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1.
  • Adedeji, Dickson O., et al. (författare)
  • Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients
  • 2023
  • Ingår i: Brain, Behavior, and Immunity - Health. - : Elsevier. - 2666-3546. ; 28
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Allostatic load (AL) is defined as the cumulative dysregulation of neuroendocrine, immunological, metabolic, and cardiovascular systems that increases the susceptibility to stress-related health problems. Several dementia and Alzheimer's disease (AD) risk factors have been identified, yet little is known about the role of AL and its associations with AD biomarkers (e.g., beta-amyloid (Aβ) or tau) and cognitive function among memory clinic patients. Hence, this study aims to assess the association between AL and AD biomarkers, cognitive performance, and cognitive decline after 3-years of follow-up.Methods: Data from 188 memory clinic patients were derived from the Cortisol and Stress in AD (Co-STAR) study in Sweden. Participants underwent baseline assessments including blood tests for AL measures (including cortisol, thyroid stimulating hormone, cobalamin, homocysteine, leukocytes, glycated hemoglobin, albumin, high-density and low-density lipoprotein cholesterol, triglycerides, and creatinine), cerebrospinal fluid (CSF) sampling for AD biomarkers and neuropsychological tests including five cognitive domains. Linear regressions were conducted, adjusting for age, sex, and education.Results: Higher AL was associated with lower CSF Aβ1-42 levels (β = −0.175, p = 0.025), reflecting higher brain levels of Aβ1-42. Stratified analyses suggested a significant association among women but not men, although the AL-sex interaction was not statistically significant. AL was not significantly associated with T-tau level (β = −0.030, p = 0.682) and P-tau level (β = 0.091, p = 0.980). There were no significant associations between AL and cognition or cognitive decline after 3 years.Conclusion: This study showed that higher AL was associated with increased brain amyloid accumulation. This suggests that AL may play a role in AD/dementia pathophysiology. Potential sex-related differences should be assessed in further larger studies.
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2.
  • Adedeji, Dickson O., et al. (författare)
  • Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients
  • 2023
  • Ingår i: Brain, Behavior, and Immunity - Health. - : Elsevier BV. - 2666-3546. ; 28
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Allostatic load (AL) is defined as the cumulative dysregulation of neuroendocrine, immunological, metabolic, and cardiovascular systems that increases the susceptibility to stress-related health problems. Several dementia and Alzheimer's disease (AD) risk factors have been identified, yet little is known about the role of AL and its associations with AD biomarkers (e.g., beta-amyloid (Aβ) or tau) and cognitive function among memory clinic patients. Hence, this study aims to assess the association between AL and AD biomarkers, cognitive performance, and cognitive decline after 3-years of follow-up.Methods: Data from 188 memory clinic patients were derived from the Cortisol and Stress in AD (Co-STAR) study in Sweden. Participants underwent baseline assessments including blood tests for AL measures (including cortisol, thyroid stimulating hormone, cobalamin, homocysteine, leukocytes, glycated hemoglobin, albumin, high-density and low-density lipoprotein cholesterol, triglycerides, and creatinine), cerebrospinal fluid (CSF) sampling for AD biomarkers and neuropsychological tests including five cognitive domains. Linear regressions were conducted, adjusting for age, sex, and education.Results: Higher AL was associated with lower CSF Aβ1-42 levels (β = −0.175, p = 0.025), reflecting higher brain levels of Aβ1-42. Stratified analyses suggested a significant association among women but not men, although the AL-sex interaction was not statistically significant. AL was not significantly associated with T-tau level (β = −0.030, p = 0.682) and P-tau level (β = 0.091, p = 0.980). There were no significant associations between AL and cognition or cognitive decline after 3 years.Conclusion: This study showed that higher AL was associated with increased brain amyloid accumulation. This suggests that AL may play a role in AD/dementia pathophysiology. Potential sex-related differences should be assessed in further larger studies.
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3.
  • Finkel, Deborah, et al. (författare)
  • Impact of Childhood and Adult Socioeconomic Position on Change in Functional Aging
  • 2024
  • Ingår i: Health Psychology. - : American Psychological Association (APA). - 0278-6133 .- 1930-7810. ; 43:5, s. 388-395
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To examine life-course models by investigating the roles of childhood and adult socioeconomic position (SEP) in longitudinal changes in a functional aging index. Method: Up to eight waves of testing, covering 25 years, were available from the Swedish Adoption/Twin Study of Aging: N = 654, intake age = 50-82. A two-slope latent growth curve model was applied to the data, and the impact of including childhood and adult SEP as covariates of the intercept (at age 70) and slopes (before and after age 70) was tested. Results: Both childhood and adult SEP contributed to the best-fitting model. Childhood SEP was significantly associated with intercept and Slope 1 (before age 70) of the latent growth curve model (p < .05). Association of adult SEP with Slope 2 (after age 70) trended toward significance (p < .10). There was a significant interaction effect of childhood and adult SEP on the intercept (p < .05). As a result, intercept at age 70 was highest and change after age 70 was fastest for those whose SEP decreased from childhood to adulthood. Conclusions: Both childhood and adult SEP impact change in functional abilities with age, supporting both critical period and social mobility models. The social environment is modifiable by policies at local, national, and international levels, and these policies need to recognize that early social disadvantage can have long-lasting health impacts.
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4.
  • Finkel, Deborah, et al. (författare)
  • Impact of Objective and Subjective Sep on Aging Trajectories of Functional Capacity
  • 2022
  • Ingår i: Innovation in Aging. - : Oxford University Press. - 2399-5300. ; 6:Supplement 1, s. 220-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Long-term stress is associated with adverse health outcomes in aging. It is important to identify not only factors that influence functioning in late adulthood, such as accumulated stress, but also the timing of such factors. The aim of the current analysis was to examine how socioeconomic stressors throughout the life course are associated with aging in functional capacity. Data were available from 740 adults ranging in age from 40 to 83 at intake (mean = 62.4, SD = 8.2) who participated in up to 8 waves of data collection (mean = 3.9, SD = 2.4). A Functional Aging Index (FAI) was created by combining measures of sensory, pulmonary, gait, and grip functioning. Both childhood and adulthood measures of objective socioeconomic position (SEP) and perceived SEP (financial strain) were available. Latent growth curve models (corrected for twinness) were used to estimate the trajectory of change in FAI over age and the impact of child and adult SEP measures on the trajectories. Results indicated that both childhood and adult objective SEP independently influenced rates of change in FAI in adulthood: higher SEP was associated with higher mean functioning and slower rates of decline. In combination, model fitting indicated that if SEP is above the median in adulthood, then childhood SEP has no impact on FAI trajectories; however, if SEP is below the median in adulthood, then childhood SEP can play a role. In addition, results indicated possible long-term effects of childhood financial strain on rates of change in FAI in adulthood.
