| 11. |
- van de Pol, L. A., et al.
(författare)
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White matter hyperintensities and medial temporal lobe atrophy in clinical subtypes of mild cognitive impairment: the DESCRIPA study
- 2009
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:10, s. 1069-1074
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clinical subtypes of mild cognitive impairment (MCI) may represent different underlying aetiologies. Methods: This European, multicentre, memory clinic based study (DESCRIPA) of non-demented subjects investigated whether MCI subtypes have different brain correlates on MRI and whether the relation between subtypes and brain pathology is modified by age. Using visual rating scales, medial temporal lobe atrophy (MTA) (0-4) and white matter hyperintensities (WMH) (0-30) were assessed. Results: Severity of MTA differed between MCI subtypes (p < 0.001), increasing from a mean of 0.8 (SD 0.7) in subjective complaints (n = 77) to 1.3 (0.8) in non-amnestic MCI (n = 93), and from 1.4 (0.9) in single domain amnestic MCI (n = 70) to 1.7 (0.9) in multiple domain amnestic MCI (n = 89). The association between MCI subtype and MTA was modified by age and mainly present in subjects >70 years of age. Severity of WMH did not differ between MCI subtypes (p = 0.21). However, the combination of MTA and WMH differed between MCI subtypes (p = 0.02) Conclusion: We conclude that MCI subtypes may have different brain substrates, especially in older subjects. Isolated MTA was mainly associated with amnestic MCI subtypes, suggesting AD as the underlying cause. In non-amnestic MCI, the relatively higher prevalence of MTA in combination with WMH may suggest a different pathophysiological origin.
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| 12. |
- Wang, R., et al.
(författare)
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Do cardiovascular risk factors explain the link between white matter hyperintensities and brain volumes in old age? : A population-based study
- 2014
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 21:8, s. 1076-1082
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: White matter hyperintensities (WMHs) and brain atrophy frequently coexist in older people. However, it is unclear whether the association between these two brain lesions is dependent on the aging process, a vascular mechanism or genetic susceptibility. It was therefore investigated whether the association between load of WMHs and brain atrophy measures is related to age, vascular risk factors (VRFs) or the APOE-epsilon 4 allele. Methods: This population-based study included 492 participants (age >= 60 years, 59.6% women) free of dementia and stroke. Data on demographics, VRFs and APOE genotypes were collected through interviews, clinical examination and laboratory tests. WMHs on magnetic resonance images were assessed using manual visual rating and automatic volumetric segmentation. Hippocampal and ventricular volumes were manually delineated, whereas total gray matter (GM) volume was measured by automatic segmentation. Data were analyzed with multivariate linear regression models. Results: More global WMHs, assessed using either a visual rating scale or a volumetric approach, were significantly associated with lower GM volume and higher ventricular volume; the associations remained significant after adjusting for age, VRFs and the APOE-epsilon 4 allele. In contrast, the association between global WMHs and hippocampal volume was no longer significant after adjusting for age, whereas adjustment for VRFs and APOE-epsilon 4 had no influential effect. Conclusion: The association of global WMHs with lower GM volume and higher ventricular volume is independent of age, VRFs and APOE-epsilon 4 allele, suggesting that the process of cerebral microvascular disease and neurodegeneration are associated independently of the normal aging process, vascular mechanisms or genetic susceptibility.
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| 13. |
- Winblad, B, et al.
(författare)
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Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.
- 2004
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Ingår i: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 256:3, s. 240-6
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Forskningsöversikt (refereegranskat)abstract
- The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.
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| 14. |
- Almkvist, O, et al.
(författare)
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Mild cognitive impairment -- An early stage of Alzheimer´s disease?
- 1998
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Ingår i: Journal of Neural Transmission. ; 53, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that mild cognitive impairment (MCI) represents an early stage of Alzheimer´s disease (AD) was investigated by reviewing recent research from three sources: asymptomatic and symptomatic individuals carrying mutations that cause AD; hospital
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| 15. |
- Cedres, N., et al.
(författare)
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Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:15
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Several pathologic processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers toward the degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals. Methods The contribution of amyloid and tau pathology was assessed through CSF levels of the A beta(42/40) ratio and phosphorylated tau (p-tau). CSF A beta(38) levels were also measured. Cerebrovascular pathology was assessed using automatic segmentations of WM lesions (WMLs) on MRI. Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE epsilon 4 carriership were also included in the analysis as variables of interest. Results We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals aged 70 years, 51% female). WM lesion burden was the most important contributor to the degeneration of both cholinergic pathways (increase in mean square error [IncMSE] = 98.8% in the external capsule pathway and IncMSE = 93.3% in the cingulum pathway). Levels of A beta(38) and p-tau also contributed to cholinergic WM degeneration, especially in the external capsule pathway (IncMSE = 28.4% and IncMSE = 23.4%, respectively). The A beta(42/40) ratio did not contribute notably to the models (IncMSE<3.0%). APOE epsilon 4 carriers showed poorer integrity in the cingulum pathway (IncMSE = 21.33%). Women showed poorer integrity of the external capsule pathway (IncMSE = 21.55%), which was independent of amyloid status as reflected by the nonsignificant differences in integrity when comparing amyloid-positive vs amyloid-negative women participants (T-201 = -1.55; p = 0.123). Discussion In cognitively unimpaired older individuals, WMLs play a central role in the degeneration of cholinergic pathways. Our findings highlight the importance of WM lesion burden in the elderly population, which should be considered in the development of prevention programs for neurodegeneration and cognitive impairment.
