Publications by authors named "Emrah Düzel"

172 Publications

Detection of Cerebral Microbleeds With Venous Connection at 7 Tesla MRI.

Neurology 2021 Mar 2. Epub 2021 Mar 2.

Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.

Objective: Cerebral microbleeds (MBs) are a common finding in cerebral small vessel disease (CSVD) and Alzheimer's disease patients as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein.

Methods: 7 Tesla (7 T) MRI was conducted and MBs were counted on Quantitative Susceptibility Mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein.

Results: 51 subjects (mean age [SD] 70.5[8.6] years, 37% females) participated in the study: 20 were patients with CSVD (cerebral amyloid angiopathy (CAA) with strictly lobar MBs (n=8), hypertensive arteriopathy (HA) with strictly deep MBs (n=5), and mixed lobar and deep MBs (n=7), 72.4 [6.1] years, 30% females) and 31 were healthy controls (69.4 [9.9] years, 42% females). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. CAA subjects showed the highest ratio of venous to total MBs (19%) (HA=9%, mixed=18%, controls=5%) CONCLUSIONS: Our findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathological studies are needed to confirm our observations.
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http://dx.doi.org/10.1212/WNL.0000000000011790DOI Listing
March 2021

Age impairs mnemonic discrimination of objects more than scenes: A web-based, large-scale approach across the lifespan.

Cortex 2021 Apr 19;137:138-148. Epub 2021 Jan 19.

German Center for Neurodegenerative Diseases, Magdeburg, Germany; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.

Recent findings suggest that the effect of aging on recognition memory is modality-dependent, affecting memory for objects and scenes differently. However, the lifespan trajectory of memory decline in these domains remains unclear. A major challenge for assessing domain-specific trajectories is the need to utilize different types of stimuli for each domain (objects and scenes). We tested the large sample required to cover much of the adult lifespan using a large stimulus range via web-based assessments. 1554 participants (18-77 years) performed an online mnemonic discrimination task, tested on a pool of 2708 stimuli (Berron et al., 2018). Using corrected hit-rate (Pr) as a measure of performance, we show age-related decline in mnemonic discrimination in both domains, notably with a stronger decline in object memory, driven by a linear increase in the false recognition rate with advancing age. These data are the first to identify a linear age-related decline in mnemonic discrimination and a stronger, linear trajectory of decline in the object domain. Our data can inform basic and clinical memory research on the effects of aging on memory and help advancing the implementation of digital cognitive research tools.
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http://dx.doi.org/10.1016/j.cortex.2020.12.017DOI Listing
April 2021

Advances in neuroimaging to support translational medicine in dementia.

J Neurol Neurosurg Psychiatry 2021 Mar 10;92(3):263-270. Epub 2021 Feb 10.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Advances in neuroimaging are ideally placed to facilitate the translation from progress made in cellular genetics and molecular biology of neurodegeneration into improved diagnosis, prevention and treatment of dementia. New positron emission tomography (PET) ligands allow one to quantify neuropathology, inflammation and metabolism in vivo safely and reliably, to examine mechanisms of human disease and support clinical trials. Developments in MRI-based imaging and neurophysiology provide complementary quantitative assays of brain function and connectivity, for the direct testing of hypotheses of human pathophysiology. Advances in MRI are also improving the quantitative imaging of vascular risk and comorbidities. In combination with large datasets, open data and artificial intelligence analysis methods, new informatics-based approaches are set to enable accurate single-subject inferences for diagnosis, prediction and treatment that have the potential to deliver precision medicine for dementia. Here, we show, through the use of critically appraised worked examples, how neuroimaging can bridge the gaps between molecular biology, neural circuits and the dynamics of the core systems that underpin complex behaviours. We look beyond traditional structural imaging used routinely in clinical care, to include ultrahigh field MRI (7T MRI), magnetoencephalography and PET with novel ligands. We illustrate their potential as safe, robust and sufficiently scalable to be viable for experimental medicine studies and clinical trials. They are especially informative when combined in multimodal studies, with model-based analyses to test precisely defined hypotheses.
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http://dx.doi.org/10.1136/jnnp-2019-322402DOI Listing
March 2021

Bayesian model selection favors parametric over categorical fMRI subsequent memory models in young and older adults.

Neuroimage 2021 04 29;230:117820. Epub 2021 Jan 29.

German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany; Leibniz Institute for Neurobiology (LIN), Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany. Electronic address:

Subsequent memory paradigms allow to identify neural correlates of successful encoding by separating brain responses as a function of memory performance during later retrieval. In functional magnetic resonance imaging (fMRI), the paradigm typically elicits activations of medial temporal lobe, prefrontal and parietal cortical structures in young, healthy participants. This categorical approach is, however, limited by insufficient memory performance in older and particularly memory-impaired individuals. A parametric modulation of encoding-related activations with memory confidence could overcome this limitation. Here, we applied cross-validated Bayesian model selection (cvBMS) for first-level fMRI models to a visual subsequent memory paradigm in young (18-35 years) and older (51-80 years) adults. Nested cvBMS revealed that parametric models, especially with non-linear transformations of memory confidence ratings, outperformed categorical models in explaining the fMRI signal variance during encoding. We thereby provide a framework for improving the modeling of encoding-related activations and for applying subsequent memory paradigms to memory-impaired individuals.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117820DOI Listing
April 2021

Reconciling the object and spatial processing views of the perirhinal cortex through task-relevant unitization.

Hippocampus 2021 Feb 1. Epub 2021 Feb 1.

Cognitive and Systems Neuroscience Group, SILS Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.

