| 21. |
- Peters, Ruth, et al.
(författare)
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An investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.
- 2020
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Ingår i: Neurology. - 1526-632X. ; 94:3
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.
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| 22. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 23. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 24. |
- Truong, Quoc Cuong, et al.
(författare)
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Establishing conversion of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly scores into interval-level data across multiple samples using Rasch methodology
- 2023
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Ingår i: Psychogeriatrics. - : Wiley. - 1346-3500 .- 1479-8301. ; 23:3, s. 411-421
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Tidskriftsartikel (refereegranskat)abstract
- Background: The 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) is a well-validated and widely-used measure of cognitive changes (CCs) among older adults. This study aimed to use Rasch methodology to establish psychometric properties of the IQCODE-16 and validate the existing ordinal-to-interval transformation algorithms across multiple large samples. Methods: A Partial Credit Rasch model was employed to examine psychometric properties of the IQCODE-16 using data (n = 918) from two longitudinal studies of participants aged 57–99 years: the Older Australian Twins Study (n = 450) and the Canberra Longitudinal Study (n = 468), and reusing the Sydney Memory and Ageing Study (MAS) sample (n = 400). Results: Initial analyses indicated good reliability for the IQCODE-16 (Person Separation Index range: 0.82–0.90). However, local dependency was identified between items, with several items showing misfit to the model. Replicating the existing Rasch solution could not reproduce the best Rasch model fit for all samples. Combining locally dependent items into three testlets resolved all misfit and local dependency issues and resulted in the best Rasch model fit for all samples with evidence of unidimensionality, strong reliability, and invariance across person factors. Accordingly, new ordinal-to-interval transformation algorithms were produced to convert the IQCODE-16 ordinal scores into interval data to improve the accuracy of its scores. Conclusions: The findings of this study support the reliability and validity of the IQCODE-16 in measuring CCs among older adults. New ordinal-to-interval conversion tables generated using samples from multiple independent datasets are more generalizable and can be used to enhance the precision of the IQCODE-16 without changing its original format. An easy-to-use converter has been made available for clinical and research use.
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| 25. |
- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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| 26. |
- Dichgans, Martin, et al.
(författare)
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METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration : An initiative of the Joint Programme for Neurodegenerative Disease Research
- 2016
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 12:12, s. 1235-1249
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Tidskriftsartikel (refereegranskat)abstract
- Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.
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| 27. |
- Hopkins, Ella G., et al.
(författare)
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Network of mental activities, cognitive function and depression in older men and women
- 2023
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Ingår i: Journal of Psychiatric Research. - 1879-1379. ; 162, s. 113-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEvidence suggests that lifestyle activities impact cognitive and mental health in older populations. However, how lifestyle factors are associated with one another, and which factors are most important for cognitive function and mental health has received comparatively little attention.DesignBayesian-Gaussian network analysis was used to investigate unique associations between mental activities (MA; i.e., activities involving cognitive engagement), global cognition, and depression at three time-points in a large sample of older adults (baseline, 2 years, and 4 years follow-up).SettingThis study used longitudinal data from participants living in Australia and participating in the Sydney Memory and Ageing Study.ParticipantsThe sample included 998 participants (55% female) aged between 70 and 90, without a diagnosis of dementia at baseline.MeasurementsNeuropsychological assessment of global cognition, self-reported depressive symptoms, and self-reported information about daily MA.ResultsCognitive functioning was positively associated with playing tabletop games and using the internet in both sexes at all time-points. MA were differentially linked in men and women. Depression was not consistently associated with MA in men across the three time-points; women who visited artistic events consistently had lower depression scores.ConclusionsEngaging with tabletop games and using the internet was associated with better cognition in both sexes, however sex acted as a modifier for other associations. These findings are useful for future investigations that consider interactive associations between MA, cognition, and mental health in older adults, and their possible roles in promoting healthy aging.
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| 28. |
- Lennon, Matthew J., et al.
(författare)
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Blood Pressure, Antihypertensive Use, and Late-Life Alzheimer and Non-Alzheimer Dementia Risk An Individual Participant Data Meta-Analysis
- 2024
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Ingår i: NEUROLOGY. - 0028-3878 .- 1526-632X. ; 103:5
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies. Methods This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age(2), sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group. Results There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with "healthy controls" and those with treated hypertension, respectively. Compared with "healthy controls" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship (p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk. Discussion Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.
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| 29. |
- Lin, Keshuo, et al.
(författare)
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Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: The COSMIC consortium
- 2024
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Ingår i: ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING. - 2352-8729. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONWhite matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions.METHODSWe investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains.RESULTSFactors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing.CONCLUSIONThe current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.
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| 30. |
- Matison, Annabel P., et al.
(författare)
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Associations between fruit and vegetable intakes and incident depression in middle-aged and older adults from 10 diverse international longitudinal cohorts
- 2024
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Ingår i: JOURNAL OF AFFECTIVE DISORDERS. - 0165-0327 .- 1573-2517. ; 359, s. 373-381
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging observational evidence supports a role for higher fruit and vegetable intake in protecting against the development of depression. However, there is a scarcity of research in older adults or in low- to middle -income countries (LMICs). Methods: Participants were 7801 community -based adults (mean age 68.6 +/- 8.0 years, 55.8 % female) without depression, from 10 diverse cohorts, including four cohorts from LMICs. Fruit and vegetable intake was selfreported via comprehensive food frequency questionnaire, short food questionnaire or diet history. Depressive symptoms were assessed using validated measures, and depression defined applying validated cut-offs. The associations between baseline fruit and vegetable intakes and incident depression over a follow-up period of three to nine years were examined using Cox regression. Analyses were performed by cohort with results metaanalysed. Results: There were 1630 cases of incident depression (21 % of participants) over 40,258 person -years of followup. Higher intake of fruit was associated with a lower risk of incident depression (HR 0.87, 95%CI [0.77, 0.99], I 2 = 4 %). No association was found between vegetable intake and incident depression (HR 0.93, 95%CI [0.84, 1.04], I 2 = 0 %).
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