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  • Hahn, Andreas, et al. (författare)
  • Association Between Earliest Amyloid Uptake and Functional Connectivity in Cognitively Unimpaired Elderly
  • 2019
  • Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 29, s. 2173-2182
  • Tidskriftsartikel (refereegranskat)abstract
    • Alterations in cognitive performance have been noted in nondemented subjects with elevated accumulation of amyloid-β (Aβ) fibrils. However, it is not yet understood whether brain function is already influenced by Aβ deposition during the very earliest stages of the disease. We therefore investigated associations between [18F]Flutemetamol PET, resting-state functional connectivity, gray and white matter structure and cognitive performance in 133 cognitively normal elderly that exhibited normal global Aβ PET levels. [18F]Flutemetamol uptake in regions known to accumulate Aβ fibrils early in preclinical AD (i.e., mainly certain parts of the default-mode network) was positively associated with dynamic but not static functional connectivity (r = 0.77). Dynamic functional connectivity was further related to better cognitive performance (r = 0.21-0.72). No significant associations were found for Aβ uptake with gray matter volume or white matter diffusivity. The findings demonstrate that the earliest accumulation of Aβ fibrils is associated with increased functional connectivity, which occurs before any structural alterations. The enhanced functional connectivity may reflect a compensatory mechanism to maintain high cognitive performance in the presence of increasing amyloid accumulation during the earliest phases of AD.
  • Hansson, Oskar, et al. (författare)
  • Cerebral hypoperfusion is not associated with an increase in amyloid β pathology in middle-aged or elderly people
  • 2018
  • Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5279 .- 1552-5260. ; 14:1, s. 54-61
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: It is hypothesized that cerebral hypoperfusion promotes the development of Alzheimer pathology. We therefore studied whether longstanding cerebral hypoperfusion is associated with Alzheimer pathology in nondemented humans.METHODS: Cerebral blood flow and amyloid β ((18)F-Flutemetamol) positron emission tomography retention were assessed in eleven patients with unilateral occlusion of precerebral arteries resulting in chronic and uneven hypoperfusion. A subset of patients underwent tau ((18)F-AV-1451) positron emission tomography.RESULTS: The blood flow was significantly reduced on the affected side of the brain in patients with unilateral occlusion of the internal carotid artery or stenosis of the middle cerebral artery. However, the cortical uptake of (18)F-Flutemetamol or (18)F-AV-1451 was not altered.DISCUSSION: Our results suggest that longstanding cerebral hypoperfusion in humans does not result in accumulation of amyloid β fibrils or tau aggregates.
  • Harper, Luke, et al. (författare)
  • Prenatal Gyrification Pattern Affects Age at Onset in Frontotemporal Dementia
  • 2022
  • Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 32:18, s. 3937-3944
  • Tidskriftsartikel (refereegranskat)abstract
    • The paracingulate sulcus is a tertiary sulcus formed during the third trimester. In healthy individuals paracingulate sulcation is more prevalent in the left hemisphere. The anterior cingulate and paracingulate gyri are focal points of neurodegeneration in behavioral variant frontotemporal dementia (bvFTD). This study aims to determine the prevalence and impact of paracingulate sulcation in bvFTD. Structural magnetic resonance images of individuals with bvFTD (n = 105, mean age 66.9 years), Alzheimer's disease (n = 92, 73.3), and healthy controls (n = 110, 62.4) were evaluated using standard protocol for hemispheric paracingulate sulcal presence. No difference in left hemisphere paracingulate sulcal frequency was observed between groups; 0.72, 0.79, and 0.70, respectively, in the bvFTD, Alzheimer's disease, and healthy control groups, (P = 0.3). A significant impact of right (but not left) hemispheric paracingulate sulcation on age at disease onset was identified in bvFTD (mean 60.4 years where absent vs. 63.8 where present [P = 0.04, Cohen's d = 0.42]). This relationship was not observed in Alzheimer's disease. These findings demonstrate a relationship between prenatal neuronal development and the expression of a neurodegenerative disease providing a gross morphological example of brain reserve.
