| 1. |
- Palmqvist, Sebastian, et al.
(författare)
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Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease
- 2015
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 85:14, s. 1240-1249
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).Methods:From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). -Amyloid (A) deposition in 9 brain regions was examined with [F-18]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.Results:The best CSF measures for identifying MCI-AD were A42/total tau (t-tau) and A42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF A42/t-tau and A42/p-tau performed better than CSF A42 and A42/40 (AUC difference 0.03-0.12, p < 0.05). Using nonoptimized cutoffs, CSF A42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.Conclusions:Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global A deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.Classification of evidence:This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.
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| 2. |
- Rosengren, Annika, 1951, et al.
(författare)
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COVID-19 in people aged 18–64 in Sweden in the first year of the pandemic: Key factors for severe disease and death
- 2022
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Ingår i: Global Epidemiology. - : Elsevier BV. - 2590-1133. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies on risk factors for severe COVID-19 in people of working age have generally not included non-working persons or established population attributable fractions (PAFs) for occupational and other factors. Objectives: We describe the effect of job-related, sociodemographic, and other exposures on the incidence, relative risks and PAFs of severe COVID-19 in individuals aged 18–64. Methods: We conducted a registry-based study in Swedish citizens aged 18–64 from 1 January 2020 to 1 February 2021 with respect to COVID-19-related hospitalizations and death. Results: Of 6,205,459 persons, 272,043 (7.5%) were registered as infected, 3399 (0.05%) needed intensive care, and 620 (0.01%) died, with an estimated case fatality rate of 0.06% over the last 4-month period when testing was adequate. Non-Nordic origin was associated with a RR for need of intensive care of 3·13, 95%CI 2·91–3·36, and a PAF of 32·2% after adjustment for age, sex, work, region and comorbidities. In a second model with occupation as main exposure, and adjusted for age, sex, region, comorbidities and origin, essential workers had an RR of 1·51, 95%CI, 1·35–1·6, blue-collar workers 1·18, 95%CI 1·06–1·31, school staff 1·21, 95%CI 1·01–1·46, and health and social care workers 1·89, 95%CI 1·67–2·135) compared with people able to work from home, with altogether about 13% of the PAF associated with these occupations. Essential workers and blue-collar workers, but no other job categories had higher risk of death, adjusted RRs of 1·79, 95%CI 1·34–2·38 and 1·37, 95%CI 1·04–1·81, with adjusted PAFs of altogether 9%. Conclusion: Among people of working age in Sweden, overall mortality and case fatality were low. Occupations that require physical presence at work were associated with elevated risk of needing intensive care for COVID-19, with 14% cases attributable to this factor, and 9% of deaths.
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| 3. |
- Spångeus, Anna, Bitr Professor, 1975-, et al.
(författare)
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Prevalence of denosumab-induced hypocalcemia: a retrospective observational study of patients routinely monitored with ionized calcium post-injection
- 2024
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Ingår i: Osteoporosis International. - : SPRINGER LONDON LTD. - 0937-941X .- 1433-2965. ; 35:1, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- Summary: We assessed the prevalence of hypocalcemia after denosumab injections in a real-world cohort routinely monitored for calcium during up to 7.5 years of treatment. Among 1096 injections in 242 patients, 6.3% resulted in hypocalcemia, and was independent of the injection number. Severe hypocalcemia was rare (1%).Purpose: To assess the prevalence of and risk factors for hypocalcemia after administration of denosumab in a patient cohort routinely monitored for ionized calcium after each dose.Methods: In this retrospective observational study, we analyzed denosumab-induced hypocalcemia in a real-world cohort who were routinely followed up with ionized calcium pre- and post-injection (within 31 days after injection) during the period 2011 to 2020.Results: In total, we included data from 1096 denosumab injections in 242 individuals (1–15 injections per patient). The mean age for the first injection was 74 ± 10 years, and 88% were female. Post-injection hypocalcemia occurred after 6.3% of all injections (4.6% mild, 0.6% moderate, and 1.1% severe) and was independent of the number of injections (rate of hypocalcemia varied from 3–8%). Risk factors for hypocalcemia were male sex, severe renal failure, pre-injection hypocalcemia, hypomagnesemia, hypophosphatemia, and vitamin D insufficiency. Furthermore, older age was not associated with an increased hypocalcemia risk.Conclusions: Denosumab-induced hypocalcemia is a prevalent adverse event, which occurs independently of the number of injections. However, severe hypocalcemia is a rare occurrence, and severe renal failure and nutritional status appear to be important predictive factors. Magnesium and phosphate might add value in the pre-injection risk assessment; however, this observation needs to be confirmed in larger cohorts.
