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Sökning: WFRF:(Lindberg Olof)

  • Resultat 1-10 av 83
  • [1]234567...9Nästa
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1.
  • Ferreira, Daniel, et al. (författare)
  • The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
  • 2017
  • Ingår i: Hippocampus. - : John Wiley and Sons. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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2.
  • Spotorno, N., 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. - 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.
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3.
  • Carlsson, Beatrice, et al. (författare)
  • Quasispecies dynamics and molecular evolution of human norovirus capsid P region during chronic infection
  • 2009
  • Ingår i: Journal of General Virology. - 0022-1317 .- 1465-2099. ; 90:2, s. 432-441
  • Tidskriftsartikel (refereegranskat)abstract
    • In this novel study, we have for the first time identified evolutionarily conserved capsid residues in an individual chronically infected with norovirus (GGII.3). From 2000 to 2003, a total of 147 P1-1 and P2 capsid sequences were sequenced and investigated for evolutionarily conserved and functionally important residues by the evolutionary trace (ET) algorithm. The ET algorithm revealed more absolutely conserved residues (ACR) in the P1-1 domain (47/53, 88 %) as compared with the P2 domain (86/133, 64 %). The capsid P1-1 and P2 domains evolved in time-dependent manner, with a distinct break point observed between autumn/winter of year 2000 (isolates P1, P3 and P5) and spring to autumn of year 2001 (isolates P11, P13 and P15), which presumably coincided with a change of clinical symptoms. Furthermore, the ET analysis revealed a similar receptor-binding pattern as reported for Norwalk and VA387 strains, with the CS-4 and CS-5 patch (Norwalk strain) including residues 329 and 377 and residues 306 and 310, respectively, all being ACR in all partitions. Most interesting was that residues 343, 344, 345, 374, 390 and 391 of the proposed receptor A and B trisaccharide binding site (VA387 strain) within the P2 domain remained ACR in all partitions, presumably because there was no selective advantage to alter the histo blood group antigens (HBGA) receptor binding specificity. In conclusion, this study provides novel insights to the evolutionary process of norovirus during chronic infection.
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4.
  • Johansson, M., et al. (författare)
  • Apathy and anxiety are early markers of Alzheimer's disease
  • 2020
  • Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 85, s. 74-82
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, we investigated associations between neuropsychiatric symptoms (i.e., apathy, anxiety, and depression) and cerebral atrophy, white matter lesions (WML), beta-amyloid (A beta) deposition, and cognitive decline in a nondemented sample. 104 cognitively unimpaired and 53 subjects with mild cognitive impairment were followed for up to 4 years within the Swedish BioFINDER study. Neuropsychiatric assessments included the Hospital Anxiety and Depression Scale and the Apathy Evaluation Scale. Magnetic resonance imaging and F-18-flutemetamol-positron emission tomography quantified brain atrophy, WML, and A beta deposition. Mini-Mental State Examination assessed longitudinal global cognition. Regression analyses were used to test for associations. Apathy and anxiety were shown related to A beta deposition and predicted cognitive decline. Anxiety also interacted with amyloid status to predict faster cognitive deterioration. Apathy was further related to frontotemporal and subcortical atrophy, as well as WML. To conclude, the associations between apathy and anxiety with A beta deposition and cognitive decline point to these symptoms as early clinical manifestations of Alzheimer's disease. (C) 2019 Elsevier Inc. All rights reserved.
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5.
  • Lindberg, Olof, et al. (författare)
  • Atrophy of the posterior subiculum is associated with memory impairment, Tau- and Aβ pathology in non-demented individuals
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S. A.. - 1663-4365. ; 9:SEP
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease (AD) is associated with atrophy of the cornu ammonis (CA) 1 and the subiculum subfield of the hippocampus (HC), and with deficits in episodic memory and spatial orientation. These deficits are mainly associated with the functionality of the posterior HC. We therefore hypothesized that key AD pathologies, i.e., β-amyloid and tau pathology would be particularly associated with the volume of the posterior subiculum in non-demented individuals. In our study we included 302 cognitively normal elderly participants (CN), 183 patients with subjective cognitive decline (SCD) and 171 patients with amnestic mild cognitive impairment (MCI), all of whom underwent 3T magnetic resonance images (MRI). The subicular subfield was segmented using Freesurfer 5.3 and divided into 10 volumetric segments moving from the most posterior (segment 1) to the most anterior part along the axis of the hippocampal head and body (segment 10). Cerebrospinal fluid (CSF) Aβ42 and phosphorylated tau (P-tau) were quantified using ELISA and were used as biomarkers for β-amyloid and tau pathology, respectively. In the total sample, tau-pathology and Aβ-pathology and (measured by elevated P-tau and low Aβ42 levels in CSF) and mild memory dysfunction were mostly associated with the volume changes of the posterior subiculum. Both SCD and MCI patients with elevated P-tau or low Aβ42 levels displayed predominantly posterior subicular atrophy in comparisons to control subjects with normal CSF biomarker levels. Finally, there was no main effect of Aβ42 or P-tau when comparing SCD with abnormal P-tau or Aβ42 with SCD with normal levels of these CSF-biomarkers. However, in the left subiculum there was a significant interaction revealing atrophy in the left posterior but not the anterior subiculum in participants with low Aβ42 levels. The same pattern was observed on the contralateral side in participants with elevated P-tau levels. In conclusion, AD pathologies and mild memory dysfunction are mainly associated with atrophy of the posterior parts of the subicular subfields of the HC in non-demented individuals. In light of these findings we suggest that segmentation of the HC subfields may benefit from considering the volume of the different anterior-posterior subsections of each subfield.
