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  • 1
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    The Parkin’Play study: protocol of a phase II randomized controlled trial to assess the effects of a health game on cognition in Parkinson’s disease
    Springer Science and Business Media LLC ; 2016
    In:  BMC Neurology Vol. 16, No. 1 ( 2016-12)
    Details
    In: BMC Neurology, Springer Science and Business Media LLC, Vol. 16, No. 1 ( 2016-12)
    Type of Medium: Online Resource
    ISSN: 1471-2377
    URL: Article
    DOI: 10.1186/s12883-016-0731-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2041347-6
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  • 2
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    Alcohol consumption and microvascular dysfunction: a J-shaped association: The Maastricht Study
    Springer Science and Business Media LLC ; 2023
    In:  Cardiovascular Diabetology Vol. 22, No. 1 ( 2023-03-24)
    Details
    In: Cardiovascular Diabetology, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2023-03-24)
    Abstract: Microvascular dysfunction (MVD) is an important contributor to major clinical disease such as stroke, dementia, depression, retinopathy, and chronic kidney disease. Alcohol consumption may be a determinant of MVD. Objective Main objectives were (1) to study whether alcohol consumption was associated with MVD as assessed in the brain, retina, skin, kidney and in the blood; and (2) to investigate whether associations differed by history of cardiovascular disease or sex. Design We used cross-sectional data from The Maastricht Study (N = 3,120 participants, 50.9% men, mean age 60 years, and 27.5% with type 2 diabetes [the latter oversampled by design]). We used regression analyses to study the association between total alcohol (per unit and in the categories, i.e. none, light, moderate, high) and MVD, where all measures of MVD were combined into a total MVD composite score (expressed in SD). We adjusted all associations for potential confounders; and tested for interaction by sex, and history of cardiovascular disease. Additionally we tested for interaction with glucose metabolism status. Results The association between total alcohol consumption and MVD was non-linear, i.e. J-shaped. Moderate versus light total alcohol consumption was significantly associated with less MVD, after full adjustment (beta [95% confidence interval], -0.10 [-0.19; -0.01] ). The shape of the curve differed with sex (P interaction  = 0.03), history of cardiovascular disease (P interaction   〈  0.001), and glucose metabolism status (P interaction  = 0.02). Conclusions The present cross-sectional, population-based study found evidence that alcohol consumption may have an effect on MVD. Hence, although increasing alcohol consumption cannot be recommended as a policy, this study suggests that prevention of MVD may be possible through dietary interventions.
    Type of Medium: Online Resource
    ISSN: 1475-2840
    URL: Article
    DOI: 10.1186/s12933-023-01783-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2093769-6
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  • 3
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    Permeability of the windows of the brain: feasibility of dynamic contrast-enhanced MRI of the circumventricular organs
    Springer Science and Business Media LLC ; 2020
    In:  Fluids and Barriers of the CNS Vol. 17, No. 1 ( 2020-12)
    Details
    In: Fluids and Barriers of the CNS, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2020-12)
    Abstract: Circumventricular organs (CVOs) are small structures without a blood–brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood–brain barrier absence. Methods Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter. Results In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter. Conclusions Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures. Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24
    Type of Medium: Online Resource
    ISSN: 2045-8118
    URL: Article
    DOI: 10.1186/s12987-020-00228-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2595406-4
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  • 4
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    Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study
    Springer Science and Business Media LLC ; 2022
    In:  European Journal of Nutrition
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    In: European Journal of Nutrition, Springer Science and Business Media LLC
    Abstract: Sulfur amino acids (SAAs) have been associated with obesity and obesity-related metabolic diseases. We investigated whether plasma SAAs (methionine, total cysteine (tCys), total homocysteine, cystathionine and total glutathione) are related to specific fat depots. Methods We examined cross-sectional subsets from the CODAM cohort ( n  = 470, 61.3% men, median [IQR]: 67 [61, 71] years) and The Maastricht Study (DMS; n  = 371, 53.4% men, 63 [55, 68] years), enriched with (pre)diabetic individuals. SAAs were measured in fasting EDTA plasma with LC–MS/MS. Outcomes comprised BMI, skinfolds, waist circumference (WC), dual-energy X-ray absorptiometry (DXA, DMS), body composition, abdominal subcutaneous and visceral adipose tissues (CODAM: ultrasound, DMS: MRI) and liver fat (estimated, in CODAM, or MRI-derived, in DMS, liver fat percentage and fatty liver disease). Associations were examined with linear or logistic regressions adjusted for relevant confounders with z-standardized primary exposures and outcomes. Results Methionine was associated with all measures of liver fat, e.g ., fatty liver disease [CODAM: OR = 1.49 (95% CI 1.19, 1.88); DMS: OR = 1.51 (1.09, 2.14)], but not with other fat depots. tCys was associated with overall obesity, e.g., BMI [CODAM: β  = 0.19 (0.09, 0.28); DMS: β  = 0.24 (0.14, 0.34)]; peripheral adiposity, e.g., biceps and triceps skinfolds [CODAM: β  = 0.15 (0.08, 0.23); DMS: β  = 0.20 (0.12, 0.29)]; and central adiposity, e.g., WC [CODAM: β  = 0.16 (0.08, 0.25); DMS: β  = 0.17 (0.08, 0.27)]. Associations of tCys with VAT and liver fat were inconsistent. Other SAAs were not associated with body fat. Conclusion Plasma concentrations of methionine and tCys showed distinct associations with different fat depots, with similar strengths in the two cohorts.
