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  • 1
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. 5 ( 2020-05), p. 804-813
    Abstract: Prospective studies on a potential association of 8‐iso‐prostaglandin F 2α (8‐iso‐PGF 2α ) levels, a biomarker of lipid peroxidation, with dementia are limited. Methods Multivariate Cox regression models were used to assess potential associations of urinary 8‐iso‐PGF 2α levels with all‐cause, Alzheimer's disease (AD), and vascular dementia (VD) incidence in 5853 older adults from a German, population‐based cohort. Results Over 14 years of follow‐up, 365 all‐cause dementia cases including 127 VD and 109 AD cases were diagnosed. Participants in the top compared to the bottom 8‐iso‐PGF 2α tertile had a 45% increased risk of all‐cause dementia incidence (hazard ratio [95% confidence interval]: 1.45 [1.12 to 1.88] ). Interaction with the apolipoprotein E (APOE) ԑ4/ԑ4 genotype was detected ( P = .02). Furthermore, continuously modeled, logarithmized 8‐iso‐PGF 2α levels were statistically significantly associated with all‐cause dementia and AD incidence. Discussion Oxidative stress may be involved in the pathogenesis of dementia. Individuals with increased 8‐iso‐PGF 2α levels and the APOE ԑ4/ԑ4 genotype showed a considerably increased dementia risk.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 2
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S6 ( 2022-12)
    Abstract: In order to determine the future of Alzheimer’s disease (AD) related blood biomarkers in the clinical setting, it is crucial to identify factors that could affect the interpretation of biomarker levels. Kidney function has been shown to influence biomarker levels, but has also exhibited associations to dementia risk and it is unclear whether kidney function plays a role in AD pathology or is merely a factor influencing blood biomarker levels. Therefore, the aim of this study was to explore the association of kidney function with risk of incident AD/dementia diagnosis within 17 years and with the blood biomarkers, neurofilament light (NfL), phosphorylated tau (p‐tau181), and glial fibrillary acidic protein (GFAP), in a community‐based cohort study. Methods Kidney function was assessed through the estimated glomerular filtration rate test (2021‐CKD‐EPI creatinine‐cystatin C equation (eGFRcr‐cys)) at baseline in 6,256 participants aged 50‐75 years, of whom 510 received a dementia diagnosis throughout 17 years of follow‐up in a community‐based prospective cohort study in Germany ( Figure 1 ). In a subset of participants (n=766, n=261 dementia cases), NfL, p‐tau181, and GFAP blood concentrations were measured at baseline using Simoa technology. Cox regression and linear regression models adjusted for age and sex were used to assess the association of kidney function with incident dementia risk and the log‐transformed blood biomarker concentrations. Results Impaired kidney function (eGFRcr 〈 60 mL/min/1.73m 2 ) at baseline was not associated to incident dementia (p=.73) or AD diagnosis (p=.94) within 17 years ( Figure 2 ). However, the blood biomarkers, NfL and P‐tau181, did exhibit significant associations to impaired kidney function (β, p‐value: NfL, 0.47, 〈 .0001; P‐tau181, 0.21, 〈 .01) and gender‐specific associations were evident in the association to GFAP (β, p‐value: Males, 0.31, 〈 .01; Females, ‐.12, .11) ( Table 1 ). Conclusions Reduced kidney function may result in increased concentrations of AD related blood biomarkers but not necessarily increased AD risk. Kidney function might influence the accuracy of AD blood biomarkers and should be considered in clinical translation. Additionally, the interaction between kidney function and sex in the association to GFAP including possible explanatory biological mechanisms should be further explored.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 3
    In: Alzheimer's & Dementia, Wiley, Vol. 19, No. 7 ( 2023-07), p. 2913-2922
    Abstract: This study assessed whether in a population with comorbidity of neurodegenerative and cerebrovascular disease (mixed pathology) the association of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau181 (p‐tau181) with dementia risk varied depending on levels of total cholesterol and apolipoprotein E ( APOE ) ε4 genotype. Methods Plasma biomarkers were measured using Simoa technology in 768 participants of a nested case‐control study embedded within an ongoing population‐based cohort. Logistic and spline regression models, and receiver operating characteristic curves were calculated. Results The strength of the association between GFAP and NfL with risk of a clinical diagnosis of dementia changed depending on cholesterol levels and on APOE ε4 genotype. No significant association was seen with p‐tau181. Discussion In individuals with mixed pathology blood GFAP and NfL are better predictors of dementia risk than p‐tau181, and their associations with dementia risk are amplified by hypercholesterolemia, also depending on APOE ε4 genotype. HIGHLIGHTS Cholesterol levels changed the association of blood biomarkers with dementia risk. Blood biomarkers seem to perform differently in community‐ and clinic‐based cohorts. Neurofilament light chain might be a biomarker candidate for dementia risk after stroke.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 4
