| 51. |
- Dahlin-Ivanoff, Synneve, 1950, et al.
(författare)
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Was it worth it? Older adults' experiences of participating in a population-based cohort study - a focus group study
- 2019
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background At present, we know relatively little about priorities and problems with topics that older adults experience when completing different examinations in longitudinal population-based studies. To examine these topics, research must be adapted to investigate the meanings, motivations, and interpretations of the individual participants themselves. Therefore, the present study aimed to explore older adults' motives, understandings and experiences regarding participating in the Gothenburg H70 Birth Cohort Studies (the H-70 study). Methods Focus group discussions were used. A total of thirty-eight persons, 19 women and 19 men participated in nine focus groups. A strategic sampling technique was used to ensure that the focus group participants represented the larger population. Results The results supported the overall theme: "It was well worth the effort," which summarized how the participants felt about the population health study. The following specific themes were also identified: an intense event, for the benefit of oneself and others, confidence in health research and the researcher, key decisions about test outcomes and the survey raising questions and providing few answers. Conclusions Knowledge of priorities and problems with topics experienced by older adults completing different examinations when participating in longitudinal population-based studies is crucial for research to improve the health and wellbeing of older people. To date, older people's involvement in population-based cohort studies has largely been as research subjects. This study is a first step toward the participants taking a more active part by allowing them to share their experiences which can be used to improve the research procedures. This requires the participation of older adults in collaboration with the researchers, to ensure the quality of longitudinal studies of older adults. Therefore, our intention when it comes to future research will be to involve older adults-the target group-in the research procedure.
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| 52. |
- de Erausquin, Gabriel A, et al.
(författare)
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Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium.
- 2022
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Ingår i: Alzheimer's & dementia (New York, N. Y.). - : Wiley. - 2352-8737. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term.This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions.Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe.The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection.The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.
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| 53. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 54. |
- De, S., et al.
(författare)
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Soluble aggregates present in cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer's disease progression
- 2019
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Soluble aggregates of amyloid-beta (A beta) have been associated with neuronal and synaptic loss in Alzheimer's disease (AD). However, despite significant recent progress, the mechanisms by which these aggregated species contribute to disease progression are not fully determined. As the analysis of human cerebrospinal fluid (CSF) provides an accessible window into the molecular changes associated with the disease progression, we characterised soluble aggregates present in CSF samples from individuals with AD, mild cognitive impairment (MCI) and healthy controls using a range of sensitive biophysical methods. We used super-resolution imaging and atomic force microscopy to characterise the size and structure of the aggregates present in CSF and correlate this with their ability to permeabilise lipid membranes and induce an inflammatory response. We found that these aggregates are extremely heterogeneous and exist in a range of sizes, varying both structurally and in their mechanisms of toxicity during the disease progression. A higher proportion of small aggregates of A beta that can cause membrane permeabilization are found in MCI CSF; in established AD, a higher proportion of the aggregates were larger and more prone to elicit a pro-inflammatory response in glial cells, while there was no detectable change in aggregate concentration. These results show that large aggregates, some longer than 100nm, are present in the CSF of AD patients and suggest that different neurotoxic mechanisms are prevalent at different stages of AD.
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| 55. |
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| 56. |
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| 57. |
- Dittrich, Anna, 1972, et al.
(författare)
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Association of Chronic Kidney Disease With Plasma NfL and Other Biomarkers of Neurodegeneration: The H70 Birth Cohort Study in Gothenburg.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 101:3, s. e277-e288
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Tidskriftsartikel (refereegranskat)abstract
- Studies associate chronic kidney disease (CKD) with neurodegeneration. This study investigated the relationship between kidney function, blood, CSF, and structural brain MRI markers of neurodegeneration in a sample including individuals with and without CKD.Participants from the Gothenburg H70 Birth Cohort Study, with data on plasma neurofilament light (P-NfL), estimated glomerular filtration rate (eGFR), and structural brain MRI were included. Participants were invited to also have the CSF collected. The primary endpoint of this study was to determine any association between CKD and P-NfL. Secondary endpoints included cross-sectional associations between CKD, eGFR, and CSF-derived and MRI-derived markers of neurodegeneration and Alzheimer disease (AD) pathology (MRI: cortical thickness, hippocampal volume, lateral ventricle volume, and white matter lesion volume; CSF: β-amyloid (Aβ) 42, Aβ42/40, Aβ42/p-tau, t-tau, p-tau, and NfL). Participants with P-NfL and eGFR at baseline were re-examined on eGFR, 5.5 (5.3-6.1) years (median; IQR) after the first visit, and the predictive value of P-NfL levels on incident CKD was estimated longitudinally, using a Cox proportional hazards model.We included 744 participants, 668 without CKD (age 71 [70-71] years, 50% males) and 76 with CKD (age 71 [70-71] years, 39% males). Biomarkers from the CSF were analyzed in 313 participants. A total of 558 individuals returned for a re-examination of eGFR (75% response rate, age 76 [76; 77] years, 48% males, 76 new cases of CKD). Participants with CKD had higher P-NfL levels than those with normal kidney function (median; 18.8 vs 14.1 pg/mL, p < 0.001), while MRI and CSF markers were similar between the groups. P-NfL was independently associated with CKD after adjustment for confounding variables, including hypertension and diabetes (OR; 3.231, p < 0.001), in a logistic regression model. eGFR and CSF Aβ 42/40: R = 0.23, p = 0.004 correlated in participants with Aβ42 pathology. P-NfL levels in the highest quartile were associated with incident CKD at follow-up (HR; 2.39 [1.21: 4.72]).In a community-based cohort of 70-year olds, P-NfL was associated with both prevalent and incident CKD, while CSF and/or imaging measures did not differ by CKD status. Participants with CKD and dementia presented similar levels of P-NfL.