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5.
  • Forouzanfar, Mohammad H, et al. (författare)
  • Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
  • 2015
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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6.
  • Hampel, Harald, et al. (författare)
  • Advances in the therapy of Alzheimer's disease : targeting amyloid beta and tau and perspectives for the future
  • 2015
  • Ingår i: Expert Review of Neurotherapeutics. - : Informa UK Limited. - 1473-7175 .- 1744-8360. ; 15:1, s. 83-105
  • Forskningsöversikt (refereegranskat)abstract
    • Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD.
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7.
  • Holleman, Jasper, et al. (författare)
  • Cortisol, cognition and Alzheimer's disease biomarkers among memory clinic patients
  • 2022
  • Ingår i: BMJ Neurology Open. - : BMJ Publishing Group Ltd. - 2632-6140. ; 4:2
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveThis study aims to investigate the relationship between diurnal cortisol patterns, cognition and Alzheimer's disease (AD) biomarkers in memory clinic patients.MethodMemory clinic patients were recruited from Karolinska University Hospital in Sweden (n=155). Diurnal cortisol patterns were assessed using five measures: awakening levels, cortisol awakening response, bedtime levels, the ratio of awakening to bedtime levels (AM/PM ratio) and total daily output. Cognition was measured in five domains: memory, working memory, processing speed, perceptual reasoning and overall cognition. AD biomarkers A beta(42), total tau and phosphorylated tau were assessed from cerebrospinal fluid (CSF). Cognition was measured at follow-up (average 32 months) in a subsample of participants (n=57).ResultsIn assessing the associations between cortisol and cognition, higher awakening cortisol levels were associated with greater processing speed at baseline. No relationship was found between diurnal cortisol patterns and change in cognition over time or CSF AD biomarkers in the total sample. After stratification by CSF A beta(42) levels, higher awakening cortisol levels were associated with worse memory performance in amyloid-positive participants. In amyloid-negative participants, higher bedtime cortisol levels and a lower AM/PM ratio were associated with lower overall cognition, greater awakening cortisol levels were associated with better processing speed, and a higher AM/PM ratio was associated with better perceptual reasoning. Additionally, higher awakening cortisol levels were associated with lower CSF A beta(42) levels in amyloid-positive participants, while higher bedtime cortisol levels and a lower AM/PM ratio were associated with higher CSF total tau in amyloid-negative participants.ConclusionsOur findings suggest that diurnal cortisol patterns are associated with cognitive function and provide new insights into the association between diurnal cortisol patterns and AD-related CSF biomarkers. Further research is needed to examine the complex relationship between cortisol, cognition and brain pathology.
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8.
  • Holleman, Jasper, et al. (författare)
  • Diurnal cortisol, neuroinflammation, and neuroimaging visual rating scales in memory clinic patients
  • 2024
  • Ingår i: Brain, behavior, and immunity. - : Elsevier. - 0889-1591 .- 1090-2139. ; 118, s. 499-509
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Neuroinflammation is a hallmark of the Alzheimer's disease (AD) pathogenic process. Cortisol dysregulation may increase AD risk and is related to brain atrophy. This cross-sectional study aims to examine interactions of cortisol patterns and neuroinflammation markers in their association with neuroimaging correlates.METHOD: 134 participants were recruited from the Karolinska University Hospital memory clinic (Stockholm, Sweden). Four visual rating scales were applied to magnetic resonance imaging or computed tomography scans: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), white matter lesions (WML), and posterior atrophy. Participants provided saliva samples for assessment of diurnal cortisol patterns, and underwent lumbar punctures for cerebrospinal fluid (CSF) sampling. Three cortisol measures were used: the cortisol awakening response, total daily output, and the ratio of awakening to bedtime levels. Nineteen CSF neuroinflammation markers were categorized into five composite scores: proinflammatory cytokines, other cytokines, angiogenesis markers, vascular injury markers, and glial activation markers. Ordinal logistic regressions were conducted to assess associations between cortisol patterns, neuroinflammation scores, and visual rating scales, and interactions between cortisol patterns and neuroinflammation scores in relation to visual rating scales.RESULT: Higher levels of angiogenesis markers were associated with more severe WML. Some evidence was found for interactions between dysregulated diurnal cortisol patterns and greater neuroinflammation-related biomarkers in relation to more severe GCA and WML. No associations were found between cortisol patterns and visual rating scales.CONCLUSION: This study suggests an interplay between diurnal cortisol patterns and neuroinflammation in relation to brain structure. While this cross-sectional study does not provide information on causality or temporality, these findings suggest that neuroinflammation may be involved in the relationship between HPA-axis functioning and AD.
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9.
