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000165172 0247_ $$2doi$$a10.1212/WNL.0000000000200667
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000165172 041__ $$aEnglish
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000165172 1001_ $$0P:(DE-2719)2810799$$aBillette, Ornella V$$b0$$eFirst author$$udzne
000165172 245__ $$aNovelty-Related fMRI Responses of Precuneus and Medial Temporal Regions in Individuals at Risk for Alzheimer Disease.
000165172 260__ $$a[S.l.]$$bOvid$$c2022
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000165172 520__ $$aWe 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.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 β-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.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.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.
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000165172 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000165172 650_7 $$2NLM Chemicals$$aBiomarkers
000165172 650_2 $$2MeSH$$aAlzheimer Disease: diagnosis
000165172 650_2 $$2MeSH$$aAmyloid beta-Peptides
000165172 650_2 $$2MeSH$$aBiomarkers
000165172 650_2 $$2MeSH$$aCognitive Dysfunction: diagnostic imaging
000165172 650_2 $$2MeSH$$aHumans
000165172 650_2 $$2MeSH$$aMagnetic Resonance Imaging: methods
000165172 650_2 $$2MeSH$$aParietal Lobe: diagnostic imaging
000165172 650_2 $$2MeSH$$aTemporal Lobe: diagnostic imaging
000165172 693__ $$0EXP:(DE-2719)DELCODE-20140101$$5EXP:(DE-2719)DELCODE-20140101$$eLongitudinal Cognitive Impairment and Dementia Study$$x0
000165172 7001_ $$0P:(DE-2719)2814076$$aZiegler, Gabriel$$b1$$udzne
000165172 7001_ $$aAruci, Merita$$b2
000165172 7001_ $$0P:(DE-2719)9001467$$aSchütze, Hartmut$$b3$$udzne
000165172 7001_ $$0P:(DE-2719)9000615$$aKizilirmak, Jasmin M$$b4$$udzne
000165172 7001_ $$00000-0001-9681-6298$$aRichter, Anni$$b5
000165172 7001_ $$0P:(DE-2719)2811720$$aAltenstein, Slawek$$b6$$udzne
000165172 7001_ $$0P:(DE-2719)9000444$$aBartels, Claudia$$b7$$udzne
000165172 7001_ $$0P:(DE-2719)2810593$$aBrosseron, Frederic$$b8$$udzne
000165172 7001_ $$0P:(DE-2719)2810750$$aCardenas-Blanco, Arturo$$b9$$udzne
000165172 7001_ $$0P:(DE-2719)9001698$$aDahmen, Philip$$b10$$udzne
000165172 7001_ $$aDechent, Peter$$b11
000165172 7001_ $$0P:(DE-2719)2811611$$aDobisch, Laura$$b12$$udzne
000165172 7001_ $$0P:(DE-2719)2811326$$aFliessbach, Klaus$$b13$$udzne
000165172 7001_ $$0P:(DE-2719)2812392$$aFreiesleben, Silka Dawn$$b14$$udzne
000165172 7001_ $$0P:(DE-2719)2811614$$aGlanz, Wenzel$$b15$$udzne
000165172 7001_ $$aGöerß, Doreen$$b16
000165172 7001_ $$aHaynes, John Dylan$$b17
000165172 7001_ $$0P:(DE-2719)2000008$$aHeneka, Michael T$$b18$$udzne
000165172 7001_ $$0P:(DE-2719)2810394$$aKilimann, Ingo$$b19$$udzne
000165172 7001_ $$aKimmich, Okka$$b20
000165172 7001_ $$0P:(DE-2719)2812139$$aKleineidam, Luca$$b21$$udzne
000165172 7001_ $$0P:(DE-2719)2000055$$aLaske, Christoph$$b22$$udzne
000165172 7001_ $$0P:(DE-2719)2811189$$aLohse, Andrea$$b23$$udzne
000165172 7001_ $$aRostamzadeh, Ayda$$b24
000165172 7001_ $$0P:(DE-2719)9000443$$aMetzger, Coraline$$b25$$udzne
000165172 7001_ $$0P:(DE-2719)9001516$$aMunk, Matthias H$$b26$$udzne
000165172 7001_ $$0P:(DE-2719)2811024$$aPeters, Oliver$$b27$$udzne
000165172 7001_ $$0P:(DE-2719)9000703$$aPreis, Lukas$$b28$$udzne
000165172 7001_ $$0P:(DE-2719)2811122$$aPriller, Josef$$b29$$udzne
000165172 7001_ $$00000-0001-6316-8773$$aScheffler, Klaus$$b30
000165172 7001_ $$0P:(DE-2719)2812035$$aSchneider, Anja$$b31$$udzne
000165172 7001_ $$0P:(DE-2719)2811324$$aSpottke, Annika$$b32$$udzne
000165172 7001_ $$0P:(DE-2719)2812446$$aSpruth, Eike Jakob$$b33$$udzne
000165172 7001_ $$0P:(DE-2719)2812825$$aRamirez, Alfredo$$b34$$udzne
000165172 7001_ $$0P:(DE-2719)2810395$$aRöske, Sandra$$b35$$udzne
000165172 7001_ $$0P:(DE-2719)2812341$$aRoy, Nina$$b36$$udzne
000165172 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan$$b37$$udzne
000165172 7001_ $$0P:(DE-2719)2000057$$aWagner, Michael$$b38$$udzne
000165172 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b39$$udzne
000165172 7001_ $$0P:(DE-2719)2810544$$aWolfsgruber, Steffen$$b40$$udzne
000165172 7001_ $$0P:(DE-2719)2812398$$aYakupov, Renat$$b41$$udzne
000165172 7001_ $$aZeidman, Peter$$b42
000165172 7001_ $$0P:(DE-2719)2000032$$aJessen, Frank$$b43$$udzne
000165172 7001_ $$0P:(DE-2719)2814326$$aSchott, Björn$$b44$$udzne
000165172 7001_ $$0P:(DE-2719)2000005$$aDüzel, Emrah$$b45$$udzne
000165172 7001_ $$0P:(DE-2719)2811815$$aMaass, Anne$$b46$$eLast author$$udzne
000165172 7001_ $$aGroup, DELCODE Study$$b47$$eCollaboration Author
000165172 773__ $$0PERI:(DE-600)1491874-2$$a10.1212/WNL.0000000000200667$$gVol. 99, no. 8, p. e775 - e788$$n8$$pe775 - e788$$tNeurology$$v99$$x0028-3878$$y2022
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