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  1. Article ; Online: Identifying novel genetic risk loci for lacunar stroke.

    Schmidt, Reinhold / Hofer, Edith

    The Lancet. Neurology

    2021  Volume 20, Issue 5, Page(s) 329–330

    MeSH term(s) Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Stroke/epidemiology ; Stroke/genetics ; Stroke, Lacunar/epidemiology ; Stroke, Lacunar/genetics
    Language English
    Publishing date 2021-03-25
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2081241-3
    ISSN 1474-4465 ; 1474-4422
    ISSN (online) 1474-4465
    ISSN 1474-4422
    DOI 10.1016/S1474-4422(21)00099-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Inclusivity insights: two urban development projects in Johannesburg

    Hofer, Edith / Musakwa, Walter / van Lanen, Sander / Gumbo, Trynos / Netsch, Stefan / Gugerell, Katharina

    J Hous and the Built Environ. 2022 Dec., v. 37, no. 4, p. 1835-1858

    2022  , Page(s) 1835–1858

    Abstract: Johannesburg, which is South Africa’s largest city and economic center, is still influenced by patterns of inequality of the past. Although spatial transformation has been rapid since 1994, spatial divisions along class lines are still prevalent long ... ...

    Abstract Johannesburg, which is South Africa’s largest city and economic center, is still influenced by patterns of inequality of the past. Although spatial transformation has been rapid since 1994, spatial divisions along class lines are still prevalent long after the apartheid era. This is despite the fact that societal values such as inclusivity, spatial justice and equal access to resources have become the core goals of Johannesburg’s spatial and urban development. This is particularly true when addressing housing, public open spaces, transport and social infrastructure embedded in a suitable land-use mix. However, despite the adoption of numerous policies by government, this research indicates that even recent urban development projects such as Fleurhof and Waterfall are falling short in delivering those objectives. Based on a case study analysis, we show that significant dysfunctionalities become evident when evaluating these two projects, despite their meeting relevant indicators of spatial inclusion on paper. Tensions are identified between theoretical approaches and the implementation of societally relevant policy goals. These include inclusivity and spatial justice by mostly privatized provision of housing and services, and deficiencies in public maintenance of infrastructure. The research reveals, that ‘ticking-the-boxes’ behavior on policy and project level does not produce equitable, inclusive neighborhoods and urban spatial patterns, but rather reproduces spatial inequalities of the past. If these policies are to result in real spatial change and improvement in the lives of Johannesburg residents, a more proactive approach by the public sector at different levels will be necessary.
    Keywords case studies ; infrastructure ; issues and policy ; land use ; public sector ; urban development ; South Africa
    Language English
    Dates of publication 2022-12
    Size p. 1835-1858
    Publishing place Springer Netherlands
    Document type Article ; Online
    ZDB-ID 2016906-1
    ISSN 1573-7772 ; 1566-4910
    ISSN (online) 1573-7772
    ISSN 1566-4910
    DOI 10.1007/s10901-021-09916-y
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Heritability of R2* iron in the basal ganglia and cortex.

    Hofer, Edith / Pirpamer, Lukas / Langkammer, Christian / Tinauer, Christian / Seshadri, Sudha / Schmidt, Helena / Schmidt, Reinhold

    Aging

    2022  Volume 14, Issue 16, Page(s) 6415–6426

    Abstract: Background: While iron is essential for normal brain functioning, elevated concentrations are commonly found in neurodegenerative diseases and are associated with impaired cognition and neurological deficits. Currently, only little is known about ... ...