  • Holleman, Jasper, et al. (författare)
  • Life-course stress, cognition, and diurnal cortisol in memory clinic patients without dementia
  • 2024
  • Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier. - 0167-4943 .- 1872-6976. ; 119
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To examine associations of life-course stress with cognition and diurnal cortisol patterns in older adulthood, as well as potential mediation effects of diurnal cortisol patterns and perceived stress on the association between life-course stress and cognition.METHODS: 127 participants without dementia were selected from a cohort of Swedish memory clinic patients. Cross-sectional associations between scores on two chronic stress questionnaires (perceived stress, stressful life events (SLEs)), five cognitive domains (overall cognition, memory, working memory, processing speed, perceptual reasoning), and two measures of diurnal cortisol patterns (total daily output, diurnal cortisol slope), as well as potential mediation effects of diurnal cortisol patterns and perceived stress on associations between life-course stress and cognition, were assessed using linear regressions.RESULTS: Greater lifetime exposure to SLEs was associated with worse memory, working memory, and processing speed performance, but not with diurnal cortisol patterns. A greater number of SLEs in late childhood was associated with worse working memory and processing speed, while a greater number of SLEs in non-recent adulthood were associated with better overall cognition and perceptual reasoning. Greater perceived stress was associated with a flattened diurnal cortisol slope, but not with cognition. No evidence for interplay between self-reported and physiological stress markers was found in relation to cognition, although there appeared to be a significant positive indirect association between economic/legal SLEs and the diurnal cortisol slope via perceived stress.CONCLUSIONS: The associations between SLEs and cognition depend on the period during which SLEs occur, but seem independent of late-life cortisol dysregulation.
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10.
  • Hooshmand, Babak, et al. (författare)
  • Serum Insulin and Cognitive Performance in Older Adults : A Longitudinal Study
  • 2019
  • Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 132:3, s. 367-373
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeThe aim of this study was to examine the association of serum glucose, insulin, and insulin resistance with cognitive functioning 7 years later in a longitudinal population-based study of Finnish older adults.MethodsSerum glucose and insulin were measured at baseline in 269 dementia-free individuals aged 65-79 years, from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study. Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). Participants were reexamined 7 years later, and global cognition, episodic memory, executive functioning, verbal expression, and psychomotor speed were assessed, both at baseline and at follow-up. Multiple linear regression was used to investigate the associations with cognitive performance at follow-up, after adjusting for several potential confounders, including common vascular risk factors.ResultsIn the multivariable-adjusted linear regression models, no associations of insulin resistance with cognitive functioning were observed. After excluding 19 incident dementia cases, higher baseline HOMA-IR values were related to worse performance in global cognition (beta [standard error (SE)] -.050 [0.02]; P =.043) and psychomotor speed (beta [SE] -.064 [. 03]; P = [.043]) 7 years later. Raised serum insulin levels were associated with lower scores on global cognition (b [SE] -.054 [.03]; P =.045) and tended to relate to poorer performance in psychomotor speed (beta [SE] -.061 [.03]; P =.070).ConclusionsSerum insulin and insulin resistance may be independent predictors of cognitive performance 7 years later in elderly individuals without dementia. Randomized controlled trials are needed to determine this issue.
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11.
  • Kåreholt, Ingemar, 1960-, et al. (författare)
  • Mid-life financial stress and cognitive and physical problems in older age : The role of potentially modifying factors
  • 2023
  • Ingår i: Innovation in Aging. - : Oxford University Press. - 2399-5300. ; 7:Supplement 1, s. 377-377
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Financial stress is an important source of chronic stress and has been associated with cognitive and physical impairments. This study investigates whether midlife financial stress is associated with the combination of cognitive and physical impairment, the role of potentially modifiable factors, and sex differences.Methods: The Cardiovascular Risk Factors, Aging, and Dementia population-based cohort study from Finland was used (n=1497) (baseline collected 1972-1987, mean age 50 years). There were two late-life re-examinations (mean total follow-up 25 years). Midlife financial stress was measured using two questions on financial situation. Cognitive impairment was based on six cognitive domains. Physical impairment was self-reported. Potential modifying factors investigated were smoking, alcohol, physical activity, cohabiting/not, non-manual work, and sleep disturbances. Sex differences were investigated. We used path analyses with full information maximum likelihood estimation.Results: Among women and men, midlife financial stress associated with cognitive impairment, physical impairment and their combination. Smoking and sleep disturbances mediated associations between financial stress, physical impairment, and combined impairments. Among men: manual/non-manual work mediated the association to cognitive impairments; cohabitation mediated to cognitive impairment; financial stress was associated with cognitive impairment only among smokers and stress had a stronger association to physical and combined impairments among non-drinkers. Among women, sleep seems to have role in the association between financial stress and cognitive impairment.Conclusions: Midlife financial stress associates with late-life impairments, and lifestyle/sociodemographic factors may modify these associations. Sex differences were observed. Interventions promoting healthier lifestyle and psychosocial factors may buffer against the deleterious role of financial stress.
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13.
  • Levak, Nicholas, et al. (författare)
  • Nutrition guidance within a multimodal intervention improves diet quality in prodromal Alzheimer’s disease: Multimodal Preventive Trial for Alzheimer’s Disease (MIND-ADmini)
  • 2024
  • Ingår i: Alzheimer's Research & Therapy. - : Springer. - 1758-9193. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundMultimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer’s disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them.MethodA 6-month MIND-ADmini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records.ResultsThe dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake.ConclusionThese results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density.Trial registrationClinicalTrials.gov NCT03249688, 2017–07-08.
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14.
  • Liu, Rui, et al. (författare)
  • Associations of sleep timing and time in bed with dementia and cognitive decline among Chinese older adults : A cohort study
  • 2022
  • Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 70:11, s. 3138-3151
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The longitudinal associations of sleep timing and time in bed (TIB) with dementia and cognitive decline in older adults are unclear.Methods: This population-based cohort study used data from 1982 participants who were aged >= 60 years, free of dementia, and living in rural communities in western Shandong, China. At the baseline (2014) and follow-up (2018) examinations, sleep parameters were assessed using standard questionnaires. Cognitive function was measured using the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the DSM-IV criteria, and the NIA-AA criteria for Alzheimer disease (AD). Data were analyzed using restricted cubic splines, Cox proportional-hazards models, and general linear models.Results: During the mean follow-up of 3.7 years, dementia was diagnosed in 97 participants (68 with AD). Restricted cubic spline curves showed J-shaped associations of sleep duration, TIB, and rise time with dementia risk, and a reverse J-shaped association with mid-sleep time. When sleep parameters were categorized into tertiles, the multivariable-adjusted hazard ratio (HR) of incident dementia was 1.69 (95%CI 1.01-2.83) for baseline sleep duration >8 hours (vs. 7-8 h), 2.17 (1.22-3.87) for bedtime before 9 p.m. (vs. 10 p.m. or later), and 2.00 (1.23-3.24) for mid-sleep time before 1 a.m. (vs. 1-1.5 a.m.). Early bedtime and mid-sleep time were significantly associated with incident AD (HR range: 2.25-2.51; p < 0.05). Among individuals who were free of dementia at follow-up, baseline long TIB, early bedtime and mid-sleep time, early and late rise time, and prolonged TIB and advanced bedtime and mid-sleep time from baseline to follow-up were associated with a greater decline in MMSE score (p < 0.05). These associations with cognitive decline were statistically evident mainly among men or participants who were aged 60-74 years.Conclusions: Long TIB and early sleep timing are associated with an increased risk of dementia, and the associations with greater cognitive decline are evident only among older people aged 60-74 years and men.
