Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging study

Background: Multimodal lifestyle interventions might help to maintain healthy cognition in older age and to delay onset of dementia. Here, we studied the effects of a multi-modal lifestyle-based intervention, based on the FINGER trial, on magnetic resonance imaging (MRI) markers of hippocampal-limbi...

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Main Authors: Frauke Beyer, Lukas Kleine, Andrea Zülke, Melanie Luppa, Toralf Mildner, Jochen Gensichen, Thomas Frese, David Czock, Birgitt Wiese, Hans-Helmut König, Hanna Kaduszkiewicz, Wolfgang Hoffmann, Jochen René Thyrian, Arno Villringer, Steffi Riedel-Heller, A.Veronica Witte
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Language:English
Published: Elsevier 2025-01-01
Series:NeuroImage: Clinical
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Online Access:http://www.sciencedirect.com/science/article/pii/S221315822500066X
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author Frauke Beyer
Lukas Kleine
Andrea Zülke
Melanie Luppa
Toralf Mildner
Jochen Gensichen
Thomas Frese
David Czock
Birgitt Wiese
Hans-Helmut König
Hanna Kaduszkiewicz
Wolfgang Hoffmann
Jochen René Thyrian
Arno Villringer
Steffi Riedel-Heller
A.Veronica Witte
author_facet Frauke Beyer
Lukas Kleine
Andrea Zülke
Melanie Luppa
Toralf Mildner
Jochen Gensichen
Thomas Frese
David Czock
Birgitt Wiese
Hans-Helmut König
Hanna Kaduszkiewicz
Wolfgang Hoffmann
Jochen René Thyrian
Arno Villringer
Steffi Riedel-Heller
A.Veronica Witte
author_sort Frauke Beyer
collection DOAJ
description Background: Multimodal lifestyle interventions might help to maintain healthy cognition in older age and to delay onset of dementia. Here, we studied the effects of a multi-modal lifestyle-based intervention, based on the FINGER trial, on magnetic resonance imaging (MRI) markers of hippocampal-limbic atrophy and cerebral small vessel disease in older adults at increased risk for dementia in Germany. Methods: Leipzig participants of the multicenter AgeWell.de randomized controlled trial underwent neuroimaging before and after a two year intervention at 3 Tesla MRI. We extracted hippocampal volume and entorhinal cortex thickness (ECT), free water fraction (FW), peak width of skeletonized mean diffusivity (PSMD), white matter hyperintensity volume and mean gray matter cerebral blood flow and assessed the effect of the intervention on these imaging markers using linear mixed models. We also tested the effect of the intervention on the hippocampus-dependent Mnemonic Similarity Test and fixel-based white matter microstructure. Results: 56 individuals (mean (sd) age: 68.8 (4.2) years, 26 females, 24/32 intervention/control group) were included at baseline and 41 returned after an average of 28 months for the second assessment. ECT and FW exhibited stronger decline in the intervention compared to the control group in preregistered models but not when adjusted for baseline differences. All other markers progressed similarly across groups, however sample size was smaller than expected. In exploratory analyses, cerebral blood flow increased more in the intervention group and this change was associated with decreases in systolic blood pressure. Conclusions: In this group of older adults at risk for dementia, we find no conclusive evidence whether a multi-modal lifestyle intervention improves brain imaging markers of neurodegeneration and small vessel disease. Preliminary evidence suggested an association of the intervention, increased cerebral blood flow and systolic blood pressure reductions.Abbreviations: ECT, entorhinal cortex thickness; FW, free water fraction; WHO, world health organization; AD, Alzheimer’s disease; VCI, vascular cognitive impairment; FINGER, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability; MTL, medial temporal lobe; MIND, Mediterranean-DASH Intervention for Neurodegenerative Delay diet; cSVD, cerebral small vessel disease; WMH, white matter hyperintensities of presumed vascular origin; PSMD, peak width of the mean diffusivity distribution; WW-FINGERS, world wide FINGER studies; CAIDE, Cardiovascular Risk Factors, Aging, and Incidence of Dementia; GPP, general practitioner praxis; MRI, magnetic resonance imaging; MST, Mnemonic Similarity Test; TE, echo time; TR, repetition time; FA, flip angle; FOV, field of view; GRAPPA, GeneRalized Autocalibrating Partial Parallel Acquisition; CMRR, Center for Magnetic Resonance Research; BOLD, blood oxygenation level dependent; pcASL: pseudo-continuous arterial spin labeling; EPI, echo-planar imaging; FLAIR, fluid attenuated inversion recovery; CBF, cerebral blood flow; QA, quality assessment; GM, gray matter; HCV, hippocampal volume; eICV, estimated intracranial volume; DWI, diffusion-weighted imaging; MD, mean diffusivity; FA, fractional anisotropy
TBSS: tract-based spatial statistics; CSF, cerebral spinal fluid; ISI, inter-stimulus interval; LDI, lure discrimination index; REC, recognition score; CG, control group; IG, intervention group; MoCA, Montreal Cognitive Assessment; CASMIN, Comparative Analysis of Social Mobility in Industrial Nations; BMI, body mass index; SBP/DBP, systolic/diastolic blood pressure; OSF, open science framework; LMM, linear mixed model; ANOVA, analysis of covariance.
