Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation

Niklas Vockert; Judith Machts; Luca Kleineidam; Aditya Nemali; Enise I Incesoy; Jose Bernal; Hartmut Schütze; Renat Yakupov; Oliver Peters; Daria Gref; Luisa Sophie Schneider; Lukas Preis; Josef Priller; Eike Jakob Spruth; Slawek Altenstein; Anja Schneider; Klaus Fliessbach; Jens Wiltfang; Ayda Rostamzadeh; Wenzel Glanz; Stefan Teipel; Ingo Kilimann; Doreen Goerss; Christoph Laske; Matthias H Munk; Annika Spottke; Nina Roy; Michael T Heneka; Frederic Brosseron; Michael Wagner; Steffen Wolfsgruber; Laura Dobisch; Peter Dechent; Stefan Hetzer; Klaus Scheffler; Peter Zeidman; Yaakov Stern; Björn H Schott; Frank Jessen; Emrah Düzel; Anne Maass; Gabriel Ziegler; DELCODE study group

doi:10.1038/s41467-024-53360-9

Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation

Niklas Vockert^*, Judith Machts, Luca Kleineidam, Aditya Nemali, Enise I Incesoy, Jose Bernal, Hartmut Schütze, Renat Yakupov, Oliver Peters, Daria Gref, Luisa Sophie Schneider, Lukas Preis, Josef Priller, Eike Jakob Spruth, Slawek Altenstein, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Ayda Rostamzadeh, Wenzel GlanzStefan Teipel, Ingo Kilimann, Doreen Goerss, Christoph Laske, Matthias H Munk, Annika Spottke, Nina Roy, Michael T Heneka, Frederic Brosseron, Michael Wagner, Steffen Wolfsgruber, Laura Dobisch, Peter Dechent, Stefan Hetzer, Klaus Scheffler, Peter Zeidman, Yaakov Stern, Björn H Schott, Frank Jessen, Emrah Düzel, Anne Maass^*, Gabriel Ziegler^*, DELCODE study group

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis, we identify a CR-related activity pattern underlying successful memory encoding that moderates the detrimental effect of AD pathological load on cognitive performance. CR is mainly represented by a more pronounced expression of the task-active network encompassing deactivation of the default mode network (DMN) and activation of inferior temporal regions including the fusiform gyrus. We devise personalized fMRI-based CR scores that moderate the impact of AD pathology on cognitive performance and are positively associated with years of education. Furthermore, higher CR scores attenuate the effect of AD pathology on cognitive decline over time. Our findings primarily provide evidence for the maintenance of core cognitive circuits including the DMN as the neural basis of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.

Original language	English
Pages (from-to)	9815
Journal	Nature Communications
Volume	15
Issue number	1
Early online date	13 Nov 2024
DOIs	https://doi.org/10.1038/s41467-024-53360-9
Publication status	E-pub ahead of print - 13 Nov 2024

Keywords / Materials (for Non-textual outputs)

Humans
Alzheimer Disease/physiopathology
Cognitive Reserve/physiology
Male
Female
Magnetic Resonance Imaging
Aged
Brain/diagnostic imaging
Memory/physiology
Cognitive Dysfunction/physiopathology
Aged, 80 and over
Middle Aged
Longitudinal Studies
Brain Mapping
Cognition/physiology
Neuropsychological Tests

Access to Document

10.1038/s41467-024-53360-9

s41467-024-53360-9Final published version, 5.55 MBLicence: Creative Commons: Attribution (CC-BY)

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Vockert, N., Machts, J., Kleineidam, L., Nemali, A., Incesoy, E. I., Bernal, J., Schütze, H., Yakupov, R., Peters, O., Gref, D., Schneider, L. S., Preis, L., Priller, J., Spruth, E. J., Altenstein, S., Schneider, A., Fliessbach, K., Wiltfang, J., Rostamzadeh, A., ... DELCODE study group (2024). Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation. Nature Communications, 15(1), 9815. Advance online publication. https://doi.org/10.1038/s41467-024-53360-9

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title = "Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation",

abstract = "The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis, we identify a CR-related activity pattern underlying successful memory encoding that moderates the detrimental effect of AD pathological load on cognitive performance. CR is mainly represented by a more pronounced expression of the task-active network encompassing deactivation of the default mode network (DMN) and activation of inferior temporal regions including the fusiform gyrus. We devise personalized fMRI-based CR scores that moderate the impact of AD pathology on cognitive performance and are positively associated with years of education. Furthermore, higher CR scores attenuate the effect of AD pathology on cognitive decline over time. Our findings primarily provide evidence for the maintenance of core cognitive circuits including the DMN as the neural basis of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.",

keywords = "Humans, Alzheimer Disease/physiopathology, Cognitive Reserve/physiology, Male, Female, Magnetic Resonance Imaging, Aged, Brain/diagnostic imaging, Memory/physiology, Cognitive Dysfunction/physiopathology, Aged, 80 and over, Middle Aged, Longitudinal Studies, Brain Mapping, Cognition/physiology, Neuropsychological Tests",

