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  • Baumeister, HannahGerman Center for Neurodegenerative Diseases (DZNE) Magdeburg (author)

A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings

  • Article/chapterEnglish

Publisher, publication year, extent ...

  • 14 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:1364b7bb-4325-4125-b650-c0b242a2e27d
  • https://lup.lub.lu.se/record/1364b7bb-4325-4125-b650-c0b242a2e27dURI
  • https://doi.org/10.1093/brain/awae118DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Vogel, Jacob WLund 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(Swepub:lu)ja8870vo (author)
  • Insel, Philip SUniversity of California, San Francisco(Swepub:lu)med-ppi (author)
  • Kleineidam, LucaGerman Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Bonn (author)
  • Wolfsgruber, SteffenUniversity Hospital Bonn,German Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Stark, MelinaUniversity Hospital Bonn (author)
  • Gellersen, Helena MGerman Center for Neurodegenerative Diseases (DZNE) Magdeburg (author)
  • Yakupov, RenatOtto von Guericke University Magdeburg,German Center for Neurodegenerative Diseases (DZNE) Magdeburg (author)
  • Schmid, Matthias CUniversity Hospital Bonn,German Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Lüsebrink, FalkGerman Center for Neurodegenerative Diseases (DZNE) Magdeburg (author)
  • Brosseron, FredericGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Ziegler, GabrielOtto von Guericke University Magdeburg (author)
  • Freiesleben, Silka DGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Preis, LukasKarolinska Institute (author)
  • Schneider, Luisa-SophieKarolinska Institute (author)
  • Spruth, Eike JGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Altenstein, SlawekGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Lohse, AndreaKarolinska Institute (author)
  • Fliessbach, KlausGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Vogt, Ina RGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Bartels, ClaudiaUniversity Medical Center Göttingen (author)
  • Schott, Björn HUniversity Medical Center Göttingen (author)
  • Rostamzadeh, AydaUniversity of Cologne (author)
  • Glanz, WenzelGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Incesoy, Enise IGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Butryn, MichaelaGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Janowitz, DanielInstitute for Stroke and Dementia Research (ISD) (author)
  • Rauchmann, Boris-StephanUniversity of Sheffield,Ludwig-Maximilian University of Munich (author)
  • Kilimann, IngoGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Goerss, DoreenGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Munk, Matthias HGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Hetzer, StefanBerlin Center for Advanced Neuroimaging (author)
  • Dechent, PeterUniversity of Göttingen (author)
  • Ewers, MichaelInstitute for Stroke and Dementia Research (ISD) (author)
  • Scheffler, KlausUniversity of Tübingen (author)
  • Wuestefeld, AnikaLund 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(Swepub:lu)an8567wu (author)
  • Strandberg, OlofLund 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(Swepub:lu)teor-osn (author)
  • van Westen, DanielleLund 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 Hospital(Swepub:lu)ront-dva (author)
  • Mattsson-Carlgren, NiklasLund 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 Hospital(Swepub:lu)med-nmn (author)
  • Janelidze, ShorenaLund 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(Swepub:lu)nkir-sje (author)
  • Stomrud, ErikLund 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 Hospital(Swepub:lu)med-esr (author)
  • Palmqvist, SebastianLund 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 Hospital(Swepub:lu)med-spa (author)
  • Spottke, AnnikaGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Laske, ChristophGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Teipel, StefanGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Perneczky, RobertLudwig-Maximilian University of Munich,German Center for Neurodegenerative Diseases (DZNE), Munich (author)
  • Buerger, KatharinaInstitute for Stroke and Dementia Research (ISD) (author)
  • Schneider, AnjaGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Priller, JosefGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Peters, OliverGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Ramirez, AlfredoGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Wiltfang, JensUniversity Medical Center Göttingen (author)
  • Heneka, Michael TUniversity of Luxembourg (author)
  • Wagner, MichaelGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Düzel, EmrahGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Jessen, FrankGerman Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Hansson, OskarLund 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 Hospital(Swepub:lu)mphy-ohn (author)
  • Berron, DavidLund 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) Magdeburg(Swepub:lu)da1401be (author)
  • German Center for Neurodegenerative Diseases (DZNE) MagdeburgInstitutionen för kliniska vetenskaper, Malmö (creator_code:org_t)

Related titles

  • In:Brain : a journal of neurology147:7, s. 2400-24131460-2156

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