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Sökning: WFRF:(van Westen D)

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  • Salvado, G., et al. (författare)
  • The protective gene dose effect of the APOE epsilon 2 allele on gray matter volume in cognitively unimpaired individuals
  • 2022
  • Ingår i: Alzheimers & Dementia. - 1552-5260.
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Harboring two copies of the apolipoprotein E (APOE) epsilon 2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired epsilon 2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of epsilon 2 genotypic groups were compared to each other and to the reference group (APOE epsilon 3/epsilon 3). Results: Carrying at least one epsilon 2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE epsilon 2 homozygotes, but not APOE epsilon 2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-beta deposition, the larger GM volumes in key brain regions may confer APOE epsilon 2 homozygotes additional protection against AD-related cognitive decline.
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  • Janelidze, S., et al. (författare)
  • Plasma beta-amyloid in Alzheimer's disease and vascular disease
  • 2016
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Implementation of amyloid biomarkers in clinical practice would be accelerated if such biomarkers could be measured in blood. We analyzed plasma levels of A beta 42 and A beta 40 in a cohort of 719 individuals (the Swedish BioFINDER study), including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer's disease (AD) dementia and cognitively healthy elderly, using a ultrasensitive immunoassay (Simoa platform). There were weak positive correlations between plasma and cerebrospinal fluid (CSF) levels for both A beta 42 and A beta 40, and negative correlations between plasma A beta 42 and neocortical amyloid deposition (measured with PET). Plasma levels of A beta 42 and A beta 40 were reduced in AD dementia compared with all other diagnostic groups. However, during the preclinical or prodromal AD stages (i.e. in amyloid positive controls, SCD and MCI) plasma concentration of A beta 42 was just moderately decreased whereas A beta 40 levels were unchanged. Higher plasma (but not CSF) levels of A beta were associated with white matter lesions, cerebral microbleeds, hypertension, diabetes and ischemic heart disease. In summary, plasma A beta is overtly decreased during the dementia stage of AD indicating that prominent changes in A beta metabolism occur later in the periphery compared to the brain. Further, increased levels of A beta in plasma are associated with vascular disease.
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  • Smith, R., et al. (författare)
  • 18 F-Flortaucipir in TDP-43 associated frontotemporal dementia
  • 2019
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Retention of 18 F-Flortaucipir is reportedly increased in the semantic variant of primary progressive aphasia (svPPA), which is dominated by TDP-43 pathology. However, it is unclear if 18 F-Flortaucipir is also increased in other TDP-43 diseases, such as bvFTD caused by a C9orf72 gene mutation. We therefore recruited six C9orf72 expansion carriers, six svPPA patients, and 54 healthy controls. All underwent 18 F-Flortaucipir PET and MRI scanning. Data from 39 Alzheimer’s Disease patients were used for comparison. PET tracer retention was assessed both at the region-of-interest (ROI) and at the voxel-level. Further, autoradiography using 3 H-Flortaucipir was performed. SvPPA patients exhibited higher 18 F-Flortaucipir retention in the lateral temporal cortex bilaterally according to ROI- and voxel-based analyses. In C9orf72 patients, 18 F-Flortaucipir binding was slightly increased in the inferior frontal lobes in the ROI based analysis, but these results were not replicated in the voxel-based analysis. Autoradiography did not show specific binding in svPPA cases or in C9orf72-mutation carriers. In conclusion, temporal lobe 18 F-Flortaucipir retention was observed in some cases of svPPA, but the uptake was of a lower magnitude compared to AD dementia. C9orf72-mutation carriers exhibited none or limited 18 F-Flortaucipir retention, indicating that 18 F-Flortaucipir binding in TDP-43 proteinopathies is not a general TDP-43 related phenomenon.
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  • Fjalldal, S., et al. (författare)
  • Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma
  • 2018
  • Ingår i: European Journal of Endocrinology. - : Society of the European Journal of Endocrinology. - 1479-683X .- 0804-4643. ; 178:6, s. 577-587
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown.OBJECTIVE: To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP.DESIGN: A cross-sectional study with a median follow-up time of 22 (6-49) years after operation.SETTING: The South Medical Region of Sweden (2.5 million inhabitants).PARTICIPANTS: Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients.MAIN OUTCOME MEASURES: Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry.RESULTS: Right uncinate fasciculus was significantly altered (P ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge (P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory.CONCLUSIONS: A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.
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