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@INPROCEEDINGS{Boscheck:283053,
author = {Boscheck, Hanna and Liebscher, Maxie and Delia, Ylenia and
Mauer, René and Peters, Oliver and Priller, Josef and
Schneider, Anja and Wiltfang, Jens and Buerger, Katharina
and Perneczky, Robert and Teipel, Stefan and Laske,
Christoph and Spottke, Annika and Brosseron, Frederic and
Yakupov, Renat and Ziegler, Gabriel and Kleineidam, Luca and
Jessen, Frank and Düzel, Emrah and Wagner, Michael and
Roeske, Sandra and Marchant, Natalie L and Gloeckner, Franka
and Klimecki-Lenz, Olga Maria and Wirth, Miranka},
collaboration = {group, DELCODE study},
title = {{A}ssociations of cognitive debt and cognitive reserve with
mixed brain pathology and cognition},
journal = {Alzheimer's and dementia},
volume = {21},
number = {Suppl 2},
issn = {1552-5260},
reportid = {DZNE-2025-01460},
pages = {e102595},
year = {2025},
abstract = {Behavioral risk or protective factors related to 'cognitive
debt' and 'cognitive reserve' may influence brain pathology
and cognition and thereby contribute to resilience in aging.
This cross-sectional study examined direct and indirect
associations of cognitive debt (risk factor) and cognitive
reserve (protective factor) with mixed brain pathologies and
cognition in older adults.A sample of N = 298 non-demented
older adults (mean age=70 years, $56\%$ male) from the
DELCODE study (DRKS00007966) were analyzed using structural
equation modeling (SEM) and an a-priori path model. We
assessed the association between cognitive debt and
cognitive reserve (modelled as latent constructs) and global
cognition (Preclinical Alzheimer Cognitive Composite 5
[PACC5] modelled as latent construct) through pathological
pathways involving beta-amyloid (Aß) burden, hippocampal
neurodegeneration, and white matter hyperintensities (WMH)
in the corpus callosum splenium (CCs), while adjusting for
age. A goodness-of-fit analysis ensured adequate model
fit.Brain pathology was associated with lower PACC5
performance via direct pathways (for WMH in the CCs and
hippocampal neurodegeneration) and indirect pathways (for
Aß deposition via hippocampal neurodegeneration) (all p <
.05). Cognitive debt and cognitive reserve were not
significantly associated with brain pathology (all p > .05).
Cognitive reserve, but not cognitive debt, was independently
associated with better PACC5 performance (p = .005).
Cognitive debt and cognitive reserve were associated at
trend level (p = .068). Results are displayed in Figure
1.Brain pathologies were linked to lower cognitive
performance. Cognitive reserve, but not cognitive debt, was
independently associated with better cognitive performance
(1). There were no significant associations of cognitive
debt and cognitive reserve with brain pathologies. The
findings suggest that cognitive reserve may influence
resilience through mechanisms independent of brain pathology
(2). Future longitudinal studies are needed to investigate
these pathways and clarify causal relationships. References
1. Vemuri P, Weigand SD, Przybelski SA, Knopman DS, Smith
GE, Trojanowski JQ, et al. Cognitive reserve and Alzheimer's
disease biomarkers are independent determinants of
cognition. Brain. 2011;134(Pt 5):1479-92. 2. Vemuri P,
Lesnick TG, Przybelski SA, Knopman DS, Roberts RO, Lowe VJ,
et al. Effect of lifestyle activities on Alzheimer disease
biomarkers and cognition. Ann Neurol. 2012;72(5):730-8.},
month = {Jul},
date = {2025-07-27},
organization = {Alzheimer’s Association
International Conference, Toronto
(Canada), 27 Jul 2025 - 31 Jul 2025},
keywords = {Humans / Male / Aged / Female / Cross-Sectional Studies /
Biomarkers / Cognitive Reserve: physiology / Brain:
pathology / Amyloid beta-Peptides: metabolism /
Neuropsychological Tests / Magnetic Resonance Imaging /
Alzheimer Disease / White Matter: pathology / Hippocampus:
pathology / Aged, 80 and over / Biomarkers (NLM Chemicals) /
Amyloid beta-Peptides (NLM Chemicals)},
cin = {AG Wirth / AG Peters / AG Priller / AG Wiltfang / Clinical
Research (Munich) / AG Dichgans / AG Teipel / AG Gasser / AG
Spottke / AG Heneka / AG Düzel / AG Jessen / AG Wagner},
ddc = {610},
cid = {I:(DE-2719)1710011 / I:(DE-2719)5000000 /
I:(DE-2719)5000007 / I:(DE-2719)1410006 / I:(DE-2719)1111015
/ I:(DE-2719)5000022 / I:(DE-2719)1510100 /
I:(DE-2719)1210000 / I:(DE-2719)1011103 / I:(DE-2719)1011303
/ I:(DE-2719)5000006 / I:(DE-2719)1011102 /
I:(DE-2719)1011201},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
experiment = {EXP:(DE-2719)DELCODE-20140101},
typ = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
pubmed = {pmid:41450093},
pmc = {pmc:PMC12741494},
doi = {10.1002/alz70856_102595},
url = {https://pub.dzne.de/record/283053},
}