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  • 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. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p>
  • Joshi, Peter K, et al. (författare)
  • Directional dominance on stature and cognition in diverse human populations
  • 2015
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P &lt; 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.</p>
  • Karami, Azadeh, et al. (författare)
  • Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
  • 2015
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279. ; 11:11, s. 1316-1328
  • Tidskriftsartikel (refereegranskat)abstract
    • The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF).
  • Nylander, Ruta, et al. (författare)
  • Relation between Cardiovascular Disease Risk Markers and Brain Infarcts Detected by Magnetic Resonance Imaging in an Elderly Population
  • 2015
  • Ingår i: Journal of Stroke & Cerebrovascular Diseases. - 1052-3057 .- 1532-8511. ; 24:2, s. 312-318
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong></p><p>Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75.</p><p><strong>METHODS:</strong></p><p>Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnaires at age 70 were used for analysis of risk markers. A history of diseases had been obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models.</p><p><strong>RESULTS:</strong></p><p>One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts.</p><p><strong>CONCLUSIONS:</strong></p><p>The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown recently.</p>
  • Aga, Cathrine, et al. (författare)
  • Risk of Revision Was Not Reduced by a Double-bundle ACL Reconstruction Technique: Results From the Scandinavian Registers
  • 2017
  • Ingår i: Clinical Orthopaedics and Related Research. - 0009921X .- 15281132. ; 475:10, s. 2503-2512
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017, The Association of Bone and Joint Surgeons®. Background: Double-bundle anterior cruciate ligament (ACL) reconstruction has demonstrated improved biomechanical properties and moderately better objective outcomes compared with single-bundle reconstructions. This could make an impact on the rerupture rate and reduce the risk of revisions in patients undergoing double-bundle ACL reconstruction compared with patients reconstructed with a traditional single-bundle technique. The National Knee Ligament Registers in Scandinavia provide information that can be used to evaluate the revision outcome after ACL reconstructions. Questions/purposes: The purposes of the study were (1) to compare the risk of revision between double-bundle and single-bundle reconstructions, reconstructed with autologous hamstring tendon grafts; (2) to compare the risk of revision between double-bundle hamstring tendon and single-bundle bone-patellar tendon-bone autografts; and (3) to compare the hazard ratios for the same two research questions after Cox regression analysis was performed. Methods: Data collection of primary ACL reconstructions from the National Knee Ligament Registers in Denmark, Norway, and Sweden from July 1, 2005, to December 31, 2014, was retrospectively analyzed. A total of 60,775 patients were included in the study; 994 patients were reconstructed with double-bundle hamstring tendon grafts, 51,991 with single-bundle hamstring tendon grafts, and 7790 with single-bundle bone-patellar tendon-bone grafts. The double-bundle ACL-reconstructed patients were compared with the two other groups. The risk of revision for each research question was detected by the risk ratio, hazard ratio, and the corresponding 95% confidence intervals. Kaplan-Meier analysis was used to estimate survival at 1, 2, and 5 years for the three different groups. Furthermore, a Cox proportional hazard regression model was applied and the hazard ratios were adjusted for country, age, sex, meniscal or chondral injury, and utilized fixation devices on the femoral and tibial sides. Results: There were no differences in the crude risk of revision between the patients undergoing the double-bundle technique and the two other groups. A total of 3.7% patients were revised in the double-bundle group (37 of 994 patients) versus 3.8% in the single-bundle hamstring tendon group (1952 of 51,991; risk ratio, 1.01; 95% confidence interval (CI), 0.73–1.39; p = 0.96), and 2.8% of the patients were revised in the bone-patellar tendon-bone group (219 of the 7790 bone-patellar tendon-bone patients; risk ratio, 0.76; 95% CI, 0.54–1.06; p = 0.11). Cox regression analysis with adjustment for country, age, sex, menisci or cartilage injury, and utilized fixation device on the femoral and tibial sides, did not reveal any further difference in the risk of revision between the single-bundle hamstring tendon and double-bundle hamstring tendon groups (hazard ratio, 1.18; 95% CI, 0.85–1.62; p = 0.33), but the adjusted hazard ratio showed a lower risk of revision in the single-bundle bone-patellar tendon-bone group compared with the double-bundle group (hazard ratio, 0.62; 95% CI, 0.43–0.90; p = 0.01). Comparisons of the graft revision rates reported separately for each country revealed that