    Abstract Background: While iron is essential for normal brain functioning, elevated concentrations are commonly found in neurodegenerative diseases and are associated with impaired cognition and neurological deficits. Currently, only little is known about genetic and environmental factors that influence brain iron concentrations.
    Methods: Heritability and bivariate heritability of regional brain iron concentrations, assessed by R2* relaxometry at 3 Tesla MRI, were estimated with variance components models in 130 middle-aged to elderly participants of the Austrian Stroke Prevention Family Study.
    Results: Heritability of R2* iron ranged from 0.46 to 0.82 in basal ganglia and from 0.65 to 0.76 in cortical lobes. Age and BMI explained up to 12% and 9% of the variance of R2* iron, while APOE ε4 carrier status, hypertension, diabetes, hypercholesterolemia, sex and smoking explained 5% or less. The genetic correlation of R2* iron among basal ganglionic nuclei and among cortical lobes ranged from 0.78 to 0.87 and from 0.65 to 0.97, respectively. R2* rates in basal ganglia and cortex were not genetically correlated.
    Conclusions: Regional brain iron concentrations are mainly driven by genetic factors while environmental factors contribute to a certain extent. Brain iron levels in the basal ganglia and cortex are controlled by distinct sets of genes.
    MeSH term(s) Aged ; Basal Ganglia ; Brain ; Cerebral Cortex/diagnostic imaging ; Humans ; Iron ; Magnetic Resonance Imaging ; Middle Aged
    Chemical Substances Iron (E1UOL152H7)
    Language English
    Publishing date 2022-08-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.204212
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cerebral white matter hyperintensities indicate severity and progression of coronary artery calcification.

    Kneihsl, Markus / Gattringer, Thomas / Hofer, Edith / Rainer, Peter P / Ranner, Gerhard / Fandler-Höfler, Simon / Haidegger, Melanie / Perl, Sabine / Enzinger, Christian / Schmidt, Reinhold

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 4664

    Abstract: Cerebral white matter hyperintensities (WMH) have been associated with subclinical atherosclerosis including coronary artery calcification (CAC). However, previous studies on this association are limited by only cross-sectional analysis. We aimed to ... ...

    Abstract Cerebral white matter hyperintensities (WMH) have been associated with subclinical atherosclerosis including coronary artery calcification (CAC). However, previous studies on this association are limited by only cross-sectional analysis. We aimed to explore the relationship between WMH and CAC in elderly individuals both cross-sectionally and longitudinally. The study population consisted of elderly stroke- and dementia-free participants from the community-based Austrian Stroke Prevention Family Study (ASPFS). WMH volume and CAC levels (via Agatston score) were analyzed at baseline and after a 6-year follow-up period. Of 324 study participants (median age: 68 years), 115 underwent follow-up. Baseline WMH volume (median: 4.1 cm
    MeSH term(s) Humans ; Aged ; Coronary Artery Disease/diagnostic imaging ; White Matter/diagnostic imaging ; Cross-Sectional Studies ; Magnetic Resonance Imaging ; Stroke ; Risk Factors ; Disease Progression ; Vascular Calcification/diagnostic imaging
    Language English
    Publishing date 2024-02-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-55305-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Incidental findings of typical iNPH imaging signs in asymptomatic subjects with subclinical cognitive decline.

    Engel, Doortje C / Pirpamer, Lukas / Hofer, Edith / Schmidt, Reinhold / Brendle, Cornelia

    Fluids and barriers of the CNS

    2021  Volume 18, Issue 1, Page(s) 37

    Abstract: Background: The etiology of idiopathic normal pressure hydrocephalus (iNPH) remains unclear. Little is known about the pre-symptomatic stage. This study aimed to investigate the association of neuropsychological data with iNPH-characteristic imaging ... ...