    Type of Medium: Online Resource
    ISSN: 1436-6207 , 1436-6215
    URL: Article
    DOI: 10.1007/s00394-022-03041-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1463312-7
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  • 5
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    Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus
    Springer Science and Business Media LLC ; 2016
    In:  Scientific Reports Vol. 6, No. 1 ( 2016-12-05)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2016-12-05)
    Abstract: We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a ‘distributed deviating voxels’ method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total ‘distributed deviating voxels’ demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-016-0003-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2615211-3
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  • 6
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    Increase in blood–brain barrier leakage in healthy, older adults
    Springer Science and Business Media LLC ; 2020
    In:  GeroScience Vol. 42, No. 4 ( 2020-08), p. 1183-1193
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    In: GeroScience, Springer Science and Business Media LLC, Vol. 42, No. 4 ( 2020-08), p. 1183-1193
    Abstract: Blood–brain barrier (BBB) breakdown can disrupt nutrient supply and waste removal, which affects neuronal functioning. Currently, dynamic contrast-enhanced (DCE) MRI is the preferred in-vivo method to quantify BBB leakage. Dedicated DCE MRI studies in normal aging individuals are lacking, which could hamper value estimation and interpretation of leakage rate in pathological conditions. Therefore, we applied DCE MRI to investigate the association between BBB disruption and age in a healthy sample. Fifty-seven cognitively and neurologically healthy, middle-aged to older participants (mean age: 66 years, range: 47–91 years) underwent MRI, including DCE MRI with intravenous injection of a gadolinium-based contrast agent. Pharmacokinetic modeling was applied to contrast concentration time-curves to estimate BBB leakage rate in each voxel. Subsequently, leakage rate was calculated in the white and gray matter, and primary (basic sensory and motor functions), secondary (association areas), and tertiary (higher-order cognition) brain regions. A difference in vulnerability to deterioration was expected between these regions, with especially tertiary regions being affected by age. Higher BBB leakage rate was significantly associated with older age in the white and gray matter, and also in tertiary, but not in primary or secondary brain regions. Even in healthy individuals, BBB disruption was stronger in older persons, which suggests BBB disruption is a normal physiologically aging phenomenon. Age-related increase in BBB disruption occurred especially in brain regions most vulnerable to age-related deterioration, which may indicate that BBB disruption is an underlying mechanism of normal age-related decline. Netherlands Trial Register number: NL6358, date of registration: 2017-03-24.
    Type of Medium: Online Resource
    ISSN: 2509-2715 , 2509-2723
    URL: Article
    DOI: 10.1007/s11357-020-00211-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2886418-9
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  • 7
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    Imaging the role of blood–brain barrier disruption in normal cognitive ageing
    Springer Science and Business Media LLC ; 2020
    In:  GeroScience Vol. 42, No. 6 ( 2020-12), p. 1751-1764
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    In: GeroScience, Springer Science and Business Media LLC, Vol. 42, No. 6 ( 2020-12), p. 1751-1764
    Abstract: To investigate whether blood–brain barrier (BBB) disruption is a potential mechanism of usual age-related cognitive decline, we conducted dynamic contrast–enhanced (DCE) MRI to measure BBB leakage in a healthy sample, and investigated the association with longitudinal cognitive decline. In a sample of neurologically and cognitively healthy, older individuals, BBB leakage rate in the white and grey matter and hippocampus was measured using DCE MRI with pharmacokinetic modelling. Regression analysis was performed to investigate whether the leakage rate was associated with decline in cognitive performance (memory encoding, memory retrieval, executive functioning and processing speed) over 12 years. White and grey matter BBB leakages were significantly associated with decline in memory retrieval. No significant relations were found between hippocampal BBB leakage and cognitive performance. BBB disruption already being associated with usual cognitive ageing, supports that this neurovascular alteration is a possible explanation for the cognitive decline inherent to the ageing process. More insight into BBB leakage during the normal ageing process could improve estimation and interpretation of leakage rate in pathological conditions. The current results might also stimulate the search for strategies to maintain BBB integrity and help increase the proportion people experiencing successful ageing. Netherlands Trial Register number: NL6358, date of registration: 2017-03-24.