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2022-12)
    Abstract: No population-based cohort study investigated a potential inverse association between long-term low-dose acetylsalicylic acid (ASA) use and all-cause dementia and its two most common sub-types Alzheimer’s disease (AD) and vascular dementia (VD) so far. Methods Cox regression models with inverse probability of treatment weighting to model the underlying cardiovascular risk were used to assess the associations of low-dose ASA use with all-cause dementia, AD, and VD incidence in community-dwelling older adults from the German ESTHER study ( N  = 5258) and the UK Biobank ( N  = 305,394). Inclusion criteria were age of 55 years or older and completed drug assessment. Meta-analyses of the individual participant data from the two prospective cohort studies were performed. Results Four hundred seventy-six cases of all-cause dementia, 157 cases of AD, and 183 cases of VD were diagnosed over a median of 14.3 years of follow-up in ESTHER. In the UK Biobank, 5584 participants were diagnosed with all-cause dementia, 2029 with AD, and 1437 with VD over a median of 11.6 years. The meta-analysis of both cohorts revealed a weak reduction in hazards for all-cause dementia (hazard ratio (HR) [95% confidence interval (CI)]: 0.96 [0.93 to 0.99] ). The strongest protective effect of low-dose ASA was observed in participants with coronary heart disease (CHD) in both cohorts, and a significant interaction was detected. In particular, in meta-analysis, a 31% reduction in hazard for AD, 69% for VD and 34% for all-cause dementia were observed (HR [95% CI]: 0.69 [0.59 to 0.80] , 0.31 [0.27 to 0.35], 0.46 [0.42 to 0.50] , respectively). Furthermore, compared to non-users, users of low-dose ASA for 10 years or longer (who likely use it because they have CHD or a related diagnosis putting them at an increased risk for cardiovascular events) demonstrated a strong protective effect on all dementia outcomes, especially for VD (HR [95% CI]: 0.48 [0.42 to 0.56] ) whereas no protective associations were observed with shorter low-dose ASA use. Conclusions The protective potential of low-dose ASA for all-cause dementia, AD, and VD seems to strongly depend on pre-existing CHD and the willingness of patients to take it for a minimum of ten years.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 5
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2022-09-09)
    Abstract: Chronic inflammation is a central feature of several forms of dementia. However, few details on the associations of blood-based inflammation-related proteins with dementia incidence have been explored yet. Methods The Olink Target 96 Inflammation panel was measured in baseline serum samples (collected 07/2000–06/2002) of 1782 older adults from a German, population-based cohort study in a case-cohort design. Logistic regression models were used to assess the associations of biomarkers with all-cause dementia, Alzheimer’s disease, and vascular dementia incidence. Results During 17 years of follow-up, 504 participants were diagnosed with dementia, including 163 Alzheimer’s disease and 195 vascular dementia cases. After correction for multiple testing, 58 out of 72 tested (80.6%) biomarkers were statistically significantly associated with all-cause dementia, 22 with Alzheimer’s disease, and 33 with vascular dementia incidence. We identified four biomarker clusters, among which the strongest representatives, CX3CL1, EN-RAGE, LAP TGF-beta-1, and VEGF-A, were significantly associated with dementia endpoints independently from other inflammation-related proteins. CX3CL1 (odds ratio [95% confidence interval] per 1 standard deviation increase: 1.41 [1.24–1.60] ) and EN-RAGE (1.41 [1.25–1.60]) were associated with all-cause dementia incidence, EN-RAGE (1.51 [1.25–1.83] ) and LAP TGF-beta-1 (1.46 [1.21–1.76]) with Alzheimer’s disease incidence, and VEGF-A (1.43 [1.20–1.70] ) with vascular dementia incidence. All named associations were stronger among APOE ε4-negative subjects. Conclusion With this large, population-based cohort study, we show for the first time that the majority of inflammation-related proteins measured in blood samples are associated with total dementia incidence. Future studies should concentrate not only on single biomarkers but also on the complex relationships in biomarker clusters.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 6