  • Håkansson, Claes, et al. (författare)
  • Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience
  • 2022
  • Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 32, s. 1127-1134
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. Methods Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's kappa (dichotomized data), Cohen's kappa(w), and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as kappa/kappa(w) >= 0.80 and ICC >= 0.80 (significance level at 95% CI >= 0.65). Results Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's kappa. All raters achieved adequate agreement expressed as Cohen's kappa(w) and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. Conclusion We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences.
  • Håkansson, Claes, et al. (författare)
  • Reporting frequency of radiology findings increases after introducing visual rating scales in the primary care diagnostic work up of subjective and mild cognitive impairment
  • 2021
  • Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 31:2, s. 666-673
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Study the effect of introducing a template for radiological reporting of non-enhanced computed tomography (NECT) in the primary care diagnostic work up of cognitive impairment using visual rating scales (VRS). Methods Radiology reports were assessed regarding compliance with a contextual report template and the reporting of the parameters medial temporal lobe atrophy (MTA), white matter changes (WMC), global cortical atrophy (GCA), and width of lateral ventricles (WLV) using established VRS in two age-matched groups examined with NECT before (n= 111) and after (n= 125) the introduction of contextual reporting at our department. True positive rate (TPR) and true negative rate (TNR) before and after were compared. Results We observed a significant increase in the percentage of radiology reports with mentioning of MTA from 29 to 76% (p< 0.001), WMC from 69 to 86% (p< 0.01), and GCA from 54 to 82% (p< 0.001). We observed a significant increase in the percentages of reports where all of the parameters were mentioned, from 6 to 29% (p< 0.001). There was a significant increase in TPR from 10 to 55% for MTA. Conclusion This study suggests that contextual radiological assessment using VRS could increase the reporting frequency of radiology findings in the diagnostic work up of cognitive impairment but compliance with templates may be difficult to endorse.
  • Håkansson, Claes, et al. (författare)
  • Structural imaging findings on non-enhanced computed tomography are severely underreported in the primary care diagnostic work-up of subjective cognitive decline
  • 2019
  • Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 0028-3940 .- 1432-1920. ; 61:4, s. 397-404
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The purpose of this study was to investigate how structural imaging findings of medial temporal lobe atrophy (MTA), posterior cortical atrophy (PCA), global cortical atrophy (GCA), white matter changes (WMC), and Evans’ index/width of lateral ventricles (EI/WLV) are reported in the primary care diagnostic work-up of patients with subjective cognitive decline or mild cognitive impairment. Methods: We included 197 patients referred to a non-enhanced computed tomography (NECT) as part of the diagnostic work-up. We compared the frequencies of reported findings in radiology reports written by neuroradiologists and general radiologists with actual pathological findings in a second view done by a single neuroradiologist using the MTA, PCA, GCA, WMC, and EI/WLV visual rating scales. Structural findings were also compared to cognitive tests. Results: We found that MTA and PCA were clearly underreported by both neuroradiologists and general radiologists. The presence of GCA and WMC was also underreported among general radiologists. Only MTA showed a clear association with cognitive test results. Conclusions: We believe that the use of visual rating scales should be put into clinical practice to increase the yield of clinical NECT exams in the investigation of cognitive impairment. Special emphasis should be put on reporting MTA.
  • Jakabek, David, et al. (författare)
  • Regional structural hypo- and hyperconnectivity of frontal–striatal and frontal–thalamic pathways in behavioral variant frontotemporal dementia
  • 2018
  • Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471. ; 39:10, s. 4083-4093
  • Tidskriftsartikel (refereegranskat)abstract
    • Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal–subcortical connections. We aim to characterize the grey and white matter components of frontal–thalamic and frontal–striatal circuits in bvFTD. Twenty-four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal–striatal–thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p =.032, and 217% in the thalamus, p =.004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p =.002, and 65% in the thalamus, p =.020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal–subcortical networks; however, longitudinal studies are necessary to test this hypothesis.