    Abstract Background: The etiology of idiopathic normal pressure hydrocephalus (iNPH) remains unclear. Little is known about the pre-symptomatic stage. This study aimed to investigate the association of neuropsychological data with iNPH-characteristic imaging changes compared to normal imaging and unspecific atrophy in a healthy population.
    Methods: We extracted data from the community-dwelling Austrian Stroke Prevention Family Study (ASPS-Fam) database (2006-2010). All subjects underwent a baseline and identical follow-up examination after 3-5 years with MR imaging and an extensive neuropsychological test battery (Trail Making Test B, short physical performance balance, walking speed, memory, visuo-practical skills, composite scores of executive function and g-factor). We categorized the subjects into "iNPH"-associated, non-specific "atrophy," and "normal" based on the rating of different radiological cerebrospinal fluid (CSF) space parameters. We noted how the categories developed over time. We assessed the association of the image categories with the neuropsychological data, different demographic, and lifestyle parameters (age, sex, education, alcohol intake, arterial hypertension, hypercholesterolemia), and the extent of white matter hyperintensities. We investigated whether neuropsychological data associated with the image categories were independent from other parameters as confounders.
    Results: One hundred and thirteen subjects, aged 50-70 years, were examined. The imaging category "iNPH" was only present at follow-up. A third of subjects with "atrophy" at baseline changed to the category "iNPH" at follow-up. More white matter hyperintensities (WMH) were present in later "iNPH" subjects. Subjects with "iNPH" performed worse than "normal" subjects on executive function (p = 0.0118), memory (p = 0.0109), and Trail Making Test B (TMT-B. p < 0.0001). Education, alcohol intake, diabetes, arterial hypertension, and hypercholesterolemia had no effect. Age, number of females, and the extent of white matter hyperintensities were higher in "iNPH" than in "normal" subjects but did not significantly confound the neuropsychological results.
    Conclusions: Apparent asymptomatic subjects with "iNPH" imaging characteristics presented with subclinical cognitive decline and showed worse executive function, memory, and TMT-B results than "normal" subjects. WMH seem to play a role in the etiology before ventriculomegaly. Clinical screening of individuals with incidental iNPH-characteristic imaging and conspicuous results sof these neurocognitive tests needs further validation.
    MeSH term(s) Aged ; Asymptomatic Diseases ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/psychology ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Hydrocephalus, Normal Pressure/diagnostic imaging ; Hydrocephalus, Normal Pressure/psychology ; Incidental Findings ; Magnetic Resonance Imaging/methods ; Male ; Mental Status and Dementia Tests ; Middle Aged ; Prospective Studies ; Retrospective Studies
    Language English
    Publishing date 2021-08-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2595406-4
    ISSN 2045-8118 ; 2045-8118
    ISSN (online) 2045-8118
    ISSN 2045-8118
    DOI 10.1186/s12987-021-00268-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Kidney function, brain morphology and cognition in the elderly: sex differences in the Austrian Stroke Prevention Study.

    Kolland, Michael / Hofer, Edith / Pirpamer, Lukas / Eibl, Daniela / Enzinger, Christian / Rosenkranz, Alexander R / Schmidt, Reinhold

    Aging

    2022  Volume 14, Issue 1, Page(s) 240–252

    Abstract: Impaired kidney function is associated with structural brain changes and cognitive dysfunction. In the aging kidney, hemodynamic and structural alterations reduce the glomerular filtration rate (eGFR). Little is known about differences between men and ... ...

    Abstract Impaired kidney function is associated with structural brain changes and cognitive dysfunction. In the aging kidney, hemodynamic and structural alterations reduce the glomerular filtration rate (eGFR). Little is known about differences between men and women regarding decline of kidney function and brain damage. In this community-based study, we assessed associations between the eGFR, focal and diffuse brain abnormalities and cognitive functions. Sex-specific effects were analyzed by interaction terms eGFR x sex on brain structure and cognition. Interactive effects were assessed using mixed-models -stratified by sex. Overall, 196 women and 129 men (median age 68 years and mean eGFR 73.8±14.9 ml/min/1.73m
    MeSH term(s) Aged ; Austria/epidemiology ; Brain/anatomy & histology ; Cognition/physiology ; Cross-Sectional Studies ; Female ; Glomerular Filtration Rate/physiology ; Humans ; Independent Living ; Kidney/physiology ; Male ; Middle Aged ; Stroke/prevention & control
    Language English
    Publishing date 2022-01-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.203829
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Free water diffusion MRI and executive function with a speed component in healthy aging.