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spelling doaj-art-d5de2bbd6c6f4526a5818c7f6800e55c2025-08-20T03:19:56ZengElsevierNeuroImage: Clinical2213-15822025-01-014610379610.1016/j.nicl.2025.103796Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging studyFrauke Beyer0Lukas Kleine1Andrea Zülke2Melanie Luppa3Toralf Mildner4Jochen Gensichen5Thomas Frese6David Czock7Birgitt Wiese8Hans-Helmut König9Hanna Kaduszkiewicz10Wolfgang Hoffmann11Jochen René Thyrian12Arno Villringer13Steffi Riedel-Heller14A.Veronica Witte15Bordeaux Population Health Research Center, University of Bordeaux, Inserm, UMR 1219, 146 rue Léo Saignat, 33076 Bordeaux, France; Cognitive Neurology, University Hospital Leipzig, University of Leipzig, Liebigstr. 18, 04103 Leipzig, GermanyCognitive Neurology, University Hospital Leipzig, University of Leipzig, Liebigstr. 18, 04103 Leipzig, GermanyInstitute of Social Medicine, Occupational Health and Public Health (ISAP), Medical Faculty, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, GermanyInstitute of Social Medicine, Occupational Health and Public Health (ISAP), Medical Faculty, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, GermanyNMR Group, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstr. 1a, 04103 Leipzig, GermanyInstitute of General Practice and Family Medicine, University Hospital LMU Munich 80336 Munich, GermanyInstitute of General Practice and Family Medicine, Martin-Luther-University Halle-Wittenberg, 06112 Halle, Saale, GermanyInternal Medicine IX – Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, 69120 Heidelberg, GermanyMHH Information Technology – Science & Laboratory, Hannover Medical School, 30625 Hannover, GermanyDepartment of Health Economics and Health Service Research, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of General Practice, University of Kiel 24105 Kiel, GermanyInstitute for Community Medicine, University Medicine Greifswald (UMG), 17489 Greifswald, GermanyGerman Centre for Neurodegenerative Diseases (DZNE), site Rostock/Greifswald 17489 Greifswald, Germany; Institute for Community Medicine, University Medicine Greifswald (UMG), 17489 Greifswald, Germany; Faculty V: School of Life Sciences, University of Siegen 57076 Siegen, GermanyCognitive Neurology, University Hospital Leipzig, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany; Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstr. 1a, 04103 Leipzig, GermanyInstitute of Social Medicine, Occupational Health and Public Health (ISAP), Medical Faculty, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, GermanyCognitive Neurology, University Hospital Leipzig, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany; Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstr. 1a, 04103 Leipzig, Germany; Corresponding author.Background: Multimodal lifestyle interventions might help to maintain healthy cognition in older age and to delay onset of dementia. Here, we studied the effects of a multi-modal lifestyle-based intervention, based on the FINGER trial, on magnetic resonance imaging (MRI) markers of hippocampal-limbic atrophy and cerebral small vessel disease in older adults at increased risk for dementia in Germany. Methods: Leipzig participants of the multicenter AgeWell.de randomized controlled trial underwent neuroimaging before and after a two year intervention at 3 Tesla MRI. We extracted hippocampal volume and entorhinal cortex thickness (ECT), free water fraction (FW), peak width of skeletonized mean diffusivity (PSMD), white matter hyperintensity volume and mean gray matter cerebral blood flow and assessed the effect of the intervention on these imaging markers using linear mixed models. We also tested the effect of the intervention on the hippocampus-dependent Mnemonic Similarity Test and fixel-based white matter microstructure. Results: 56 individuals (mean (sd) age: 68.8 (4.2) years, 26 females, 24/32 intervention/control group) were included