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| 4. |
- van Westen, Danielle, et al.
(författare)
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Cerebral white matter lesions - associations with A beta isoforms and amyloid PET
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6:20709
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Tidskriftsartikel (refereegranskat)abstract
- Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of beta-amyloid (A beta) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of A beta in cerebrospinal fluid (CSF) and cortical A beta in 831 subjects with cognitive performance ranging from normal to Alzheimer's disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of A beta 38 and A beta 40 were consistently associated with increased WML in all subgroups, while lower levels of CSF A beta 42 were associated with WML mainly in AD. CSF A beta 38 and A beta 40 were associated with regional WML in all regions, while CSF A beta 42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with A beta isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of A beta species, particularly of A beta 38 and A beta 40. However, in AD cases, A beta 42 pathology might be associated with WML, especially in the temporal lobe.
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| 5. |
- Holm, Hannes, et al.
(författare)
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N-Terminal Prosomatostatin and Risk of Vascular Dementia
- 2017
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Ingår i: Cerebrovascular Diseases. - : S. Karger. - 1015-9770 .- 1421-9786. ; 44:5-6, s. 259-265
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults.METHODS: In the prospective population-based Malmö Preventive Project, 5,347 study participants (mean age: 69 ± 6years; 70% men) provided plasma for the determination of NT-proSST concentration. Of these, 373 participants (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) during a follow-up period of 4.6 ± 1.3 years. The association of NT-proSST with the risk of dementia and its subtypes was studied using multivariable-adjusted Cox regression models controlling for age, gender, body mass index, systolic blood pressure, antihypertensive treatment, smoking, diabetes, lipid levels and prevalent stroke.RESULTS: Higher levels of NT-proSST were significantly associated with an increased risk of vascular dementia (hazard ratio [HR] per 1 SD: 1.29; 95% CI 1.05-1.59; p = 0.016), whereas no association was observed with Alzheimer's disease (HR per 1 SD: 0.99; 95% CI 0.81-1.20; p = 0.91), all-cause dementia (HR per 1 SD: 1.04; 95% CI 0.94-1.16; p = 0.44), and mixed dementia (HR per 1 SD: 0.98; 95% CI 0.79-1.21; p = 0.84). Levels of NT-proSST above 563 pmol/L (highest quartile) conferred distinctly increased risk of vascular dementia (HR 1.66; 95% CI 1.05-2.63; p = 0.029) compared with lower values.CONCLUSIONS: Higher levels of circulating N-terminal-prosomatostatin are associated with increased incidence of vascular dementia. Our findings might be of importance for the understanding of dementia development in older adults.