The perirhinal cortex is situated on the border between sensory association cortex and the hippocampal formation. It serves an important function as a transition area between the sensory neocortex and the medial temporal lobe. While the perirhinal cortex has traditionally been associated with object coding and the "what" pathway of the temporal lobe, current evidence suggests a broader function of the perirhinal cortex in solving feature ambiguity and processing complex stimuli. Besides fulfilling functions in object coding, recent neurophysiological findings in freely moving rodents indicate that the perirhinal cortex also contributes to spatial and contextual processing beyond individual sensory modalities. Here, we address how these two opposing views on perirhinal cortex-the object-centered and spatial-contextual processing hypotheses-may be reconciled. The perirhinal cortex is consistently recruited when different features can be merged perceptually or conceptually into a single entity. Features that are unitized in these entities include object information from multiple sensory domains, reward associations, semantic features and spatial/contextual associations. We propose that the same perirhinal network circuits can be flexibly deployed for multiple cognitive functions, such that the perirhinal cortex performs similar unitization operations on different types of information, depending on behavioral demands and ranging from the object-related domain to spatial, contextual and semantic information.
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http://dx.doi.org/10.1002/hipo.23304DOI Listing
February 2021

Longitudinal Reproducibility of Neurite Orientation Dispersion and Density Imaging (NODDI) Derived Metrics in the White Matter.

Neuroscience 2021 03 17;457:165-185. Epub 2021 Jan 17.

Faculty of Human Sciences, Institute III, Department of Sport Science, Otto von Guericke University, Zschokkestraße 32, 39104 Magdeburg, Germany; Center for Behavioral and Brain Science (CBBS), Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany.

Diffusion-weighted magnetic resonance imaging (DWI) is undergoing constant evolution with the ambitious goal of developing in-vivo histology of the brain. A recent methodological advancement is Neurite Orientation Dispersion and Density Imaging (NODDI), a histologically validated multi-compartment model to yield microstructural features of brain tissue such as geometric complexity and neurite packing density, which are especially useful in imaging the white matter. Since NODDI is increasingly popular in clinical research and fields such as developmental neuroscience and neuroplasticity, it is of vast importance to characterize its reproducibility (or reliability). We acquired multi-shell DWI data in 29 healthy young subjects twice over a rescan interval of 4 weeks to assess the within-subject coefficient of variation (CV), between-subject coefficient of variation (CV) and the intraclass correlation coefficient (ICC), respectively. Using these metrics, we compared regional and voxel-by-voxel reproducibility of the most common image analysis approaches (tract-based spatial statistics [TBSS], voxel-based analysis with different extents of smoothing ["VBM-style"], ROI-based analysis). We observed high test-retest reproducibility for the orientation dispersion index (ODI) and slightly worse results for the neurite density index (NDI). Our findings also suggest that the choice of analysis approach might have significant consequences for the results of a study. Collectively, the voxel-based approach with Gaussian smoothing kernels of ≥4 mm FWHM and ROI-averaging yielded the highest reproducibility across NDI and ODI maps (CV mostly ≤3%, ICC mostly ≥0.8), respectively, whilst smaller kernels and TBSS performed consistently worse. Furthermore, we demonstrate that image quality (signal-to-noise ratio [SNR]) is an important determinant of NODDI metric reproducibility. We discuss the implications of these results for longitudinal and cross-sectional research designs commonly employed in the neuroimaging field.
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http://dx.doi.org/10.1016/j.neuroscience.2021.01.005DOI Listing
March 2021

Association between composite scores of domain-specific cognitive functions and regional patterns of atrophy and functional connectivity in the Alzheimer's disease spectrum.

Neuroimage Clin 2021 17;29:102533. Epub 2020 Dec 17.

German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany.

Background: Cognitive decline has been found to be associated with gray matter atrophy and disruption of functional neural networks in Alzheimer's disease (AD) in structural and functional imaging (fMRI) studies. Most previous studies have used single test scores of cognitive performance among monocentric cohorts. However, cognitive domain composite scores could be more reliable than single test scores due to the reduction of measurement error. Adopting a multicentric resting state fMRI (rs-fMRI) and cognitive domain approach, we provide a comprehensive description of the structural and functional correlates of the key cognitive domains of AD.

Method: We analyzed MRI, rs-fMRI and cognitive domain score data of 490 participants from an interim baseline release of the multicenter DELCODE study cohort, including 54 people with AD, 86 with Mild Cognitive Impairment (MCI), 175 with Subjective Cognitive Decline (SCD), and 175 Healthy Controls (HC) in the AD-spectrum. Resulting cognitive domain composite scores (executive, visuo-spatial, memory, working memory and language) from the DELCODE neuropsychological battery (DELCODE-NP), were previously derived using confirmatory factor analysis. Statistical analyses examined the differences between diagnostic groups, and the association of composite scores with regional atrophy and network-specific functional connectivity among the patient subgroup of SCD, MCI and AD.

Result: Cognitive performance, atrophy patterns and functional connectivity significantly differed between diagnostic groups in the AD-spectrum. Regional gray matter atrophy was positively associated with visuospatial and other cognitive impairments among the patient subgroup in the AD-spectrum. Except for the visual network, patterns of network-specific resting-state functional connectivity were positively associated with distinct cognitive impairments among the patient subgroup in the AD-spectrum.

Conclusion: Consistent associations between cognitive domain scores and both regional atrophy and network-specific functional connectivity (except for the visual network), support the utility of a multicentric and cognitive domain approach towards explicating the relationship between imaging markers and cognition in the AD-spectrum.
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http://dx.doi.org/10.1016/j.nicl.2020.102533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770965PMC
December 2020

Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status.

J Alzheimers Dis 2021 ;79(2):493-509

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Background: Amyloid-β accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer's continuum in the 2018 NIA-AA research framework.

Objective: This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus.