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15.
  • Liu, Rui, et al. (författare)
  • Self-reported sleep characteristics associated with dementia among rural-dwelling Chinese older adults : a population-based study
  • 2022
  • Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sleep characteristics associated with dementia are poorly defined and whether their associations vary by demographics and APOE genotype among older adults are unclear.Methods: This population-based cross-sectional study included 4742 participants (age ≥ 65 years, 57.1% women) living in rural China. Sleep parameters were measured using the self-rated questionnaires of the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, and the National Institute on Aging-Alzheimer’s Association criteria for Alzheimer’s disease (AD). Data were analysed using multiple logistic and general linear regression models.Results: Dementia was diagnosed in 173 participants (115 with AD). Multivariable-adjusted odds ratio (OR) of dementia was 1.71 (95%CI, 1.07-2.72) for sleep duration ≤4 h/night (vs. > 6-8 h/night), 0.76 (0.49-1.18) for > 4-6 h/night, 1.63 (1.05-2.55) for > 8 h/night, 1.11 (1.03-1.20) for lower sleep efficiency (per 10% decrease), and 1.85 (1.19-2.89) for excessive daytime sleepiness. Very short sleep duration (≤4 h/night), lower sleep efficiency, and excessive daytime sleepiness were significantly associated with being diagnosed with AD (multivariable-adjusted OR range = 1.12-2.07; p < 0.05). The associations of sleep problems with dementia and AD were evident mainly among young-old adults (65-74 years) or APOE ε4 carriers. Among dementia-free participants, these sleep characteristics were significantly associated with a lower MMSE score.Conclusions: Self-reported sleep problems in dementia are characterized by very short or long sleep duration, low sleep efficiency, and excessive daytime sleepiness, especially among young-old people and APOE ε4 carriers.
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16.
  • Naghavi, Mohsen, et al. (författare)
  • 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
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Tidskriftsartikel (refereegranskat)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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17.
  • Norgren, Jakob, et al. (författare)
  • APOE-Genotype and Insulin Modulate Estimated Effect of Dietary Macronutrients on Cognitive Performance : Panel Analyses in Nondiabetic Older Adults at Risk of Dementia
  • 2023
  • Ingår i: Journal of Nutrition. - : Elsevier. - 0022-3166 .- 1541-6100. ; 153:12, s. 3506-3520
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The apolipoprotein E gene (APOE e-2/3/4, combined as 6 different genotypes: e-22/23/24/33/34/44) and insulin status modulate dementia risk and play a role in the metabolism of macronutrients.Objectives: We aimed to examine APOE-genotype and fasting insulin as effect modifiers of the slopes between dietary macronutrients and cognitive performance among older adults at risk of dementia. Methods: Panel analyses-with diet and cognition measured at baseline and follow-up at years 1 and 2-were performed in a sub-sample from the FINGER (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) trial (n = 676, 60-77 y, 46% fe -males, all nondiabetics). The associations between macronutrients (3-d food records, z-scores) and global cognition (modified Neuropsy-chological Test Battery, z-score) were analyzed in mixed regression models adjusted for confounders selected a priori. After a gradient was implied by the point estimates in categorical APOE analyses, we investigated a continuous APOE variable [APOE-gradient, coded-1 (for e-23), -0.5 (e-24), 0 (e-33), 1 (e-34), 2 (e-44)] as an effect-modifier.Results: At increasing levels of the APOE-gradient, a relatively more favorable slope between diet and cognition was observed for a lower carbohydrate/fat ratio [p = -0.040, 95% confidence interval (CI): -0.074, -0.006; P = 0.020 for interaction diet x APOE-gradient), and higher protein (p = 0.075, 95% CI: 0.042, 0.109; P = 9.4 x 10-6). Insulin concentration (log-linear) modulated the association between the car-bohydrate/fat ratio and cognition by a quadratic interaction (p = -0.016, P = 0.039). Coherent findings for exploratory predictors (fiber, fat subtypes, composite score, metabolic biomarkers) were compatible with published hypotheses of differential dietary adaptation by APOE, with cognition among e-33 being relatively independent of dietary parameters-implying metabolic flexibility. Antagonistic slopes to cognition for e-23 (positive) compared with e-34 and e-44 (negative) were found for a Higher-carbohydrates-fiber-Lower-fat-protein composite score, even as within-subjects effects. Conclusions: APOE-based precision nutrition appears conceptually promising, but replications in wider samples are warranted, as well as support from trials. Both relative hyper-and hypoinsulinemia might modulate the effect of diet on cognition.
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18.
  • Norgren, Jakob, et al. (författare)
  • Capillary blood tests may overestimate ketosis : triangulation between three different measures of beta-hydroxybutyrate
  • 2020
  • Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 318:2, s. e184-E188
  • Tidskriftsartikel (refereegranskat)abstract
    • The ketone body beta-hydroxybutyrate (BHB), assessed by a point-of-care meter in venous whole blood (BHBv), was used as the main outcome in a study on nutritional ketosis in healthy older adults. Two other BHB measures were also used in the study for validation and exploratory purposes, and here we report findings on correlation and agreement between those three methods. Ketosis in the range of 0-1.5 mmol/L was induced in 15 healthy volunteers by intake of medium-chain fatty acids after a 12-h fast. BHBv was assessed at 12 time points for 4 h. The same point-of-care meter was also used to test capillary blood (BHBc) at three time points, and a laboratory test determined total ketones (TK) in plasma (BHBp + acetoacetate) at four time points. A total of 180 cases included simultaneous data on BHBv, BHBc, BHBp, and TK. TK correlated with BHBp (Pearson's r = 0.99), BHBv (r = 0.91), and BHBc (r = 0.91), all P < 0.0001. BHBv and BHBp had good agreement in absolute values. However, the slope between BHBc and BHBv, measured with the same device, was in the range of 0.64-0.78 in different regression models, indicating substantially higher BHB concentrations in capillary versus venous blood. We conclude that all three methods are valid to detect relative changes in ketosis, but our results highlight the importance of method considerations and the possible need to adjust cutoffs, e.g., in the management of ketoacidosis and in the evaluation and comparison of dietary interventions.
