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FältnamnIndikatorerMetadata
00012570naa a2201045 4500
001oai:lup.lub.lu.se:1364b7bb-4325-4125-b650-c0b242a2e27d
003SwePub
008240705| | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/1364b7bb-4325-4125-b650-c0b242a2e27d2 URI
0247 a https://doi.org/10.1093/brain/awae1182 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Baumeister, Hannahu German Center for Neurodegenerative Diseases (DZNE) Magdeburg4 aut0 (Swepub:lu)ha1752ba
2451 0a A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings
300 a 14 s.
520 a Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± SD age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (CU; n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (SCD; n = 342), mild cognitive impairment (MCI; n = 118), or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid AD biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5), as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test if baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and MCI conversion rates of CU and SCD participants. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy first affected the medial temporal lobes, followed by further temporal and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological AD biomarker levels, APOE ε4 carriership, and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive AD biomarkers and was associated with more generalised cognitive impairment. Limbic-predominant atrophy, in all and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of MCI conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, both on the subject and group level, were excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for AD in applied settings. The implementation of atrophy subtype- and stage-specific end-points may increase the statistical power of pharmacological trials targeting early AD.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng
653 a disease heterogeneity
653 a Alzeimer's disease
653 a Structural MRI
653 a executive function
653 a episodic memory
7001 a Vogel, Jacob Wu Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups4 aut0 (Swepub:lu)ja8870vo
7001 a Insel, Philip Su University of California, San Francisco4 aut0 (Swepub:lu)med-ppi
7001 a Kleineidam, Lucau German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Bonn4 aut
7001 a Wolfsgruber, Steffenu University Hospital Bonn,German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Stark, Melinau University Hospital Bonn4 aut
7001 a Gellersen, Helena Mu German Center for Neurodegenerative Diseases (DZNE) Magdeburg4 aut
7001 a Yakupov, Renatu Otto von Guericke University Magdeburg,German Center for Neurodegenerative Diseases (DZNE) Magdeburg4 aut
7001 a Schmid, Matthias Cu University Hospital Bonn,German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Lüsebrink, Falku German Center for Neurodegenerative Diseases (DZNE) Magdeburg4 aut
7001 a Brosseron, Fredericu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Ziegler, Gabrielu Otto von Guericke University Magdeburg4 aut
7001 a Freiesleben, Silka Du German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Preis, Lukasu Karolinska Institute4 aut
7001 a Schneider, Luisa-Sophieu Karolinska Institute4 aut
7001 a Spruth, Eike Ju German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Altenstein, Slaweku German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Lohse, Andreau Karolinska Institute4 aut
7001 a Fliessbach, Klausu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Vogt, Ina Ru German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Bartels, Claudiau University Medical Center Göttingen4 aut
7001 a Schott, Björn Hu University Medical Center Göttingen4 aut
7001 a Rostamzadeh, Aydau University of Cologne4 aut
7001 a Glanz, Wenzelu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Incesoy, Enise Iu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Butryn, Michaelau German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Janowitz, Danielu Institute for Stroke and Dementia Research (ISD)4 aut
7001 a Rauchmann, Boris-Stephanu University of Sheffield,Ludwig-Maximilian University of Munich4 aut
7001 a Kilimann, Ingou German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Goerss, Doreenu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Munk, Matthias Hu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Hetzer, Stefanu Berlin Center for Advanced Neuroimaging4 aut
7001 a Dechent, Peteru University of Göttingen4 aut
7001 a Ewers, Michaelu Institute for Stroke and Dementia Research (ISD)4 aut
7001 a Scheffler, Klausu University of Tübingen4 aut
7001 a Wuestefeld, Anikau Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups4 aut0 (Swepub:lu)an8567wu
7001 a Strandberg, Olofu Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups4 aut0 (Swepub:lu)teor-osn
7001 a van Westen, Danielleu Lund University,Lunds universitet,Diagnostisk radiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Diagnostic Radiology, (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)ront-dva
7001 a Mattsson-Carlgren, Niklasu Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Skåne University Hospital4 aut0 (Swepub:lu)med-nmn
7001 a Janelidze, Shorenau Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups4 aut0 (Swepub:lu)nkir-sje
7001 a Stomrud, Eriku Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)med-esr
7001 a Palmqvist, Sebastianu Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)med-spa
7001 a Spottke, Annikau German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Laske, Christophu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Teipel, Stefanu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Perneczky, Robertu Ludwig-Maximilian University of Munich,German Center for Neurodegenerative Diseases (DZNE), Munich4 aut
7001 a Buerger, Katharinau Institute for Stroke and Dementia Research (ISD)4 aut
7001 a Schneider, Anjau German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Priller, Josefu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Peters, Oliveru German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Ramirez, Alfredou German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Wiltfang, Jensu University Medical Center Göttingen4 aut
7001 a Heneka, Michael Tu University of Luxembourg4 aut
7001 a Wagner, Michaelu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Düzel, Emrahu German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Jessen, Franku German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Hansson, Oskaru Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)mphy-ohn
7001 a Berron, Davidu Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,Otto von Guericke University Magdeburg,German Center for Neurodegenerative Diseases (DZNE) Magdeburg4 aut0 (Swepub:lu)da1401be
7102 a German Center for Neurodegenerative Diseases (DZNE) Magdeburgb Institutionen för kliniska vetenskaper, Malmö4 org
7730 t Brain : a journal of neurologyg 147:7, s. 2400-2413q 147:7<2400-2413x 1460-2156
8564 u http://dx.doi.org/10.1093/brain/awae118x freey FULLTEXT
8564 8u https://lup.lub.lu.se/record/1364b7bb-4325-4125-b650-c0b242a2e27d
8564 8u https://doi.org/10.1093/brain/awae118

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