| 1. |
|
|
| 2. |
- Ballard, Clive, et al.
(författare)
-
alpha-synuclein antibodies recognize a protein present at lower levels in the CSF of patients with dementia with Lewy bodies
- 2010
-
Ingår i: International Psychogeriatrics. - 1741-203X. ; 22:2, s. 321-327
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Dementia with Lewy bodies (DLB) accounts for 15-20%, of the millions of people worldwide with dementia. Accurate diagnosis is essential to avoid harm and optimize clinical management. There is therefore an urgent need to identify reliable biomarkers. Methods: Mass spectrometry was used to determine the specificity of antibody alpha-synuclein (211) for alpha-synuclein. Using gel electrophoresis we measured protein levels detected by alpha-synuclein specific antibodies in the cerebrospinal fluid (CSF) of DLB patients and compared them to age matched controls. Results: A 24 kDa band was detected using alpha-synuclein specific antibodies which was significantly reduced in the CSF of DLB patients compared to age matched controls (p < 0.05). Further analysis confirmed that even DLB patients with mild dementia showed significant reductions in this protein in comparison to controls. Conclusions: The current study emphasizes the necessity for further studies of CSF alpha-synuclein as a biomarker of DLB and extends our previous knowledge by establishing a potential relationship between alpha-synuclein and the severity of cognitive impairment. The identification of this 24 kDa protein is the next important step in these studies.
|
|
| 3. |
- Creese, Byron, et al.
(författare)
-
Determining the Association of the 5HTTLPR Polymorphism with Delusions and Hallucinations in Lewy Body Dementias
- 2014
-
Ingår i: The American Journal of Geriatric Psychiatry. - : Elsevier BV. - 1545-7214 .- 1064-7481. ; 22:6, s. 580-586
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine whether the 5HTTLPR serotonin transporter polymorphism is associated with delusions and hallucinations in people with dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). Design: Prospective cohort study. Participants: A total of 187 individuals, recruited from centres in Norway, Sweden, and the United Kingdom were included in this study; 97 with clinically or neuropathologically diagnosed DLB/PDD and 90 cognitively normal individuals as a comparison group. Measurements: All participants with dementia underwent serial evaluation of neuropsychiatric symptoms to assess the presence of persistent delusions and hallucinations using the Columbia University Scale for Psychopathology in Alzheimer disease, the Neuropsychiatric Inventory, or the Present Behavioural Examination. Severity of cognitive impairment was measured using the Mini Mental State Examination (MMSE). Individuals were genotyped for the 5HTTLPR polymorphism. Results: Logistic regression demonstrated that homozygosity for the L/L genotype and lower MMSE were associated with an increased risk for delusions (odds ratio: 11.5 and 1.16, respectively). Neither was significantly associated with hallucinations. Conclusions: This study is the first to demonstrate the 5HTTLPR polymorphism is associated with delusions in Lewy body dementias, with important implications regarding the mechanisms underlying this symptom across the AD/DLB/PDD spectrum. Further studies are warranted to investigate this relationship further and examine treatment opportunities.
|
|
| 4. |
- Creese, Byron, et al.
(författare)
-
No association of COMT val158met polymorphism and psychotic symptoms in Lewy body dementias
- 2012
-
Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 531:1, s. 1-4
-
Tidskriftsartikel (refereegranskat)abstract
- We sought to determine whether the COMT val158met polymorphism (rs4680) is associated with delusions and hallucinations in people with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). A total of 218 individuals, recruited from centres in Norway, Sweden and the UK were included in this study; 121 with clinically or neuropathologically diagnosed DLB/PDD and 97 age-matched, cognitively normal controls. All participants with dementia underwent serial evaluation of neuropsychiatric symptoms to assess the presence of persistent delusions and hallucinations using the Columbia University Scale for Psychopathology in Alzheimer's disease, the Neuropsychiatric Inventory or the Present Behavioural Examination. Severity of cognitive impairment was measured using the Mini Mental State Examination (MMSE). Both controls and participants with dementia were genotyped for rs4680. In contrast to previous findings, analysis by logistic regression failed to find any associations between rs4680 and psychotic symptoms. Larger studies in well characterised cohorts are warranted in order to investigate this relationship further. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
|
|
| 5. |
- Feigin, Valery L., et al.