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6.
  • Lindberg, Olof, et al. (författare)
  • Cortical morphometric subclassification of frontotemporal lobar degeneration
  • 2009
  • Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 30:6, s. 1233-1239
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration (FTLD) is a primary neurodegenerative disease comprising 3 clinical subtypes: frontotemporal dementia (FTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). The subdivision is primarily based on the characteristic clinical symptoms displayed by each subtype. We hypothesized that these symptoms would be correlated to characteristic patterns of brain atrophy, which could be indentified and used for subclassification of subjects with FTLD. MATERIALS AND METHODS: Volumes of 9 cortical regions were manually parcellated and measured on both hemispheres on 27 controls, 12 patients with FTD, 9 patients with PNFA, and 13 patients with SD. The volumetric data were analyzed by traditional t tests and by a multivariate discriminant analysis (partial least squares discriminant analysis). RESULTS: The ensemble or pattern of atrophy was a good discriminator in pair-wise comparison between the subtypes: FTD compared with SD (sensitivity 100% [12/12], specificity 100% [13/13]); FTD compared with PNFA (sensitivity 92% [11/12], specificity 89% [8/9]); and SD compared with PNFA (sensitivity 86% [11/13], specificity 100% [9/9]). Temporal-versus-frontal atrophy was the most important pattern for discriminating SD from the other 2 subtypes. Right-sided versus left-sided atrophy was the most important pattern for discriminating between subjects with FTD and PNFA. CONCLUSIONS: FTLD subtypes generally display a characteristic pattern of atrophy, which may be considered in diagnosing patients with FTLD.
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7.
  • Lindberg, Olof, et al. (författare)
  • Hippocampal Shape Analysis in Alzheimer's Disease and Frontotemporal Lobar Degeneration Subtypes
  • 2012
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 30:2, s. 355-365
  • Tidskriftsartikel (refereegranskat)abstract
    • Hippocampal pathology is central to Alzheimer's disease (AD) and other forms of dementia such as frontotemporal lobar degeneration (FTLD). Autopsy studies have shown that certain hippocampal subfields are more vulnerable than others to AD and FTLD pathology, in particular the subiculum and cornu ammonis 1 (CA1). We conducted shape analysis of hippocampi segmented from structural T1 MRI images on clinically diagnosed dementia patients and controls. The subjects included 19 AD and 35 FTLD patients [13 frontotemporal dementia (FTD), 13 semantic dementia (SD), and 9 progressive nonfluent aphasia (PNFA)] and 21 controls. Compared to controls, SD displayed severe atrophy of the whole left hippocampus. PNFA and FTD also displayed atrophy on the left side, restricted to the hippocampal head in FTD. Finally, AD displayed most atrophy in left hippocampal body with relative sparing of the hippocampal head. Consistent with neuropathological studies, most atrophic deformation was found in CA1 and subiculum areas in FTLD and AD.
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8.