at baseline and 41 returned after an average of 28 months for the second assessment. ECT and FW exhibited stronger decline in the intervention compared to the control group in preregistered models but not when adjusted for baseline differences. All other markers progressed similarly across groups, however sample size was smaller than expected. In exploratory analyses, cerebral blood flow increased more in the intervention group and this change was associated with decreases in systolic blood pressure. Conclusions: In this group of older adults at risk for dementia, we find no conclusive evidence whether a multi-modal lifestyle intervention improves brain imaging markers of neurodegeneration and small vessel disease. Preliminary evidence suggested an association of the intervention, increased cerebral blood flow and systolic blood pressure reductions.Abbreviations: ECT, entorhinal cortex thickness; FW, free water fraction; WHO, world health organization; AD, Alzheimer’s disease; VCI, vascular cognitive impairment; FINGER, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability; MTL, medial temporal lobe; MIND, Mediterranean-DASH Intervention for Neurodegenerative Delay diet; cSVD, cerebral small vessel disease; WMH, white matter hyperintensities of presumed vascular origin; PSMD, peak width of the mean diffusivity distribution; WW-FINGERS, world wide FINGER studies; CAIDE, Cardiovascular Risk Factors, Aging, and Incidence of Dementia; GPP, general practitioner praxis; MRI, magnetic resonance imaging; MST, Mnemonic Similarity Test; TE, echo time; TR, repetition time; FA, flip angle; FOV, field of view; GRAPPA, GeneRalized Autocalibrating Partial Parallel Acquisition; CMRR, Center for Magnetic Resonance Research; BOLD, blood oxygenation level dependent; pcASL: pseudo-continuous arterial spin labeling; EPI, echo-planar imaging; FLAIR, fluid attenuated inversion recovery; CBF, cerebral blood flow; QA, quality assessment; GM, gray matter; HCV, hippocampal volume; eICV, estimated intracranial volume; DWI, diffusion-weighted imaging; MD, mean diffusivity; FA, fractional anisotropy
TBSS: tract-based spatial statistics; CSF, cerebral spinal fluid; ISI, inter-stimulus interval; LDI, lure discrimination index; REC, recognition score; CG, control group; IG, intervention group; MoCA, Montreal Cognitive Assessment; CASMIN, Comparative Analysis of Social Mobility in Industrial Nations; BMI, body mass index; SBP/DBP, systolic/diastolic blood pressure; OSF, open science framework; LMM, linear mixed model; ANOVA, analysis of covariance.http://www.sciencedirect.com/science/article/pii/S221315822500066XDementiaLifestyleMulti-component interventionMagnetic Resonance ImagingHippocampusCerebral Small Vessel Disease
spellingShingle Frauke Beyer
Lukas Kleine
Andrea Zülke
Melanie Luppa
Toralf Mildner
Jochen Gensichen
Thomas Frese
David Czock
Birgitt Wiese
Hans-Helmut König
Hanna Kaduszkiewicz
Wolfgang Hoffmann
Jochen René Thyrian
Arno Villringer
Steffi Riedel-Heller
A.Veronica Witte
Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging study
NeuroImage: Clinical
Dementia
Lifestyle
Multi-component intervention
Magnetic Resonance Imaging
Hippocampus
Cerebral Small Vessel Disease
title Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging study
title_full Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging study
title_fullStr Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging study
title_full_unstemmed Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging study
title_short Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging study
title_sort exploring the effect of multi modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the agewell de imaging study
topic Dementia
Lifestyle
Multi-component intervention
Magnetic Resonance Imaging
Hippocampus
Cerebral Small Vessel Disease
url http://www.sciencedirect.com/science/article/pii/S221315822500066X
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