    Berger, Martin / Pirpamer, Lukas / Hofer, Edith / Ropele, Stefan / Duering, Marco / Gesierich, Benno / Pasternak, Ofer / Enzinger, Christian / Schmidt, Reinhold / Koini, Marisa

    NeuroImage

    2022  Volume 257, Page(s) 119303

    Abstract: Extracellular free water (FW) increases are suggested to better provide pathophysiological information in brain aging than conventional biomarkers such as fractional anisotropy. The aim of the present study was to determine the relationship between ... ...

    Abstract Extracellular free water (FW) increases are suggested to better provide pathophysiological information in brain aging than conventional biomarkers such as fractional anisotropy. The aim of the present study was to determine the relationship between conventional biomarkers, FW in white matter hyperintensities (WMH), FW in normal appearing white matter (NAWM) and in white matter tracts and executive functions (EF) with a speed component in elderly persons. We examined 226 healthy elderly participants (median age 69.83 years, IQR: 56.99-74.42) who underwent brain MRI and neuropsychological examination. FW in WMH and in NAWM as well as FW corrected diffusion metrics and measures derived from conventional MRI (white matter hyperintensities, brain volume, lacunes) were used in partial correlation (adjusted for age) to assess their correlation with EF with a speed component. Random forest analysis was used to assess the relative importance of these variables as determinants. Lastly, linear regression analyses of FW in white matter tracts corrected for risk factors of cognitive and white matter deterioration, were used to examine the role of specific tracts on EF with a speed component, which were then ranked with random forest regression. Partial correlation analyses revealed that almost all imaging metrics showed a significant association with EF with a speed component (r = -0.213 - 0.266). Random forest regression highlighted FW in WMH and in NAWM as most important among all diffusion and structural MRI metrics. The fornix (R
    MeSH term(s) Aged ; Biomarkers ; Diffusion Magnetic Resonance Imaging ; Diffusion Tensor Imaging/methods ; Executive Function/physiology ; Healthy Aging ; Humans ; Leukoaraiosis ; Water ; White Matter/diagnostic imaging
    Chemical Substances Biomarkers ; Water (059QF0KO0R)
    Language English
    Publishing date 2022-05-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1147767-2
    ISSN 1095-9572 ; 1053-8119
    ISSN (online) 1095-9572
    ISSN 1053-8119
    DOI 10.1016/j.neuroimage.2022.119303
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Impaired Kidney Function, Cerebral Small Vessel Disease and Cognitive Disorders: The Framingham Heart Study.

    Kelly, Dearbhla M / Pinheiro, Adlin A / Koini, Marisa / Anderson, Christopher D / Aparicio, Hugo / Hofer, Edith / Kern, Daniela / Blacker, Deborah / DeCarli, Charles / Hwang, Shih-Jen / Viswanathan, Anand / Gonzales, Mitzi M / Beiser, Alexa S / Seshadri, Sudha / Schmidt, Reinhold / Demissie, Serkalem / Romero, Jose R

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2024  

    Abstract: Background and hypothesis: It remains unclear if the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel ... ...

    Abstract Background and hypothesis: It remains unclear if the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD) and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring Cohort participants.
    Methods: We included Framingham Offspring participants free of dementia, attending an examination during midlife (exam cycle 6, baseline) for ascertainment of kidney function status, with brain MRI late in life (exam cycles 7-9), cognitive outcome data and available interim hypertension and blood pressure assessments. We related CKD (estimated glomerular filtration rate < 60 ml/min/1.73m2) and albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g) to CSVD markers and cognitive outcomes using multivariable regression analyses.
    Results: Among 2604 participants (mean age 67.4 ± 9.2, 64% women, 7% had CKD and 9% albuminuria), albuminuria was independently associated with covert infarcts (adjusted OR, 1.55 [1.00-2.38]; P = 0.049) and incident MCI and dementia (adjusted HR, 1.68 [1.18-2.41]; P = 0.005 and 1.71, [1.11-2.64]; P = 0.015, respectively). CKD was not associated with CSVD markers but was associated with higher risk of incident dementia (HR, 1.53 [1.02-2.29]; P = 0.041), While albuminuria was predictive of the Alzheimer's disease subtype (Adjusted HR = 1.68, [1.03-2.74]; P = 0.04), CKD was predictive of vascular dementia (Adjusted HR, 2.78, [1.16-6.68]; P = 0.023).
    Conclusions: Kidney disease was associated with CSVD and cognitive disorders in asymptomatic community dwelling participants. The relation was independent of premorbid BP, suggesting that the link between kidney and brain disease may involve additional mechanisms beyond blood pressure related injury.
    Language English
    Publishing date 2024-04-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfae079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Evidence of polygenic regulation of the physiological presence of neurofilament light chain in human serum.

