| 1. |
- Eratne, Dhamidhu, et al.
(författare)
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Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from non-progressors
- 2022
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X. ; 442
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Tidskriftsartikel (refereegranskat)abstract
- Background: Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non-neurodegenerative ‘non-progressor’ mimics of frontal lobe dysfunction, can be one of the most challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay. Methods: Cerebrospinal fluid (CSF) NfL, amyloid beta 1–42 (AB42), total and phosphorylated tau (T-tau, P-tau) levels were examined in patients with an initial diagnosis of bvFTD. Based on follow-up information, patients were categorised as Progressors or Non-Progressors: further subtyped into Non-Progressor Revised (non-neurological/neurodegenerative final diagnosis), and Non-Progressor Static (static deficits, not fully explained by non-neurological/neurodegenerative causes). Results: Forty-three patients were included: 20 Progressors, 23 Non-Progressors (15 Non-Progressor Revised, 8 Non-Progressor Static), and 20 controls. NfL concentrations were lower in Non-Progressors (Non-Progressors Mean, M = 554 pg/mL, 95%CI:[461, 675], Non-Progressor Revised M = 459 pg/mL, 95%CI:[385, 539], and Non-Progressor Static M = 730 pg/mL, 95%CI:[516, 940]), compared to Progressors (M = 2397 pg/mL, 95%CI:[1607, 3332]). NfL distinguished Progressors from Non-Progressors with the highest accuracy (area under the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive value, 88% accuracy). Non-Progressor Static tended to have higher T-tau and P-tau levels compared to Non-Progressor Revised Diagnoses. Conclusion: This study demonstrated strong diagnostic utility of CSF NfL to distinguish bvFTD from non-progressor variants, at baseline, with high accuracy, in a real-world clinical setting. This has important clinical implications, to improve outcomes for patients and clinicians facing this challenging clinical dilemma, healthcare services, and clinical trials. Further research is required to investigate heterogeneity within the non-progressor group and potential diagnostic algorithms, and prospective studies are underway assessing plasma NfL.
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| 2. |
- Eratne, Dhamidhu, et al.
(författare)
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Plasma neurofilament light chain is increased in Niemann-Pick Type C but glial fibrillary acidic protein remains normal
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Ingår i: Acta Neuropsychiatrica. - 0924-2708. ; , s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Niemann-Pick Type C (NPC) is a genetic neurodegenerative lysosomal storage disorder commonly associated with psychiatric symptoms and delays to accurate diagnosis and treatment. This study investigated biomarker levels and diagnostic utility of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in NPC compared to healthy controls. METHODS: Patients with NPC were recruited from a specialist assessment and management service. Data was available from an age and sex-matched healthy control group. NfL and GFAP were measured on Quanterix Simoa HD-X analysers and groups compared using generalised linear models. NfL levels were compared to, and percentiles derived from, recently developed NfL reference ranges. RESULTS: Plasma NfL was significantly elevated in 11 patients with NPC compared to 25 controls (mean 17.1pg/mL vs 7.4pg/mL, p<0.001), and reference ranges (all >98th percentile). NfL distinguished NPC from controls with high accuracy. GFAP levels were not elevated in NPC (66.6pg/mL vs 75.1pg/mL). DISCUSSION: The study adds important evidence on the potential diagnostic utility of plasma NfL in NPC, extends the literature of NfL as a diagnostic tool to differentiate neurodegenerative from primary psychiatric disorders, and adds support to the pathology in NPC primarily involving neuronal, particularly axonal, degeneration.
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| 3. |
- Jakabek, David, et al.
(författare)
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Regional structural hypo- and hyperconnectivity of frontal–striatal and frontal–thalamic pathways in behavioral variant frontotemporal dementia
- 2018
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471. ; 39:10, s. 4083-4093
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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.
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| 4. |
- Jakabek, David, et al.
