Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults
Abstract Background For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce. Methods We applied global and r...
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2024-10-01
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| Online Access: | https://doi.org/10.1186/s13195-024-01606-5 |
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| author | Jose Bernal Inga Menze Renat Yakupov Oliver Peters Julian Hellmann-Regen Silka Dawn Freiesleben Josef Priller Eike Jakob Spruth Slawek Altenstein Anja Schneider Klaus Fliessbach Jens Wiltfang Björn H. Schott Frank Jessen Ayda Rostamzadeh Wenzel Glanz Enise I. Incesoy Katharina Buerger Daniel Janowitz Michael Ewers Robert Perneczky Boris-Stephan Rauchmann Stefan Teipel Ingo Kilimann Christoph Laske Sebastian Sodenkamp Annika Spottke Anna Esser Falk Lüsebrink Peter Dechent Stefan Hetzer Klaus Scheffler Stefanie Schreiber Emrah Düzel Gabriel Ziegler |
| author_facet | Jose Bernal Inga Menze Renat Yakupov Oliver Peters Julian Hellmann-Regen Silka Dawn Freiesleben Josef Priller Eike Jakob Spruth Slawek Altenstein Anja Schneider Klaus Fliessbach Jens Wiltfang Björn H. Schott Frank Jessen Ayda Rostamzadeh Wenzel Glanz Enise I. Incesoy Katharina Buerger Daniel Janowitz Michael Ewers Robert Perneczky Boris-Stephan Rauchmann Stefan Teipel Ingo Kilimann Christoph Laske Sebastian Sodenkamp Annika Spottke Anna Esser Falk Lüsebrink Peter Dechent Stefan Hetzer Klaus Scheffler Stefanie Schreiber Emrah Düzel Gabriel Ziegler |
| author_sort | Jose Bernal |
| collection | DOAJ |
| description | Abstract Background For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce. Methods We applied global and regional bivariate latent growth curve modelling to determine the extent to which WMH and cortical thickness were interrelated over a four-year period. For this purpose, we leveraged longitudinal MRI data from 451 cognitively unimpaired participants (DELCODE; median age 69.71 [IQR 65.51, 75.50] years; 52.32% female). Participants underwent MRI sessions annually over a four-year period (1815 sessions in total, with roughly four MRI sessions per participant). We adjusted all models for demographics and cardiovascular risk. Results Our findings were three-fold. First, larger WMH volumes were linked to lower cortical thickness (σ = -0.165, SE = 0.047, Z = -3.515, P < 0.001). Second, individuals with higher WMH volumes experienced more rapid cortical thinning (σ = -0.226, SE = 0.093, Z = -2.443, P = 0.007), particularly in temporal, cingulate, and insular regions. Similarly, those with lower initial cortical thickness had faster WMH progression (σ = -0.141, SE = 0.060, Z = -2.336, P = 0.009), with this effect being most pronounced in temporal, cingulate, and insular cortices. Third, faster WMH progression was associated with accelerated cortical thinning (σ = -0.239, SE = 0.139, Z = -1.710, P = 0.044), particularly in frontal, occipital, and insular cortical regions. Conclusions Our study suggests that cortical thinning and WMH progression could be mutually reinforcing rather than parallel, unrelated processes, which become entangled before cognitive deficits are detectable. Trial registration German Clinical Trials Register (DRKS00007966, 04/05/2015). |
| format | Article |
| id | doaj-art-2fc8b02963e64d939d0391d39c8e28cb |
| institution | OA Journals |
| issn | 1758-9193 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
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| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-2fc8b02963e64d939d0391d39c8e28cb2025-08-20T02:18:20ZengBMCAlzheimer’s Research & Therapy1758-91932024-10-0116111410.1186/s13195-024-01606-5Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adultsJose Bernal0Inga Menze1Renat Yakupov2Oliver Peters3Julian Hellmann-Regen4Silka Dawn Freiesleben5Josef Priller6Eike Jakob Spruth7Slawek Altenstein8Anja Schneider9Klaus Fliessbach10Jens Wiltfang11Björn H. Schott12Frank Jessen13Ayda Rostamzadeh14Wenzel Glanz15Enise I. Incesoy16Katharina Buerger17Daniel Janowitz18Michael Ewers19Robert Perneczky20Boris-Stephan Rauchmann21Stefan Teipel22Ingo Kilimann23Christoph Laske24Sebastian Sodenkamp25Annika Spottke26Anna Esser27Falk Lüsebrink28Peter Dechent29Stefan Hetzer30Klaus Scheffler31Stefanie Schreiber32Emrah Düzel33Gabriel Ziegler34Institute of