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  • 1
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2022
    In:  The Journals of Gerontology: Series A Vol. 77, No. 6 ( 2022-06-01), p. 1245-1249
    In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 77, No. 6 ( 2022-06-01), p. 1245-1249
    Kurzfassung: Adipokines are hormones secreted by adipose tissue with roles in energy homeostasis and regulation of metabolism. Their dysregulation is suggested to contribute to the increased risk of dementia seen with midlife obesity, but longitudinal studies investigating this are scarce. We determined the association between plasma levels of adiponectin, leptin, and resistin with the risk of dementia. Methods We performed a case–cohort study embedded in the prospective, population-based Rotterdam Study. Plasma levels of the adiponectin, leptin, and resistin were measured at baseline (1997–1999) in a random subcohort of 945 participants without dementia, and additionally in 177 participants, who were diagnosed with dementia during follow-up (until January 1, 2018). Results Higher levels of leptin and resistin were associated with a decreased risk of dementia (adjusted hazard ratio [95% confidence interval] per SD increase of log-transformed values: 0.85 [0.72–1.00] for leptin; 0.82 [0.71–0.95] for resistin). The association of leptin with dementia was further modified by body mass index and by APOE ε4 carrier status. Adiponectin levels were not associated with the risk of dementia. Conclusions These findings support the hypothesis that adipokines have a role in the pathophysiology of dementia. Future studies are warranted to confirm the findings and to explore the underlying mechanisms.
    Materialart: Online-Ressource
    ISSN: 1079-5006 , 1758-535X
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2022
    ZDB Id: 2043927-1
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: European Journal of Preventive Cardiology, Oxford University Press (OUP), Vol. 28, No. 18 ( 2022-02-09), p. e14-e16
    Materialart: Online-Ressource
    ISSN: 2047-4873 , 2047-4881
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2022
    ZDB Id: 2646239-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Online-Ressource
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    Springer Science and Business Media LLC ; 2021
    In:  European Journal of Epidemiology Vol. 36, No. 5 ( 2021-05), p. 497-506
    In: European Journal of Epidemiology, Springer Science and Business Media LLC, Vol. 36, No. 5 ( 2021-05), p. 497-506
    Kurzfassung: Early-life environmental factors have been suggested in the pathophysiology of dementia. Season of birth has previously been used as a proxy for these external exposures. We investigated the link between season of birth and the risk of dementia and further explored underlying pathways by studying structural brain changes on MRI. From the Dutch, population-based Rotterdam Study, 12,964 participants born between 1887 and 1960 were followed between 1990 and 2018 for dementia. Cox regression was conducted to assess the association between season of birth and dementia. In addition, we distinguished between mild and cold winters. The association of season of birth with structural brain markers on MRI was examined in 5237 participants. The risk of dementia in participants born in winter and fall was higher than of those born in summer (hazard ratio (HR) 1.15 [95% confidence interval (CI) 1.01–1.31] for winter and HR 1.17 [95% CI 1.01–1.33] for fall), especially for Alzheimer’s disease (HR 1.23 [1.06–1.43] for winter and HR 1.15 [95% CI 0.99–1.35] for fall). The risk was particularly increased for participants born in a cold winter. Except for slightly lower hippocampus in fall born participants (β − 0.03; 95% CI − 0.06 to 0.00), we did not find associations with brain imaging markers. In conclusion, winter and fall births were associated with a higher incidence of dementia, especially of AD. We did not find evidence for structural brain changes as an underlying mechanism.
