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- Eckerström, Carl, et al.
(author)
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High white matter lesion load is associated with hippocampal atrophy in mild cognitive impairment.
- 2011
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 31:2, s. 132-8
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Journal article (peer-reviewed)abstract
- Mild cognitive impairment (MCI) is a heterogeneous condition suggested as a prodromal state of Alzheimer's disease (AD) and subcortical vascular dementia (SVD). Recent findings suggest that white matter lesions (WML) may be associated with hippocampal atrophy. The objective of the study was to examine hippocampal and WML volumes in MCI patients and to examine if WML were linked to hippocampal atrophy.
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2. |
- Eckerström, Carl, et al.
(author)
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Multimodal Prediction of Dementia with up to 10 Years Follow Up: The Gothenburg MCI Study
- 2015
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 44:1, s. 205-214
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Journal article (peer-reviewed)abstract
- Background: Neuropsychological tests, CSF A beta(42,) T-tau, P-tau181, hippocampal volume, and white matter lesions have been shown to predict conversion to dementia in patients with mild cognitive impairment (MCI). Objective: To examine the predictive value of combinations of these markers and to examine if the absence of pathological markers provides a lasting reduction of conversion rates. Methods: The Gothenburg MCI study is a clinically based study. Seventy-three MCI patients were included in the present sub-study and followed for a maximum of ten years. Thirty-four patients converted to dementia (18 to AD) and 39 remained stable. At inclusion, patients were classified into positive or negative risk groups according to results from neuropsychological testing (Rey auditory verbal learning test, Boston naming test, Trail making test B), CSF biomarkers (amyloid beta(42), T-tau, and P-tau181) and MRI scans (hippocampal volume, white matter lesions). Results: Trail making test B (TMT-B) was the best single predictor for the prediction of dementia (AUC 0.89, HR 25), and T-tau was the best predictor ofAD(AUC 0.97, HR 41). The combination of hippocampal volume and TMT-Bwas the best combination for the prediction of dementia (HR 25), and the combination of hippocampal volume and T-tau was the best combination for the prediction of AD (HR 37). Conclusion: Neuropsychological tests, CSF markers, and hippocampal volume predicted conversion from MCI to AD and general dementia. The absence of pathological markers provided a long-time protection from dementia.
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3. |
- Eckerström, Carl, et al.
(author)
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Similar pattern of atrophy in early- and late-onset Alzheimer's disease
- 2018
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In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 10, s. 253-259
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Journal article (peer-reviewed)abstract
- Introduction: Previous research on structural changes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) have reported inconsistent findings. Methods: In the present substudy of the Gothenburg MCI study, 1.5 T scans were used to estimate lobar and hippocampal volumes using FreeSurfer. Study participants (N = 145) included 63 patients with AD, (24 patients with EOAD [aged ≤65 years], 39 patients with LOAD [aged >65 years]), 25 healthy controls aged ≤65 years, and 57 healthy controls aged >65 years. Results: Hippocampal atrophy is the most prominent feature of both EOAD and LOAD compared with controls. Direct comparison between EOAD and LOAD showed that the differences between the groups did not remain after correcting for age. Discussion: Structurally, EOAD and LOAD does not seem to be different nosological entities. The difference in brain volumes between the groups compared with controls is likely due to age-related atrophy. © 2018 The Authors
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4. |
- Holmberg, Mats, 1958, et al.
