| 1. |
- Jansen, Willemijn J, et al.
(author)
-
Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
-
In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
-
Journal article (peer-reviewed)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
|
|
| 2. |
|
|
| 3. |
- Dahl, Izabela A., 1972, et al.
(author)
-
Zur Einstimmung: Einleitende Worte zum Projekt
- 2014
-
In: Der Norden in der neuen Mitte. Zur Gründung des Nordeuropa-Instituts; Kleine Schriften des Nordeuropa-Institutes, Nr 45. - Berlin : Nordeuropa-Institut; Humboldt-Universität zu Berlin. - 9783932406935 ; , s. 9-19
-
Book chapter (other academic/artistic)
|
|
| 4. |
- Hedström, Erik, et al.
(author)
-
The effect of initial teaching on evaluation of left ventricular volumes by cardiovascular magnetic resonance imaging : Comparison between complete and intermediate beginners and experienced observers
- 2017
-
In: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 17:1
-
Journal article (peer-reviewed)abstract
- Background: High reproducibility and low intra- and interobserver variability are important strengths of cardiac magnetic resonance (CMR). In clinical practice a significant learning curve may however be observed. Basic CMR courses offer an average of 1.4 h dedicated to lecturing and demonstrating left ventricular (LV) function analysis. The purpose of this study was to evaluate the effect of initial teaching on complete and intermediate beginners' quantitative measurements of LV volumes and function by CMR. Methods: Standard clinical cine CMR sequences were acquired in 15 patients. Five observers (two complete beginners, one intermediate, two experienced) measured LV volumes. Before initial evaluation beginners read the SCMR guidelines on CMR analysis. After initial evaluation, beginners participated in a two-hour teaching session including cases and hands-on training, representative for most basic CMR courses, after which it is uncertain to what extent different centres provide continued teaching and feedback in-house. Dice Similarity Coefficient (DSC) assessed delineations. Agreement, accuracy, precision, repeatability and reliability were assessed by Bland-Altman, coefficient of variation, and intraclass correlation coefficient methods. Results: Endocardial DSC improved after teaching (+0.14 ± 0.17;p < 0.001) for complete beginners. Low intraobserver variability was found before and after teaching, however with wide limits of agreement. Beginners underestimated volumes by up to 44 ml (EDV), 27 ml (ESV) and overestimated LVM by up to 53 g before teaching, improving to an underestimation of up to 9 ml (EDV), 7 ml (ESV) and an overestimation of up to 30 g (LVM) after teaching. For the intermediate beginner, however, accuracy was quite high already before teaching. Conclusions: Initial teaching to complete beginners increases accuracy for assessment of LV volumes, however with high bias and low precision even after standardised teaching as offered in most basic CMR courses. Even though the intermediate beginner showed quite high accuracy already before teaching, precision did generally not improve after standardised teaching. To maintain CMR as a technique known for high accuracy and reproducibility and low intra- and inter-observer variability for quantitative measurements, internationally standardised training should be encouraged including high-quality feedback mechanisms. Objective measurements of training methods, training duration and, above all, quality of assessments are required.
|
|
| 5. |
- Liu, Enchi, et al.
(author)
-
Biomarker pattern of ARIA-E participants in phase 3 randomized clinical trials with bapineuzumab.
- 2018
-
In: Neurology. - 1526-632X. ; 90:10
-
Journal article (peer-reviewed)abstract
- To evaluate whether amyloid-related imaging abnormalities with edema/effusion (ARIA-E) observed in bapineuzumab clinical trials was associated with specific biomarker patterns.Bapineuzumab, an anti-β-amyloid monoclonal antibody, was evaluated in patients with mild to moderate Alzheimer disease. Amyloid PET imaging, CSF biomarkers, or volumetric MRI (vMRI) were assessed.A total of 1,512 participants underwent one or more biomarker assessments; 154 developed incident ARIA-E. No differences were observed at baseline between ARIA-E and non-ARIA-E participants in brain amyloid burden by PET, the majority of vMRI measures, or CSF biomarkers, with the exception of lower baseline CSF Aβ42inAPOEε4 noncarrier ARIA-E vs non-ARIA-E groups (bapineuzumab non-ARIA-Ep= 0.027; placebo non-ARIA-Ep= 0.012). At week 71, bapineuzumab-treated participants with ARIA-E vs non-ARIA-E showed greater reduction in brain amyloid PET, greater reductions in CSF phosphorylated tau (p-tau) (all comparisonsp< 0.01), and total tau (t-tau) (all comparisonsp< 0.025), and greater hippocampal volume reduction and ventricular enlargement (allp< 0.05). Greater reduction in CSF Aβ40concentrations was observed for ARIA-E versus both non-ARIA-E groups (bapineuzumab/placebo non-ARIA-Ep= 0.015/0.049). No group differences were observed at week 71 for changes in whole brain volume or CSF Aβ42.Baseline biomarkers largely do not predict risk for developing ARIA-E. ARIA-E was associated with significant longitudinal changes in several biomarkers, with larger reductions in amyloid PET and CSF p-tau and t-tau concentrations, and paradoxically greater hippocampal volume reduction and ventricular enlargement, suggesting that ARIA-E in bapineuzumab-treated cases may be related to increased Aβ efflux from the brain and affecting downstream pathogenic processes.
|
|
| 6. |
- Nelson, Peter T., et al.