Methods: From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAβ+) and amyloidnegative SCD (SCDβ-) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences with global and precuneal amyloid load, as measured by FBB standard uptake value ratios (SUVR=⫖FBB).

Results: ReHo was significantly higher (voxel-wise p < 0.01, cluster-level p < 0.05) in the bilateral precuneus for SCDAβ+patients, whereas fALFF was not altered between groups. Relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in SCDAβ+ patients. In this latter cluster, precuneus-occipital FC correlated positively with global (SCDAβ+) and precuneus SUVRFBB (both groups).

Conclusion: While partial confounding influences due to a higher APOE ε4 carrier ratio among SCDAβ+ patients cannot be excluded, exploratory results indicate functional alterations in the precuneus hub region that were related to amyloid-β load, highlighting incipient pathology in stage 2 of the AD continuum.
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http://dx.doi.org/10.3233/JAD-200472DOI Listing
January 2021

MRI phenotyping of underlying cerebral small vessel disease in mixed hemorrhage patients.

J Neurol Sci 2020 Dec 9;419:117173. Epub 2020 Oct 9.

Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, 39120 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address:

Objective: To investigate underlying cerebral small vessel disease (CSVD) in patients with mixed cerebral hemorrhages patterns and phenotype them according to the contribution of the two most common sporadic CSVD subtypes: cerebral amyloid angiopathy (CAA) vs. hypertensive arteriopathy (HA).

Methods: Brain MRIs of patients with intracerebral hemorrhages (ICHs) and/or cerebral microbleeds (CMBs) were assessed for the full spectrum of CSVD markers using validated scales: ICHs, CMBs, cortical superficial siderosis (cSS), white matter hyperintensities, MRI-visible perivascular spaces (PVS). PVS predominance pattern was grouped as centrum-semiovale (CSO)-PVS predominance, basal-ganglia (BG)-PVS predominance, CSO-PVS and BG-PVS equality. Patients with mixed cerebral hemorrhages were classified into mixed CAA-pattern or mixed HA-pattern according to the existence of cSS and/or a CSO-PVS predominance pattern and comparisons were performed.

Results: We included 110 patients with CAA (strictly lobar ICHs/CMBs), 33 with HA (strictly deep ICHs/CMBs) and 97 with mixed lobar/deep ICHs/CMBs. Mixed patients were more similar to HA with respect to their MRI-CSVD markers, vascular risk profile and cerebrospinal fluid (CSF) measures. In the mixed patients, 33 (34%) had cSS, a CSO-PVS predominance pattern, or both, and were defined as mixed CAA-pattern cases. The mixed CAA-pattern patients were more alike CAA patients regarding their MRI-CSVD markers, CSF and genetic profile.

Conclusion: Our findings suggest that the heterogeneous group of patients with mixed cerebral hemorrhages distribution can be further phenotyped according to the predominant underlying CSVD. cSS presence and a CSO-PVS predominance pattern could serve as strongly suggestive markers of a contribution from CAA among patients with mixed hemorrhages.
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http://dx.doi.org/10.1016/j.jns.2020.117173DOI Listing
December 2020

Ratio and index of Neurofilament light chain indicate its origin in Guillain-Barré Syndrome.

Ann Clin Transl Neurol 2020 11 8;7(11):2213-2220. Epub 2020 Oct 8.

Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.

Objective: Neurofilament light chain (NfL) has been established as a biomarker of axonal damage in many diseases of the central nervous system (CNS). Increased levels of serum NfL (sNfL) can derive as well from damage in the peripheral nervous system (PNS) as from CNS, but little is known about the quantities contributing to sNfL. Peripheral nerve damage may be reflected by an increase in sNfL levels, while the NfL CSF/serum ratio and NfL index decreases.

Methods: We collected serum and cerebrospinal fluid (CSF) from 21 Guillain-Barré Syndrome (GBS) patients and measured NfL in serum and CSF and compared them with 19 neurologically healthy controls.

Results: In general, NfL in CSF and serum was significantly higher in GBS patients. Serum NfL was higher in GBS patients admitted to the intensive care unit (P = 0.02). Controls had a mean CSF/serum NfL ratio of 26.7 (ranging from 5.8 to 69.5) indicating a central origin of NfL. Three GBS patients had a similar range (23.9 to 42.7, mean 33.3) all of them with demyelinating pathology in the PNS. Eighteen GBS patients with axonal or mixed axonal-demyelinating pathology showed significantly lower CSF/serum ratios (0.02-12.2, mean 4.4), indicative of a peripheral origin of NfL. When applying the NfL index subdivisions remain the same.

Interpretation: These results demonstrate that the PNS is a relevant contributor to sNfL levels and that the distribution can be identified by a lowered NfL CSF/serum ratio of NfL index. Furthermore, acute or subacute polyneuropathies are likely confounding factors in interpreting sNfL levels in CNS diseases.
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http://dx.doi.org/10.1002/acn3.51207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664266PMC
November 2020

Learning in anticipation of reward and punishment: perspectives across the human lifespan.

Neurobiol Aging 2020 12 22;96:49-57. Epub 2020 Aug 22.

Center for Behavioral Brain Sciences, University of Magdeburg, Magdeburg, Germany; Department of Child and Adolescent Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany.

Learning to act to receive reward and to withhold to avoid punishment has been found to be easier than learning the opposite contingencies in young adults. To what extent this type of behavioral adaptation might develop during childhood and adolescence and differ during aging remains unclear. We therefore tested 247 healthy individuals across the human life span (7-80 years) with an orthogonalized valenced go/no-go learning task. Computational modeling revealed that peak performance in young adults was attributable to greater sensitivity to both reward and punishment. However, in children and adolescents, we observed an increased bias toward action but not reward sensitivity. By contrast, reduced learning in midlife and older adults was accompanied by decreased reward sensitivity and especially punishment sensitivity along with an age-related increase in the Pavlovian bias. These findings reveal distinct motivation-dependent learning capabilities across the human life span, which cannot be probed using conventional go/reward no-go/punishment style paradigms that have important implications in lifelong education.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.08.011DOI Listing
December 2020

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients.