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19.
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20.
  • Norgren, Jakob, et al. (författare)
  • Ketosis After Intake of Coconut Oil and Caprylic Acid-With and Without Glucose : A Cross-Over Study in Healthy Older Adults
  • 2020
  • Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Medium-chain-triglycerides (MCT), formed by fatty acids with a length of 6-12 carbon atoms (C6-C12), constitute about two thirds of coconut oil (Coc). MCT have specific metabolic properties which has led them to be described as ketogenic even in the absence of carbohydrate restriction. This effect has mainly been demonstrated for caprylic acid (C8), which constitutes about 6-8% of coconut oil. Our aim was to quantify ketosis and blood glucose after intake of Coc and C8, with and without glucose intake. Sunflower oil (Suf) was used as control, expected to not break fasting ketosis, nor induce supply-driven ketosis. Method: In a 6-arm cross-over design, 15 healthy volunteers-age 65-73, 53% women-were tested once a week. After a 12-h fast, ketones were measured during 4 h after intake of coffee with cream, in combination with each of the intervention arms in a randomized order: 1. Suf (30 g); 2. C8 (20 g) + Suf (10 g); 3. C8 (20 g) + Suf (10 g) + Glucose (50 g); 4. Coc (30 g); 5. Coc (30 g) + Glucose (50 g); 6. C8 (20 g) + Coc (30 g). The primary outcome was absolute blood levels of the ketone beta-hydroxybutyrate, area under the curve (AUC). ANOVA for repeated measures was performed to compare arms. Results: beta-hydroxybutyrate, AUC/time (mean +/- SD), for arms were 1: 0.18 +/- 0.11; 2: 0.45 +/- 0.19; 3: 0.28 +/- 0.12; 4: 0.22 +/- 0.12; 5: 0.08 +/- 0.04; 6: 0.45 +/- 0.20 (mmol/L). Differences were significant (all p <= 0.02), except for arm 2 vs. 6, and 4 vs. 1 & 3. Blood glucose was stable in arm 1, 2, 4, & 6, at levels slightly below baseline (p <= 0.05) at all timepoints hours 1-4 after intake. Conclusions: C8 had a higher ketogenic effect than the other components. Coc was not significantly different from Suf, or C8 with glucose. In addition, we report that a 16-h non-carbohydrate window contributed to a mild ketosis, while blood glucose remained stable. Our results suggest that time-restricted feeding regarding carbohydrates may optimize ketosis from intake of MCT.
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21.
  • Norgren, Jakob, et al. (författare)
  • Serum proBDNF Is Associated With Changes in the Ketone Body β-Hydroxybutyrate and Shows Superior Repeatability Over Mature BDNF : Secondary Outcomes From a Cross-Over Trial in Healthy Older Adults
  • 2021
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: β-hydroxybutyrate (BHB) can upregulate brain-derived neurotrophic factor (BDNF) in mice, but little is known about the associations between BHB and BDNF in humans. The primary aim here was to investigate whether ketosis (i.e., raised BHB levels), induced by a ketogenic supplement, influences serum levels of mature BDNF (mBDNF) and its precursor proBDNF in healthy older adults. A secondary aim was to determine the intra-individual stability (repeatability) of those biomarkers, measured as intra-class correlation coefficients (ICC).Method: Three of the arms in a 6-arm randomized cross-over trial were used for the current sub-study. Fifteen healthy volunteers, 65–75 y, 53% women, were tested once a week. Test oils, mixed in coffee and cream, were ingested after a 12-h fast. Labeled by their level of ketosis, the arms provided: sunflower oil (lowK); coconut oil (midK); caprylic acid + coconut oil (highK). Repeated blood samples were collected for 4 h after ingestion. Serum BDNF levels were analyzed for changes from baseline to 1, 2 and 4 h to compare the arms. Individual associations between BHB and BDNF were analyzed cross-sectionally and for a delayed response (changes in BHB 0–2 h to changes in BDNF at 0–4 h). ICC estimates were calculated from baseline levels from the three study days.Results: proBDNF increased more in highK vs. lowK between 0 and 4 h (z-score: β = 0.25, 95% CI 0.07–0.44; p = 0.007). Individual change in BHB 0–2 h, predicted change in proBDNF 0–4 h, (β = 0.40, CI 0.12–0.67; p = 0.006). Change in mBDNF was lower in highK vs. lowK at 0–2 h (β = −0.88, CI −1.37 to −0.40; p < 0.001) and cumulatively 0–4 h (β = −1.01, CI −1.75 to −0.27; p = 0.01), but this could not be predicted by BHB levels. ICC was 0.96 (95% CI 0.92–0.99) for proBDNF, and 0.72 (CI 0.47–0.89) for mBDNF.Conclusions: The findings support a link between changes in peripheral BHB and proBDNF in healthy older adults. For mBDNF, changes differed between arms but independent to BHB levels. Replication is warranted due to the small sample. Excellent repeatability encourages future investigations on proBDNF as a predictor of brain health.Clinical Trial Registration: ClinicalTrials.gov, NCT03904433.
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22.
