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- Bethlehem, RAI, et al.
(author)
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Brain charts for the human lifespan
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:7906, s. 525-
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Journal article (peer-reviewed)abstract
- Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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- Aguilar, C., et al.
(author)
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Automated CT-based segmentation and quantification of total intracranial volume
- 2015
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In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 25:11, s. 3151-3160
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Journal article (peer-reviewed)abstract
- Objectives To develop an algorithm to segment and obtain an estimate of total intracranial volume (tICV) from computed tomography (CT) images. Materials and methods Thirty-six CT examinations from 18 patients were included. Ten patients were examined twice the same day and eight patients twice six months apart (these patients also underwent MRI). The algorithm combines morphological operations, intensity thresholding and mixture modelling. The method was validated against manual delineation and its robustness assessed from repeated imaging examinations. Using automated MRI software, the comparability with MRI was investigated. Volumes were compared based on average relative volume differences and their magnitudes; agreement was shown by a Bland-Altman analysis graph. Results We observed good agreement between our algorithm and manual delineation of a trained radiologist: the Pearson's correlation coefficient was r = 0.94, tICVml[manual] = 1.05 x tICVml[automated] - 33.78 (R-2 = 0.88). Bland-Altman analysis showed a bias of 31 mL and a standard deviation of 30 mL over a range of 1265 to 1526 mL. Conclusions tICV measurements derived from CT using our proposed algorithm have shown to be reliable and consistent compared to manual delineation. However, it appears difficult to directly compare tICV measures between CT and MRI.
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- Badji, A., et al.
(author)
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Cerebrospinal Fluid Biomarkers, Brain Structural and Cognitive Performances Between Normotensive and Hypertensive Controlled, Uncontrolled and Untreated 70-Year-Old Adults
- 2022
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In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
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Journal article (peer-reviewed)abstract
- Background: Hypertension is an important risk factor for Alzheimer's disease (AD). The pathophysiological mechanisms underlying the relationship between AD and hypertension are not fully understood, but they most likely involve microvascular dysfunction and cerebrovascular pathology. Although previous studies have assessed the impact of hypertension on different markers of brain integrity, no study has yet provided a comprehensive comparison of cerebrospinal fluid (CSF) biomarkers and structural brain differences between normotensive and hypertensive groups in a single and large cohort of older adults in relationship to cognitive performances.Objective: The aim of the present work was to investigate the differences in cognitive performances, CSF biomarkers and magnetic resonance imaging (MRI) of brain structure between normotensive, controlled hypertensive, uncontrolled hypertensive, and untreated hypertensive older adults from the Gothenburg H70 Birth Cohort Studies.Methods: As an indicator of vascular brain pathology, we measured white matter hyperintensities (WMHs), lacunes, cerebral microbleeds, enlarged perivascular space (epvs), and fractional anisotropy (FA). To assess markers of AD pathology/neurodegeneration, we measured hippocampal volume, temporal cortical thickness on MRI, and amyloid-beta(42), phosphorylated tau, and neurofilament light protein (NfL) in cerebrospinal fluid. Various neuropsychological tests were used to assess performances in memory, attention/processing speed, executive function, verbal fluency, and visuospatial abilities.Results: We found more white matter pathology in hypertensive compared to normotensive participants, with the highest vascular burden in uncontrolled participants (e.g., lower FA, more WMHs, and epvs). No significant difference was found in any MRI or CSF markers of AD pathology/neurodegeneration when comparing normotensive and hypertensive participants, nor among hypertensive groups. No significant difference was found in most cognitive functions between groups.Conclusion: Our results suggest that good blood pressure control may help prevent cerebrovascular pathology. In addition, hypertension may contribute to cognitive decline through its effect on cerebrovascular pathology rather than AD-related pathology. These findings suggest that hypertension is associated with MRI markers of vascular pathology in the absence of a significant decline in cognitive functions.
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- Cedres, N., et al.