double-bundle hamstring tendon reconstructions in Sweden had a lower hazard ratio compared with the single-bundle hamstring tendon reconstructions (hazard ratio, 1.00 versus 1.89; 95% CI, 1.09–3.29; p = 0.02). Survival at 5 years after index surgery was 96.0% for the double-bundle group, 95.4% for the single-bundle hamstring tendon group, and 97.0% for the single-bundle bone-patellar tendon-bone group. Conclusions: Based on the data from all three national registers, the risk of revision was not influenced by the reconstruction technique in terms of using single- or double-bundle hamstring tendons, although national differences in survival existed. Using bone-patellar tendon-bone grafts lowered the risk of revision compared with double-bundle hamstring tendon grafts. These findings should be considered when deciding what reconstruction technique to use in ACL-deficient knees. Future studies identifying the reasons for graft rerupture in single- and double-bundle reconstructions would be of interest to understand the findings of the present study. Level of Evidence: Level III, therapeutic study.
  • Ax, Erika, et al. (författare)
  • Circulating levels of environmental contaminants are associated with dietary patterns in older adults
  • 2015
  • Ingår i: Environment International. - 0160-4120 .- 1873-6750. ; 75, s. 93-102
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> Food intake contributes substantially to our exposure to environmental contaminants. Still, little is known about our dietary habits' contribution to exposure variability.</p><p><strong>OBJECTIVE:</strong> The aim of this study was to assess circulating levels of environmental contaminants in relation to predefined dietary patterns in an elderly Swedish population.</p><p><strong>METHODS:</strong> Dietary data and serum concentrations of environmental contaminants were obtained from 844 70-year-old Swedish subjects (50% women) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Dietary data from 7-day food records was used to assess adherence to a Mediterranean-like diet, a low carbohydrate-high protein diet and the WHO dietary recommendations. Circulating levels of 6 polychlorinated biphenyl markers, 3 organochlorine pesticides, 1 dioxin and 1 polybrominated diphenyl ether, the metals cadmium, lead, mercury and aluminum and serum levels of bisphenol A and 4 phthalate metabolites were investigated in relation to dietary patterns in multivariate linear regression models.</p><p><strong>RESULTS:</strong> A Mediterranean-like diet was positively associated with levels of several polychlorinated biphenyls (118, 126, 153, and 209), trans-nonachlor and mercury. A low carbohydrate-high protein diet was positively associated with polychlorinated biphenyls 118 and 153, trans-nonachlor, hexachlorobenzene and p, p'-dichlorodiphenyldichloroethylene, mercury and lead. The WHO recommended diet was negatively related to levels of dioxin and lead, and borderline positively to polychlorinated biphenyl 118 and trans-nonachlor.</p><p><strong>CONCLUSION:</strong> Dietary patterns were associated in diverse manners with circulating levels of environmental contaminants in this elderly Swedish population. Following the WHO dietary recommendations seems to be associated with a lower burden of environmental contaminants.</p>
  • Beijer, Kristina, et al. (författare)
  • Interaction between physical activity and television time on blood pressure level : Cross-sectional data from 45 000 individuals
  • 2018
  • Ingår i: Journal of Hypertension. - Lippincott Williams & Wilkins. - 0263-6352. ; 36:5, s. 1041-1050
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim was to investigate if there is an interaction between sitting time and leisure time physical activity on blood pressure and if there are age differences and sex differences in this respect. Methods: Linear regression analysis on cross-sectional data was performed in more than 45 000 men and women from two Swedish cohort studies, EpiHealth (45-75 years) and LifeGene (18-45 years). Self-reported leisure time physical activity was given in five levels from low (level 1) to vigorous physical activity (level 5) and television time was used as a proxy measure of sitting time. Results: High physical activity was associated with lower DBP (P = 0.001), but not SBP. Active middle-aged men had lower DBP (-1.1 mmHg; 95% CI -1.7 to -0.4) compared with inactive participants. Prolonged television time was associated with higher SBP (P < 0.001) and DBP (P = 0.011) in both sexes and in most age groups. Watching 3 h instead of 1 h television per day was associated with higher SBP in middle-aged women (SBP: 1.1 mmHg; 95% CI 0.7-1.4) and men (SBP: 1.2 mmHg; 95% CI 0.8-1.6). Only in young men, a high physical activity (level 4 instead of level 1) could compensate for a prolonged television time (3 h per day) in terms of DBP. Conclusion: Prolonged television time was associated with higher SBP and DBP in both sexes and at most ages, whereas an increased physical activity was mainly associated with a lower DBP. Only in young men, a high physical activity could compensate for prolonged television time regarding DBP.