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| 16. |
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| 17. |
- Eyjolfsdottir, H., et al.
(författare)
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Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device
- 2016
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion. Methods: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day. Results: All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable. Conclusions: The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.
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| 18. |
- Herique, A., et al.
(författare)
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Direct observations of asteroid interior and regolith structure : Science measurement requirements
- 2018
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Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 62:8, s. 2141-2162
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge of the internal structure of asteroids is, so far, indirect - relying entirely on inferences from remote sensing observations of the surface, and theoretical modeling of formation and evolution. What are the bulk properties of the regolith and deep interior? And what are the physical processes that shape asteroid internal structures? Is the composition and size distribution observed on the surface representative of the bulk? These questions are crucial to understand small bodies' history from accretion in the early Solar System to the present, and direct measurements are needed to answer these questions for the benefit of science as well as for planetary defense or exploration. Radar is one of the main instruments capable of sounding asteroids to characterize internal structure from sub-meter to global scale. In this paper, we review the science case for direct observation of the deep internal structure and regolith of a rocky asteroid of kilometer size or smaller. We establish the requirements and model dielectric properties of asteroids to outline a possible instrument suite, and highlight the capabilities of radar instrumentation to achieve these observations. We then review the expected science return including secondary objectives contributing to the determination of the gravitational field, the shape model, and the dynamical state. This work is largely inherited from MarcoPolo-R and AIDA/AIM studies.
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| 19. |
- Lammer, H., et al.
(författare)
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What makes a planet habitable?
- 2009
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Ingår i: The Astronomy and Astrophysics Review. - : Springer Science and Business Media LLC. - 0935-4956 .- 1432-0754. ; 17:2, s. 181-249
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Forskningsöversikt (refereegranskat)abstract
- This work reviews factors which are important for the evolution of habitable Earth-like planets such as the effects of the host star dependent radiation and particle fluxes on the evolution of atmospheres and initial water inventories. We discuss the geodynamical and geophysical environments which are necessary for planets where plate tectonics remain active over geological time scales and for planets which evolve to one-plate planets. The discoveries of methane-ethane surface lakes on Saturn's large moon Titan, subsurface water oceans or reservoirs inside the moons of Solar System gas giants such as Europa, Ganymede, Titan and Enceladus and more than 335 exoplanets, indicate that the classical definition of the habitable zone concept neglects more exotic habitats and may fail to be adequate for stars which are different from our Sun. A classification of four habitat types is proposed. Class I habitats represent bodies on which stellar and geophysical conditions allow Earth-analog planets to evolve so that complex multi-cellular life forms may originate. Class II habitats includes bodies on which life may evolve but due to stellar and geophysical conditions that are different from the class I habitats, the planets rather evolve toward Venus- or Mars-type worlds where complex life-forms may not develop. Class III habitats are planetary bodies where subsurface water oceans exist which interact directly with a silicate-rich core, while class IV habitats have liquid water layers between two ice layers, or liquids above ice. Furthermore, we discuss from the present viewpoint how life may have originated on early Earth, the possibilities that life may evolve on such Earth-like bodies and how future space missions may discover manifestations of extraterrestrial life.
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| 20. |
- Looi, JC, et al.
(författare)
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Putaminal volume in frontotemporal lobar degeneration and Alzheimer disease: differential volumes in dementia subtypes and controls
- 2009
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Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 30:8, s. 1552-1560
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Frontostriatal (including the putamen) circuit-mediated cognitive dysfunction has been implicated in frontotemporal lobar degeneration (FTLD), but not in Alzheimer disease (AD) or healthy aging. We sought to assess putaminal volume as a measure of the structural basis of relative frontostriatal dysfunction in these groups. MATERIALS AND METHODS: We measured putaminal volume in FTLD subtypes: frontotemporal dementia (FTD, n = 12), semantic dementia (SD, n = 13), and progressive nonfluent aphasia (PNFA, n = 9) in comparison with healthy controls (n = 25) and patients with AD (n = 18). Diagnoses were based on accepted clinical criteria. We conducted manual volume measurement of the putamen blinded to the diagnosis on T1 brain MR imaging by using a standardized protocol. RESULTS: Paired t tests (P < .05) showed that the left putaminal volume was significantly larger than the right in all groups combined. Multivariate analysis of covariance with a Bonferroni correction was used to assess statistical significance among the subject groups (AD, FTD, SD, PNFA, and controls) as independent variables and right/left putaminal volumes as dependent variables (covariates, age and intracranial volume; P < .05). The right putamen in FTD was significantly smaller than in AD and controls; whereas in SD, it was smaller compared with controls with a trend toward being smaller than in AD. There was also a trend toward the putamen in the PNFA being smaller than that in controls and in patients with AD. Across the groups, there was a positive partial correlation between putaminal volume and Mini-Mental State Examination (MMSE). CONCLUSIONS: Right putaminal volume was significantly smaller in FTD, the FTLD subtype with the greatest expected frontostriatal dysfunction; whereas in SD and PNFA, it showed a trend towards being smaller, consistent with expectation, compared to controls and AD; and in SD, compared with AD and controls. Putaminal volume weakly correlated with MMSE.
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