  • Overton, Marieclaire, et al. (författare)
  • Sleep disturbances and change in multiple cognitive domains among older adults: a multicenter study of five Nordic cohorts
  • 2024
  • Ingår i: SLEEP. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 47:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Objectives: We examined and compared cross-sectional and longitudinal associations between self-reported sleep disturbances and various cognitive domains in five separate Nordic European longitudinal aging studies (baseline N = 5631, mean age = 77.7, mean follow-up = 4.16 years).Methods: Comparable sleep parameters across studies included reduced sleep duration/quality, insomnia symptoms (sleep latency, waking up at night, and early awakenings), short and long sleep duration, and daytime napping. The cognitive domains were episodic memory, verbal fluency, perceptual speed, executive functioning, and global cognition (aggregated measure). A series of mixed linear models were run separately in each study and then compared to assess the level and rate of change in cognitive functioning across each sleep disturbance parameter. Models were adjusted for age, sex, education, hypnotic usage, depressive symptoms, lifestyle factors, cardiovascular, and metabolic conditions. By using a coordinated analytic approach, comparable construct-level measurements were generated, and results from identical statistical models were qualitatively compared across studies.Results: While the pattern of statistically significant results varied across studies, subjective sleep disturbances were consistently associated with worse cognition and steeper cognitive decline. Insomnia symptoms were associated with poorer episodic memory and participants sleeping less or more than 7-8 hours had a steeper decline in perceptual speed. In addition, daytime napping (>2 hours) was cross-sectionally and longitudinally associated with all examined cognitive domains. Most observed associations were study-specific (except for daytime napping), and a majority of association estimates remained significant after adjusting for covariates.Conclusion: This rigorous multicenter investigation further supports the importance of sleep disturbance, including insomnia, long and short sleep duration, and daytime napping on baseline cognitive functioning and rate of change among older adults. These sleep factors may be targeted in future lifestyle interventions to reduce cognitive decline.
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23.
  • Parmar, Priya, et al. (författare)
  • The Stroke Riskometer (TM) App: Validation of a data collection tool and stroke risk predictor
  • 2015
  • Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4949 .- 1747-4930. ; 10:2, s. 231-244
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe greatest potential to reduce the burden of stroke is by primary prevention of first-ever stroke, which constitutes three quarters of all stroke. In addition to population-wide prevention strategies (the mass' approach), the high risk' approach aims to identify individuals at risk of stroke and to modify their risk factors, and risk, accordingly. Current methods of assessing and modifying stroke risk are difficult to access and implement by the general population, amongst whom most future strokes will arise. To help reduce the burden of stroke on individuals and the population a new app, the Stroke Riskometer(TM), has been developed. We aim to explore the validity of the app for predicting the risk of stroke compared with current best methods. Methods752 stroke outcomes from a sample of 9501 individuals across three countries (New Zealand, Russia and the Netherlands) were utilized to investigate the performance of a novel stroke risk prediction tool algorithm (Stroke Riskometer(TM)) compared with two established stroke risk score prediction algorithms (Framingham Stroke Risk Score [FSRS] and QStroke). We calculated the receiver operating characteristics (ROC) curves and area under the ROC curve (AUROC) with 95% confidence intervals, Harrels C-statistic and D-statistics for measure of discrimination, R-2 statistics to indicate level of variability accounted for by each prediction algorithm, the Hosmer-Lemeshow statistic for calibration, and the sensitivity and specificity of each algorithm. ResultsThe Stroke Riskometer(TM) performed well against the FSRS five-year AUROC for both males (FSRS=750% (95% CI 723%-776%), Stroke Riskometer(TM)=740(95% CI 713%-767%) and females [FSRS=703% (95% CI 679%-728%, Stroke Riskometer(TM)=715% (95% CI 690%-739%)], and better than QStroke [males - 597% (95% CI 573%-620%) and comparable to females=711% (95% CI 690%-731%)]. Discriminative ability of all algorithms was low (C-statistic ranging from 051-056, D-statistic ranging from 001-012). Hosmer-Lemeshow illustrated that all of the predicted risk scores were not well calibrated with the observed event data (P<0006). ConclusionsThe Stroke Riskometer(TM) is comparable in performance for stroke prediction with FSRS and QStroke. All three algorithms performed equally poorly in predicting stroke events. The Stroke Riskometer(TM) will be continually developed and validated to address the need to improve the current stroke risk scoring systems to more accurately predict stroke, particularly by identifying robust ethnic/race ethnicity group and country specific risk factors.
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24.
  • Plusquellec, Pierrich, et al. (författare)
  • Pilot study on the effects of the DeStresse et Progresse program for 6th grade children integrated in a secondary school
  • 2015
  • Ingår i: Éducation et Francophonie. - : Consortium Erudit. - 0849-1089 .- 1916-8659. ; 43:2, s. 6-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Selon des études précédentes, l’événement que représente la transition du primaire au secondaire suscite une augmentation significative de cortisol (hormone de stress) chez les adolescents. Le programme DéStresse et Progresse est un programme de prévention du stress et de ses troubles associés, issu des travaux réalisés ces dernières années dans le domaine de la biologie du stress. Ce programme, testé et validé auprès d’adolescents en première année de l’école secondaire, a montré des effets significatifs sur le niveau de cortisol et sur le niveau de symptômes dépressifs des jeunes les plus à risque. La présente étude a pour objectif d’évaluer les effets du programme sur un groupe restreint de sujets vivant leur dernière année du primaire, mais dans une structure particulière, puisque ce groupe est déjà intégré à une école secondaire. Quarante-neuf sujets, répartis dans deux classes, ont donc participé à une étude selon un devis prétest / post-test à mesures répétées. Contrairement à ce qui était attendu, les résultats montrent une augmentation moyenne significative de cortisol salivaire au cours de notre étude, augmentation qui pourrait être attribuée à la transition précoce résultant de l’intégration de notre échantillon à l’école secondaire. Par contre, une amélioration des performances cognitives et de l’estime de soi ainsi qu’une diminution des symptômes dépressifs pour l’ensemble des élèves peuvent être suggérés à la suite du programme.
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25.