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| 58. |
- Dittrich, Anna, 1972, et al.
(författare)
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Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community-based sample of 70-year-olds
- 2022
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light protein (NfL) in cerebrospinal fluid (CSF) and plasma (P) are suggested to be interchangeable markers of neurodegeneration. However, evidence is scarce from community-based samples. NfL was examined in a small-scale sample of 287 individuals from the Gothenburg H70 Birth cohort 1944 study, using linear models in relation to CSF and magnetic resonance imaging (MRI) biomarker evidence of neurodegeneration. CSF-NfL and P-NfL present distinct associations with biomarker evidence of Alzheimer's disease (AD) pathology and neurodegeneration. P-NfL was associated with several markers that are characteristic of AD, including smaller hippocampal volumes, amyloid beta (A beta)(42), A beta(42/40), and A beta(42)/t-tau (total tau). CSF-NfL demonstrated associations with measures of synaptic and neurodegeneration, including t-tau, phosphorylated tau (p-tau), and neurogranin. Our findings suggest that P-NfL and CSF-NfL may exert different effects on markers of neurodegeneration in a small-scale community-based sample of 70-year-olds.
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| 59. |
- Dorr, Felix, et al.
(författare)
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Dissociating memory and executive function impairment through temporal features in a word list verbal learning task
- 2023
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Ingår i: NEUROPSYCHOLOGIA. - 0028-3932 .- 1873-3514. ; 189
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Tidskriftsartikel (refereegranskat)abstract
- The Rey Auditory Verbal Learning Test (RAVLT) is an established verbal learning test commonly used to quantify memory impairments due to Alzheimer's Disease (AD) both at a clinical dementia stage or prodromal stage of mild cognitive impairment (MCI). Focal memory impairment-as quantified e.g. by the RAVLT-at an MCI stage is referred to as amnestic MCI (aMCI) and is often regarded as the cognitive phenotype of prodromal AD. However, recent findings suggest that not only learning and memory but also other cognitive domains, especially executive functions (EF) and processing speed (PS), influence verbal learning performance. This research investigates whether additional temporal features extracted from audio recordings from a participant's RAVLT response can better dissociate memory and EF in such tasks and eventually help to better describe MCI subtypes. 675 age-matched participants from the H70 Swedish birth cohort were included in this analysis; 68 participants were classified as MCI (33 aMCI and 35 due to executive impairment). RAVLT performances were recorded and temporal features extracted. Novel temporal features were correlated with established neuropsychological tests measuring EF and PS. Lastly, the downstream diagnostic potential of temporal features was estimated using group differences and a machine learning (ML) classification scenario. Temporal features correlated moderately with measures of EF and PS. Performance of an ML classifier could be improved by adding temporal features to traditional counts. We conclude that RAVLT temporal features are in general related to EF and that they might be capable of dissociating memory and EF in a word list learning task.
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| 60. |
- Duberstein, P R, et al.
(författare)
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Personality and risk for depression in a birth cohort of 70-year-olds followed for 15 years.
- 2008
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Ingår i: Psychological medicine. - 0033-2917. ; 38:5, s. 663-71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The association between personality traits and the first lifetime onset of clinically significant depression has not been studied in older adults. METHOD: Experienced psychiatrists conducted interviews and chart reviews at baseline and throughout the 15-year follow-up period. Survival analyses were conducted on the presence/absence of a DSM-III-R mood disorder at follow-up. RESULTS: There were 59 cases of first lifetime episodes of depression. Analyses showed that Neuroticism [hazard ratio (HR) per one point increase in the Maudsley Personality Inventory (MPI)=1.05, 95% confidence interval (CI) 1.02-1.08] but not Extroversion (HR 1.02, 95% CI 0.97-1.06) amplified risk for mood disorder. CONCLUSIONS: This prospective study on a randomly sampled birth cohort of older adults showed that Neuroticism confers risk for a first lifetime episode of clinically significant depression. Findings have implications for understanding the etiology of late-life depression (LLD) and could also aid in the identification and treatment of people at risk.
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