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- 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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- Cedres, N, et al.
(författare)
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Brain Atrophy Subtypes and the ATN Classification Scheme in Alzheimer's Disease
- 2021
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Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 20:4, s. 153-164
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> We investigated the association between atrophy subtypes of Alzheimer’s disease (AD), the ATN classification scheme, and key demographic and clinical factors in 2 cohorts with different source characteristics (a highly selective research-oriented cohort, the Alzheimer’s Disease Neuroimaging Initiative [ADNI]; and a naturalistic heterogeneous clinically oriented cohort, Karolinska Imaging Dementia Study [KIDS]). <b><i>Methods:</i></b> A total of 382 AD patients were included. Factorial analysis of mixed data was used to investigate associations between AD subtypes based on brain atrophy patterns, ATN profiles based on cerebrospinal fluid biomarkers, and age, sex, Mini Mental State Examination (MMSE), cerebrovascular disease (burden of white matter signal abnormalities, WMSAs), and <i>APOE</i> genotype. <b><i>Results:</i></b> Older patients with high WMSA burden, belonging to the typical AD subtype and showing A+T+N+ or A+T+N− profiles clustered together and were mainly from ADNI. Younger patients with low WMSA burden, limbic-predominant or minimal atrophy AD subtypes, and A+T−N− or A+T−N+ profiles clustered together and were mainly from KIDS. <i>APOE</i> ε4 carriers more frequently showed the A+T−N− and A+T+N− profiles. <b><i>Conclusions:</i></b> Our findings align with the recent framework for biological subtypes of AD: the combination of risk factors, protective factors, and brain pathologies determines belonging of AD patients to distinct subtypes.
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- Pilyugin, L. S., et al.
(författare)
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On the electron temperatures in high-metallicity H ii regions
- 2009
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 398:1, s. 485-496
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Tidskriftsartikel (refereegranskat)abstract
- The electron temperatures of high-metallicity [12 + log (O/H) > 8.2] H ii regions have been studied. The empirical flux-flux relations which express the nebular-to-auroral [O iii] line ratio Q(3,O) (as well as the nebular-to-auroral [O ii] line ratio Q(2,O), and the nebular-to-auroral [N ii] line ratio Q(2,N)) in terms of the nebular R-3 and R-2 line fluxes in spectra of high-metallicity H ii regions are derived, and the electron temperatures t(3,O), t(2,O) and t(2,N) in a number of extragalactic H ii regions are also determined. Furthermore, the t(2)- t(3) diagram is discussed. It is found that there is a one-to-one correspondence between t(2) and t(3) electron temperatures for H ii regions with a weak nebular R-3 lines (log R-3 less than or similar to 0.5). The derived t(2,N)-t(3,O) relation for these H ii regions is similar to commonly used t(2)-t(3) relations. The H ii regions with a strong nebular R-3 line flux (log R-3 greater than or similar to 0.5) do not follow this relation. A discrepancy between t(2,N) and t(2,O) temperatures is found, being the t(2,N) temperatures systematically lower than the t(2,O) ones. The differences are small at low electron temperatures, and increase with increasing electron temperatures up to 10 per cent at t = 1. The uncertainties in the atomic data may be the cause of this discrepancy.
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