Alzheimers Dement 2020 11 18;16(11):1504-1514. Epub 2020 Aug 18.

Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany.

Introduction: Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer's disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations.

Methods: We studied six samples (N = 365 participants) covering the spectrum of AD and SVD, including genetically defined samples. We calculated diffusion measures from DTI and free water imaging. Simple linear, multivariable random forest, and voxel-based regressions were used to evaluate associations between AD biomarkers (amyloid beta, tau), SVD imaging markers, and diffusion measures.

Results: SVD markers were strongly associated with diffusion measures and showed a higher contribution than AD biomarkers in multivariable analysis across all memory clinic samples. Voxel-wise analyses between tau and diffusion measures were not significant.

Discussion: In memory clinic patients, the effect of SVD on diffusion alterations largely exceeds the effect of AD, supporting the value of diffusion measures as markers of SVD.
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http://dx.doi.org/10.1002/alz.12150DOI Listing
November 2020

Minor neuropsychological deficits in patients with subjective cognitive decline.

Neurology 2020 09 7;95(9):e1134-e1143. Epub 2020 Jul 7.

From the German Center for Neurodegenerative Diseases (S.W., L.K., J.G., A.P., I.F., S.R., M.T., A. Spottke, A.R., B.K., K.F., A. Schneider, M.H., F.B., D.M., F.J., M.W.); Department of Neurodegenerative Diseases and Geriatric Psychiatry (S.W., L.K., J.G., A.P., I.F., A.R., B.K., K.F., A. Schneider, M.T.H., F.B., M.W.), University of Bonn; German Center for Neurodegenerative Diseases (E.J.S., J.P., O.P., F.M., M.F.C.); Department of Psychiatry and Psychotherapy (E.J.S., C.F., J.P.), Charité-Universitätsmedizin Berlin; German Center for Neurodegenerative Diseases (I.K., S.T.); Department of Psychosomatic Medicine (I.K., S.T.), Rostock University Medical Center; German Center for Neurodegenerative Diseases (K.B.); Institute for Stroke and Dementia Research (K.B., D.J.), University Hospital, LMU Munich; German Center for Neurodegenerative Diseases (C.L., M.B.); Section for Dementia Research (C.L., M.B.), Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen; Charité-Universitätsmedizin Berlin (O.P., F.M., M.F.C.), corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin; (O.P., F.M., M.F.C.), Berlin Institute of Health, Institute of Psychiatry and Psychotherapy; German Center for Neurodegenerative Diseases (J.W., C.B.); Department of Psychiatry and Psychotherapy (J.W., C.B.), University Medical Center Goettingen, University of Goettingen; German Center for Neurodegenerative Diseases (E.D., C.M.); Institute of Cognitive Neurology and Dementia Research (E.D., C.M., W.G.) and Department of Psychiatry and Psychotherapy (C.M.), Otto-von-Guericke University, Magdeburg; Department of Neurology (A. Spottke), University Hospital Bonn; and Division of Neurogenetics and Molecular Psychiatry (A.R.) and Department of Psychiatry (M.T., D.M., F.J.), Medical Faculty University of Cologne, Germany.

Objective: To determine the nature and extent of minor neuropsychological deficits in patients with subjective cognitive decline (SCD) and their association with CSF biomarkers of Alzheimer disease (AD).

Method: We analyzed data from n = 449 cognitively normal participants (n = 209 healthy controls, n = 240 patients with SCD) from an interim data release of the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE). An extensive neuropsychological test battery was applied at baseline for which we established a latent, 5 cognitive domain factor structure comprising learning and memory, executive functions, language abilities, working memory, and visuospatial functions. We compared groups in terms of global and domain-specific performance and correlated performance with different CSF markers of AD pathology.

Results: We observed worse performance (Cohen d = ≈0.25-0.5, adjusted for age, sex differences with analysis of covariance) in global performance, memory, executive functions, and language abilities for the SCD group compared to healthy controls. In addition, worse performance in these domains was moderately ( = ≈0.3) associated with lower CSF β-amyloid and CSF β-amyloid/phosphorylated tau181 in the whole sample and specifically in the SCD subgroup.

Conclusions: Within the spectrum of clinically unimpaired (i.e., before mild cognitive impairment) cognitive performance, SCD is associated with minor deficits in memory, executive function, and language abilities. The association of these subtle cognitive deficits with AD CSF biomarkers speaks to their validity and potential use for the early detection of underlying preclinical AD.
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http://dx.doi.org/10.1212/WNL.0000000000010142DOI Listing
September 2020

Reply: Heterogeneity of the circle of Willis and its implication in hippocampal perfusion.

Brain 2020 07;143(7):e59

Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.

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http://dx.doi.org/10.1093/brain/awaa170DOI Listing
July 2020

Neurocan genome-wide psychiatric risk variant affects explicit memory performance and hippocampal function in healthy humans.

Eur J Neurosci 2020 Jun 24. Epub 2020 Jun 24.

Leibniz Institute for Neurobiology, Magdeburg, Germany.

