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  • 1
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    Online Resource
    C-factor: a summary measure for systemic arterial calcifications
    Springer Science and Business Media LLC ; 2021
    In:  BMC Cardiovascular Disorders Vol. 21, No. 1 ( 2021-12)
    Details
    In: BMC Cardiovascular Disorders, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: Arterial calcification, the hallmark of arteriosclerosis, has a widespread distribution in the human body with only moderate correlation among sites. Hitherto, a single measure capturing the systemic burden of arterial calcification was lacking. In this paper, we propose the C-factor as an overall measure of calcification burden. Methods To quantify calcification in the coronary arteries, aortic arch, extra- and intracranial carotid arteries, and vertebrobasilar arteries, 2384 Rotterdam Study participants underwent cardiac and extra-cardiac non-enhanced CT. We performed principal component analyses on the calcification volumes of all twenty-six possible combinations of these vessel beds. Each analysis’ first principal component represents the C-factor. Subsequently, we determined the correlation between the C-factor derived from all vessel beds and the other C-factors with intraclass correlation coefficient (ICC) analyses. Finally, we examined the association of the C-factor and calcification in the separate vessel beds with cardiovascular, non-cardiovascular, and overall mortality using Cox–regression analyses. Results The ICCs ranged from 0.80 to 0.99. Larger calcification volumes and a higher C-factor were all individually associated with higher risk of cardiovascular, non-cardiovascular, and overall mortality. When included simultaneously in a model, the C-factor was still associated with all three mortality types (adjusted hazard ratio per standard deviation increase (HR)  〉  1.52), whereas associations of the separate vessel beds with mortality attenuated substantially (HR  〈  1.26). Conclusions The C-factor summarizes the systemic component of arterial calcification on an individual level and appears robust among different combinations of vessel beds. Importantly, when mutually adjusted, the C-factor retains its strength of association with mortality while the site-specific associations attenuate.
    Type of Medium: Online Resource
    ISSN: 1471-2261
    URL: Article
    DOI: 10.1186/s12872-021-02126-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2059859-2
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  • 2
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    Assessment of Advanced Glycation End Products and Receptors and the Risk of Dementia
    American Medical Association (AMA) ; 2021
    In:  JAMA Network Open Vol. 4, No. 1 ( 2021-01-08), p. e2033012-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 4, No. 1 ( 2021-01-08), p. e2033012-
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2020.33012
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
    detail.hit.zdb_id: 2931249-8
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  • 3
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    Long-term trajectories of decline in cognition and daily functioning before and after stroke
    BMJ ; 2021
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 92, No. 11 ( 2021-11), p. 1158-1163
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 92, No. 11 ( 2021-11), p. 1158-1163
    Abstract: Although knowledge on poststroke cognitive and functional decline is increasing, little is known about the possible decline of these functions before stroke. We determined the long-term trajectories of cognition and daily functioning before and after stroke. Methods Between 1990 and 2016, we repeatedly assessed cognition (Mini-Mental State Examination (MMSE), 15-Word Learning, Letter–Digit Substitution, Stroop, Verbal Fluency, Purdue Pegboard) and basic and instrumental activities of daily living (BADL and IADL) in 14 712 participants within the population-based Rotterdam Study. Incident stroke was assessed through continuous monitoring of medical records until 2018. We matched participants with incident stroke to stroke-free participants (1:3) based on sex and birth year. Trajectories of cognition and daily functioning of patients who had a stroke 10 years before and 10 years after stroke and the corresponding trajectories of stroke-free individuals were constructed using adjusted linear mixed effects models. Results During a mean follow-up of 12.5±6.8 years, a total of 1662 participants suffered a first-ever stroke. Patients who had a stroke deviated from stroke-free controls up to 10 years before stroke diagnosis in cognition and daily functioning. Significant deviations before stroke were seen in scores of MMSE (6.4 years), Stroop (5.7 years), Purdue Pegboard (3.8 years) and BADL and IADL (2.2 and 3.0 years, respectively). Conclusion Patients who had a stroke have steeper declines in cognition and daily functioning up to 10 years before their first-ever stroke compared with stroke-free individuals. Our findings suggest that accumulating intracerebral pathology already has a clinical impact before stroke.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2021-326043
