Billette, Ornella, V, Ziegler, Gabriel, Aruci, Merita, Schuetze, Hartmut, Kizilirmak, Jasmin M., Richter, Anni ORCID: 0000-0001-9681-6298, Altenstein, Slawek ORCID: 0000-0003-2753-5999, Bartels, Claudia, Brosseron, Frederic ORCID: 0000-0003-3137-7516, Cardenas-Blanco, Arturo, Dahmen, Philip, Dechent, Peter, Dobisch, Laura, Fliessbach, Klaus, Freiesleben, Silka Dawn, Glanz, Wenzel, Goeerss, Doreen, Haynes, John Dylan, Heneka, Michael T., Kilimann, Ingo, Kimmich, Okka, Kleineidam, Luca, Laske, Christoph, Lohse, Andrea, Rostamzadeh, Ayda ORCID: 0000-0001-5189-134X, Metzger, Coraline, Munk, Matthias H., Peters, Oliver ORCID: 0000-0003-0568-2998, Preis, Lukas ORCID: 0000-0001-7601-6410, Priller, Josef, Scheffler, Klaus, Schneider, Anja ORCID: 0000-0001-9540-8700, Spottke, Annika, Spruth, Eike Jakob, Ramirez, Alfredo ORCID: 0000-0003-4991-763X, Roeske, Sandra, Roy, Nina, Teipel, Stefan, Wagner, Michael, Wiltfang, Jens, Wolfsgruber, Steffen, Yakupov, Renat, Zeidman, Peter ORCID: 0000-0003-3610-6619, Jessen, Frank, Schott, Bjorn H., Duezel, Emrah and Maass, Anne (2022). Novelty-Related fMRI Responses of Precuneus and Medial Temporal Regions in Individuals at Risk for Alzheimer Disease. Neurology, 99 (8). S. E775 - 14. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1526-632X

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Abstract

Background and Objectives We assessed whether novelty-related fMRI activity in medial temporal lobe regions and the precuneus follows an inverted U-shaped pattern across the clinical spectrum of increased Alzheimer disease (AD) risk as previously suggested. Specifically, we tested for potentially increased activity in individuals with a higher AD risk due to subjective cognitive decline (SCD) or mild cognitive impairment (MCI). We further tested whether activity differences related to diagnostic groups were accounted for by CSF markers of AD or brain atrophy. Methods We studied 499 participants aged 60-88 years from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE) who underwent task-fMRI. Participants included 163 cognitively normal (healthy control, HC) individuals, 222 SCD, 82 MCI, and 32 patients with clinical diagnosis of mild AD. CSF levels of beta-amyloid 42/40 ratio and phosphorylated-tau181 were available from 232 participants. We used region-based analyses to assess novelty-related activity (novel > highly familiar scenes) in entorhinal cortex, hippocampus, and precuneus as well as whole-brain voxel-wise analyses. First, general linear models tested differences in fMRI activity between participant groups. Complementary regression models tested quadratic relationships between memory impairment and activity. Second, relationships of activity with AD CSF biomarkers and brain volume were analyzed. Analyses were controlled for age, sex, study site, and education. Results In the precuneus, we observed an inverted U-shaped pattern of novelty-related activity across groups, with higher activity in SCD and MCI compared with HC, but not in patients with AD who showed relatively lower activity than MCI. This nonlinear pattern was confirmed by a quadratic relationship between memory impairment and precuneus activity. Precuneus activity was not related to AD biomarkers or brain volume. In contrast to the precuneus, hippocampal activity was reduced in AD dementia compared with all other groups and related to AD biomarkers. Discussion Novelty-related activity in the precuneus follows a nonlinear pattern across the clinical spectrum of increased AD risk. Although the underlying mechanism remains unclear, increased precuneus activity might represent an early signature of memory impairment. Our results highlight the nonlinearity of activity alterations that should be considered in clinical trials using functional outcome measures or targeting hyperactivity.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Billette, Ornella, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziegler, GabrielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aruci, MeritaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuetze, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kizilirmak, Jasmin M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richter, AnniUNSPECIFIEDorcid.org/0000-0001-9681-6298UNSPECIFIED
Altenstein, SlawekUNSPECIFIEDorcid.org/0000-0003-2753-5999UNSPECIFIED
Bartels, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brosseron, FredericUNSPECIFIEDorcid.org/0000-0003-3137-7516UNSPECIFIED
Cardenas-Blanco, ArturoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dahmen, PhilipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dechent, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dobisch, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fliessbach, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freiesleben, Silka DawnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glanz, WenzelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goeerss, DoreenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haynes, John DylanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heneka, Michael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilimann, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kimmich, OkkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kleineidam, LucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laske, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lohse, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rostamzadeh, AydaUNSPECIFIEDorcid.org/0000-0001-5189-134XUNSPECIFIED
Metzger, CoralineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munk, Matthias H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, OliverUNSPECIFIEDorcid.org/0000-0003-0568-2998UNSPECIFIED
Preis, LukasUNSPECIFIEDorcid.org/0000-0001-7601-6410UNSPECIFIED
Priller, JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheffler, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, AnjaUNSPECIFIEDorcid.org/0000-0001-9540-8700UNSPECIFIED
Spottke, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spruth, Eike JakobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
Roeske, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roy, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teipel, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiltfang, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolfsgruber, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yakupov, RenatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeidman, PeterUNSPECIFIEDorcid.org/0000-0003-3610-6619UNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schott, Bjorn H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duezel, EmrahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maass, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-694629
DOI: 10.1212/WNL.0000000000200667
Journal or Publication Title: Neurology
Volume: 99
Number: 8
Page Range: S. E775 - 14
Date: 2022
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Place of Publication: PHILADELPHIA
ISSN: 1526-632X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MILD COGNITIVE IMPAIRMENT; AMYLOID DEPOSITION; DEFAULT-MODE; HIPPOCAMPAL ACTIVATION; NEURAL COMPENSATION; FUNCTIONAL MRI; OLDER-PEOPLE; MEMORY; TAU; NETWORKMultiple languages
Clinical NeurologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69462

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