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2023-07-29)
    Abstract: In order to utilize polygenic risk scores (PRSs) for Alzheimer’s disease (AD) in a meaningful way, influential factors (i.e. training set) and prediction across groups such as APOE e4 (APOE4) genotype as well as associations to dementia-related biomarkers should be explored. Therefore, we examined the association of APOE4 and various PRSs, based on training sets that utilized differing AD definitions, with incident AD and all-cause dementia (ACD) within 17 years, and with levels of phosphorylated tau181 (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) in blood. Secondarily, effect modification by APOE4 status and sex was examined. Methods In this prospective, population-based cohort study and nested case–control study, 9,940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed for up to 17 years. Participants were included in this study if dementia status and genetic data were available. A subsample of participants additionally had measurements of P-tau181, NfL, and GFAP obtained from blood samples. Cox and logistic regression analyses were used to assess the association of genetic risk ( APOE genotype and PRS noAPOE ) with incident ACD/AD and log-transformed blood levels of P-tau181, NfL, and GFAP. Results Five thousand seven hundred sixty-five participants (54% female, aged 50-75years at baseline) were included in this study, of whom 464 received an all-cause dementia diagnosis within 17 years. The PRSs were not more predictive of dementia than APOE4 . An APOE4 specific relationship was apparent with PRSs only exhibiting associations to dementia among APOE4 carriers. In the nested case–control study including biomarkers ( n  = 712), APOE4 status and polygenic risk were significantly associated to levels of GFAP in blood. Conclusions The use of PRSs may be beneficial for increased precision in risk estimates among APOE4 carriers. While APOE4 may play a crucial etiological role in initial disease processes such as Aβ deposition, the PRS may be an indicator of further disease drivers as well as astrocyte activation. Further research is necessary to confirm these findings, especially the association to GFAP.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2024
    In:  Frontiers in Genetics Vol. 15 ( 2024-5-15)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 15 ( 2024-5-15)
    Abstract: Introduction : Advances in biosciences have significantly expanded our knowledge and capabilities in medicine and technology. Genetic tests can now predict hereditary predisposition or susceptibility to diseases, while gene-editing tools like CRISPR/Cas enable easy repair of disease genes in both somatic and germline cells, ensuring permanent genome correction. Despite these advancements, there is a shortage of valid instruments for studying the knowledge about these technologies. To fill this gap, our study aims to translate and validate various scales to effectively measure the public’s knowledge of genetics. Methods: A convenience sample of N = 567 (Germany n = 317, Greece n = 250) participants completed a Google Forms questionnaire between December 2022 and June 2023, which included the General Knowledge of Genes and Heredity (GKGH), Knowledge about Gene-Environment Interaction (KGEI), and Knowledge of Modern Genetics and Genomics (KMGG) questionnaires. Analyses included internal consistency, structural validity, construct validity, and retest reliability with a subset of n = 72 (DE) and n = 50 (GR). Correlation analyses and group differences were evaluated for gender, education, religiosity, age, prior experience with genetic testing, and preferences toward potential providers of genetic testing. This study used the STROBE checklist for reporting. Results: The GKGH exhibited low values in internal consistency and item analysis, along with a ceiling effect within the German group. However, it demonstrated good values in retest and construct validity. In the Greek group, all properties were highly satisfactory. The KMGG consistently displayed excellent properties across all analyses, whereas the KGEI only showed convincing results in construct validity and item analysis. Discussion: The GKGH and KMGG demonstrated strong psychometric properties with varying difficulty levels dependent on the sample, with the German sample demonstrating a notably higher understanding of genetic technologies. Despite displaying acceptable properties, the KGEI fell short of measuring what its title suggests. Participants’ level of education showed a significant correlation with knowledge of genetic technologies, and only in the Greek sample did experiences with genetic tests influence knowledge. Preferences regarding availability of genetic testing are comparable between the two countries, with variations influenced by factors such as age, gender and religiosity.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2606823-0