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1480429-3
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  • 4
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    Lower complexity and higher variability in beat‐to‐beat systolic blood pressure are associated with elevated long‐term risk of dementia: The Rotterdam Study
    Wiley ; 2021
    In:  Alzheimer's & Dementia Vol. 17, No. 7 ( 2021-07), p. 1134-1144
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. 7 ( 2021-07), p. 1134-1144
    Abstract: We hypothesized that subclinical disruption in blood pressure (BP) dynamics, captured by lower complexity and higher variability, may contribute to dementia risk, above and beyond BP levels. Methods This prospective cohort study followed 1835 older adults from 1997 to 2016, with BP complexity quantified by sample entropy and BP variability quantified by coefficient of variation using beat‐to‐beat BP measured at baseline. Results Three hundred thirty‐four participants developed dementia over 20 years. Reduced systolic BP (SBP) complexity was associated with a higher risk of dementia (hazard ratio [HR] comparing extreme quintiles: 1.55; 95% confidence interval [CI] : 1.09‐2.20). Higher SBP variability was also associated with a higher risk of dementia (HR comparing extreme quintiles: 1.57; 95% CI: 1.11‐2.22. These findings were observed after adjusting for age, sex, apolipoprotein E ( APOE ) genotype, mean SBP, and other confounding factors. Discussions Our findings suggest that lower complexity and higher variability of beat‐to‐beat SBP are potential novel risk factors or biomarkers for dementia.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v17.7
    DOI: 10.1002/alz.12288
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
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  • 5
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    Physical Exercise Interventions Targeting Cognitive Functioning and the Cognitive Domains in Nondementia Samples: A Systematic Review of Meta-Analyses
    SAGE Publications ; 2021
    In:  Journal of Geriatric Psychiatry and Neurology Vol. 34, No. 2 ( 2021-03), p. 91-101
    Details
    In: Journal of Geriatric Psychiatry and Neurology, SAGE Publications, Vol. 34, No. 2 ( 2021-03), p. 91-101
    Abstract: We investigated whether physical exercise interventions improve cognitive functioning in nondementia populations. Methods: We conducted a systematic review of meta-analyses including only randomized controlled trials (RCTs). Two reviewers completed a systematic search of PubMed, Embase, PsychInfo, and Cochrane Controlled Register of Trials. Study characteristics, effect size data, and heterogeneity estimates were extracted and presented in tabular form. Methodological quality was assessed by 2 reviewers using the AMSTAR-2 checklist. The validity of results was considered based on AMSTAR-2 scores and study characteristics. Results: We included 11 meta-analyses: 6 focused on disease-free older adults and 5 on mild cognitive impairment (MCI) excluding dementia. These meta-analyses summarized 97 unique RCTs. Methodological quality ranged from critically low to high. For overall cognitive functioning, which was the outcome of 6 meta-analyses, 1 showed improvement due to exercise interventions in disease-free older adults ( g = 0.29, P 〈 .01), while 2 reported nonsignificant effects. In patients with MCI, 3 meta-analyses reported significant benefits of exercise interventions on overall cognitive functioning ( g = 0.25-0.57, P 〈 .01). For cognitive domains such as attention and memory, there was limited evidence of beneficial effects of exercise demonstrated in either disease-free or MCI samples. Conclusions: Exercise may improve overall cognitive functioning in disease-free older adults, but there is too little high-quality evidence to conclude whether this is achieved through improvement in any of the specific cognitive domains assessed. There is clearer evidence that exercise may improve cognitive functioning in MCI, but again there is limited evidence across most cognitive domains.
