| 1. |
- Spotorno, Nicola, et al.
(författare)
-
Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia
- 2020
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
-
Tidskriftsartikel (refereegranskat)abstract
- Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo, especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process.
|
|
| 2. |
- 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.
|
|
| 3. |
- Janelidze, Shorena, et al.
(författare)
-
Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype
- 2017
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 51, s. 104-112
-
Tidskriftsartikel (refereegranskat)abstract
- Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF bio-markers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage. (C) 2016 The Authors. Published by Elsevier Inc.
|
|
| 4. |
- Mårtensson, Johanna, et al.
(författare)
-
Spatial analysis of diffusion tensor tractography statistics along the inferior fronto-occipital fasciculus with application in progressive supranuclear palsy
- 2013
-
Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 26:6, s. 527-537
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to develop a method for analysis of diffusion parameters along white matter (WM) tracts, using spatial normalization based on anatomical landmarks, and to introduce the apparent area coefficient (AAC). The method's applicability was tested in the inferior fronto-occipital fasciculus (IFO) in patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). A framework for analysis of diffusion parameters was developed. Spatial normalization of the tracts was performed using anatomical landmarks, to avoid deformations caused by cerebral atrophy. Initially, 38 HCs were used to optimize a threshold for the minimal size of regions that differ between groups. The fractional anisotropy, mean diffusivity, AAC, and the hemispheric asymmetry index (AI), were compared between 11 PSP patients and 15 HCs. The method was feasible for analysis of PSP patients and HCs. The AI showed that the observed hemispheric asymmetry of AAC was significantly larger in PSP patients compared with HCs in small regions of the IFO. The method was successfully employed for analysis of diffusion parameters along the IFO in a patient group. This method can be potentially useful in studies of WM diseases, with or without cerebral atrophy.
|
|
| 5. |
- Puschmann, Andreas, et al.
(författare)
-
A Swedish family with de novo alpha-synuclein A53T mutation: Evidence for early cortical dysfunction.
- 2009
-
Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 15, s. 627-632
-
Tidskriftsartikel (refereegranskat)abstract
- A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G > A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected, but was not associated with disease state.
|
|
| 6. |
|
|
| 7. |
- Santillo, Alexander Frizell, et al.
(författare)
-
Diffusion Tensor Tractography versus Volumetric Imaging in the Diagnosis of Behavioral Variant Frontotemporal Dementia
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7, s. e66932-
-
Tidskriftsartikel (refereegranskat)abstract
- MRI diffusion tensor imaging (DTI) studies of white matter integrity in behavioral variant frontotemporal dementia have consistently shown involvement of frontal and temporal white matter, corresponding to regional loss of cortical volume. Volumetric imaging has a suboptimal sensitivity as a diagnostic tool and thus we wanted to explore if DTI is a better method to discriminate patients and controls than volumetric imaging. We examined the anterior cingulum bundle in 14 patients with behavioral variant frontotemporal dementia and 22 healthy controls using deterministic manual diffusion tensor tractography, and compared DTI parameters with two measures of cortical atrophy, VBM and cortical thickness, of the anterior cingulate cortex (ACC). Statistically significant changes between patients and controls were detected in all DTI parameters, with large effect sizes. ROC-AUC was for the best DTI parameters: 0.92 (fractional anisotropy) to 0.97 (radial diffusivity), 0.82 for the best cortical parameter, VBM of the ACC. Results from the AUC were confirmed with binary logistic regression analysis including demographic variables, but only for fractional anisotropy and mean diffusivity. Ability to classify patient/nonpatient status was significantly better for mean diffusivity vs. VBM (p = 0.031), and borderline significant for fractional anisotropy vs. VBM (p = 0.062). The results indicate that DTI could offer advantages in comparison with the assessment of cortical volume in differentiating patients with behavioral variant frontotemporal dementia and controls.
|
|
| 8. |
- Santillo, Alexander Frizell, et al.
(författare)
-
Grey and white matter clinico-anatomical correlates of disinhibition in neurodegenerative disease
- 2016
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:10
-
Tidskriftsartikel (refereegranskat)abstract
- Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico- anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information- based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insularorbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the prefrontal syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control.
|
|
| 9. |
|
|
| 10. |
|
|