  • Looi Chee Leong, Jeffrey, et al. (författare)
  • Caudate nucleus volumes in frontotemporal lobar degeneration : differential atrophy in subtypes
  • 2008
  • Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 29:8, s. 1537-1543
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Frontostriatal circuits involving the caudate nucleus have been implicated in frontotemporal lobar degeneration (FTLD). We assessed caudate nucleus volumetrics in FTLD and subtypes: frontotemporal dementia (FTD, n = 12), semantic dementia (SD, n = 13), and progressive nonfluent aphasia (PNFA, n = 9) in comparison with healthy controls (n = 27) and subjects with Alzheimer disease (AD, n = 19). MATERIALS AND METHODS: Diagnoses were based on accepted clinical criteria. Manual volume measurement of the head and body of the caudate, excluding the tail, was conducted on T1-weighted brain MR imaging scans, using a published protocol, by a single analyst blinded to the diagnosis. RESULTS: Paired t tests (P < .05) showed that the right caudate nucleus volume was significantly larger than the left in controls and PNFA. No hemispheric asymmetry was found in AD, ETD, and SD. Across the groups, there was a positive partial correlation between the left caudate nucleus volume and Mini-Mental State Examination (MMSE) scores (r = 0.393, n = 76, P = .001) with higher left caudate volumes associated with higher MMSE scores. Multivariate analysis of covariance was used to assess the statistical significance between the subject groups (AD, ETD, SD, PNFA, and controls) as independent variables and raw right/left caudate volumes at the within-subject level (covariates: age and intracranial volume; P < .05). Control volume was largest, followed by AD (93% of control volume), SD (92%), PNFA (79%), and ETD (75%). CONCLUSIONS: Volume of the head and body of the caudate nucleus differs in subtypes of FTLD, due to differential frontostriatal dysfunction in subtypes being reflected in structural change in the caudate, and is correlated with cognition
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9.
  • Looi, Jefferey Chee Leong, et al. (författare)
  • Shape analysis of the neostriatum in frontotemporal lobar degeneration, Alzheimer's disease, and controls
  • 2010
  • Ingår i: NeuroImage. - 1053-8119 .- 1095-9572. ; 51:3, s. 970-986
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Frontostriatal circuit mediated cognitive dysfunction has been implicated in frontotemporal lobar degeneration (FTLD), but not Alzheimer's disease, or healthy aging. We measured the neostriatum (caudate nucleus and putamen) volume in FTLD (n=34), in comparison with controls (n=27) and Alzheimer's disease (AD, n=19) subjects. Methods: Diagnoses were based on international consensus criteria. Manual bilateral segmentation of the caudate nucleus and putamen was conducted blind to diagnosis by a single analyst, on MRI scans using a standardized protocol. Intra-cranial volume was calculated via a stereological point counting technique and was used for scaling the shape analysis. The manual segmentation binaries were analyzed using UNC Shape Analysis tools (University of North Carolina) to perform comparisons among FTLD, AD, and controls for global shape, local p-value significance maps, and mean magnitude of shape displacement. Results: Shape analysis revealed that there was significant shape difference between FTLD, AD, and controls, consistent with the predicted frontostriatal dysfunction and of significant magnitude, as measured by displacement maps. There was a lateralized difference in shape for the left caudate for FTLD compared to AD; non-specific global atrophy in AD compared to controls; while FTLD showed a more specific pattern in regions relaying fronto- and corticostriatal circuits. Conclusions: Shape analysis shows regional specificity of atrophy, manifest as shape deflation, with implications for frontostriatal and corticostriatal motoric circuits, in FTLD, AD, and controls.
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10.
  • Looi, Jeffrey Chee Leong, et al. (författare)
  • Shape analysis of the neostriatum in subtypes of frontotemporal lobar degeneration : neuroanatomically significant regional morphologic change
  • 2011
  • Ingår i: Psychiatry Research. - 0925-4927 .- 1872-7506. ; 191:2, s. 98-111
  • Tidskriftsartikel (refereegranskat)abstract
    • Frontostriatal circuit mediated cognitive dysfunction has been implicated in frontotemporal lobar degeneration (FTLD) and may differ across subtypes of FTLD. We manually segmented the neostriatum (caudate nucleus and putamen) in FTLD subtypes: behavioral variant frontotemporal dementia, FTD, n=12; semantic dementia, SD, n=13; and progressive non-fluent aphasia, PNFA, n=9); in comparison with controls (n=27). Diagnoses were based on international consensus criteria. Manual bilateral segmentation of the caudate nucleus and putamen was conducted blind to diagnosis by a single analyst, on MRI scans using a standardized protocol. Intracranial volume was calculated via a stereological point counting technique and was used for normalizing the shape analysis. Segmented binaries were analyzed using the Spherical Harmonic (SPHARM) Shape Analysis tools (University of North Carolina) to perform comparisons between FTLD subtypes and controls for global shape difference, local significance maps and mean magnitude maps of shape displacement. Shape analysis revealed that there was significant shape difference between FTLD subtypes and controls, consistent with the predicted frontostriatal dysfunction and of significant magnitude, as measured by displacement maps. These differences were not significant for SD compared to controls; lesser for PNFA compared to controls; whilst FTD showed a more specific pattern in regions relaying fronto- and corticostriatal circuits. Shape analysis shows regional specificity of atrophy, manifest as shape deflation, with a differential between FTLD subtypes, compared to controls.
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