  • Rydstrom, Anders, et al. (författare)
  • The role of brain integrity in the association between occupational complexity and cognitive performance in subjects with increased risk of dementia
  • 2023
  • Ingår i: Gerontology. - : S. Karger. - 0304-324X .- 1423-0003. ; 69:8, s. 972-985
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Mechanisms underlying the positive association between occupational mental demands and late-life cognition are poorly understood. The objective of this study was to assess whether the association between occupational complexity and cognition is related to and moderated by brain integrity in individuals at-risk for dementia. Brain integrity was appraised throughout structural measures (Magnetic Resonance Imaging, MRI) and amyloid accumulation (Pittsburgh Compound B (PiB)-positron emission tomography, PiB-PET).Methods: Participants from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) neuroimaging sample -MRI (N=126), PiB-PET (N=41)- were included in a post-hoc cross-sectional analysis. Neuroimaging parameters comprised the Alzheimer ' s Disease signature cortical thickness (ADS, Freesurfer 5.3), medial temporal atrophy (MTA), and amyloid accumulation (PiB-PET). Cognition was assessed using the Neuropsychological Test Battery. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Linear regression models included cognition as dependent variable, occupational complexity, measures of brain integrity, and their interaction terms as predictors.Results: Occupational complexity with data and substantive complexity were associated with better cognition (overall cognition, executive function) when adjusting for ADS and MTA (independent association). Significant interaction effects between occupational complexity and brain integrity were also found, indicating that, for some indicators of brain integrity and cognition (e.g., overall cognition, processing speed), the positive association between occupational complexity and cognition occurred only among persons with higher brain integrity (moderated association).Conclusion: Among individuals at-risk for dementia, occupational complexity does not seem to contribute towards resilience against neuropathology. These exploratory findings require validation in larger populations.
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26.
  • Rydström, Anders, et al. (författare)
  • Occupational complexity and cognition in the FINGER multidomain intervention trial
  • 2022
  • Ingår i: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 18:12, s. 2438-2447
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Lifetime exposure to occupational complexity is linked to late-life cognition, and may affect benefits of preventive interventions. Methods In the 2-year multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated, through post hoc analyses (N = 1026), the association of occupational complexity with cognition. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Results Higher levels of occupational complexity were associated with better baseline cognition. Measures of occupational complexity had no association with intervention effects on cognition, except for occupational complexity with data, which was associated with the degree of intervention-related gains for executive function. Discussion In older adults at increased risk for dementia, higher occupational complexity is associated with better cognition. The cognitive benefit of the FINGER intervention did not vary significantly among participants with different levels of occupational complexity. These exploratory findings require further testing in larger studies.
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27.
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28.
  • Sindi, Shireen, et al. (författare)
  • Healthy Dietary Changes in Midlife Are Associated with Reduced Dementia Risk Later in Life
  • 2018
  • Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Diet is an important modifiable lifestyle factor related to dementia risk. Yet, the role of midlife dietary changes is unclear. The goal is to investigate whether midlife healthy dietary changes are associated with late-life dementia risk. Data were collected within the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) population-based cohort study (n = 2000) (mean baseline age = 56 years). Participants returned for two late-life re-examinations (mean age = 70 and 78 years). Self-reported midlife diet was measured in a sub-sample (n = 341) (mean total follow-up = 16.8 years). Changes in specific dietary components (fats, vegetables, sugar, salt) were measured in midlife. Dementia diagnoses were ascertained with detailed examinations. Analyses adjusted for potential confounders. Total midlife healthy dietary changes (improving quality of fats, increasing vegetables, decreasing sugar and salt) were associated with a reduced risk of dementia (fully adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) = 0.20-0.85). In contrast, when each factor was assessed individually, associations were not significant. This study is the first to show that beneficial midlife dietary changes are associated with a reduced dementia risk later in life. The results highlight the importance of targeting dietary patterns, where various food items may have synergistic effects.
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29.
  • Sindi, Shireen, et al. (författare)
  • Mid-life work-related stress increases dementia risk in late-life : The CAIDE 30-year study
  • 2014
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 10:4, Supplement, s. P746-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The associations between work-related stress and various health outcomes in mid-life are well documented, yet less is known about the effects on late-life cognitive process and dementia. The current study investigated the associations between work-related stress in mid-life and the development of cognitive impairment and Alzheimer’s disease in late-life. Methods: The data was derived from the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) study; a prospective cohort study. Participants were randomly selected from four independent population-based samples that completed cardiovascular surveys. First baseline examinations occurred when participants were 50 years old on average, in 1972, 1977, 1982, or 1987. A random sample of 2,000 individ- uals was selected for re-examinations (carried out in 1998 and 2005-2008), where 1,511 subjects participated in at least one re-examination. The re- examinations included an extensive neuropsychological and cognitive assessment. Follow-up time was on average 28 (S.E.M. 1⁄4 0.17) years. Work-related stress comprised the total score of two questions adminis- tered in mid-life. The questions asked participants to rate their stress related to meeting demands at work, and constant hurry at work. Groups were categorized so that those with high or medium levels of stress were compared to those with low levels or no work-related stress. Results: High levels of work-related stress in mid-life were associated with higherrisk of cognitive impairment (where participants with cognitive impair- ment and dementia were compared to the group with no cognitive impair- ment) [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.1], and Alzheimer’s disease [OR, 2.1; CI, 1.1-3.9], when assessed at the first or second follow-up. Results remained significant after adjusting for age, ed- ucation, marital status, chronic health conditions, apolipoprotein E ε 4 allele (APOE ε 4), measures of hopelessness and loneliness. Conclusions: High levels of mid-life work-related stress predict the risk of developing dementia in late-life. The evidence suggests that individuals experiencing high levels of work-related stress form an important at-risk population. Preventive interventions are needed for this population in order to post- pone or prevent the development of cognitive impairment and Alzheimer’s disease. 
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30.