  • Jakabek, David, et al. (författare)
  • Structural and microstructural thalamocortical network disruption in sporadic behavioural variant frontotemporal dementia
  • 2023
  • Ingår i: NeuroImage: Clinical. - 2213-1582. ; 39, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
  • Jalakas, Mattis, et al. (författare)
  • A quick test of cognitive speed can predict development of dementia in Parkinson’s disease
  • 2019
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Parkinson’s disease (PD) patients frequently develop cognitive impairment. There is a need for brief clinical assessments identifying PD patients at high risk of progressing to dementia. In this study, we look into predicting dementia in PD and underlying structural and functional correlates to cognitive decline in PD. We included 175 patients with PD, 30 with PD dementia, 51 neurologically healthy controls and 121 patients with Alzheimer’s disease (AD) from Skane University Hospital, BIOFINDER cohorts. All underwent cognitive tests, including MMSE, 10-word list delayed recall (ADAS-cog), A Quick Test of cognitive speed (AQT), Letter S fluency, Clock Drawing Test (CDT) and pentagon copying. In non-demented patients with PD, abnormal AQT and CDT results predicted an increased risk of subsequent development of dementia (hazard ratio 2.2 for both). When comparing the cognitive profile between PD and AD, decreased performance on AQT, which measures attention and processing speed, was more typical in PD. Lastly, we investigated the underlying structural and functional correlates for the PD-specific test AQT with magnetic resonance imaging. In PD patients, decreased performance on AQT was associated with i) cortical thinning in temporoparietal regions, ii) changes in diffusion MRI, especially in the cingulum tract, and iii) decreased functional connectivity in posterior brain networks.
  • Janelidze, Shorena, et al. (författare)
  • CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios : better diagnostic markers of Alzheimer disease
  • 2016
  • Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 3:3, s. 65-154
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) must be improved before widespread clinical use. This study aimed to determine whether CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios are better diagnostic biomarkers of AD during both predementia and dementia stages in comparison to CSF Aβ42 alone.METHODS: The study comprised three different cohorts (n = 1182) in whom CSF levels of Aβ42, Aβ40, and Aβ38 were assessed. CSF Aβs were quantified using three different immunoassays (Euroimmun, Meso Scale Discovery, Quanterix). As reference standard, we used either amyloid ((18)F-flutemetamol) positron emission tomography (PET) imaging (n = 215) or clinical diagnosis (n = 967) of well-characterized patients.RESULTS: When using three different immunoassays in cases with subjective cognitive decline and mild cognitive impairment, the CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios were significantly better predictors of abnormal amyloid PET than CSF Aβ42. Lower Aβ42, Aβ42/Aβ40, and Aβ42/Aβ38 ratios, but not Aβ40 and Aβ38, correlated with smaller hippocampal volumes measured by magnetic resonance imaging. However, lower Aβ38, Aβ40, and Aβ42, but not the ratios, correlated with non-AD-specific subcortical changes, that is, larger lateral ventricles and white matter lesions. Further, the Aβ42/Aβ40 and Aβ42/Aβ38 ratios showed increased accuracy compared to Aβ42 when distinguishing AD from dementia with Lewy bodies or Parkinson's disease dementia and subcortical vascular dementia, where all Aβs (including Aβ42) were decreased.INTERPRETATION: The CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios are significantly better than CSF Aβ42 to detect brain amyloid deposition in prodromal AD and to differentiate AD dementia from non-AD dementias. The ratios reflect AD-type pathology better, whereas decline in CSF Aβ42 is also associated with non-AD subcortical pathologies. These findings strongly suggest that the ratios rather than CSF Aβ42 should be used in the clinical work-up of AD.
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