Alterations of the brain extracellular matrix (ECM) can perturb the structure and function of brain networks like the hippocampus, a key region in human memory that is commonly affected in psychiatric disorders. Here, we investigated the potential effects of a genome-wide psychiatric risk variant in the NCAN gene encoding the ECM proteoglycan neurocan (rs1064395) on memory performance, hippocampal function and cortical morphology in young, healthy volunteers. We assessed verbal memory performance in two cohorts (N = 572, 302) and found reduced recall performance in risk allele (A) carriers across both cohorts. In 117 participants, we performed functional magnetic resonance imaging using a novelty-encoding task with visual scenes. Risk allele carriers showed higher false alarm rates during recognition, accompanied by inefficiently increased left hippocampal activation. To assess effects of rs1064395 on brain morphology, we performed voxel-based morphometry in 420 participants from four independent cohorts and found lower grey matter density in the ventrolateral and rostral prefrontal cortex of risk allele carriers. In silico eQTL analysis revealed that rs1064395 SNP is linked not only to increased prefrontal expression of the NCAN gene itself, but also of the neighbouring HAPLN4 gene, suggesting a more complex effect of the SNP on ECM composition. Our results suggest that the NCAN rs1064395 A allele is associated with lower hippocampus-dependent memory function, variation of prefrontal cortex structure and ECM composition. Considering the well-documented hippocampal and prefrontal dysfunction in bipolar disorder and schizophrenia, our results may reflect an intermediate phenotype by which NCAN rs1064395 contributes to disease risk.
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http://dx.doi.org/10.1111/ejn.14872DOI Listing
June 2020

Corrigendum: The Role of the Striatum in Learning to Orthogonalize Action and Valence: A Combined PET and 7 T MRI Aging Study.

Cereb Cortex 2020 May;30(6):3857

Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg, Leipzigerstr. 44, 39120, Magdeburg, Germany.

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http://dx.doi.org/10.1093/cercor/bhaa114DOI Listing
May 2020

Corrigendum to in vivo visualization of age-related differences in the locus coeruleus Neurobiology of Aging Volume 74, February 2019, Pages 101-111.

Neurobiol Aging 2020 07 18;91:172-174. Epub 2020 Apr 18.

Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, University College London, London, UK; Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany; Institute of Cognitive Neuroscience, University College London, London, UK.

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http://dx.doi.org/10.1016/j.neurobiolaging.2020.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242897PMC
July 2020

Effects of Physical Exercise on Working Memory and Attention-Related Neural Oscillations.

Front Neurosci 2020 31;14:239. Epub 2020 Mar 31.

Institute of Cognitive Neurology and Dementia Research, Otto von Guericke University Magdeburg, Magdeburg, Germany.

Cognitive functions, such as working memory (WM) and attention, have been shown to benefit from physical exercise. Quantifying frequency-band-specific neural oscillatory patterns during the use of such cognitive functions can provide insight into exercise-induced benefits in the brain. Specifically, we investigated whether a 4-month physical exercise training influenced theta and alpha power measured in visual WM and attention tasks. The delayed match-to-sample (DMS) task required mnemonic discrimination of similar visual stimuli, akin to pattern separation, while the visual-attention search (VAS) task required detecting the presence of a specific object (i.e., target) in an image. Behavioral and electroencephalographic data were acquired during a DMS visual WM task and VAS task both before and after the intervention. Forty-three sedentary young adults (19-34 years) were pseudorandomly assigned to a training group (indoor treadmill, = 20) or to a control group ( = 23). Compared to the preintervention baseline, the exercise group showed increased frontal alpha power (9-12 Hz) during the VAS task after the intervention. In addition, alpha power changes correlated positively with fitness changes. Behaviorally, there were no exercise-related effects on reaction times or accuracy in either task. Our findings substantiate that aerobic training of sedentary young adults may influence neural dynamics underlying visual attention rather than visual WM and mnemonic discrimination.
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http://dx.doi.org/10.3389/fnins.2020.00239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136837PMC
March 2020

Older adults show a reduced tendency to engage in context-dependent decision biases.

Neuropsychologia 2020 05 7;142:107445. Epub 2020 Apr 7.

Faculty of Economics and Management, Otto-von-Guericke-University Magdeburg, Germany; Institute of Social Medicine and Health Economics, Otto-von-Guericke-University Magdeburg, Germany.

When we make decisions, we usually consider the context. This can sometimes lead to suboptimal choices or choice abnormalities. One such abnormality is the compromise effect, according to which deciders tend to favour options positioned as a compromise in an available set of extreme options. Theoretical accounts consider that these effects relate to available cognitive resources, which, in turn, have been found to depend on an individual's dopaminergic innervation. Referring to a correlative triad between cognition, dopamine and aging, the present study demonstrates that the compromise effect is replicable in a group of younger adults (n = 27, 20-32 years of age) yet is attenuated in older adults (n = 27, 62-80 years of age). Results from an [F]-FDOPA-PET analysis in older adults indicate a positive association between older adults' inclination to engage in compromise effects and their striatal dopamine synthesis capacity. These results demonstrate altered context-dependent decision biases in older adults and suggest a neuromodulatory mechanism underlying this irregular choice.
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http://dx.doi.org/10.1016/j.neuropsychologia.2020.107445DOI Listing
May 2020

Noradrenergic-dependent functions are associated with age-related locus coeruleus signal intensity differences.

Nat Commun 2020 04 6;11(1):1712. Epub 2020 Apr 6.

German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.

The locus coeruleus (LC), the origin of noradrenergic modulation of cognitive and behavioral function, may play an important role healthy ageing and in neurodegenerative conditions. We investigated the functional significance of age-related differences in mean normalized LC signal intensity values (LC-CR) in magnetization-transfer (MT) images from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) cohort - an open-access, population-based dataset. Using structural equation modelling, we tested the pre-registered hypothesis that putatively noradrenergic (NA)-dependent functions would be more strongly associated with LC-CR in older versus younger adults. A unidimensional model (within which LC-CR related to a single factor representing all cognitive and behavioral measures) was a better fit with the data than the a priori two-factor model (within which LC-CR related to separate NA-dependent and NA-independent factors). Our findings support the concept that age-related reduction of LC structural integrity is associated with impaired cognitive and behavioral function.
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http://dx.doi.org/10.1038/s41467-020-15410-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136271PMC
April 2020

Prominent White Matter Involvement in Multiple System Atrophy of Cerebellar Type.

