| 1. |
- Culverhouse, R. C., et al.
(författare)
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Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:1, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.
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| 2. |
- Oh, D. J., et al.
(författare)
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Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study
- 2023
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Ingår i: Psychiatry and Clinical Neurosciences. - 1323-1316 .- 1440-1819. ; 77:8, s. 449-456
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. Methods: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. Results: The mean age of the participants was 72.8 +/- 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). Conclusions: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.
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| 4. |
- Wynberg, Elke, et al.
(författare)
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Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis
- 2023
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Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875 .- 1475-2875. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance.Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference.Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve precision of parasitaemia estimation. Imprecision of parasite clearance estimates was only affected by the within-patient WBC variability over time, and remained < 10% for 79% of patients.Conclusions: Using an assumed WBC value for parasite density estimation from a thick smear may lead to underdiagnosis of hyperparasitaemia and could adversely affect clinical management; but does not result in clinically consequential inaccuracies in the estimation of the prevalence of prolonged parasite clearance and artemisinin resistance.
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| 5. |
- Peters, R., et al.
(författare)
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Evaluation of High Cholesterol and Risk of Dementia and Cognitive Decline in Older Adults Using Individual Patient Meta-Analysis
- 2021
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 50, s. 318-325
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially relevant in older adults where individual studies report non-linear relationships between cholesterol and cognition and, in some cases, find higher cholesterol associated with a lower risk of subsequent cognitive decline or dementia. Prior evidence synthesis based on published results has not allowed us to focus on older adults or to standardize analyses across studies. Given our ageing population, an increased risk of dementia in older adults, and the need for proportionate treatment in this age group, an individual participant data (IPD) meta-analysis is timely. Method: We combined data from 8 studies and over 21,000 participants aged 60 years and over in a 2-stage IPD to examine the relationship between total, high-density, and low-density lipoprotein (HDL and LDL) cholesterol and subsequent incident dementia or cognitive decline, with the latter categorized using a reliable change index method. Results: Meta-analyses found no relationship between total, HDL, or LDL cholesterol (per millimoles per litre increase) and risk of cognitive decline in this older adult group averaging 76 years of age. For total cholesterol and cognitive decline: odds ratio (OR) 0.93 (95% confidence interval [CI] 0.86: 1.01) and for incident dementia: OR 1.01 [95% CI 0.89: 1.13]. This was not altered by rerunning the analyses separately for statin users and non-users or by the presence of an APOE e4 allele. Conclusion: There were no clear consistent relationships between cholesterol and cognitive decline or dementia in this older adult group, nor was there evidence of effect modification by statin use. Further work is needed in younger populations to understand the role of cholesterol across the life-course and to identify any relevant intervention points. This is especially important if modification of cholesterol is to be further evaluated for its potential influence on risk of cognitive decline or dementia.
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| 6. |
- Sexton, C. E., et al.
(författare)
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Alzheimer's disease research progress in Australia: The Alzheimer's Association International Conference Satellite Symposium in Sydney
- 2022
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:1, s. 178-190
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Tidskriftsartikel (refereegranskat)abstract
- The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.
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| 7. |
- Mewton, L., et al.
(författare)
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The relationship between alcohol use and dementia in adults aged more than 60 years: a combined analysis of prospective, individual-participant data from 15 international studies
- 2023
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 118:3, s. 412-424
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To synthesize international findings on the alcohol–dementia relationship, including representation from low- and middle-income countries. Methods: Individual participant data meta-analysis of 15 prospective epidemiological cohort studies from countries situated in six continents. Cox regression investigated the dementia risk associated with alcohol use in older adults aged over 60 years. Additional analyses assessed the alcohol–dementia relationship in the sample stratified by sex and by continent. Participants included 24 478 community dwelling individuals without a history of dementia at baseline and at least one follow-up dementia assessment. The main outcome measure was all-cause dementia as determined by clinical interview. Results: At baseline, the mean age across studies was 71.8 (standard deviation = 7.5, range = 60–102 years), 14 260 (58.3%) were female and 13 269 (54.2%) were current drinkers. During 151 636 person-years of follow-up, there were 2124 incident cases of dementia (14.0 per 1000 person-years). When compared with abstainers, the risk for dementia was lower in occasional [hazard ratio (HR) = 0.78; 95% confidence interval (CI) = 0.68–0.89], light–moderate (HR = 0.78; 95% CI = 0.70–0.87) and moderate–heavy drinkers (HR = 0.62; 95% CI = 0.51–0.77). There was no evidence of differences between life-time abstainers and former drinkers in terms of dementia risk (HR = 0.98; 95% CI = 0.81–1.18). In dose–response analyses, moderate drinking up to 40 g/day was associated with a lower risk of dementia when compared with lif-time abstaining. Among current drinkers, there was no consistent evidence for differences in terms of dementia risk. Results were similar when the sample was stratified by sex. When analysed at the continent level, there was considerable heterogeneity in the alcohol–dementia relationship. Conclusions: Abstinence from alcohol appears to be associated with an increased risk for all-cause dementia. Among current drinkers, there appears to be no consistent evidence to suggest that the amount of alcohol consumed in later life is associated with dementia risk. © 2022 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.
