in plasma p-tau217 were assessed in both cohorts. Results: In DDI (n=431), participants were classified as CN A-/T- (n=169), A+/T- (CN=26, MCI=24), A+/T+ (CN=40, MCI=105), and A-/T+ (CN=34, MCI=33), with a mean age of 64.1 years and 55.9% females. In PREVENT-AD (n=190), participants were categorized as CN A- (n=118), CN A+ (n=49), and MCI A+ (n=21), with a mean age of 67.8 years and 72.6% females. In DDI, plasma p-tau217 showed high accuracy in identifying A+ participants (AUC: 0.85) and a moderate correlation with CSF p-tau217 (rho=0.65, p&lt;.001). Plasma p-tau217 diagnostic accuracy was greater in MCI A+ (AUC: 0.89) than CN A+ (AUC: 0.79, p&lt;.05) and in A+/T+ (AUC: 0.88) versus A+/T- (AUC: 0.78, p&lt;.05). P-tau181 and p-tau231 had weaker CSF-plasma correlations (rho=0.47 and rho=0.32, p&lt;.001) and were less associated with cognitive status in A+ individuals. Higher plasma p-tau217 in A+ MCI vs. A+ CN (p&lt;.001) was confirmed in PREVENT-AD. All CSF p-tau markers, but only plasma p-tau217, were associated with future memory decline (β=0.05, p&lt;0.05). Discussion: Our findings suggest that, unlike p-tau181 and p-tau231, plasma p-tau217 consistently aligns with cognitive status in A+ individuals and better reflects CSF biomarker abnormalities, reducing discrepancies between clinical and biochemical findings. Its association with baseline and future memory decline highlights its diagnostic and prognostic value, particularly when CSF analysis or PET is unavailable.<br/

Jord- og vannovervåking i landbruket (JOVA). Feltrapporter fra programmet i 2008

Program for Jord- og vannovervåking i landbruket (JOVA) ledes av Bioforsk Jord og miljø, og utføres i samarbeid med flere andre institusjoner. Programmet rapporterer årlig overvåkingsresultater fra jordbruksdominerte nedbørfelt over hele landet. Feltene representerer ulike driftsformer, jordbunnsforhold, og hydrologiske og klimatiske forhold. De årlige feltrapportene beskriver jordbruksdrift, og avrenning og tap av næringsstoffer og partikler i de ulike feltene. Tap av partikler og næringsstoffer rapporteres for agrohydrologisk år, 1. mai – 1. mai, mens tap av plantevernmidler rapporteres for kalenderår.publishedVersio

Jord- og vannovervåking i landbruket (JOVA). Feltrapporter fra programmet i 2006.

Program for Jord- og vannovervåking i landbruket (JOVA) ledes av Bioforsk Jord og miljø, og utføres i samarbeid med en rekke andre institusjoner. Programmet rapporterer årlig overvåkingsresultater fra jordbruksdominerte nedbørfelt over hele landet. Feltene representerer ulike driftsformer, jordbunnsforhold, og hydrologiske og klimatiske forhold. De årlige feltrapportene beskriver jordbruksdrift, og avrenning og tap av næringsstoffer og partikler i de ulike feltene. Tap av partikler og næringsstoffer rapporteres for agrohydrologisk år, 1. mai - 30. april, mens tap av pesticider rapporteres for kalenderår.publishedVersio

What is known about the health and living conditions of the indigenous people of northern Scandinavia, the Sami?

The Sami are the indigenous ethnic population of northern Scandinavia. Their health condition is poorly known, although the knowledge has improved over the last decade.The aim was to review the current information on mortality, diseases, and risk factor exposure in the Swedish Sami population.Health-related research on Sami cohorts published in scientific journals and anthologies was used to compare the health condition among the Sami and the majority non-Sami population. When relevant, data from the Sami populations in Swedish were compared with corresponding data from Norwegian and Finnish Sami populations.Life expectancy and mortality patterns of the Sami are similar to those of the majority population. Small differences in incidences of cancer and cardiovascular diseases have been reported. The traditional Sami lifestyle seems to contain elements that reduce the risk to develop cancer and cardiovascular diseases, e.g. physical activity, diet rich in antioxidants and unsaturated fatty acids, and a strong cultural identity. Reindeer herding is an important cultural activity among the Sami and is associated with high risks for accidents. Pain in the lower back, neck, shoulders, elbows, and hands are frequent among both men and women in reindeer-herding families. For men, these symptoms are related to high exposure to terrain vehicles, particularly snowmobile, whereas for women psychosocial risk factors seem to more important, e.g. poor social support, high effort, low reward, and high economical responsibilities.Although the health condition of the Sami population appears to be rather similar to that of the general Swedish population, a number of specific health problems have been identified, especially among the reindeer-herding Sami. Most of these problems have their origin in marginalization and poor knowledge of the reindeer husbandry and the Sami culture in the majority population. It is suggested that the most sustainable measure to improve the health among the reindeer-herding Sami would be to improve the conditions of the reindeer husbandry and the Sami culture

Impaired synaptic function is linked to cognition in Parkinson's disease

Objective Cognitive impairment is frequent in Parkinson's disease, but the underlying mechanisms are insufficiently understood. Because cortical metabolism is reduced in Parkinson's disease and closely associated with cognitive impairment, and CSF amyloid‐β species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloid‐β release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloid‐β, and presynaptic deposits of α‐synuclein. We expect a correlation between hypometabolism, CSF amyloid‐β, and the synapse related‐markers CSF neurogranin and α‐synuclein. Methods Thirty patients with mild‐to‐moderate Parkinson's disease and 26 healthy controls underwent a clinical assessment, lumbar puncture, MRI, 18F‐fludeoxyglucose‐PET, and a neuropsychological test battery (repeated for the patients after 2 years). Results All subjects had CSF amyloid‐β 1‐42 within normal range. In Parkinson's disease, we found strong significant correlations between cortical glucose metabolism, CSF Aβ, α‐synuclein, and neurogranin. All PET CSF biomarker‐based cortical clusters correlated strongly with cognitive parameters. CSF neurogranin levels were significantly lower in mild‐to‐moderate Parkinson's disease compared to controls, correlated with amyloid‐β and α‐synuclein, and with motor stage. There was little change in cognition after 2 years, but the cognitive tests that were significantly different, were also significantly associated with cortical metabolism. No such correlations were found in the control group. Interpretation CSF Aβ, α‐synuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to Aβ and α‐synuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease.publishedVersio