(author)
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Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals
- 2022
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:15
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Journal article (peer-reviewed)abstract
- Background and Objectives Several pathologic processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers toward the degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals. Methods The contribution of amyloid and tau pathology was assessed through CSF levels of the A beta(42/40) ratio and phosphorylated tau (p-tau). CSF A beta(38) levels were also measured. Cerebrovascular pathology was assessed using automatic segmentations of WM lesions (WMLs) on MRI. Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE epsilon 4 carriership were also included in the analysis as variables of interest. Results We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals aged 70 years, 51% female). WM lesion burden was the most important contributor to the degeneration of both cholinergic pathways (increase in mean square error [IncMSE] = 98.8% in the external capsule pathway and IncMSE = 93.3% in the cingulum pathway). Levels of A beta(38) and p-tau also contributed to cholinergic WM degeneration, especially in the external capsule pathway (IncMSE = 28.4% and IncMSE = 23.4%, respectively). The A beta(42/40) ratio did not contribute notably to the models (IncMSE<3.0%). APOE epsilon 4 carriers showed poorer integrity in the cingulum pathway (IncMSE = 21.33%). Women showed poorer integrity of the external capsule pathway (IncMSE = 21.55%), which was independent of amyloid status as reflected by the nonsignificant differences in integrity when comparing amyloid-positive vs amyloid-negative women participants (T-201 = -1.55; p = 0.123). Discussion In cognitively unimpaired older individuals, WMLs play a central role in the degeneration of cholinergic pathways. Our findings highlight the importance of WM lesion burden in the elderly population, which should be considered in the development of prevention programs for neurodegeneration and cognitive impairment.
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- Lindberg, O., et al.
(author)
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Effects of amyloid pathology and the APOE epsilon 4 allele on the association between cerebrospinal fluid A beta 38 and A beta 40 and brain morphology in cognitively normal 70-years-olds
- 2021
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 101, s. 1-12
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Journal article (peer-reviewed)abstract
- The association between cerebrospinal fluid (CSF) amyloid beta (A beta) A beta 38 or A beta 40 and brain grey- and white matter integrity is poorly understood. We studied this in 213 cognitively normal 70-year-olds, and in subgroups defined by presence/absence of the APOE epsilon 4 allele and A beta pathology: A beta-/APOE-, A beta+/APOE-, A beta-/APOE+ and A beta+/APOE+. CSF A beta was quantified using ELISA and genotyping for APOE was performed. Low CSF A beta 42 defined A beta plaque pathology. Brain volumes were assessed using Freesurfer-5.3, and white matter integrity using tract-based statistics in FSL. A beta 38 and A beta 40 were positively correlated with cortical thickness, some subcortical volumes and white matter integrity in the total sample, and in 3 of the subgroups: A beta-/APOE-, A beta+/APOE- and A beta-/APOE+. In A beta+/APOE+ subjects, higher A beta 38 and A beta 40 were linked to reduced cortical thickness and subcortical volumes. We hypothesize that production of all A beta species decrease in brain regions with atrophy. In A beta+/APOE+, A beta-dysregulation may be linked to cortical atrophy in which high A beta levels is causing pathological changes in the gray matter of the brain. (C) 2020 The Author(s). Published by Elsevier Inc.
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| 9. |
- Salvado, G., et al.
(author)
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The protective gene dose effect of the APOE epsilon 2 allele on gray matter volume in cognitively unimpaired individuals
- 2022
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:7, s. 1383-1395
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Journal article (peer-reviewed)abstract
- Introduction: Harboring two copies of the apolipoprotein E (APOE) epsilon 2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired epsilon 2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of epsilon 2 genotypic groups were compared to each other and to the reference group (APOE epsilon 3/epsilon 3). Results: Carrying at least one epsilon 2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE epsilon 2 homozygotes, but not APOE epsilon 2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-beta deposition, the larger GM volumes in key brain regions may confer APOE epsilon 2 homozygotes additional protection against AD-related cognitive decline.
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