author = "Niklas Vockert and Judith Machts and Luca Kleineidam and Aditya Nemali and Incesoy, {Enise I} and Jose Bernal and Hartmut Sch{\"u}tze and Renat Yakupov and Oliver Peters and Daria Gref and Schneider, {Luisa Sophie} and Lukas Preis and Josef Priller and Spruth, {Eike Jakob} and Slawek Altenstein and Anja Schneider and Klaus Fliessbach and Jens Wiltfang and Ayda Rostamzadeh and Wenzel Glanz and Stefan Teipel and Ingo Kilimann and Doreen Goerss and Christoph Laske and Munk, {Matthias H} and Annika Spottke and Nina Roy and Heneka, {Michael T} and Frederic Brosseron and Michael Wagner and Steffen Wolfsgruber and Laura Dobisch and Peter Dechent and Stefan Hetzer and Klaus Scheffler and Peter Zeidman and Yaakov Stern and Schott, {Bj{\"o}rn H} and Frank Jessen and Emrah D{\"u}zel and Anne Maass and Gabriel Ziegler and {DELCODE study group}",

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doi = "10.1038/s41467-024-53360-9",

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Vockert, N, Machts, J, Kleineidam, L, Nemali, A, Incesoy, EI, Bernal, J, Schütze, H, Yakupov, R, Peters, O, Gref, D, Schneider, LS, Preis, L, Priller, J, Spruth, EJ, Altenstein, S, Schneider, A, Fliessbach, K, Wiltfang, J, Rostamzadeh, A, Glanz, W, Teipel, S, Kilimann, I, Goerss, D, Laske, C, Munk, MH, Spottke, A, Roy, N, Heneka, MT, Brosseron, F, Wagner, M, Wolfsgruber, S, Dobisch, L, Dechent, P, Hetzer, S, Scheffler, K, Zeidman, P, Stern, Y, Schott, BH, Jessen, F, Düzel, E, Maass, A, Ziegler, G & DELCODE study group 2024, 'Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation', Nature Communications, vol. 15, no. 1, pp. 9815. https://doi.org/10.1038/s41467-024-53360-9

TY - JOUR

T1 - Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation

AU - Vockert, Niklas

AU - Machts, Judith

AU - Kleineidam, Luca

AU - Nemali, Aditya

AU - Incesoy, Enise I

AU - Bernal, Jose

AU - Schütze, Hartmut

AU - Yakupov, Renat

AU - Peters, Oliver

AU - Gref, Daria

AU - Schneider, Luisa Sophie

AU - Preis, Lukas

AU - Priller, Josef

AU - Spruth, Eike Jakob

AU - Altenstein, Slawek

AU - Schneider, Anja

AU - Fliessbach, Klaus

AU - Wiltfang, Jens

AU - Rostamzadeh, Ayda

AU - Glanz, Wenzel

AU - Teipel, Stefan

AU - Kilimann, Ingo

AU - Goerss, Doreen

AU - Laske, Christoph

AU - Munk, Matthias H

AU - Spottke, Annika

AU - Roy, Nina

AU - Heneka, Michael T

AU - Brosseron, Frederic

AU - Wagner, Michael

AU - Wolfsgruber, Steffen

AU - Dobisch, Laura

AU - Dechent, Peter

AU - Hetzer, Stefan

AU - Scheffler, Klaus

AU - Zeidman, Peter

AU - Stern, Yaakov

AU - Schott, Björn H

AU - Jessen, Frank

AU - Düzel, Emrah

AU - Maass, Anne

AU - Ziegler, Gabriel

AU - DELCODE study group

PY - 2024/11/13

Y1 - 2024/11/13

N2 - The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis, we identify a CR-related activity pattern underlying successful memory encoding that moderates the detrimental effect of AD pathological load on cognitive performance. CR is mainly represented by a more pronounced expression of the task-active network encompassing deactivation of the default mode network (DMN) and activation of inferior temporal regions including the fusiform gyrus. We devise personalized fMRI-based CR scores that moderate the impact of AD pathology on cognitive performance and are positively associated with years of education. Furthermore, higher CR scores attenuate the effect of AD pathology on cognitive decline over time. Our findings primarily provide evidence for the maintenance of core cognitive circuits including the DMN as the neural basis of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.

AB - The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis, we identify a CR-related activity pattern underlying successful memory encoding that moderates the detrimental effect of AD pathological load on cognitive performance. CR is mainly represented by a more pronounced expression of the task-active network encompassing deactivation of the default mode network (DMN) and activation of inferior temporal regions including the fusiform gyrus. We devise personalized fMRI-based CR scores that moderate the impact of AD pathology on cognitive performance and are positively associated with years of education. Furthermore, higher CR scores attenuate the effect of AD pathology on cognitive decline over time. Our findings primarily provide evidence for the maintenance of core cognitive circuits including the DMN as the neural basis of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.

KW - Humans

KW - Alzheimer Disease/physiopathology

KW - Cognitive Reserve/physiology

KW - Male

KW - Female

KW - Magnetic Resonance Imaging

KW - Aged

KW - Brain/diagnostic imaging

KW - Memory/physiology

KW - Cognitive Dysfunction/physiopathology

KW - Aged, 80 and over

KW - Middle Aged

KW - Longitudinal Studies

KW - Brain Mapping

KW - Cognition/physiology

KW - Neuropsychological Tests

U2 - 10.1038/s41467-024-53360-9

DO - 10.1038/s41467-024-53360-9

M3 - Article

C2 - 39537609

SN - 2041-1723

VL - 15

SP - 9815

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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