  • Beijer, Kristina, et al. (författare)
  • Physical activity may compensate for prolonged TV time regarding pulse rate—a cross-sectional study
  • 2018
  • Ingår i: Upsala Journal of Medical Sciences. - Taylor & Francis. - 0300-9734. ; 123:4, s. 247-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Regular exercise reduces pulse rate, but it is less clear how prolonged sitting time affects pulse rate. Our hypothesis was that high physical activity could compensate for prolonged sitting time regarding the pulse rate. Methods. Regression analysis was performed on cross-sectional data including 47,457 men and women based on two Swedish cohort studies, EpiHealth (18–45 years) and LifeGene (45–75 years). Self-reported leisure time physical activity was given in five levels, from low (level 1) to vigorous (level 5), and television time was used as a proxy of sitting time. Results. A higher physical activity (level 4 compared to level 1) was associated with a lower pulse rate in middle-aged females (-2.7 beats per minute [bpm]; 95% CI -3.3 to -2.2) and males (-4.0 bpm; 95% CI -4.7 to -3.4). The relationship between physical activity and pulse rate was strongest in the young. A prolonged television time (3 h compared to 1 h per day) was associated with a slightly higher pulse rate in middle-aged females (+0.6 bpm; 95% CI +0.3 to +0.8) and males (+0.9 bpm; 95% CI +0.7 to +1.2). Among participants with a prolonged television time (3 h), those with a high physical activity (level 4) had a lower pulse rate compared to those with a low physical activity (level 1). Conclusions. A prolonged television time was associated with a high pulse rate, while high physical activity was associated with a low pulse rate. The results suggest that a high physical activity could compensate for a prolonged television time regarding pulse rate.
  • Benedict, Christian, et al. (författare)
  • Self-reported sleep disturbance is associated with Alzheimer's disease risk in men
  • 2015
  • Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 11:9, s. 1090-1097
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>OBJECTIVE:</strong> To study the association between self-reported sleep disturbances and dementia risk.</p><p><strong>METHODS:</strong> Self-reported sleep disturbances and established risk factors for dementia were measured in men at ages 50 (n = 1574) and 70 (n = 1029) years. Dementia incidence was determined by reviewing their patient history between ages 50 and 90 years. In addition, plasma levels of β-amyloid (Aβ) peptides 1-40 and 1-42 were measured at ages 70, 77, and 82 years.</p><p><strong>RESULTS:</strong> Cox regression demonstrated that men with self-reported sleep disturbances had a higher risk of developing dementia (+33%) and Alzheimer's disease (AD, +51%) than men without self-reported sleep disturbances (both P &lt; .05). Binary logistic regression showed the increased risk for both dementia (+114%) and AD (+192%) were highest when sleep disturbance was reported at age 70 years (both P &lt; .001). No group differences were found in Aβ levels.</p><p><strong>CONCLUSION:</strong> Improving sleep quality may help reduce the neurodegenerative risk in older men.</p>
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