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| 6. |
- E:son Jennersjö, Pär, 1956-
(författare)
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Risk factors in type 2 diabetes with emphasis on blood pressure, physical activity and serum vitamin D
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundType 2 diabetes is a common chronic disease with a two-fold increased risk for cardiovascular morbidity and mortality and has an increasing prevalence worldwide. This thesis is based on a study conducted in primary health care in Östergötland and Jönköping, Sweden. The aim of the thesis was to evaluate new risk markers to identify patients with high risk of developing cardiovascular disease in middle-aged men and women with type 2 diabetes.MethodsData from the cohort study CArdiovascular Risk in type 2 DIabetes – a Prospective study in Primary care (CARDIPP) was used. In paper III data were also used from CARDIPP-Revisited where all participants in the CARDIPP study were invited four years after the baseline investigation for a re-investigation. In paper IV data were used from CAREFUL which is a control group of 185 subjects without diabetes. The investigation included a standard medical history including data on diabetes duration and on-going medication. Anthropometric data were recorded and both office and ambulatory blood pressure were measured. The patients filled out a detailed questionnaire and physical activity was measured by using waist-mounted pedometers. Pedometer-determined physical activity was classified in four groups: Group 1: <5000 steps/day (‘sedentary’); Group 2: 5000-7499 steps/day (‘low active’); Group 3: 7500-9999 steps/day (‘somewhat active’); Group 4: and ≥10 000 steps/day (‘active’). Blood samples were drawn for routine analyses and also frozen for later analyses. The investigations at the departments of physiology included echocardiography, measurements of the carotid intima-media thickness, applanation tonometry and measurements of sagittal abdominal diameter.ResultsPaper 1:Patients with a non-dipping systolic blood pressure pattern showed higher left ventricular mass index and pulse wave velocity (PWV) compared with patients with ≥10% decline in nocturnal systolic blood pressure. Patients with <10% decline in nocturnal systolic blood pressure had higher BMI and sagittal abdominal diameter, lower GFR and higher albumin:creatinine ratio and also higher levels of NT-proBNP than patients with a dipping pattern of the nocturnal blood pressure.Paper 2:The number of steps/day were inversely significantly associated with BMI, waist circumference and sagittal abdominal diameter, levels of CRP, levels of interleukin-6 and PWV.Paper 3:At the 4-year follow-up the change in PWV (ΔPWV) from baseline was calculated. The group with the lowest steps/day had a significantly higher increase in ΔPWV compared with the group with the highest steps/day. The associations between baseline steps/day and ΔPWV remained after further adjustment in a multivariate linear regression statistically significant (p=0.005). 23% of the variation in the study could be explained by our model. Every 1000 extra steps at baseline reduced the change in ΔPWV by 0.103 m/s between baseline and follow-up.Paper 4:Low vitamin D levels were associated with significantly increased risk for premature mortality in men with type 2 diabetes. High levels of parathyroid hormone were associated with significantly increased risk for premature mortality in women with type 2 diabetes. These relationships were still statistically significant also when two other well-established risk markers for mortality, PWV and carotid intima-media thickness, were added to the analyses.ConclusionsAmbulatory blood pressure recording can by addressing the issue of diurnal blood pressure variation, explore early cardiovascular organ damage and microvascular complications that goes beyond effects of standardised office blood pressure measurements. Pedometer-determined physical activity may serve as a surrogate marker for inflammation and subclinical organ damage in patients with type 2 diabetes. There is novel support for the durable vascular protective role of a high level of daily physical activity, which is independent of BMI and systolic blood pressure. The use of pedometers is feasible in clinical practice and provides objective information not only about physical activity but also the future risk for subclinical organ damage in middle-aged people with type 2 diabetes. Our results indicate that low vitamin D levels in men or high parathyroid hormone levels in women give independent prognostic information of an increased risk for total mortality.
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| 7. |
- Jennersjö, Pär, et al.
(författare)
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Pedometer-determined physical activity level and change in arterial stiffness in Type 2 diabetes over 4 years
- 2016
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Ingår i: Diabetic Medicine. - : John Wiley & Sons. - 0742-3071 .- 1464-5491. ; 33:7, s. 992-997
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Tidskriftsartikel (refereegranskat)abstract
- Aim To explore prospectively the correlation between the level of pedometer-determined physical activity at the start of the study and the change in pulse wave velocity from baseline to 4 years later in people with Type 2 diabetes.Methods We analysed data from 135 men and 53 women with Type 2 diabetes, aged 54–66 years. Physical activity was measured with waist-mounted pedometers on 3 consecutive days and the numbers of steps/day at baseline were classified into four groups: <5000 steps/day, 5000–7499 steps/day, 7500–9999 steps/day and ≥10 000 steps/day. Pulse wave velocity was measured using applanation tonometry over the carotid and femoral arteries at baseline and after 4 years.Results The mean (±sd; range) number of steps/day was 8022 (±3765; 956–20 921). The participants with the lowest level of physical activity had a more pronounced increase in the change in pulse wave velocity compared with the participants with the highest. When change in pulse wave velocity was analysed as a continuous variable and adjusted for sex, age, diabetes duration, HbA1c, BMI, systolic blood pressure, pulse wave velocity at baseline, β-blocker use, statin use, unemployment, smoking and diabetes medication, the number of steps/day at baseline was significantly associated with a less steep increase in change in pulse wave velocity (P=0.005). Every 1000 extra steps at baseline corresponded to a lower increase in change in pulse wave velocity of 0.103 m/s.Conclusions We found that a high level of pedometer-determined physical activity was associated with a slower progression of arterial stiffness over 4 years in middle-aged people with Type 2 diabetes.