(author)
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A Longitudinal Study of Medial Temporal Lobe Volumes in Graves Disease
- 2022
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:4, s. 1040-1052
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Journal article (peer-reviewed)abstract
- Context: Neuropsychiatric symptoms are common features of Graves disease (GD) in hyperthyroidism and after treatment. The mechanism behind these symptoms is unknown, but reduced hippocampal volumes have been observed in association with increased thyroid hormone levels. Objective: This work aimed at investigating GD influence on regional medial temporal lobe (MTL) volumes. Methods: Sixty-two women with newly diagnosed GD underwent assessment including magnetic resonance (MR) imaging in hyperthyroidism and 48 of them were followed up after a mean of 16.4±4.2 SD months of treatment. Matched thyroid-healthy controls were also assessed twice at a 15-month interval. MR images were automatically segmented using multiatlas propagation with enhanced registration. Regional medial temporal lobe (MTL) volumes for amygdalae and hippocampi were compared with clinical data and data from symptom questionnaires and neuropsychological tests. Results: Patients had smaller MTL regions than controls at inclusion. At follow-up, all 4 MTL regions had increased volumes and only the volume of the left amygdala remained reduced compared to controls. There were significant correlations between the level of thyrotropin receptor antibodies (TRAb) and MTL volumes at inclusion and also between the longitudinal difference in the levels of free 3,5,3′-triiodothyronine and TRAb and the difference in MTL volumes. There were no significant correlations between symptoms or test scores and any of the 4 MTL volumes. Conclusion: Dynamic alterations in the amygdalae and hippocampi in GD reflect a previously unknown level of brain involvement both in the hyperthyroid state of the condition and after treatment. The clinical significance, as well as the mechanisms behind these novel findings, warrant further study of the neurological consequences of GD.
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6. |
- Holmberg, Mats, 1958, et al.
(author)
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Structural brain changes in hyperthyroid Graves' disease: protocol for an ongoing longitudinal, case-controlled study in Göteborg, Sweden-the CogThy project.
- 2019
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In: BMJ open. - : BMJ. - 2044-6055. ; 9:11
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Journal article (peer-reviewed)abstract
- Cognitive impairment and reduced well-being are common manifestations of Graves' disease (GD). These symptoms are not only prevalent during the active phase of the disease but also often prevail for a long time after hyperthyroidism is considered cured. The pathogenic mechanisms involved in these brain-derived symptoms are currently unknown. The overall aim of the CogThy study is to identify the mechanism behind cognitive impairment to be able to recognise GD patients at risk.The study is a longitudinal, single-centre, case-controlled study conducted in Göteborg, Sweden on premenopausal women with newly diagnosed GD. The subjects are examined: at referral, at inclusion and then every 3.25 months until 15 months. Examinations include: laboratory measurements; eye evaluation; neuropsychiatric and neuropsychological testing; structural MRI of the whole brain, orbits and medial temporal lobe structures; functional near-infrared spectroscopy of the cerebral prefrontal cortex and self-assessed quality of life questionnaires. The primary outcome measure is the change in medial temporal lobe structure volume. Secondary outcome measures include neuropsychological, neuropsychiatric, hormonal and autoantibody variables. The study opened for inclusion in September 2012 and close for inclusion in October 2019. It will provide novel information on the effect of GD on medial temporal lobe structures and cerebral cortex functionality as well as whether these changes are associated with cognitive and affective impairment, hormonal levels and/or autoantibody levels. It should lead to a broader understanding of the underlying pathogenesis and future treatment perspectives.The study has been reviewed and approved by the Regional Ethical Review Board in Göteborg, Sweden. The results will be actively disseminated through peer-reviewed journals, national and international conference presentations and among patient organisations after an appropriate embargo time.44321 at the public project database for research and development in Västra Götaland County, Sweden (https://www.researchweb.org/is/vgr/project/44321).
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7. |
- Klasson, Niklas, et al.
(author)
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Delineation of two intracranial areas and the perpendicular intracranial width is sufficient for intracranial volume estimation
- 2018
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In: Insights into Imaging. - : Springer Science and Business Media LLC. - 1869-4101. ; 9:1, s. 25-34
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Journal article (peer-reviewed)abstract
- Objectives The aim of the present study is to determine if the delineation of one or two optimally chosen intracranial areas (ICA) is enough to achieve adequate estimates of intracranial volume (ICV) in magnetic resonance imaging. MethodsThe correlations of 62 fully delineated ICVs with four types of ICV estimates were calculated. The estimate types were: (1) a single midsagittal ICA, (2) single ICA multiplied by the intracranial width perpendicular to the ICA, (3) sum of two ICAs multiplied by the perpendicular intracranial width and (4) shape-preserving piecewise cubic interpolation using two ICAs. For methods 2-4, the fully delineated ICVs were randomly separated into an evaluation and a validation set of equal size. Method 1 was validated against all of the fully delineated ICVs. Result Estimates from method 1 had a Pearson correlation of 0.904 with fully delineated ICV. For method 2, the correlation was 0.986 when delineating the sagittal ICA at 31% of the sagittal intracranial width. For methods 3 and 4, the correlations were both 0.997 when delineating the sagittal ICAs at 17.5 and 64% and at 12 and 64% respectively. conclusions Delineation of two specific intracranial areas is sufficient for intracranial volume estimation. Delineation of two specific intracranial areas is sufficient for intracranial volume estimation. The estimates had a Pearson correlation of 0.997 with intracranial volume.