    Herrera-Rivero, Marisol / Hofer, Edith / Maceski, Aleksandra / Leppert, David / Benkert, Pascal / Kuhle, Jens / Schmidt, Reinhold / Khalil, Michael / Wiendl, Heinz / Stoll, Monika / Berger, Klaus

    Frontiers in neurology

    2023  Volume 14, Page(s) 1145737

    Abstract: Introduction: The measurement of neurofilament light chain (NfL) in blood is a promising biomarker of neurological injury and disease. We investigated the genetic factors that underlie serum NfL levels (sNfL) of individuals without neurological ... ...

    Abstract Introduction: The measurement of neurofilament light chain (NfL) in blood is a promising biomarker of neurological injury and disease. We investigated the genetic factors that underlie serum NfL levels (sNfL) of individuals without neurological conditions.
    Methods: We performed a discovery genome-wide association study (GWAS) of sNfL in participants of the German BiDirect Study (
    Results: Our discovery GWAS identified 12 genomic loci at the suggestive threshold ((
    Discussion: Our findings suggest that polygenic regulation of neuronal processes, inflammation, metabolism and clearance modulate the variability of NfL in the circulation. These could aid in the interpretation of sNfL measurements in a personalized manner.
    Language English
    Publishing date 2023-03-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2023.1145737
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Arterial stiffness and its influence on cerebral morphology and cognitive function.

    Haidegger, Melanie / Lindenbeck, Simon / Hofer, Edith / Rodler, Christina / Zweiker, Robert / Perl, Sabine / Pirpamer, Lukas / Kneihsl, Markus / Fandler-Höfler, Simon / Gattringer, Thomas / Enzinger, Christian / Schmidt, Reinhold

    Therapeutic advances in neurological disorders

    2023  Volume 16, Page(s) 17562864231180715

    Abstract: Background: Recently, arterial stiffness has been associated with cerebral small vessel disease (SVD), brain atrophy and vascular dementia. Arterial stiffness is assessed : Objectives: We here investigated the association between PWV and its ... ...

    Abstract Background: Recently, arterial stiffness has been associated with cerebral small vessel disease (SVD), brain atrophy and vascular dementia. Arterial stiffness is assessed
    Objectives: We here investigated the association between PWV and its circadian changes on brain morphology and cognitive function in community-dwelling individuals.
    Design: Single-centre, prospective, community-based follow-up study.
    Methods: The study cohort comprised elderly community-based participants of the Austrian Stroke Prevention Family Study which was started in 2006. Patients with any history of cerebrovascular disease or dementia were excluded. The study consists of 84 participants who underwent ambulatory 24-h PWV measurement. White matter hyperintensity volume and brain volume were evaluated by 3-Tesla magnetic resonance imaging (MRI). A subgroup of patients was evaluated for cognitive function using an extensive neuropsychological test battery.
    Results: PWV was significantly related to reduced total brain volume (
    Conclusions: This study shows a relationship of arterial stiffness and reduced total brain volume. Elevations in PWV during night-time are of greater importance than day-time measures.
    Language English
    Publishing date 2023-06-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2442245-9
    ISSN 1756-2864 ; 1756-2856
    ISSN (online) 1756-2864
    ISSN 1756-2856
    DOI 10.1177/17562864231180715
    Database MEDical Literature Analysis and Retrieval System OnLINE

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