(author)
-
Limbic-predominant age-related TDP-43 encephalopathy (LATE) : consensus working group report
- 2019
-
In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 142, s. 1503-1527
-
Research review (peer-reviewed)abstract
- We describe a recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE neuropathological change (LATE-NC) is defined by a stereotypical TDP-43 proteinopathy in older adults, with or without coexisting hippocampal sclerosis pathology. LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer's-type dementia in retrospective autopsy studies. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology based on its epidemiology (LATE generally affects older subjects), and relatively restricted neuroanatomical distribution of TDP-43 proteinopathy. In community-based autopsy cohorts, similar to 25% of brains had sufficient burden of LATE-NC to be associated with discernible cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-beta plaques and tauopathy. Given that the oldest-old' are at greatest risk for LATE-NC, and subjects of advanced age constitute a rapidly growing demographic group in many countries, LATE has an expanding but under-recognized impact on public health. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming both to stimulate research and to promote awareness of this pathway to dementia. We report consensus-based recommendations including guidelines for diagnosis and staging of LATE-NC. For routine autopsy workup of LATE-NC, an anatomically-based preliminary staging scheme is proposed with TDP-43 immunohistochemistry on tissue from three brain areas, reflecting a hierarchical pattern of brain involvement: amygdala, hippocampus, and middle frontal gyrus. LATE-NC appears to affect the medial temporal lobe structures preferentially, but other areas also are impacted. Neuroimaging studies demonstrated that subjects with LATE-NC also had atrophy in the medial temporal lobes, frontal cortex, and other brain regions. Genetic studies have thus far indicated five genes with risk alleles for LATE-NC: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. The discovery of these genetic risk variants indicate that LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer's disease, but also suggests disease-specific underlying mechanisms. Large gaps remain in our understanding of LATE. For advances in prevention, diagnosis, and treatment, there is an urgent need for research focused on LATE, including in vitro and animal models. An obstacle to clinical progress is lack of diagnostic tools, such as biofluid or neuroimaging biomarkers, for ante-mortem detection of LATE. Development of a disease biomarker would augment observational studies seeking to further define the risk factors, natural history, and clinical features of LATE, as well as eventual subject recruitment for targeted therapies in clinical trials.
|
|
| 7. |
- Nelson, Peter T., et al.
(author)
-
Reply : LATE to the PART-y
- 2019
-
In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 142
-
Journal article (other academic/artistic)
|
|
| 8. |
- Sharma, Shantanu, et al.
(author)
-
Associations between birth parameters and skin autofluorescence advanced glycation end and ankle-brachial index in young adulthood : the Malmö Offspring Study
- 2023
-
In: Journal of Hypertension. - 1473-5598. ; 41:7, s. 1184-1190
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Low birth weight (LBW), advanced glycation end-products (AGE), and ankle-brachial index (ABI) have all been independently associated with risk of cardiovascular disease. Evidence is lacking on the effect of LBW on adult AGE, a marker of glucose metabolism, and ABI, a marker of peripheral atherosclerosis. The objective was to study these associations in a population-based cohort.METHODS: Data from the Malmö Offspring Study, Sweden, were used for 2012 participants (958 men, 1054 women) born between 1973 and 2000, linked to the Medical Birth Register. General linear regression analysis (with β coefficients and 95% confidence intervals) was applied for associations between birth weight and skin auto-fluorescence (sf)AGE as well as mean ABI (right/left), before and after adjusting for gestational age, sex, glucose, lipids, smoking, BMI and SBP.RESULTS: The mean (SD) age of men was 29.3 (7.3) and of women 28.6 (7.3) years. There was an average 0.054 decrease in sfAGE value per 1 kg increase in birth weight (adjusted for gestational age and sex). Similarly, 1 kg increase in birth weight (adjusted for gestational age and confounders) was associated with an average 0.016 decrease in mean ABI.CONCLUSION: Birth weight, adjusted for gestational age and other confounding variables, is inversely associated with ABI in young adulthood, an age range when ABI may represent hemodynamic changes more than atherosclerosis, but for sfAGE, the association was attenuated upon further adjustment. These risk markers may, therefore, represent mediating pathways for early life factors affecting cardiovascular risk later in life.
|
|
| 9. |
|
|
| 10. |
- Sperling, Johannes, et al.
(author)
-
Does early life programming influence arterial stiffness and central hemodynamics in adulthood?
- 2020
-
In: Journal of Hypertension. - 0263-6352. ; 38:3, s. 481-488
-
Journal article (peer-reviewed)abstract
- Objectives:We aimed to investigate possible associations between birth weight and adult life carotid-femoral pulse wave velocity (cfPWV) and augmentation pressure index (AIx).Design and method:This study included 1598 participants, that is, 340 elderly individuals from the Malmö Birth Data Cohort (MBDC) and 1258 young-middle aged individuals from the Malmö Offspring Study (MOS) with full data on birth weight and gestational age. Participants underwent cfPWV and AIx measurements with Sphygmocor (AtCor, Australia). Analysis of data was performed with multiple linear regression models including adjustments for age, sex, gestational age and risk factors. Furthermore, comparisons were made between participants born prematurely or at term or born small-for-gestational age (SGA) or appropriate-for-gestational age (AGA).Results:Birth weight was positively associated with cfPWV after full adjustment (β = 0.057; P < 0.001), a finding that remained significant in the younger age group 18-27 years (β = 0.138, P = 0.008). Furthermore, birth weight was inversely associated with AIx (β = -0.058, P = 0.001). Participants born SGA had significantly higher AIx (P = 0.007) and MAP (P = 0.037) compared with AGA born. Preterm-born participants showed significantly higher SBP compared with term-born (P = 0.034). Finally, birth weight was inversely associated with MAP (β = -0.058, P = 0.017) and SBP (β = -0.047, P = 0.031), respectively.Conclusion:Birth weight is positively associated with cfPWV, shown strongest in the youngest individuals, a finding that could possibly be explained by increasing trends for maternal overweight/obesity in recent decades. Furthermore, birth weight is inversely associated with AIx, a risk marker of cardiovascular disease. This calls for screening of risk factors in subjects with adverse conditions at birth.
|
|
