| 1. |
- 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.
|
|
| 2. |
- Langensee, Lara, et al.
(författare)
-
Beyond the language network : Associations between reading, receptive vocabulary, and grey matter volume in 10-year-olds
- 2023
-
Ingår i: Neuropsychologia. - 0028-3932. ; 191
-
Tidskriftsartikel (refereegranskat)abstract
- Most research on the neurostructural basis of language abilities in children stems from small samples and surface-based measures. To complement and expand the existent knowledge, we investigated associations between grey matter volume and language performance in a large sample of 9-to-11-year-old children, using data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 1865) and an alternative measure of grey matter morphology. We estimated whole-brain grey matter volume for one half of the sample (N = 939) and tested for correlations with scores on a picture vocabulary and a letter and word reading test, with and without factoring in general intelligence and total grey matter volume as additional covariates. The initial analyses yielded correlations between grey matter in the right occipital fusiform gyrus, the right lingual gyrus, and the cerebellum for both vocabulary and reading. Employing the significant clusters from the first analyses as regions of interest in the second half of the cohort (N = 926) in correlational and multiple regression analyses suggests the cluster in the right occipital fusiform and lingual gyri to be most robust. Overall, the amount of variance explained by grey matter volume is limited and factoring in additional covariates paints an inconsistent picture. The present findings reinforce existent doubt with respect to explaining individual differences in reading and vocabulary performance based on unique contributions of macrostructural brain features.
|
|
| 3. |
- Spotorno, Nicola, et al.
(författare)
-
Measures of cortical microstructure are linked to amyloid pathology in Alzheimer's disease
- 2023
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 146:4, s. 1602-1614
-
Tidskriftsartikel (refereegranskat)abstract
- Markers of downstream events are a key component of clinical trials of disease-modifying therapies for Alzheimer's disease. Morphological metrics like cortical thickness are established measures of atrophy but are not sensitive enough to detect amyloid-beta (Aβ)- related changes that occur before overt atrophy become visible. We aimed to investigate to what extent diffusion MRI can provide sensitive markers of cortical microstructural changes and to test their associations with multiple aspects of the Alzheimer's disease pathological cascade, including both Aβ and tau accumulation, astrocytic activation and cognitive deficits. We applied the mean apparent diffusion propagator model to diffusion MRI data from 492 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER-2 cohort. Participants were stratified in Aβ-negative/tau-negative, Aβ-positive/tau-negative and Aβ-positive/tau-positive based on Aβ- and tau-PET uptake. Cortical regional values of diffusion MRI metrics and cortical thickness were compared across groups. Associations between regional values of diffusion MRI metrics and both Aβ- and tau-PET uptake were also investigated along with the association with plasma level of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation (available in 292 participants). Mean squared displacement revealed widespread microstructural differences already between Aβ-negative/tau-negative and Aβ-positive/tau-negative participants with a spatial distribution that closely resembled the pattern of Aβ accumulation. In contrast, differences in cortical thickness were clearly more limited. Mean squared displacement was also correlated with both Aβ- and tau-PET uptake even independently from one another and from cortical thickness. Further, the same metric exhibited significantly stronger correlations with PET uptake than cortical thickness (P < 0.05). Mean squared displacement was also positively correlated with GFAP with a pattern that resembles Aβ accumulation, and GFAP partially mediated the association between Aβ accumulation and mean squared displacement. Further, impairments in executive functions were significantly more associated with mean squared displacement values extracted from a meta-region of interest encompassing regions accumulating Aβ early in the disease process, than with cortical thickness (P < 0.05). Similarly, impairments in memory functions were significantly more associated with mean squared displacement values extracted from a temporal meta-region of interest than with cortical thickness (P < 0.05). Metrics of cortical microstructural alteration derived from diffusion MRI are highly sensitive to multiple aspects of the Alzheimer's disease pathological cascade. Of particular interest is the link with both Aβ-PET and GFAP, suggesting diffusion MRI might reflects microstructural changes related to the astrocytic response to Aβ aggregation. Therefore, metrics of cortical diffusion might be important outcome measures in anti-Aβ treatments clinical trials for detecting drug-induced changes in cortical microstructure.
|
|
| 4. |
- Wuestefeld, Anika, et al.
(författare)
-
Age-related and amyloid-beta-independent tau deposition and its downstream effects
- 2023
-
Ingår i: Brain : a journal of neurology. - 1460-2156. ; 146:8, s. 3192-3205
-
Tidskriftsartikel (refereegranskat)abstract
- Amyloid-β (Aβ) is hypothesized to facilitate the spread of tau pathology beyond the medial temporal lobe. However, there is evidence that, independently of Aβ, age-related tau pathology might be present outside of the medial temporal lobe. We therefore aimed to study age-related Aβ-independent tau deposition outside the medial temporal lobe in two large cohorts and to investigate potential downstream effects of this on cognition and structural measures. We included 545 cognitively unimpaired adults (40-92 years) from the BioFINDER-2 study (in vivo) and 639 (64-108 years) from the Rush Alzheimer's Disease Center cohorts (ex vivo). 18F-RO948- and 18F-flutemetamol-PET standardized uptake value ratios were calculated for regional tau and global/regional Aβ in vivo. Immunohistochemistry was used to estimate Aβ load and tangle density ex vivo. In vivo medial temporal lobe volumes (subiculum, cornu ammonis 1) and cortical thickness (entorhinal cortex, Brodmann area 35) were obtained using Automated Segmentation for Hippocampal Subfields packages. Thickness of early and late neocortical Alzheimer's disease regions was determined using FreeSurfer. Global cognition and episodic memory were estimated to quantify cognitive functioning. In vivo age-related tau deposition was observed in the medial temporal lobe and in frontal and parietal cortical regions, which was statistically significant when adjusting for Aβ. This was also observed in individuals with low Aβ load. Tau deposition was negatively associated with cortical volumes and thickness in temporal and parietal regions independently of Aβ. The associations between age and cortical volume or thickness were partially mediated via tau in regions with early Alzheimer's disease pathology, i.e. early tau and/or Aβ pathology (subiculum/Brodmann area 35/precuneus/posterior cingulate). Finally, the associations between age and cognition were partially mediated via tau in Brodmann area 35, even when including Aβ-PET as covariate. Results were validated in the ex vivo cohort showing age-related and Aβ-independent increases in tau aggregates in and outside the medial temporal lobe. Ex vivo age-cognition associations were mediated by medial and inferior temporal tau tangle density, while correcting for Aβ density. Taken together, our study provides support for primary age-related tauopathy even outside the medial temporal lobe in vivo and ex vivo, with downstream effects on structure and cognition. These results have implications for our understanding of the spreading of tau outside the medial temporal lobe, also in the context of Alzheimer's disease. Moreover, this study suggests the potential utility of tau-targeting treatments in primary age-related tauopathy, likely already in preclinical stages in individuals with low Aβ pathology.
|
|