Mov Disord 2020 05 29;35(5):816-824. Epub 2020 Jan 29.

Clinical Research, German Center for Neurodegenerative Diseases, Bonn, Germany.

Background: Sporadic degenerative ataxia patients fall into 2 major groups: multiple system atrophy with predominant cerebellar ataxia (MSA-C) and sporadic adult-onset ataxia (SAOA). Both groups have cerebellar volume loss, but little is known about the differential involvement of gray and white matter in MSA-C when compared with SAOA.

Objectives: The objective of this study was to identify structural differences of brain gray and white matter between both patient groups.

Methods: We used magnetic resonance imaging to acquire T1-weighted images and diffusion tensor images from 12 MSA-C patients, 31 SAOA patients, and 55 healthy controls. Magnetic resonance imaging data were analyzed with voxel-based-morphometry, tract-based spatial statistics, and tractography-based regional diffusion tensor images analysis.

Results: Whole-brain and cerebellar-focused voxel-based-morphometry analysis showed gray matter volume loss in both patient groups when compared with healthy controls, specifically in the cerebellar areas subserving sensorimotor functions. When compared with controls, the SAOA and MSA-C patients showed white matter loss in the cerebellum, whereas brainstem white matter was reduced only in the MSA-C patients. The tract-based spatial statistics revealed reduced fractional anisotropy within the pons and cerebellum in the MSA-C patients both in comparison with the SAOA patients and healthy controls. In addition, tractography-based regional analysis showed reduced fractional anisotropy along the corticospinal tracts in MSA-C, but not SAOA.

Conclusion: Although in our cohort extent and distribution of gray and white matter loss were similar between the MSA-C and SAOA patients, magnetic resonance imaging data showed prominent microstructural white matter involvement in the MSA-C patients that was not present in the SAOA patients. Our findings highlight the significance of microstructural white matter changes in the differentiation between both conditions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27987DOI Listing
May 2020

Hippocampal vascular reserve associated with cognitive performance and hippocampal volume.

Brain 2020 02;143(2):622-634

Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University, Magdeburg, Germany.

Medial temporal lobe dependent cognitive functions are highly vulnerable to hypoxia in the hippocampal region, yet little is known about the relationship between the richness of hippocampal vascular supply and cognition. Hippocampal vascularization patterns have been categorized into a mixed supply from both the posterior cerebral artery and the anterior choroidal artery or a single supply by the posterior cerebral artery only. Hippocampal arteries are small and affected by pathological changes when cerebral small vessel disease is present. We hypothesized, that hippocampal vascularization patterns may be important trait markers for vascular reserve and modulate (i) cognitive performance; (ii) structural hippocampal integrity; and (iii) the effect of cerebral small vessel disease on cognition. Using high-resolution 7 T time-of-flight angiography we manually classified hippocampal vascularization patterns in older adults with and without cerebral small vessel disease in vivo. The presence of a mixed supplied hippocampus was an advantage in several cognitive domains, including verbal list learning and global cognition. A mixed supplied hippocampus also was an advantage for verbal memory performance in cerebral small vessel disease. Voxel-based morphometry showed higher anterior hippocampal grey matter volume in mixed, compared to single supply. We discuss that a mixed hippocampal supply, as opposed to a single one, may increase the reliability of hippocampal blood supply and thereby provide a hippocampal vascular reserve that protects against cognitive impairment.
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http://dx.doi.org/10.1093/brain/awz383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009470PMC
February 2020

The Role of the Striatum in Learning to Orthogonalize Action and Valence: A Combined PET and 7 T MRI Aging Study.

Cereb Cortex 2020 05;30(5):3340-3351

Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg, Leipzigerstr. 44, 39120, Magdeburg, Germany.

Pavlovian biases influence instrumental learning by coupling reward seeking with action invigoration and punishment avoidance with action suppression. Using a probabilistic go/no-go task designed to orthogonalize action (go/no-go) and valence (reward/punishment), recent studies have shown that the interaction between the two is dependent on the striatum and its key neuromodulator dopamine. Using this task, we sought to identify how structural and neuromodulatory age-related differences in the striatum may influence Pavlovian biases and instrumental learning in 25 young and 31 older adults. Computational modeling revealed a significant age-related reduction in reward and punishment sensitivity and marked (albeit not significant) reduction in learning rate and lapse rate (irreducible noise). Voxel-based morphometry analysis using 7 Tesla MRI images showed that individual differences in learning rate in older adults were related to the volume of the caudate nucleus. In contrast, dopamine synthesis capacity in the dorsal striatum, assessed using [18F]-DOPA positron emission tomography in 22 of these older adults, was not associated with learning performance and did not moderate the relationship between caudate volume and learning rate. This multiparametric approach suggests that age-related differences in striatal volume may influence learning proficiency in old age.
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http://dx.doi.org/10.1093/cercor/bhz313DOI Listing
May 2020

Multicenter Tract-Based Analysis of Microstructural Lesions within the Alzheimer's Disease Spectrum: Association with Amyloid Pathology and Diagnostic Usefulness.

J Alzheimers Dis 2019 ;72(2):455-465

German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.