(författare)
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Structural and microstructural thalamocortical network disruption in sporadic behavioural variant frontotemporal dementia
- 2023
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Ingår i: NeuroImage: Clinical. - 2213-1582. ; 39, s. 1-11
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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.
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| 5. |
- Kang, Matthew J.Y., et al.
(författare)
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Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders
- 2023
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Ingår i: Acta Neuropsychiatrica. - 0924-2708. ; 36:1, s. 17-28
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Tidskriftsartikel (refereegranskat)abstract
- Objective People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown. Methods We collected longitudinal diagnostic information (mean=36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other), and PSY. We pre-specified NfL>582pg/mL as indicative of ND/MCI/other. Results Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone. Conclusions CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.
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| 6. |
- Macfarlane, Matthew D, et al.
(författare)
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Striatal Atrophy in the Behavioural Variant of Frontotemporal Dementia: Correlation with Diagnosis, Negative Symptoms and Disease Severity.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Behavioural variant frontotemporal dementia (bvFTD) is associated with changes in dorsal striatal parts of the basal ganglia (caudate nucleus and putamen), related to dysfunction in the cortico-striato-thalamic circuits which help mediate executive and motor functions. We aimed to determine whether the size and shape of striatal structures correlated with diagnosis of bvFTD, and measures of clinical severity, behaviour and cognition.
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| 7. |
- Power, Brian D., et al.
(författare)
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Morphometric analysis of thalamic volume in progressive supranuclear palsy : In vivo evidence of regionally specific bilateral thalamic atrophy
- 2017
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Ingår i: Psychiatry Research - Neuroimaging. - : Elsevier BV. - 0925-4927. ; 265, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether differences were detectable in the volume and shape of the dorsal thalamus on magnetic resonance imaging in patients with progressive supranuclear palsy (PSP). Manual segmentation of the left and right thalami on magnetic resonance imaging scans occurred in 22 patients with clinically diagnosed PSP and 23 healthy controls; thalamic volumes (left, right, total) were calculated. Between group differences were explored by multivariate analysis of co-variance, using age and intracranial volume as covariates. Analysis of the shape of the thalamus was performed using the spherical harmonic point distribution method software package. Patients with PSP were found to have significant bilateral thalamic atrophy on magnetic resonance imaging; there was significant shape deflation over the anterior-lateral and anterior-ventral surfaces bilaterally, and over the right caudal thalamus. Recognizing decreased thalamic morphology in PSP patients in vivo may be an important component of an ensemble of diagnostic biomarkers in the future, particularly given the difficulty of distinguishing PSP from other Parkinsonian conditions early in the disease course.
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| 8. |
- Power, Brian D, et al.
(författare)
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Validation of a protocol for manual segmentation of the thalamus on magnetic resonance imaging scans.
- 2015
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0925-4927. ; 232:1, s. 98-105
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Tidskriftsartikel (refereegranskat)abstract
- We present a validated protocol for manual segmentation of the thalamus on T1-weighted magnetic resonance imaging (MRI) scans using brain image analysis software. The MRI scans of five normal control subjects were randomly selected from a larger cohort recruited from Lund University Hospital and Landskrona Hospital, Sweden. MRIs were performed using a 3.0T Philips MR scanner, with an eight-channel head coil, and high resolution images were acquired using a T1-weighted turbo field echo (T1 TFE) pulse sequence, with resulting voxel size 1×1×1mm(3). Manual segmentation of the left and right thalami and volume measurement was performed on 28-30 contiguous coronal slices, using ANALYZE 11.0 software. Reliability of image analysis was performed by measuring intra-class correlations between initial segmentation and random repeated segmentation of the left and right thalami (in total 10 thalami for segmentation); inter-rater reliability was measured using volumes obtained by two other experienced tracers. Intra-class correlations for two independent raters were 0.95 and 0.98; inter-class correlations between the expert rater and two independent raters were 0.92 and 0.98. We anticipate that mapping thalamic morphology in various neuropsychiatric disorders may yield clinically useful disease-specific biomarkers.
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