    Type of Medium: Online Resource
    ISSN: 0891-9887 , 1552-5708
    URL: Article
    DOI: 10.1177/0891988720915523
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2094096-8
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  • 6
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    Circulatory MicroRNAs as Potential Biomarkers for Stroke Risk : The Rotterdam Study
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke Vol. 52, No. 3 ( 2021-03), p. 945-953
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 3 ( 2021-03), p. 945-953
    Abstract: MicroRNAs (miRNAs) are post-transcriptionally regulators of gene expression that can be released extracellularly upon pathophysiological processes. By complementary binding of target transcripts, miRNAs can modulate the expression of an abundance of genes. Increasing evidence recognize miRNAs as promising biomarkers for complex traits, including cardiovascular disease and stroke. We conducted a longitudinal study to determine the association between circulatory miRNAs and incident stroke in a population-based setting. Methods: Next-generation sequencing was used to measure expression levels of 2083 miRNAs in plasma samples, collected between 2002 and 2005, from 1914 stroke-free participants of the Rotterdam Study. Participants were assessed for incident stroke through continuous monitoring of medical records until January 1, 2016. Cox proportional hazards regression models adjusted for age, sex, and vascular risk factors were used to investigate the association between the levels of 591 miRNAs well-expressed in plasma and incident stroke. Furthermore, stroke subtype analysis was performed to assess the link between identified miRNAs and ischemic, hemorrhagic, and unspecified stroke. Subsequently, post hoc analyses were conducted to gain insight into the association between putative target genes of miRNAs and stroke. Results: Of 1914 participants (mean age 71.5 years ±7.6; 57.7% women), 138 were diagnosed with incident stroke during a mean follow-up of 9.7±3.2 years. After adjusting for potential confounders, we found plasma levels of 3 miRNAs to be associated with incident stroke (false discovery rate-adjusted P 〈 0.05). These include miR-6124 (hazard ratio, 1.66 [95% CI, 1.31–2.09]), miR-5196-5p (hazard ratio, 1.90 [95% CI, 1.39–2.61] ), and miR-4292 (hazard ratio, 2.65 [95% CI, 1.62–4.34]). In silico analysis of the putative target genes of these miRNAs showed associations of variants in several target genes with stroke. Conclusions: This study indicates that plasma levels of 3 miRNAs are associated with the risk of stroke, proposing them as potential biomarkers for early detection of the disease.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.031543
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 7
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    Immunity and amyloid beta, total tau and neurofilament light chain: Findings from a community‐based cohort study
    Wiley ; 2021
    In:  Alzheimer's & Dementia Vol. 17, No. 3 ( 2021-03), p. 446-456
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. 3 ( 2021-03), p. 446-456
    Abstract: We investigated how components of immunity relate to biomarkers of Alzheimer's disease (AD) in plasma and explored the influence of AD genetic risk factors in the population‐based Rotterdam Study. Methods In 7397 persons, we calculated the granulocyte‐to‐lymphocyte ratio (GLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII). In 3615 of these persons, plasma amyloid‐beta (Aβ)42 and Aβ40 were measured. Next, we constructed an overall genetic risk score (GRS) based on genome‐wide significant variants, both including and excluding APOE ε 4. Results All innate immunity phenotypes were related to higher Aβ, most strongly with a doubling in GLR leading to a 1.9% higher Aβ42 (95% confidence interval [95% CI] 0.4 to 3.3%) and 3.2% higher Aβ40 (95% CI 2.0 to 4.3%). Higher AD GRS including APOE ε 4 was associated with higher immunity markers. Discussion Higher levels of immunity markers were associated with higher Aβ in plasma. Participants with a higher genetic predisposition to AD had higher immunity markers, where these effects were mainly driven by APOE ε 4.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v17.3
    DOI: 10.1002/alz.12212
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
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  • 8
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    The association of serum immunoglobulins with cognition and dementia: The Rotterdam Study