    Materialart: Online-Ressource
    ISSN: 0393-2990 , 1573-7284
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2021
    ZDB Id: 2004992-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: European Journal of Neurology, Wiley, Vol. 29, No. 6 ( 2022-06), p. 1587-1599
    Kurzfassung: This study was undertaken to compare risk factors, neuroimaging characteristics and prognosis between two clinical prodromes of dementia, namely, the motoric cognitive risk syndrome (MCRS) and mild cognitive impairment (MCI). Methods Between 2009 and 2015, dementia‐free participants of the population‐based Rotterdam Study were classified with a dementia prodrome if they had subjective cognitive complaints and scored 〉 1 SD below the population mean of gait speed (MCRS) or 〉 1.5 SD below the population mean of cognitive test scores (MCI). Using multinomial logistic regression models, we determined cross‐sectional associations of risk factors and structural neuroimaging markers with MCRS and MCI, followed by subdistribution hazard models, to determine risk of incident dementia until 2016. Results Of 3025 included participants (mean age = 70.4 years, 54.7% women), 231 had MCRS (7.6%), 132 had MCI (4.4%), and 62 (2.0%) fulfilled criteria for both. Although many risk factors were shared, a higher body mass index predisposed to MCRS, whereas male sex and hypercholesterolemia were associated with MCI only. Gray matter volumes, hippocampal volumes, white matter hyperintensities, and structural white matter integrity were worse in both MCRS and MCI. During a mean follow‐up of 3.9 years, 71 individuals developed dementia and 200 died. Five‐year cumulative risk of dementia was 7.0% (2.5%–11.5%) for individuals with MCRS, versus 13.3% (5.8%–20.8%) with MCI and only 2.3% (1.5%–3.1%) in unaffected individuals. Conclusions MCRS is associated with imaging markers of neurodegeneration and risk of dementia, even in the absence of MCI, highlighting the potential of motor function assessment in early risk stratification for dementia.
    Materialart: Online-Ressource
    ISSN: 1351-5101 , 1468-1331
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2022
    ZDB Id: 2020241-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Alzheimer's & Dementia, Wiley, Vol. 9, No. 4S_Part_13 ( 2013-07)
    Materialart: Online-Ressource
    ISSN: 1552-5260 , 1552-5279
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2013
    ZDB Id: 2201940-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Springer Science and Business Media LLC ; 2023
    In:  BMC Neurology Vol. 23, No. 1 ( 2023-10-02)
    In: BMC Neurology, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-10-02)
    Kurzfassung: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal neurodegenerative condition caused by prions. The clinical symptoms of CJD vary with its subtype, and may include dementia, visual hallucinations, myoclonus, ataxia, (extra)pyramidal signs and akinetic mutism. In the early course of disease however, several clinical symptoms of CJD may mimic those of co-existing morbidities. Case presentation We report a male in his 60s with a history of situs inversus totalis and Churg Strauss syndrome, who presented with speech fluency disturbances, neuropsychiatric symptoms and allodynia, a few months after becoming a widower. Initially presumed a bereavement disorder along with a flare-up of Churg Strauss, his symptoms gradually worsened with apraxia, myoclonic jerks and eventually, akinetic mutism. MRI revealed hyperintensities at the caudate nucleus and thalami, while the cerebrospinal fluid was positive for the 14-3-3 protein and the real-time quick test, making the diagnosis of CJD highly probable. This case illustrates the complexities that may arise in diagnosing CJD when pre-existing multimorbidity may cloud the clinical presentation. We also discuss the potential mechanisms underlying the co-occurrence of three rare conditions (situs inversus totalis, Churg Strauss syndrome, CJD) in one patient, taking into consideration the possibility of coincidence as well as common underlying factors. Conclusions The diagnosis of CJD may be easily missed when its clinical symptoms are obscured by those of pre-existing (rare) multimorbidity. This case highlights that when the multimorbidity has neurological manifestations, an extensive evaluation remains crucial to establish the diagnosis, minimize the risk of prion-transmission and provide appropriate guidance to patients and their caregivers.