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8. |
- Klasson, Niklas, et al.
(author)
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Estimated intracranial volume from FreeSurfer is biased by total brain volume
- 2018
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In: European Radiology Experimental. - : Springer Science and Business Media LLC. - 2509-9280. ; 2
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Journal article (peer-reviewed)abstract
- Background Estimated intracranial volume (eTIV) from FreeSurfer is not segmentation-based but calculated from the alignment of the input magnetic resonance (MR) images to the MNI305 brain atlas, an approach that could lead to a bias by total brain volume. If eTIV is unbiased, variance beyond that explained by intracranial volume should be random. Our null hypothesis was that no correlation would remain between eTIV and total brain volume when controlling for intracranial volume. Methods eTIV and total brain volume for 62 participants were calculated on 1.5-T, T1-weighted MR images using FreeSurfer (version 6.0.0). Manual delineations of the intracranial volume were also made for the same images. To evaluate the null hypothesis, the partial correlation between eTIV and total brain volume was calculated when controlling for intracranial volume. Results The partial correlation between eTIV and total brain volume when controlling for intracranial volume was 0.355 (p=0.026). The null hypothesis was rejected. Conclusion eTIV from FreeSurfer is biased by total brain volume.
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9. |
- Klasson, Niklas
(author)
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Intracranial volume in neuroimaging: estimation and use in regional brain volume normalization
- 2019
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Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis is to validate methods for estimation of intracranial volume in magnetic resonance images and to improve our understanding of the effect of intracranial volume normalization. To achieve the first part of the aim, 62 gold standard estimates of intracranial volume were generated by manually segmenting 1.5 T T1-weighted magnetic resonance images. These estimates were then used to validate a more work-efficient manual method that is frequently used in neuroimaging research. We also proposed an even more work-efficient method for situations where only a strong linear association between estimate and gold standard are required (rather than a strong agreement). Finally, we evaluated the validity of a frequently used automatic method for estimation of intracranial volume. To achieve the second part of the aim, we presented mathematical functions that predict the effect of intracranial volume normalization on the mean value and variance of the brain estimates and their Pearson’s correlation to intracranial volume. We found that segmentations of one intracranial area every 10th mm in magnetic resonance images will result in valid estimates of intracranial volume (intraclass correlation with absolute agreement to gold standard estimates >0.998). The segmentation of two intracranial areas and the estimation of the perpendicular intracranial width will result in estimates with strong linear association to gold standard estimates (Pearson’s correlation >0.99). It was also shown that FreeSurfer’s automatic estimates of intracranial volume risk being biased by total brain volume. Further, the presented mathematical functions closely predicted the effect of intracranial volume normalization on certain statistics of brain estimates, both in a simulation and compared to actual data from other studies. All these findings contribute to an improved intracranial volume estimation and a better use of intracranial volume in regional brain volume normalization.
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10. |
- Klasson, Niklas, et al.