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| 8. |
- Piccinin, M, et al.
(författare)
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Cross-national coordinated analysis (IALSA) of age, sex, and education effects on change in MMSE scores
- 2006
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Ingår i: 59th Annual Scientific Meeting of the Gerontological Society of America, Dallas, TX, USA..
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Konferensbidrag (refereegranskat)abstract
- In a cross-national, multi-study (ALSA, CLS, H-70, HOPE, NAS, OCTO-Twin, LASA) analysis, we systematically address concerns regarding the effect of educational attainment on Mini-Mental Status Exam (MMSE) scores in a descriptive comparison of between-person dif-ferences and within-person age changes. We describe the coordinated analysis process and the first results from the IALSA network. Marked country and birth cohort differences in educa-tional attainment required a flexible modeling approach: median years in school ranged from 6 in LASA and the older Swedish cohorts to 12 in CLS and NAS. For studies with similarly coded education, higher educated participants scored higher and showed less decline. Ignoring the impact of declining health, on average, at age 80, men with six years of education scored between 25 and 27 on the MMSE and declined about 0.3 points per year. Older individuals tend to score lower and decline at a faster rate. Gender differences were mixed.
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| 9. |
- Wahlin, Åke, et al.
(författare)
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The International Network on Public Health and Aging (INOPA) : Introducing a Life Course Perspective to the Public Health Agenda
- 2008
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Ingår i: Journal of Cross-Cultural Gerontology. - : Springer Science and Business Media LLC. - 0169-3816 .- 1573-0719. ; 23:1, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we present an international network of researchers from projects examining the human aging process and its consequences. It is both vital and urgent to include aging and a life course perspective on the public health agenda, particularly in low-income countries. By announcing the network in a publication, we wish not just to position the network but, more importantly, to attract the attention of other potential collaborators either at the project, institutional, decision making, or applied level.
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| 10. |
- Chowdhary, N, et al.
(författare)
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Reducing the Risk of Cognitive Decline and Dementia: WHO Recommendations
- 2022
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 12, s. 765584-
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Tidskriftsartikel (refereegranskat)abstract
- With population ageing worldwide, dementia poses one of the greatest global challenges for health and social care in the 21st century. In 2019, around 55 million people were affected by dementia, with the majority living in low- and middle-income countries. Dementia leads to increased costs for governments, communities, families and individuals. Dementia is overwhelming for the family and caregivers of the person with dementia, who are the cornerstone of care and support systems throughout the world. To assist countries in addressing the global burden of dementia, the World Health Organisation (WHO) developed the Global Action Plan on the Public Health Response to Dementia 2017–2025. It proposes actions to be taken by governments, civil society, and other global and regional partners across seven action areas, one of which is dementia risk reduction. This paper is based on WHO Guidelines on risk reduction of cognitive decline and dementia and presents recommendations on evidence-based, multisectoral interventions for reducing dementia risks, considerations for their implementation and policy actions. These global evidence-informed recommendations were developed by WHO, following a rigorous guideline development methodology and involved a panel of academicians and clinicians with multidisciplinary expertise and representing geographical diversity. The recommendations are considered under three broad headings: lifestyle and behaviour interventions, interventions for physical health conditions and specific interventions. By supporting health and social care professionals, particularly by improving their capacity to provide gender and culturally appropriate interventions to the general population, the risk of developing dementia can be potentially reduced, or its progression delayed.
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