    Wiley ; 2021
    In:  Alzheimer's & Dementia Vol. 17, No. S5 ( 2021-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S5 ( 2021-12)
    Abstract: Chronic neuro‐inflammation has emerged in recent years as important pathological process underlying dementia, including Alzheimer’s disease. Most studies so far have investigated the innate immune system, but the role of the adaptive immune system remains largely unknown. We investigated the association of serum immunoglobulins (IgA, IgG, IgM) as markers of the adaptive immune system with cognitive function and risk of dementia. Method This study was embedded in the Rotterdam Study, an ongoing prospective population based cohort study, and included participants with baseline measurements (between 1997 and 2009) of serum immunoglobulins and informed consent for follow‐up. We performed Cox proportional hazard regression analyses to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between serum immunoglobulins and risk of dementia until 2016 (longitudinal). We performed linear regression analyses to quantify the cross‐sectional association between serum immunoglobulins and cognition summarized into global cognition as well as separate cognitive test scores. Effect estimates are adjusted for age, sex, lifestyle and cardiovascular factors. Result We have included 8,768 participants with a mean age of 64 years and of whom 57% are female. Due to non‐proportional hazards, the follow‐up time was divided into two strata (≤10 and 〉 10 years). We found that IgM was associated with a lower risk of dementia after ten years in women (HR: 0.71; 95% CI: 0.58‐0.86). When restricting analyses to participants with immunoglobulin levels within the reference range and excluding users of immunomodulating medication, we found that IgM was associated with a lower risk of dementia after 10 years in the entire population (HR: 0.78; 95% CI: 0.62‐0.97). We furthermore found that higher IgG levels were associated with lower scores of global cognition, Stroop I, and Stroop II (betas ranging from ‐0.01 to ‐0.02; p‐value 〈 0.002 for all). Conclusion Higher IgM levels are associated with a decreased risk of dementia in women and in all participants with reference range immunoglobulin levels. Higher IgG levels are associated with worse cognitive test outcomes. Our results suggest a protective effect of the adaptive immune system on dementia onset, but possibly a reversed effect on cognitive function.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v17.S5
    DOI: 10.1002/alz.053612
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
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  • 9
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    Recommendations and Associated Levels of Evidence for Statin Use in Primary Prevention of Cardiovascular Disease: A Comparison at Population Level of the American Heart Association/American College of Cardiology/Multisociety, US Preventive Services Task Force, Department of Veterans Affairs/Department of Defense, Canadian Cardiovascular Society, and European Society of Cardiology/European Atherosclerosis Society Clinical Practice Guidelines
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation: Cardiovascular Quality and Outcomes Vol. 14, No. 9 ( 2021-09)
    Details
    In: Circulation: Cardiovascular Quality and Outcomes, Ovid Technologies (Wolters Kluwer Health), Vol. 14, No. 9 ( 2021-09)
    Abstract: Despite using identical evidence to support practice guidelines for lipid-lowering treatment in primary prevention of cardiovascular disease (CVD), it is unclear to what extent the 2018 American Heart Association/American College of Cardiology/Multisociety, 2016 US Preventive Services Task Force (USPSTF), 2020 Department of Veterans Affairs/Department of Defense, 2021 Canadian Cardiovascular Society, and 2019 European Society of Cardiology/European Atherosclerosis Society guidelines differ in grading and assigning levels of evidence and classes of recommendations (LOE/class) at a population level. Methods: We included 7262 participants, aged 45 to 75 years, without history of CVD from the prospective population-based Rotterdam Study. Per guideline, proportions of the population recommended statin therapy by LOE/class, sensitivity and specificity for CVD events, and numbers needed to treat at 10 years were calculated. Results: Mean age was 61.1 (SD 6.9) years; 58.2% were women. American Heart Association/American College of Cardiology/Multisociety, USPSTF, Department of Veterans Affairs/Department of