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| 8. |
- Janelidze, Shorena, et al.
(författare)
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Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 51, s. 104-112
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Tidskriftsartikel (refereegranskat)abstract
- Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF bio-markers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage. (C) 2016 The Authors. Published by Elsevier Inc.
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| 9. |
- Lindgren, Emma, et al.
(författare)
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Differences in Dementia Care Between Swedish-Born and Foreign-Born from Countries with Different Country Level Socioeconomic Position : A Nationwide Register-Based Study
- 2021
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 84:3, s. 1363-1371
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Tidskriftsartikel (refereegranskat)abstract
- Background: With a growing elderly population worldwide, the prevalence of dementia is rapidly increasing. Studies from high income countries have shown that belonging to a minority ethnic group increases the risk of health disadvantages. Objective: The aim of the present registry-based study was to identify potential differences in diagnostics, treatment, and care of individuals with dementia focusing on foreign-born in Sweden and the impact of country level socioeconomic position (SEP). Methods: The study was based on a large dataset from the Swedish Dementia Registry (SveDem) and the Swedish Tax Agency's population registry. Data on demographic variables, cognitive tests, clinical assessments, medication, diagnosis, and interventions initiated at diagnosis were collected. Country level SEP was determined by country of birth as classified by World Bank Country and Lending groups. Results: Of 57,982 patients with dementia registered in SveDem, 7,171 (12.4%) were foreign-born. The foreign-born were significantly younger at diagnosis (p < 0.001), had a lower MMSE score (p < 0.001), lower odds of receiving a specific dementia diagnosis (p < 0.001), lower use of acetylcholinesterase inhibitors (p < 0.001), and overall a higher use of neuroleptics compared with the Swedish-born group. The lower SEP, the greater differences to Swedish-born were seen in many of the examined variables. Conclusion: There were significant differences in dementia diagnostics, treatment, and care between foreign-born and Swedish-born, a lower SEP indicating greater differences. Further research should focus on various socioeconomic aspects and health care outcomes for a more profound analysis of equity in dementia care.
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| 10. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Weight gain and blood pressure
- 2020
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 38:3, s. 387-394
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Although the causality of the obesity—hypertension association is established, the potential for prevention is not. We hypothesized that weight gain between early adulthood and mid-life is associated with higher mid-life blood pressure.METHODS: We investigated the hypothesis using a large contemporaneous population-based mid-life cohort of men and women aged 50-64 years. Recalled body weight at age 20 years was self-reported, and mid-life body weight and office blood pressures were measured in accordance with a detailed protocol.RESULTS: On average, men had gained 14.9 (95% CI 14.6-15.2) kg of weight, and women 14.6 (95% CI 14.4-14.9) kg, between age 20 years and the mid-life examination, corresponding to 0.40 (95% CI 0.39-0.41) kg/year for men and women. Both weight at age 20 years and weight at the mid-life examination were associated with mid-life blood pressures. On average, a 10 kg weight increase between age 20 years and mid-life was associated with 2.2 (95% CI 0.9-3.5) mmHg higher systolic and 1.7 (95% CI 0.9-2.5) mmHg higher diastolic mid-life blood pressure in men, and 3.2 (2.5-4.0) mmHg higher systolic and 2.4 (1.9-2.9) mmHg higher diastolic mid-life blood pressure in women. Mid-life weight was more closely associated than weight at age 20 years with mid-life blood pressure. For a given mid-life weight, blood pressure was higher in persons with higher weight gain from age 20 years.CONCLUSION: In sum, weight gain between early adulthood and mid-life was associated with higher mid-life blood pressure. The magnitude of the association indicates a potentially great public health impact of strategies to prevent weight gain throughout adulthood.
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