| 39971. |
- Vergallo, A., et al.
(författare)
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Plasma amyloid beta 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:6, s. 764-775
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Blood-based biomarkers of pathophysiological brain amyloid beta (A beta) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the A beta(1-40)/A beta(1-42) ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain A beta positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-apriori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma A beta(1-40)/A beta(1-42) ratio. The accuracy is not affected by the apolipoprotein E (APOE) epsilon 4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma A beta(1-40)/A beta(1-42) ratio, assessed via Simoa, may improve future standard of care and clinical trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 39972. |
- Vergallo, Andrea, et al.
(författare)
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Plasma β-secretase1 concentrations correlate with basal forebrain atrophy and neurodegeneration in cognitively healthy individuals at risk for AD.
- 2021
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 17:4, s. 629-640
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Tidskriftsartikel (refereegranskat)abstract
- Increased β-secretase 1 (BACE1) protein concentration, in body fluids, is a candidate biomarker of Alzheimer's disease (AD).We reported that plasma BACE1 protein concentrations are associated with the levels of brain amyloidβ (Αβ) accumulation in cognitively healthy individuals with subjective memory complaint (SMC).In 302 individuals from the same cohort, we investigated the cross-sectional and longitudinal association between plasma BACE1 protein concentrations and AD biomarkers of neurodegeneration (plasma t-tau and Neurofilament light chain (NfL), fluorodeoxyglucose-positron emission tomography (FDG-PET), brain volumes in the basal forebrain [BF], hippocampus, and entorhinal cortex).We report a positive longitudinal correlation of BACE1 with both NfL and t-tau, as well as a correlation between annual BACE1 changes and bi-annual reduction of BF volume. We show a positive association between BACE1 and FDG-PET signal at baseline.The association between plasma BACE1 protein concentrations and BF atrophy we found in cognitively healthy individuals with SMC corroborates translational studies, suggesting a role of BACE1 in neurodegeneration.
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| 39973. |
- Verharen, J. P. H., et al.
(författare)
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Corticolimbic mechanisms of behavioral inhibition under threat of punishment
- 2019
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Ingår i: Journal of Neuroscience. - 0270-6474. ; 39:22, s. 4353-4364
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Tidskriftsartikel (refereegranskat)abstract
- Being able to limit the pursuit of reward to prevent negative consequences is an important expression of behavioral inhibition. Everyday examples of an inability to exert such control over behavior are the overconsumption of food and drugs of abuse, which are important factors in the development of obesity and addiction, respectively. Here, we use a behavioral task that assesses the ability of male rats to exert behavioral restraint at the mere sight of palatable food during the presentation of an audiovisual threat cue to investigate the corticolimbic underpinnings of behavioral inhibition. We demonstrate a prominent role for the medial prefrontal cortex in the exertion of control over behavior under threat of punishment. Moreover, task engagement relies on function of the ventral striatum, whereas the basolateral amygdala mediates processing of the threat cue. Together, these data show that inhibition of reward pursuit requires the coordinated action of a network of corticolimbic structures. © 2019, Society for Neuroscience. All rights reserved.
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| 39974. |
- Verharen, J. P. H., et al.
(författare)
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Insensitivity to Losses: A Core Feature in Patients With Anorexia Nervosa?
- 2019
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Ingår i: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. - : Elsevier BV. - 2451-9022.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with anorexia nervosa (AN) demonstrate aberrations in choice behavior, including impairments in laboratory measures of decision making. Although a wealth of studies suggest that these aberrations arise from alterations in value processing, it remains unclear by which core component of value processing this is mediated. Methods: We fit trial-by-trial data of patients with AN (n = 60 first cohort, n = 216 second cohort) and healthy control participants (n = 55) performing the Iowa Gambling Task to a computational model based on prospect utility theory. We determined, per participant, the best-fit model parameters and compared these between the groups. Results: Analyses revealed a decreased estimate of model parameter λ in patients with AN, indicative of an attenuation of loss-aversive behavior in the Iowa Gambling Task. In comparison, measures of reward sensitivity, value-based learning, and exploration versus exploitation were unaltered in patients with AN. A measurement in a second independent cohort replicated the finding that loss aversion, typically observed in healthy individuals, is reduced in patients with AN. Conclusions: We show that patients with AN, in contrast to healthy control participants, demonstrate reduced loss-aversive behavior. This finding provides important fundamental insights into the decision-making capacity of patients with AN, suggesting alterations in the mechanisms involved in value processing related to negative feedback. © 2019
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| 39975. |
- Vermunt, L., et al.
(författare)
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Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings
- 2020
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. Methods We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean +/- SD age = 64 +/- 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. Results A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95-0.99]), high education (OR = 1.64 [1.23-2.17]), male sex (OR = 1.56 [1.19-2.04]), and positive family history of dementia (OR = 1.66 [1.19-2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02-1.10]) and APOE e4 allele carriership (OR = 2.99 [1.81-4.94]). These results were similar across prescreen settings. Conclusions Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD.
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| 39976. |
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| 39977. |
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| 39978. |
- Verrel, Julius, et al.
(författare)
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Motor-equivalent covariation stabilizes step parameters and center of mass position during treadmill walking
- 2010
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 207:1-2, s. 13-26
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Tidskriftsartikel (refereegranskat)abstract
- We investigated motor-equivalent stabilization of task-related variables (TRV) at times of heel strike in eight healthy young men (23-30 years) who walked on a motorized treadmill at self-selected and prescribed speeds within the normal walking speed range. The TRV consisted of step parameters (step length and width) and the center of mass (CoM) position relative to the support (back and front feet). Motor-equivalent stabilization of the TRV was assessed using a decorrelation technique, comparing empirical to decorrelated (covariation-free) variability. Analysis indicated reliable covariation for all TRV. In both the fore-aft and lateral directions, stabilization by covariation was highest for CoM position relative to the front foot, indicating a prioritization of equilibrium-related variables. Correlations among TRV revealed that the relation between CoM and step parameter control differed between the fore-aft and lateral directions. While stabilization of lateral foot position appears to be due to control of CoM relative to each foot, step length showed small, but reliable, stabilization beyond CoM stabilization, which may be related to spatiotemporal regularity of the step pattern.
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| 39979. |
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| 39980. |
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