(författare)
-
Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
-
Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
|
|
| 6. |
|
|
| 7. |
- Haghighi, Mona, et al.
(författare)
-
A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
|
|
| 8. |
- Haya, Nir, et al.
(författare)
-
Prolapse and continence surgery in countries of the Organization for Economic Cooperation and Development in 2012
- 2015
-
Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 212:6
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to report the rates and types of pelvic organ prolapse (POP) and female continence surgery performed in member countries of the Organization for Economic Co-operation and Development (OECD) in 2012. STUDY DESIGN: The published health outcome data sources of the 34 OECD countries were contacted for data on POP and female continence interventions from 2010-2012. In nonresponding countries, data were sought from national or insurer databases. Extracted data were entered into an age-specific International Classification of Disease, edition 10 (ICD-10)-compliant Excel spreadsheet by 2 authors independently in English-speaking countries and a single author in non-English-speaking countries. Data were collated centrally and discrepancies were resolved by mutual agreement. RESULTS: We report on 684,250 POP and 410,352 continence procedures that were performed in 15 OECD countries in 2012. POP procedures (median rate, 1.38/1000 women; range, 0.51-2.55 prolapse procedures/1000 women) were performed 1.8 times more frequently than continence procedures (median rate, 0.75/1000 women; range, 0.46-1.65 continence procedures/1000 women). Repairs of the anterior vaginal compartment represented 54% of POP procedures; posterior repairs represented 43% of the procedures, and apical compartment repairs represented 20% of POP procedures. Median rate of graft usage was 15.7% of anterior vaginal repairs (range, 3.3-25.6%) and 8.5% (range, 3.2-17%) of posterior vaginal repairs. Apical compartment repairs were repaired vaginally at a median rate of 70% (range, 35-95%). Sacral colpopexy represented a median rate of 17% (range, 5-65%) of apical repairs; 61% of sacral colpopexies were performed minimally invasively. Between 2010 and 2012, there was a 3.7% median reduction in transvaginal grafts, a 4.0% reduction in midurethral slings, and a 25% increase in sacral colpopexies that were performed per 1000 women. Midurethral slings represented 82% of female continence surgeries. CONCLUSION: The 5-fold variation in the rate of prolapse interventions within OECD countries needs further evaluation. The significant heterogeneity (> 10 times) in the rates at which individual POP procedures are performed indicates a lack of uniformity in the delivery of care to women with POP and demands the development of uniform guidelines for the surgical management of prolapse. In contrast, the midurethral slings were the standard female continence surgery performed throughout OECD countries in 2012.
|
|
| 9. |
- Jones, Emma L., et al.
(författare)
-
A Pilot Study Examining Associations between DYRK1A and alpha-Synuclein Dementias
- 2012
-
Ingår i: Neurodegenerative Diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 10:1-4, s. 229-231
-
Tidskriftsartikel (refereegranskat)abstract
- Background: DYRK1A is a kinase targeting several proteins associated with the pathology of dementias, including alpha-synuclein and amyloid precursor protein. It is not clear if DYRK1A genetics are associated with neurodegenerative conditions. Objective: To determine if DYRK1A also has a genetic association with alpha-synuclein dementias such as dementia with Lewy bodies and Parkinson's disease dementia. Methods: DNA samples from prospectively followed cohorts of control and dementia individuals were genotyped for the DYRK1A rs8126696 polymorphism. Results: The rs8126696 polymorphism altered the risk of developing an alpha-synuclein-associated dementia. Conclusion: DYRK1A could prove to be an important therapeutic target as it interacts with several proteins associated with the development of pathology in dementia. Copyright (C) 2012 S. Karger AG, Basel
|
|
| 10. |
- Lozano, Rafael, et al.
(författare)
-
Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
|
|
