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- Bejanin, A., et al.
(författare)
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Association of Apolipoprotein e ϵ4 Allele with Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults with down Syndrome
- 2021
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 78:8, s. 937-947
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Alzheimer disease (AD) is the leading cause of death in individuals with Down syndrome (DS). Previous studies have suggested that the APOE ϵ4 allele plays a role in the risk and age at onset of dementia in DS; however, data on in vivo biomarkers remain scarce. Objective: To investigate the association of the APOE ϵ4 allele with clinical and multimodal biomarkers of AD in adults with DS. Design, Setting, and Participants: This dual-center cohort study recruited adults with DS in Barcelona, Spain, and in Cambridge, UK, between June 1, 2009, and February 28, 2020. Included individuals had been genotyped for APOE and had at least 1 clinical or AD biomarker measurement; 2 individuals were excluded because of the absence of trisomy 21. Participants were either APOE ϵ4 allele carriers or noncarriers. Main Outcomes and Measures: Participants underwent a neurological and neuropsychological assessment. A subset of participants had biomarker measurements: Aβ1-42, Aβ1-40, phosphorylated tau 181 (pTau181) and neurofilament light chain (NfL) in cerebrospinal fluid (CSF), pTau181, and NfL in plasma; amyloid positron emission tomography (PET); fluorine 18-labeled-fluorodeoxyglucose PET; and/or magnetic resonance imaging. Age at symptom onset was compared between APOE ϵ4 allele carriers and noncarriers, and within-group local regression models were used to compare the association of biomarkers with age. Voxelwise analyses were performed to assess topographical differences in gray matter metabolism and volume. Results: Of the 464 adults with DS included in the study, 97 (20.9%) were APOE ϵ4 allele carriers and 367 (79.1%) were noncarriers. No differences between the 2 groups were found by age (median [interquartile range], 45.9 [36.4-50.2] years vs 43.7 [34.9-50.2] years; P =.56) or sex (51 male carriers [52.6%] vs 199 male noncarriers [54.2%]). APOE ϵ4 allele carriers compared with noncarriers presented with AD symptoms at a younger age (mean [SD] age, 50.7 [4.4] years vs 52.7 [5.8] years; P =.02) and showed earlier cognitive decline. Locally estimated scatterplot smoothing curves further showed between-group differences in biomarker trajectories with age as reflected by nonoverlapping CIs. Specifically, carriers showed lower levels of the CSF Aβ1-42 to Aβ1-40 ratio until age 40 years, earlier increases in amyloid PET and plasma pTau181, and earlier loss of cortical metabolism and hippocampal volume. No differences were found in NfL biomarkers or CSF total tau and pTau181. Voxelwise analyses showed lower metabolism in subcortical and parieto-occipital structures and lower medial temporal volume in APOE ϵ4 allele carriers. Conclusions and Relevance: In this study, the APOE ϵ4 allele was associated with earlier clinical and biomarker changes of AD in DS. These results provide insights into the mechanisms by which APOE increases the risk of AD, emphasizing the importance of APOE genotype for future clinical trials in DS. © 2021 American Medical Association. All rights reserved.
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| 4. |
- Annus, T, et al.
(författare)
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Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren
- 2001
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 31:12, s. 1846-1853
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. Objective: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. Methods: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Link÷ping (n = 911) and ╓stersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Results: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in ╓stersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Link÷ping and 58% in ╓stersund) bronchial hyper-responsiveness (BHR) (48% in Link÷ping and ╓stersund) and anti-asthmatic treatment (63% in Link÷ping and 81% in ╓stersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (╓stersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. Conclusions: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.
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| 6. |
- Riikjarv, M.-A., et al.
(författare)
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Similar prevalence of respiratory symptoms and atopy in estonian schoolchildren with changing lifestyle over 4 yrs
- 2000
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 16:1, s. 86-90
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of allergic sensitization and clinical manifestations is low in Eastern Europe, despite a continuous increase in industrialized countries with a market economy. The aim of the present study was to study changes in the prevalence of respiratory symptoms and atopic sensitization over time among schoolchildren in Estonia, in relation to environmental changes as the country transformed into a market economy. A cross-sectional study of 10-yr-old children was carried out between October 1996 and April 1997, employing a questionnaire regarding the prevalence of wheezing, rhinitis and itching rash (n=979) and skin-prick tests with seven inhalant allergens (n=640). The results were compared with those of a similar study performed in 19921993. The 12-month prevalence of wheeze was 8.3%, as compared to 9.4% in 1992-1993 (NS) and of asthma was 2.5 versus 3.2% (NS). The prevalence of a positive skin-prick test result was 14.3% in both studies. Furthermore, the prevalence of sensitivity to the individual allergens was similar, except for a significantly higher prevalence of dog sensitivity in 1996-1997 (4.7 versus 2.0%). The prevalence of respiratory and other potentially allergic symptoms, as well as the prevalence of atopic sensitization, remains low in Estonian 10-yr-old children, despite a changing lifestyle over the past 4 yrs. This could indicate that the time period was too short for environmental changes to affect the prevalence of allergy, or alternatively that risk factors associated with a 'western lifestyle' are of particular significance earlier in life. (C)ERS Journals Ltd 2000.
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| 7. |
- Sandin, Anna, et al.
(författare)
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Prevalence of self-reported food allergy and IgE antibodies to food allergens in Swedish and Estonian schoolchildren
- 2005
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 59:3, s. 399-403
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the prevalence of self-reported food allergy and IgE antibodies to food allergens in wheezing and non-wheezing Estonian and Swedish schoolchildren, in the light of the disparities in the standard of living, food consumption and prevalence of respiratory allergies that still exist between Estonia and the Scandinavian countries. Design and setting: As a part of the ISAAC Phase II study, children from a random sample of schools in Tallinn in Estonia and Linköping and Östersund in Sweden participated in skin prick tests to inhalant allergens and the parents replied to questionnaires. IgE antibodies against a panel of food allergens (egg white, milk, soy bean, fish, wheat and peanut) were taken from children with questionnaire-reported wheezing and a random sample of nonwheezing children. Subjects: Children aged 10-11 y. Results: The prevalence of self-reported food allergy was similar in Estonia and Sweden and about twice as high in wheezing children than in nonwheezing children. In Estonia, however, 3% of the children with perceived food allergy reported reactions from at least four different foods, as compared to 31% in Sweden. The prevalence of sensitisation to food allergens was similar in wheezing and nonwheezing children in Estonia (8%) while, in Swedish children, IgE antibodies to food allergens were more likely among wheezing children (Linköping 38 vs 11%, crude OR 5.1, 95% CI 2.2-11.6, and Östersund 24 vs 7%, crude OR 4.1, 95% CI 1.9-8.5). Conclusion: Our study suggests that IgE-mediated food reactions were less likely in Estonian schoolchildren. Moreover, the perception of food allergy and thereby the meaning of self-reported food allergy appears to be different in the two countries. © 2005 Nature Publishing Group. All rights reserved.
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