  • Sindi, Shireen, et al. (författare)
  • Midlife Work-Related Stress Increases Dementia Risk in Later Life : The CAIDE 30-Year Study
  • 2017
  • Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press (OUP). - 1079-5014 .- 1758-5368. ; 72:6, s. 1044-1053
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the associations between midlife work-related stress and mild cognitive impairment (MCI), dementia, and Alzheimer's disease later in life, in a large representative population. Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study participants were randomly selected from independent population-based surveys (mean age 50 years). A random sample of 2,000 individuals was invited for two reexaminations including cognitive tests (at mean age 71 and mean age 78), and 1,511 subjects participated in at least one reexamination (mean follow-up 28.5 years). Work-related stress was measured using two questions on work demands that were administered in midlife. Analyses adjusted for important confounders. Higher levels of midlife work-related stress were associated with higher risk of MCI (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.08-1.76), dementia (OR, 1.53; CI, 1.13-2.07), and Alzheimer's disease (OR, 1.55; CI, 1.19-2.36) at the first follow-up among the CAIDE participants. Results remained significant after adjusting for several possible confounders. Work-related stress was not associated with MCI and dementia during the extended follow-up. Midlife work-related stress increases the risk for MCI, dementia, and Alzheimer's disease in later life. The association was not seen after the extended follow-up possibly reflecting selective survival/participation, heterogeneity in dementia among the oldest old, and a critical time window for the effects of midlife stress.
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31.
  • Sindi, Shireen, et al. (författare)
  • Midlife work-related stress is associated with late-life cognition
  • 2017
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 264:9, s. 1996-2002
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the associations between midlife work-related stress and late-life cognition in individuals without dementia from the general population. The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study population (n = 2000) was randomly selected from independent Finnish population-based surveys (baseline mean age 50 years). Participants underwent two re-examinations in late life (mean age 71 and 78 years, respectively). 1511 subjects participated in at least one re-examination (mean total follow-up 25 years). Work-related stress was measured using two questions on work demands administered in midlife. Multiple cognitive domains were assessed. Analyses were adjusted for several potential confounders. Higher levels of midlife work-related stress were associated with poorer performance on global cognition [beta-coefficient, -0.02; 95% confidence interval (CI), -0.05 to -0.00], and processing speed [beta -0.03, CI -0.05 to -0.01]. Results remained significant after adjusting for potential confounders. Work-related stress was not significantly associated with episodic memory, executive functioning, verbal fluency or manual dexterity. This study shows that global cognition and processing speed may be particularly susceptible to the effects of midlife work-related stress.
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32.
  • Sindi, Shireen, et al. (författare)
  • Psychosocial working conditions and cognitive and physical impairment in older age
  • 2023
  • Ingår i: Archives of Gerontology and Geriatrics. - : Elsevier. - 0167-4943 .- 1872-6976. ; 104
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Psychosocial working conditions are associated with cognitive and physical impairments. The aim of this study was to investigate the associations between mid-late life psychosocial working conditions and the combination of physical and cognitive impairment among older adults, and the potential sex differences in these associations.Methods: Data were derived from two Swedish nationally representative surveys (n = 839; follow-up: 20-24 years). Multinomial and binary logistic regressions assessed the associations between work stressors (job demand-control model), and a combination of cognitive and physical impairment.Results: Low control jobs were significantly associated with higher odds of cognitive (OR: 1.41, CI: 1.15-1.72) and physical impairment (OR: 1.23, CI: 1.02-1.47), and cognitive and physical impairment combined (OR: 1.50, CI: 1.19-1.89). Passive jobs (low control, low demand) were associated with higher odds of cognitive impairment (OR: 1.57, CI: 1.12-2.20), and combined cognitive and physical impairment (OR: 1.59, CI: 1.07-2.36). Active jobs (high control, high demand) were associated with lower odds of cognitive impairment (OR: 0.48, CI: 0.29-0.80). Sex-stratified analyses showed stronger associations among men; passive jobs were associated with both cognitive (OR: 2.18, CI: 1.31-3.63) and physical impairment (OR: 1.78, CI: 1.13-2.81), while low strain jobs were associated with less physical impairment (OR: 0.55, CI: 0.33-0.89). No significant associations between work stressors and impairment were found for women.Conclusions: These results highlight the importance of psychosocial working conditions for late-life physical and cognitive impairment, especially among men. Jobs characterised by low control and low demands are associated with higher risk for impairments.
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33.
  • Sindi, Shireen, et al. (författare)
  • Psychosocial Working Conditions in Midlife And Cognitive and Physical Impairment in Older Age
  • 2022
  • Ingår i: Innovation in Aging. - : Oxford University Press. - 2399-5300. ; 6:Supplement 1, s. 610-610
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Psychosocial working conditions have been associated with cognitive and physical impairment among older adults. However, less is known on whether psychosocial working conditions are associated with a combination of cognitive and physical impairments. The aim of this study was to investigate the associations between midlife psychosocial working conditions and physical and cognitive impairment among older adults, and to assess whether there are sex differences in these associations. Methods: The data were derived from two Swedish nationally representative surveys (n=839) with a follow-up time of 20-24 years. Multinomial and binary logistic regressions were used to assess the associations between work stressors according to the job demand-control model, and a combination of cognitive and physical impairment. Results: Low control jobs were significantly associated with higher odds of both cognitive and physical impairment as well as a combination of cognitive and physical impairment. Passive jobs (low control, low demand) were associated with higher odds of cognitive impairment, and cognitive and physical impairment in combination. Active jobs (high control, high demand) were associated with lower odds of cognitive impairment. Sex-stratified analyses showed stronger associations among men than among women. Among men passive jobs were significantly associated with both cognitive and physical impairment. Low strain jobs were significantly associated with less physical impairment. Conclusions: These results highlight the importance of midlife psychosocial working conditions for late-life physical and cognitive impairment, and especially among men. Jobs characterised by higher control, lower strain and active jobs may promote resilience and cognitive reserve among older populations.
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34.
  • Thunborg, Charlotta, 1965-, et al. (författare)
  • Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial
  • 2024
  • Ingår i: Alzheimer's Research & Therapy. - : Springer. - 1758-9193. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.MethodsMIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.ResultsDuring September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.ConclusionsThe multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.Trial registrationClinicalTrials.gov NCT03249688.
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35.
  • Thunborg, Charlotta, 1965-, et al. (författare)
  • Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial
  • 2024
  • Ingår i: Alzheimer's Research & Therapy. - : Springer Nature. - 1758-9193. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.Methods: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.Results: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.Conclusions: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.
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36.
  • Vos, Theo, et al. (författare)
  • Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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37.
  • Wang, Haidong, et al. (författare)
  • Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
  • 2016
  • Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
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