    Type of Medium: Online Resource
    ISSN: 2509-2715 , 2509-2723
    URL: Article
    DOI: 10.1007/s11357-020-00282-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2886418-9
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  • 8
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    The Cognitive Profile of Ethosuximide in Children
    Springer Science and Business Media LLC ; 2016
    In:  Pediatric Drugs Vol. 18, No. 5 ( 2016-10), p. 379-385
    Details
    In: Pediatric Drugs, Springer Science and Business Media LLC, Vol. 18, No. 5 ( 2016-10), p. 379-385
    Type of Medium: Online Resource
    ISSN: 1174-5878 , 1179-2019
    URL: Article
    DOI: 10.1007/s40272-016-0187-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2043681-6
    SSG: 15,3
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  • 9
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    Extracerebral microvascular dysfunction is related to brain MRI markers of cerebral small vessel disease: The Maastricht Study
    Springer Science and Business Media LLC ; 2022
    In:  GeroScience Vol. 44, No. 1 ( 2022-02), p. 147-157
    Details
    In: GeroScience, Springer Science and Business Media LLC, Vol. 44, No. 1 ( 2022-02), p. 147-157
    Abstract: Cerebral small vessel disease (cSVD) is a late consequence of cerebral microvascular dysfunction (MVD). MVD is hard to measure in the brain due to its limited accessibility. Extracerebral MVD (eMVD) measures can give insights in the etiology of cerebral MVD, as MVD may be a systemic process. We aim to investigate whether a compound score consisting of several eMVD measures is associated with structural cSVD MRI markers. Methods Cross-sectional data of the population-based Maastricht Study was used ( n  = 1872, mean age 59 ± 8 years, 49% women). Measures of eMVD included flicker light-induced retinal arteriolar and venular dilation response (retina), albuminuria and glomerular filtration rate (kidney), heat-induced skin hyperemia (skin), and plasma biomarkers of endothelial dysfunction (sICAM-1, sVCAM-1, sE-selectin, and von Willebrand factor). These measures were standardized into z scores and summarized into a compound score. Linear and logistic regression analyses were used to investigate the associations between the compound score and white matter hyperintensity (WMH) volume, and the presence of lacunes and microbleeds, as measured by brain MRI. Results The eMVD compound score was associated with WMH volume independent of age, sex, and cardiovascular risk factors (St β 0.057 [95% CI 0.010–0.081], p value 0.01), but not with the presence of lacunes (OR 1.011 [95% CI 0.803–1.273], p value 0.92) or microbleeds (OR 1.055 [95% CI 0.896–1.242], p value 0.52). Conclusion A compound score of eMVD is associated with WMH volume. Further research is needed to expand the knowledge about the role of systemic MVD in the pathophysiology of cSVD.
    Type of Medium: Online Resource
    ISSN: 2509-2715 , 2509-2723
    URL: Article
    DOI: 10.1007/s11357-021-00493-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2886418-9
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  • 10
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    Serum sex hormone-binding globulin is a mediator of the association between intrahepatic lipid content and type 2 diabetes: the Maastricht Study
    Springer Science and Business Media LLC ; 2023
    In:  Diabetologia Vol. 66, No. 1 ( 2023-01), p. 213-222
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    In: Diabetologia, Springer Science and Business Media LLC, Vol. 66, No. 1 ( 2023-01), p. 213-222
    Abstract: Serum sex hormone-binding globulin (SHBG) has been proposed to act as a hepatokine that contributes to the extrahepatic complications observed in non-alcoholic fatty liver disease (NAFLD). However, it remains uncertain whether serum SHBG mediates the association between intrahepatic lipids (IHL) and type 2 diabetes. Therefore, we studied whether, and to what extent, serum SHBG mediates the association between IHL content and type 2 diabetes. Methods We used cross-sectional data from the Maastricht Study ( n =1554), a population-based cohort study with oversampling of individuals with type 2 diabetes. Type 2 diabetes status was assessed by oral glucose tolerance test, and IHL content was measured using 3T Dixon MRI. Mediation analyses were performed to assess the role of serum SHBG in mediating the association between IHL content and type 2 diabetes. Results IHL content was significantly associated with type 2 diabetes in women and men (OR 1.08 [95% CI 1.04, 1.14] and OR 1.12 [95% CI 1.08, 1.17] , respectively). Serum SHBG significantly mediated the association between IHL content and type 2 diabetes. The contribution of serum SHBG was higher in women (OR 1.04 [95% CI 1.02, 1.07]; proportion mediated 50.9% [95% CI 26.7, 81.3] ) than in men (OR 1.02 [95% CI 1.01, 1.03]; proportion mediated 17.2% [95% CI 9.6, 27.6] ). Repeat analyses with proxies of type 2 diabetes and adjustment for covariates did not substantially affect the results. Conclusions/interpretation In this large-scale population-based cohort study, serum SHBG was found to be a mediator of the association between IHL content and type 2 diabetes. These findings extend our understanding of the potential mechanisms by which NAFLD is a risk factor for type 2 diabetes, and further elaborate on the role of SHBG as a hepatokine. Graphical abstract
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s00125-022-05790-7
    RVK:
    XA 40615
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1458993-X
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