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@ARTICLE{Billette:165172,
author = {Billette, Ornella V and Ziegler, Gabriel and Aruci, Merita
and Schütze, Hartmut and Kizilirmak, Jasmin M and Richter,
Anni and Altenstein, Slawek and Bartels, Claudia and
Brosseron, Frederic and Cardenas-Blanco, Arturo and Dahmen,
Philip and Dechent, Peter and Dobisch, Laura and Fliessbach,
Klaus and Freiesleben, Silka Dawn and Glanz, Wenzel and
Göerß, Doreen and Haynes, John Dylan and Heneka, Michael T
and Kilimann, Ingo and Kimmich, Okka and Kleineidam, Luca
and Laske, Christoph and Lohse, Andrea and Rostamzadeh, Ayda
and Metzger, Coraline and Munk, Matthias H and Peters,
Oliver and Preis, Lukas and Priller, Josef and Scheffler,
Klaus and Schneider, Anja and Spottke, Annika and Spruth,
Eike Jakob and Ramirez, Alfredo and Röske, Sandra and Roy,
Nina and Teipel, Stefan and Wagner, Michael and Wiltfang,
Jens and Wolfsgruber, Steffen and Yakupov, Renat and
Zeidman, Peter and Jessen, Frank and Schott, Björn and
Düzel, Emrah and Maass, Anne},
collaboration = {Group, DELCODE Study},
title = {{N}ovelty-{R}elated f{MRI} {R}esponses of {P}recuneus and
{M}edial {T}emporal {R}egions in {I}ndividuals at {R}isk for
{A}lzheimer {D}isease.},
journal = {Neurology},
volume = {99},
number = {8},
issn = {0028-3878},
address = {[S.l.]},
publisher = {Ovid},
reportid = {DZNE-2022-01474},
pages = {e775 - e788},
year = {2022},
abstract = {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.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.},
keywords = {Alzheimer Disease: diagnosis / Amyloid beta-Peptides /
Biomarkers / Cognitive Dysfunction: diagnostic imaging /
Humans / Magnetic Resonance Imaging: methods / Parietal
Lobe: diagnostic imaging / Temporal Lobe: diagnostic imaging
/ Amyloid beta-Peptides (NLM Chemicals) / Biomarkers (NLM
Chemicals)},
cin = {AG Maaß / AG Düzel / AG Wiltfang / AG Endres / Biomarker
/ AG Speck / AG Peters / Patient Studies Bonn / KAP / AG
Teipel / AG Gasser / AG Priller / AG Wagner / Clinical
Research Platform (CRP) / AG Klockgether / AG Schneider / AG
Jessen / AG Fischer / Delcode},
ddc = {610},
cid = {I:(DE-2719)1311001 / I:(DE-2719)5000006 /
I:(DE-2719)1410006 / I:(DE-2719)1811005 / I:(DE-2719)1011301
/ I:(DE-2719)1340009 / I:(DE-2719)5000000 /
I:(DE-2719)1011101 / I:(DE-2719)1340013 / I:(DE-2719)1510100
/ I:(DE-2719)1210000 / I:(DE-2719)5000007 /
I:(DE-2719)1011201 / I:(DE-2719)1011401 / I:(DE-2719)1011001
/ I:(DE-2719)1011305 / I:(DE-2719)1011102 /
I:(DE-2719)1410002 / I:(DE-2719)5000034},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
experiment = {EXP:(DE-2719)DELCODE-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35995589},
pmc = {pmc:PMC9484732},
doi = {10.1212/WNL.0000000000200667},
url = {https://pub.dzne.de/record/165172},
}