(author)
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Valid and efficient manual estimates of intracranial volume from magnetic resonance images
- 2015
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In: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 15
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Journal article (peer-reviewed)abstract
- Background: Manual segmentations of the whole intracranial vault in high-resolution magnetic resonance images are often regarded as very time-consuming. Therefore it is common to only segment a few linearly spaced intracranial areas to estimate the whole volume. The purpose of the present study was to evaluate how the validity of intracranial volume estimates is affected by the chosen interpolation method, orientation of the intracranial areas and the linear spacing between them. Methods: Intracranial volumes were manually segmented on 62 participants from the Gothenburg MCI study using 1.5 T, T-1-weighted magnetic resonance images. Estimates of the intracranial volumes were then derived using subsamples of linearly spaced coronal, sagittal or transversal intracranial areas from the same volumes. The subsamples of intracranial areas were interpolated into volume estimates by three different interpolation methods. The linear spacing between the intracranial areas ranged from 2 to 50 mm and the validity of the estimates was determined by comparison with the entire intracranial volumes. Results: A progressive decrease in intra-class correlation and an increase in percentage error could be seen with increased linear spacing between intracranial areas. With small linear spacing (<= 15 mm), orientation of the intracranial areas and interpolation method had negligible effects on the validity. With larger linear spacing, the best validity was achieved using cubic spline interpolation with either coronal or sagittal intracranial areas. Even at a linear spacing of 50 mm, cubic spline interpolation on either coronal or sagittal intracranial areas had a mean absolute agreement intra-class correlation with the entire intracranial volumes above 0.97. Conclusion: Cubic spline interpolation in combination with linearly spaced sagittal or coronal intracranial areas overall resulted in the most valid and robust estimates of intracranial volume. Using this method, valid ICV estimates could be obtained in less than five minutes per patient.
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11. |
- Malmgren, Helge, 1945, et al.
(author)
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Modelling complex Hebbian reverberations with sets of spiking oscillators
- 2017
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In: The 21th annual meeting of the Association for the Scientific Study of Consciousness, Beijing 13–16 June 2017.
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Conference paper (other academic/artistic)abstract
- In 1949, Donald Hebb suggested that sensory information can be held in the form of reverberating neural activity before being coded as synaptic modifications. The idea has won widespread acceptance, but one central question remains: by what mechanism can an incoming sensory sequence force the output of a neuronal assembly to enter a closed trajectory that mimics the sequence? We here offer a radically new answer. Our model assumes the existence of a large set of neural oscillators, having a wide spectrum of frequencies, that interact with the input through a resonant layer. In the learning phase the activity in the resonant layer mirrors input. At each moment, oscillators that are close to firing threshold are set either to be silent or to fire depending on the present input. This entrainment gives rise to a frequency-phase transform, coded as the current activity in the set of oscillators, of the input sequence. In the retrieval phase, the input signal is shut off from access to the resonant layer. This layer now mirrors the activity of the oscillators, or of a chosen subset of oscillators. If, in the simple discrete-time case, only oscillators with a period of N are allowed to influence the resonant layer, the input during the last N moments will be replayed in this layer during the following N moments. The choice of oscillator period may correspond to a conscious decision to recall the immediately past N moments. We show results from two simulations of the proposed mechanism.
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13. |
- Olsson, Erik, 1960, et al.
(author)
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White Matter Lesion Assessment in Patients with Cognitive Impairment and Healthy Controls: Reliability Comparisons between Visual Rating, a Manual, and an Automatic Volumetrical MRI Method-The Gothenburg MCI Study.
- 2013
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In: Journal of aging research. - : Hindawi Limited. - 2090-2204 .- 2090-2212. ; 2013
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Journal article (peer-reviewed)abstract
- Age-related white matter lesions (WML) are a risk factor for stroke, cognitive decline, and dementia. Different requirements are imposed on methods for the assessment of WML in clinical settings and for research purposes, but reliability analysis is of major importance. In this study, WML assessment with three different methods was evaluated. In the Gothenburg mild cognitive impairment study, MRI scans from 152 participants were used to assess WML with the Fazekas visual rating scale on T2 images, a manual volumetric method on FLAIR images, and FreeSurfer volumetry on T1 images. Reliability was acceptable for all three methods. For low WML volumes (2/3 of the patients), reliability was overall lower and nonsignificant for the manual volumetric method. Unreliability in the assessment of patients with low WML with manual volumetry may mainly be due to intensity variation in the FLAIR sequence used; hence, intensity standardization and normalization methods must be used for more accurate assessments. The FreeSurfer segmentations resulted in smaller WML volumes than the volumes acquired with the manual method and showed deviations from visible hypointensities in the T1 images, which quite likely reduces validity.
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