Diffusion changes as determined by diffusion tensor imaging are potential indicators of microstructural lesions in people with mild cognitive impairment (MCI), prodromal Alzheimer's disease (AD), and AD dementia. Here we extended the scope of analysis toward subjective cognitive complaints as a pre-MCI at risk stage of AD. In a cohort of 271 participants of the prospective DELCODE study, including 93 healthy controls and 98 subjective cognitive decline (SCD), 45 MCI, and 35 AD dementia cases, we found reductions of fiber tract integrity in limbic and association fiber tracts in MCI and AD dementia compared with controls in a tract-based analysis (p < 0.05, family wise error corrected). In contrast, people with SCD showed spatially restricted white matter alterations only for the mode of anisotropy and only at an uncorrected level of significance. DTI parameters yielded a high cross-validated diagnostic accuracy of almost 80% for the clinical diagnosis of MCI and the discrimination of Aβ positive MCI cases from Aβ negative controls. In contrast, DTI parameters reached only random level accuracy for the discrimination between Aβ positive SCD and control cases from Aβ negative controls. These findings suggest that in prodromal stages of AD, such as in Aβ positive MCI, multicenter DTI with prospectively harmonized acquisition parameters yields diagnostic accuracy meeting the criteria for a useful biomarker. In contrast, automated tract-based analysis of DTI parameters is not useful for the identification of preclinical AD, including Aβ positive SCD and control cases.
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http://dx.doi.org/10.3233/JAD-190446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918918PMC
November 2020

Higher CSF Tau Levels Are Related to Hippocampal Hyperactivity and Object Mnemonic Discrimination in Older Adults.

J Neurosci 2019 10 20;39(44):8788-8797. Epub 2019 Sep 20.

Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, 39120 Magdeburg, Germany.

Mnemonic discrimination, the ability to distinguish similar events in memory, relies on subregions in the human medial temporal lobes (MTLs). Tau pathology is frequently found within the MTL of older adults and therefore likely to affect mnemonic discrimination, even in healthy older individuals. The MTL subregions that are known to be affected early by tau pathology, the perirhinal-transentorhinal region (area 35) and the anterior-lateral entorhinal cortex (alEC), have recently been implicated in the mnemonic discrimination of objects rather than scenes. Here we used an object-scene mnemonic discrimination task in combination with fMRI recordings and analyzed the relationship between subregional MTL activity, memory performance, and levels of total and phosphorylated tau as well as Aβ42/40 ratio in CSF. We show that activity in alEC was associated with mnemonic discrimination of similar objects but not scenes in male and female cognitively unimpaired older adults. Importantly, CSF tau levels were associated with increased fMRI activity in the hippocampus, and both increased hippocampal activity as well as tau levels were associated with mnemonic discrimination of objects, but again not scenes. This suggests that dysfunction of the alEC-hippocampus object mnemonic discrimination network might be a marker for tau-related cognitive decline. Subregions in the human medial temporal lobe are critically involved in episodic memory and, at the same time, affected by tau pathology. Impaired object mnemonic discrimination performance as well as aberrant activity within the entorhinal-hippocampal circuitry have been reported in earlier studies involving older individuals, but it has thus far remained elusive whether and how tau pathology is implicated in this specific impairment. Using task-related fMRI in combination with measures of tau pathology in CSF, we show that measures of tau pathology are associated with increased hippocampal activity and reduced mnemonic discrimination of similar objects but not scenes. This suggests that object mnemonic discrimination tasks could be promising markers for tau-related cognitive decline.
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http://dx.doi.org/10.1523/JNEUROSCI.1279-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820211PMC
October 2019

Memorability of photographs in subjective cognitive decline and mild cognitive impairment: Implications for cognitive assessment.

Alzheimers Dement (Amst) 2019 Dec 5;11:610-618. Epub 2019 Sep 5.

Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.

Introduction: Impaired long-term memory is a defining feature of mild cognitive impairment (MCI). We tested whether this impairment is item specific, limited to some memoranda, whereas some remain consistently memorable.

Methods: We conducted item-based analyses of long-term visual recognition memory. Three hundred ninety-four participants (healthy controls, subjective cognitive decline [SCD], and MCI) in the multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) were tested with images from a pool of 835 photographs.

Results: We observed consistent memorability for images in healthy controls, SCD, and MCI, predictable by a neural network trained on another healthy sample. Looking at memorability differences between groups, we identified images that could successfully categorize group membership with higher success and a substantial image reduction than the original image set.

Discussion: Individuals with SCD and MCI show consistent memorability for specific items, while other items show significant diagnosticity. Certain stimulus features could optimize diagnostic assessment, while others could support memory.
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http://dx.doi.org/10.1016/j.dadm.2019.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732671PMC
December 2019

[Innovation in diagnostics-mobile technologies].

Nervenarzt 2019 Sep;90(9):914-920

Institut für Kognitive Neurologie und Demenzforschung (IKND), Magdeburg, Deutschland.

Background: Progressive cognitive deficits are the main clinical symptom of Alzheimer's disease; however, the precise recording of cognitive deficits and assessment of their progression pose major problems in patient care and early interventions.

Objective: Which problems for care and early intervention result from the current practice of cognitive assessment of patients with memory problems and which opportunities arise from the use of mobile apps?

Material And Methods: Evaluation of current care structures, discussion of basic work, expert recommendations and current developments.

Results: The current practice of the pencil and paper-based diagnostics of cognitive deficits, which is temporally and spatially bound to a clinical environment, constrains the feasibility, validity and reliability of cognitive assessment and the quantification of progression. This limits the meaningful use of further diagnostic measures, such as magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analyses. Recent progress in mobile app-based technologies, illustrated here with the example of the neotiv app, can help to overcome these problems.

