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- Naghavi, Mohsen, et al.
(author)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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In: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Journal article (peer-reviewed)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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2. |
- Bendlin, Barbara B, et al.
(author)
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CSF T-Tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease.
- 2012
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ(42) are linked with Alzheimer's disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ(42), total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ(42) were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ(42) levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter.
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3. |
- Berman, Sara E, et al.
(author)
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Intracranial Arterial 4D Flow in Individuals with Mild Cognitive Impairment is Associated with Cognitive Performance and Amyloid Positivity.
- 2017
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In: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 60:1, s. 243-252
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Journal article (peer-reviewed)abstract
- It is becoming increasingly recognized that cerebrovascular disease is a contributing factor in the pathogenesis of Alzheimer's disease (AD). A unique 4D-Flow magnetic resonance imaging (MRI) technique, phase contrast vastly undersampled isotropic projection imaging (PC VIPR), enables examination of angiographic and quantitative metrics of blood flow in the arteries of the Circle of Willis within a single MRI acquisition. Thirty-eight participants with mild cognitive impairment (MCI) underwent a comprehensive neuroimaging protocol (including 4D-Flow imaging) and a standard neuropsychological battery. A subset of participants (n=22) also underwent lumbar puncture and had cerebrospinal fluid (CSF) assayed for AD biomarkers. Cut-offs for biomarker positivity in CSF resulting from a receiver operating characteristic curve analysis of AD cases and controls from the larger Wisconsin Alzheimer's Disease Research Center cohort were used to classify MCI participants as biomarker positive or negative on amyloid-β (Aβ42), total-tau and total-tau/Aβ42 ratio. Internal carotid artery (ICA) and middle cerebral artery (MCA) mean flow were associated with executive functioning performance, with lower mean flow corresponding to worse performance. MCI participants who were biomarker positive for Aβ42 had lower ICA mean flow than did those who were Aβ42 negative. In sum, mean ICA and MCA arterial flow was associated with cognitive performance in participants with MCI and lower flow in the ICA was associated with amyloid positivity. This provides further evidence for vascular health as a contributing factor in the etiopathogenesis of AD, and could represent a point to intervene in the disease process.
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4. |
- Berman, Sara E, et al.
(author)
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Intracranial Arterial 4D-Flow is Associated with Metrics of Brain Health and Alzheimer's Disease.
- 2015
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In: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 1:4, s. 420-428
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Journal article (peer-reviewed)abstract
- While cerebrovascular disease has long been known to co-occur with Alzheimer's disease (AD), recent studies suggest an etiologic contribution to AD pathogenesis. We used 4D-Flow magnetic resonance imaging (MRI) to evaluate blood flow and pulsatility indices in the Circle of Willis. We hypothesized decreased mean blood flow and increased pulsatility, metrics indicative of poor vascular health, would be associated with cerebral atrophy and an AD cerebrospinal fluid (CSF) profile.
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6. |
- Motovylyak, Alice, et al.
(author)
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Age-related differences in white matter microstructure measured by advanced diffusion MRI in healthy older adults at risk for Alzheimer’s disease
- 2022
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In: Aging Brain. - : Elsevier. - 2589-9589. ; 2
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Journal article (peer-reviewed)abstract
- Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric—fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO—is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer’s disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.
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7. |
- Wang, Rui, et al.
(author)
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Impact of sex and APOE ε4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults : A longitudinal study.
- 2021
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In: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016. ; 41:11, s. 3016-3027
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Journal article (peer-reviewed)abstract
- Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer's disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40-89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13-8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (β=-1.43), hippocampus (-1.25), superior frontal gyrus (-1.70), middle frontal gyrus (-1.99), posterior cingulate (-2.46), and precuneus (-2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.
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8. |
- Allison, Samantha L, et al.
(author)
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Neurodegeneration, Alzheimer's disease biomarkers, and longitudinal verbal learning and memory performance in late middle age.
- 2021
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In: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 102, s. 151-160
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Journal article (peer-reviewed)abstract
- This study examined the effect of neurodegeneration, and its interaction with Alzheimer's disease (AD) cerebrospinal fluid biomarkers, on longitudinal verbal learning and memory performance in cognitively unimpaired (CU) late middle-aged adults. Three hundred and forty-two CU adults (cognitive baseline mean age=58.4), with cerebrospinal fluid and structural MRI, completed 2-10 (median=5) cognitive assessments. Learning and memory were assessed using the Rey Auditory Verbal Learning Test (RAVLT). We used sequential comparison of nested linear mixed effects models to analyze the data. Model selection preserved a significant ptau181/Aβ42×global atrophy×age interaction; individuals with less global atrophy and lower ptau181/Aβ42 levels had less learning and delayed recall decline than individuals with more global atrophy and/or higher levels of ptau181/Aβ42. The hippocampal volume×age×ptau181/Aβ42 interaction was not significant. Findings suggest that in a sample of CU late middle-aged adults, individuals with AD biomarkers, global atrophy, or both evidence greater verbal learning and memory decline than individuals without either risk factor.
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9. |
- Racine, Annie M, et al.
(author)
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Biomarker clusters are differentially associated with longitudinal cognitive decline in late midlife.
- 2016
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 139:Pt 8, s. 2261-74
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Journal article (peer-reviewed)abstract
- The ability to detect preclinical Alzheimer's disease is of great importance, as this stage of the Alzheimer's continuum is believed to provide a key window for intervention and prevention. As Alzheimer's disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 ± 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-β42/amyloid-β40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer's disease; (ii) mixed Alzheimer's disease and vascular aetiology; (iii) suspected non-Alzheimer's disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal ageing. Our results demonstrate that pathology, as indicated by biomarkers, in a preclinical timeframe is related to patterns of longitudinal cognitive decline. Such biomarker patterns may be useful for identifying at-risk populations to recruit for clinical trials.
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