    Materialart: Online-Ressource
    ISSN: 1471-2377
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 2041347-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Alzheimer's & Dementia, Wiley, Vol. 19, No. 4 ( 2023-04), p. 1194-1203
    Kurzfassung: MicroRNAs (miRNAs) are post‐transcriptional regulators of gene expression. Their role in the pathophysiology of dementia and potential as biomarkers remains undetermined. Methods We conducted a single‐ (one‐by‐one) and multi‐marker (joint) analysis to identify well‐expressed circulating miRNAs in plasma (total = 591) associated with general cognition and incident dementia, for 1615 participants of the population‐based Rotterdam Study. Results During single‐marker analysis, 47 miRNAs were nominally ( P  ≤ .05) associated with cognition and 18 miRNAs were nominally associated with incident dementia, after adjustment for potential confounders. Three miRNAs were common between cognition and dementia (miR‐4539, miR‐372‐3p, and miR‐566), with multi‐marker analysis revealing another common miRNA (miR‐7106‐5p). In silico analysis of these four common miRNAs led to several putative target genes expressed in the brain, highlighting the mitogen‐activated protein kinase signaling pathway. Discussion We provide population‐based evidence on the relationship between circulatory miRNAs with cognition and dementia, including four common miRNAs that may elucidate downstream mechanisms. HIGHLIGHTS MicroRNAs (miRNAs) are involved in the (dys)function of the central nervous system. Four circulating miRNAs in plasma are associated with cognition and incident dementia. Several predicted target genes of these four miRNAs are expressed in the brain. These four miRNAs may be linked to pathways underlying dementia. Although miRNAs are promising biomarkers, experimental validation remains essential.
    Materialart: Online-Ressource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 2201940-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2019
    In:  Frontiers in Neurology Vol. 10 ( 2019-12-6)
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 10 ( 2019-12-6)
    Materialart: Online-Ressource
    ISSN: 1664-2295
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2019
    ZDB Id: 2564214-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2019
    In:  International Journal of Epidemiology Vol. 48, No. 4 ( 2019-08-01), p. 1286-1293
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 48, No. 4 ( 2019-08-01), p. 1286-1293
    Kurzfassung: Recently, using a counterfactual framework, a causal mediation analysis has been formalized to decompose the total effect of a time-fixed exposure on an outcome into four components that can be loosely defined as being components due to mediation only, interaction only, mediated interaction and neither. The interpretation of the estimated effect sizes is challenging when these components of the total effect are of the opposite sign compared with each other. Particularly, a negative mediated interaction might be intuitively difficult to conceptualize and, so far, lacks an easy-to-understand biological or mechanical interpretation. Methods In this paper, we focus on negative mediated interaction, and propose an interpretation using biological examples. For negative mediated interaction to be present, the effect of interaction on the outcome and the effect of the exposure on the mediator should be in opposite directions. Results In this article, we give examples of biological and biochemical processes that may exhibit negative mediated interaction, such as drug treatment in clinical practice, allosteric effects of enzymes, different adaptations in the cardiovascular system and its effect on brain health, and antibiotic drug–drug interactions. Conclusions We aim to make researchers realize that negative-effect estimates might reflect relevant biological processes in the mechanism under study.
    Materialart: Online-Ressource
    ISSN: 0300-5771 , 1464-3685
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2019
    ZDB Id: 1494592-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Alzheimer's & Dementia, Wiley, Vol. 19, No. 2 ( 2023-02), p. 646-657
    Kurzfassung: Volumetric and morphological changes in subcortical brain structures are present in persons with dementia, but it is unknown if these changes occur prior to diagnosis. Methods Between 2005 and 2016, 5522 Rotterdam Study participants (mean age: 64.4) underwent cerebral magnetic resonance imaging (MRI) and were followed for development of dementia until 2018. Volume and shape measures were obtained for seven subcortical structures. Results During 12 years of follow‐up, 272 dementia cases occurred. Mean volumes of thalamus (hazard ratio [HR] per standard deviation [SD] decrease 1.94, 95% confidence interval [CI]: 1.55–2.43), amygdala (HR 1.66, 95% CI: 1.44–1.92), and hippocampus (HR 1.64, 95% CI: 1.43–1.88) were strongly associated with dementia risk. Associations for accumbens, pallidum, and caudate volumes were less pronounced. Shape analyses identified regional surface changes in the amygdala, limbic thalamus, and caudate. Discussion Structure of the amygdala, thalamus, hippocampus, and caudate is associated with risk of dementia in a large population‐based cohort of older adults.
    Materialart: Online-Ressource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 2201940-6
    Standort Signatur Einschränkungen Verfügbarkeit
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