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  • 8
    In: Alzheimer's & Dementia, Wiley, Vol. 19, No. 1 ( 2023-01), p. 25-35
    Abstract: Blood biomarkers for Alzheimer's disease (AD) are the future of AD risk assessment. The aim of this study was to determine the association between plasma‐measured phosphorylated tau (p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) levels and risk of clinical AD incidence with consideration to the impact of cardiovascular health. Methods Within a community‐based cohort, biomarker levels were measured at baseline using single molecule array technology in 768 participants (aged 50–75) followed over 17 years. Associations among biomarkers and AD, vascular dementia, and mixed dementia incidence were assessed. Results GFAP was associated with clinical AD incidence even more than a decade before diagnosis (9–17 years), while p‐tau181 and NfL were associated with more intermediate AD risk (within 9 years). Significant interaction was detected between cardiovascular health and p‐tau181/NfL. Discussion GFAP may be an early AD biomarker increasing before p‐tau181 and NfL and the effect modifying role of cardiovascular health should be considered in biomarker risk stratification.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 9
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 1 ( 2023-01-24), p. e2252387-
    Abstract: Previous research has suggested an association of kidney function with risk of Alzheimer disease (AD) or other dementias and dementia-related blood biomarkers, but a distinct association remains unclear. Objective To evaluate the association of kidney function with risk of diagnosis of incident AD or dementia within 17 years and with the blood biomarkers neurofilament light (NfL), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP). Design, Setting, and Participants In this prospective, population-based cohort study and nested case-control study, 9940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed up for up to 17 years. Participants were included if information on dementia status and creatinine/cystatin C measurements were available. A subsample of participants additionally had measurements of NfL, p-tau181, and GFAP obtained from blood samples. Statistical analysis was performed from January 3 to November 25, 2022. Exposures Impaired kidney function, based on estimated glomerular filtration rate less than 60 mL/min/1.73 m 2 according to the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine–cystatin C equation. Main Outcomes and Measures All-cause dementia, AD, and vascular dementia diagnosis, as well as log-transformed levels of NfL, p-tau181, and GFAP in blood. Results Of 6256 participants (3402 women [54.4%]; mean [SD] age at baseline, 61.7 [6.6] years), 510 received an all-cause dementia diagnosis within 17 years of baseline. The dementia-related blood biomarker nested case-control sample included 766 participants. After adjusting for age and sex, impaired kidney function at baseline was not associated with a higher risk of all-cause dementia (hazard ratio [HR] , 0.95; 95% CI, 0.69-1.29), AD (HR, 0.94; 95% CI, 0.55-1.63), or vascular dementia diagnosis (HR, 1.06; 95% CI, 0.65-1.70) within 17 years. In the cross-sectional analysis, after adjusting for age and sex, impaired kidney function was significantly associated with NfL and p-tau181 levels in blood (NfL: β = 0.47 and P   & amp;lt; .001; p-tau181: β = 0.21 and P  = .003). After adjusting for age and sex, significant associations with GFAP levels were evident only among men (men: β = 0.31 and P  = .006; women: β = −0.12 and P  = .11). Conclusions and Relevance In this population-based study of community-dwelling adults, reduced kidney function was associated with increased levels of dementia-related blood biomarkers but not increased dementia risk. Kidney function might influence the accuracy of dementia-related blood biomarkers and should be considered in clinical translation.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2931249-8
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