Conclusion: Mobile app-based technologies can help to improve the cognitive assessment of patients with the main symptom of memory complaints. They can reduce overuse and underuse of diagnostic and therapeutic pathways and enable a targeted and meaningful use of advanced diagnostics. In addition, they can structure risk-modifying preventive measures, identify iatrogenic impairment of cognition and in this respect also strengthen patient competence.
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http://dx.doi.org/10.1007/s00115-019-0773-8DOI Listing
September 2019

Holistic Recollection via Pattern Completion Involves Hippocampal Subfield CA3.

J Neurosci 2019 10 12;39(41):8100-8111. Epub 2019 Aug 12.

Institute of Cognitive Neuroscience, University College London, London WC1N 3AZ, United Kingdom.

Episodic memories typically comprise multiple elements. A defining characteristic of episodic retrieval is holistic recollection, i.e., comprehensive recall of the elements a memorized event encompasses. A recent study implicated activity in the human hippocampus with holistic recollection of multi-element events based on cues (Horner et al., 2015). Here, we obtained ultra-high resolution functional neuroimaging data at 7 tesla in 30 younger adults (12 female) using the same paradigm. In accordance with anatomically inspired computational models and animal research, we found that metabolic activity in hippocampal subfield CA3 (but less pronounced in dentate gyrus) correlated with this form of mnemonic pattern completion across participants. Our study provides the first evidence in humans for a strong involvement of hippocampal subfield CA3 in holistic recollection via pattern completion. Memories of daily events usually involve multiple elements, although a single element can be sufficient to prompt recollection of the whole event. Such holistic recollection is thought to require reactivation of brain activity representing the full event from one event element ("pattern completion"). Computational and animal models suggest that mnemonic pattern completion is accomplished in a specific subregion of the hippocampus called CA3, but empirical evidence in humans was lacking. Here, we leverage the ultra-high resolution of 7 tesla neuroimaging to provide first evidence for a strong involvement of the human CA3 in holistic recollection of multi-element events via pattern completion.
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http://dx.doi.org/10.1523/JNEUROSCI.0722-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786823PMC
October 2019

European Ultrahigh-Field Imaging Network for Neurodegenerative Diseases (EUFIND).

Alzheimers Dement (Amst) 2019 Dec 31;11:538-549. Epub 2019 Jul 31.

German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Magdeburg, Germany.

Introduction: The goal of European Ultrahigh-Field Imaging Network in Neurodegenerative Diseases (EUFIND) is to identify opportunities and challenges of 7 Tesla (7T) MRI for clinical and research applications in neurodegeneration. EUFIND comprises 22 European and one US site, including over 50 MRI and dementia experts as well as neuroscientists.

Methods: EUFIND combined consensus workshops and data sharing for multisite analysis, focusing on 7 core topics: clinical applications/clinical research, highest resolution anatomy, functional imaging, vascular systems/vascular pathology, iron mapping and neuropathology detection, spectroscopy, and quality assurance. Across these topics, EUFIND considered standard operating procedures, safety, and multivendor harmonization.

Results: The clinical and research opportunities and challenges of 7T MRI in each subtopic are set out as a roadmap. Specific MRI sequences for each subtopic were implemented in a pilot study presented in this report. Results show that a large multisite 7T imaging network with highly advanced and harmonized imaging sequences is feasible and may enable future multicentre ultrahigh-field MRI studies and clinical trials.

Discussion: The EUFIND network can be a major driver for advancing clinical neuroimaging research using 7T and for identifying use-cases for clinical applications in neurodegeneration.
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http://dx.doi.org/10.1016/j.dadm.2019.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675944PMC
December 2019

Which features of subjective cognitive decline are related to amyloid pathology? Findings from the DELCODE study.

Alzheimers Res Ther 2019 07 31;11(1):66. Epub 2019 Jul 31.

German Center for Neurodegenerative Diseases/Clinical Research, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE), Zentrum für klinische Forschung/AG Neuropsychologie, Sigmund-Freud-Str. 27, 53127, Bonn, Germany.

Background: Subjective cognitive decline (SCD) has been proposed as a pre-MCI at-risk condition of Alzheimer's disease (AD). Current research is focusing on a refined assessment of specific SCD features associated with increased risk for AD, as proposed in the SCD-plus criteria. We developed a structured interview (SCD-I) for the assessment of these features and tested their relationship with AD biomarkers.

Methods: We analyzed data of 205 cognitively normal participants of the DELCODE study (mean age = 68.9 years; 52% female) with available CSF AD biomarkers (Aß-42, p-Tau181, Aß-42/Tau ratio, total Tau). For each of five cognitive domains (including memory, language, attention, planning, others), a study physician asked participants about the following SCD-plus features: the presence of subjective decline, associated worries, onset of SCD, feeling of worse performance than others of the same age group, and informant confirmation. We compared AD biomarkers of subjects endorsing each of these questions with those who did not, controlling for age. SCD was also quantified by two summary scores: the number of fulfilled SCD-plus features, and the number of domains with experienced decline. Covariate-adjusted linear regression analyses were used to test whether these SCD scores predicted abnormality in AD biomarkers.

Results: Lower Aß-42 levels were associated with a reported decline in memory and language abilities, and with the following SCD-plus features: onset of subjective decline within 5 years, confirmation of cognitive decline by an informant, and decline-related worries. Furthermore, both quantitative SCD scores were associated with lower Aß42 and lower Aß42/Tau ratio, but not with total Tau or p-Tau181.

Conclusions: Findings support the usefulness of a criterion-based interview approach to assess and quantify SCD in the context of AD and validate the current SCD-plus features as predictors of AD pathology. While some features seem to be more closely associated with AD biomarkers than others, aggregated scores over several SCD-plus features or SCD domains may be the best predictors of AD pathology.
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http://dx.doi.org/10.1186/s13195-019-0515-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668160PMC
July 2019