Defense, Canadian Cardiovascular Society, and European Society of Cardiology/European Atherosclerosis Society strongly recommended statin initiation in respective 59.4%, 40.2%, 45.2%, 73.7%, and 42.1% of the eligible population based on high-quality evidence. Sensitivity for CVD events for treatment recommendations supported with strong LOE/class was 86.3% for American Heart Association/American College of Cardiology/Multisociety (IA or IB), 69.4% for USPSTF (USPSTF-B), 74.5% for Department of Veterans Affairs/Department of Defense (strong for), 93.3% for Canadian Cardiovascular Society (strong), and 66.6% for European Society of Cardiology/European Atherosclerosis Society (IA). Specificity was highest for the USPSTF at 45.3% and lowest for European Society of Cardiology/European Atherosclerosis Society at 10.0%. Estimated numbers needed to treat at 10 years for those with the strongest LOE/class were ranging from 20 to 26 for moderate-intensity and 12 to 16 for high-intensity statins. Conclusions: Sensitivity, specificity, and numbers needed to treat at 10 years for assigned LOE/class varied greatly among 5 CVD prevention guidelines. The level of variability seems to be driven by differences in how the evidence is graded and translated into LOE/class underlying the treatment recommendations by different professional societies. Efforts towards harmonizing evidence grading systems for clinical guidelines in primary prevention of CVD may reduce ambiguity and reinforce updated evidence-based recommendations.
    Type of Medium: Online Resource
    ISSN: 1941-7713 , 1941-7705
    URL: Article
    DOI: 10.1161/CIRCOUTCOMES.120.007183
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2453882-6
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  • 10
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    Clinical Relevance of Cortical Cerebral Microinfarcts on 1.5T Magnetic Resonance Imaging in the Late-Adult Population
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke Vol. 52, No. 3 ( 2021-03), p. 922-930
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 3 ( 2021-03), p. 922-930
    Abstract: Cortical cerebral microinfarcts (CMIs) have been linked with dementia and impaired cognition in cross-sectional studies. However, the clinical relevance of CMIs in a large population-based setting is lacking. We examine the association of cortical CMIs detected on 1.5T magnetic resonance imaging with cardiovascular risk factors, cerebrovascular disease, and brain tissue volumes. We further explore the association between cortical CMIs with cognitive decline and risk of stroke, dementia, and mortality in the general population. Methods: Two thousand one hundred fifty-six participants (age: 75.7±5.9 years, women: 55.6%) with clinical history and baseline magnetic resonance imaging (January 2009–December 2013) were included from the Rotterdam Study. Cortical CMIs were graded based on a previously validated method. Markers of cerebrovascular disease and brain tissue volumes were assessed on magnetic resonance imaging. Cognition was assessed using a detailed neuropsychological test at baseline and at 5 years of follow-up. Data on incident stroke, dementia, and mortality were included until January 2016. Results: Two hundred twenty-seven individuals (10.5%) had ≥1 cortical CMIs. The major risk factors of cortical CMIs were male sex, current smoking, history of heart disease, and stroke. Furthermore, presence of cortical CMIs was associated with infarcts and smaller brain volume. Persons with cortical CMIs showed cognitive decline in Stroop tests (color-naming and interference subtasks; β for color-naming, 0.18 [95% CI, 0.04–0.33], P interaction ≤0.001 and β for interference subtask, 1.74, [95% CI, 0.66–2.82], P interaction ≤0.001). During a mean follow-up of 5.2 years, 73 (4.3%) individuals developed incident stroke, 95 (5.1%) incident dementia, and 399 (19.2%) died. People with cortical CMIs were at an increased risk of stroke (hazard ratio, 1.18 [95% CI, 1.09–1.28]) and mortality (hazard ratio, 1.09 [95% CI, 1.00–1.19] ). Conclusions: Cortical CMIs are highly prevalent in a population-based setting and are associated with cardiovascular disease, cognitive decline, and increased risk of stroke and mortality. Future investigations will have to show whether cortical CMIs are a useful biomarker to intervene upon to reduce the burden of stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.032085
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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