Cognitive Neurology and Dementia Research, Otto-Von-Guericke University MagdeburgInstitute of Cognitive Neurology and Dementia Research, Otto-Von-Guericke University MagdeburgInstitute of Cognitive Neurology and Dementia Research, Otto-Von-Guericke University MagdeburgGerman Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)UK Dementia Research Institute Centre at the University of EdinburghGerman Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)Department of Psychiatry, Medical Faculty, University of CologneGerman Centre for Neurodegenerative Diseases (DZNE)Institute of Cognitive Neurology and Dementia Research, Otto-Von-Guericke University MagdeburgGerman Centre for Neurodegenerative Diseases (DZNE)Institute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichGerman Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)Department of Psychiatry and Psychotherapy, University Hospital, LMU MunichGerman Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)German Centre for Neurodegenerative Diseases (DZNE)Department of Cognitive Neurology, MR-Research in Neurosciences, Georg-August-UniversityBerlin Centre for Advanced Neuroimaging, Charité – Universitätsmedizin BerlinDepartment for Biomedical Magnetic Resonance, University of TübingenGerman Centre for Neurodegenerative Diseases (DZNE)Institute of Cognitive Neurology and Dementia Research, Otto-Von-Guericke University MagdeburgInstitute of Cognitive Neurology and Dementia Research, Otto-Von-Guericke University MagdeburgAbstract Background For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce. Methods We applied global and regional bivariate latent growth curve modelling to determine the extent to which WMH and cortical thickness were interrelated over a four-year period. For this purpose, we leveraged longitudinal MRI data from 451 cognitively unimpaired participants (DELCODE; median age 69.71 [IQR 65.51, 75.50] years; 52.32% female). Participants underwent MRI sessions annually over a four-year period (1815 sessions in total, with roughly four MRI sessions per participant). We adjusted all models for demographics and cardiovascular risk. Results Our findings were three-fold. First, larger WMH volumes were linked to lower cortical thickness (σ = -0.165, SE = 0.047, Z = -3.515, P < 0.001). Second, individuals with higher WMH volumes experienced more rapid cortical thinning (σ = -0.226, SE = 0.093, Z = -2.443, P = 0.007), particularly in temporal, cingulate, and insular regions. Similarly, those with lower initial cortical thickness had faster WMH progression (σ = -0.141, SE = 0.060, Z = -2.336, P = 0.009), with this effect being most pronounced in temporal, cingulate, and insular cortices. Third, faster WMH progression was associated with accelerated cortical thinning (σ = -0.239, SE = 0.139, Z = -1.710, P = 0.044), particularly in frontal, occipital, and insular cortical regions. Conclusions Our study suggests that cortical thinning and WMH progression could be mutually reinforcing rather than parallel, unrelated processes, which become entangled before cognitive deficits are detectable. Trial registration German Clinical Trials Register (DRKS00007966, 04/05/2015).https://doi.org/10.1186/s13195-024-01606-5White Matter HyperintensitiesCortical ThicknessLatent Growth Curve ModelLongitudinal ModellingStructural Magnetic Resonance Imaging |
| spellingShingle | Jose Bernal Inga Menze Renat Yakupov Oliver Peters Julian Hellmann-Regen Silka Dawn Freiesleben Josef Priller Eike Jakob Spruth Slawek Altenstein Anja Schneider Klaus Fliessbach Jens Wiltfang Björn H. Schott Frank Jessen Ayda Rostamzadeh Wenzel Glanz Enise I. Incesoy Katharina Buerger Daniel Janowitz Michael Ewers Robert Perneczky Boris-Stephan Rauchmann Stefan Teipel Ingo Kilimann Christoph Laske Sebastian Sodenkamp Annika Spottke Anna Esser Falk Lüsebrink Peter Dechent Stefan Hetzer Klaus Scheffler Stefanie Schreiber Emrah Düzel Gabriel Ziegler Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults Alzheimer’s Research & Therapy White Matter Hyperintensities Cortical Thickness Latent Growth Curve Model Longitudinal Modelling Structural Magnetic Resonance Imaging |
| title | Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults |
| title_full | Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults |
| title_fullStr | Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults |
| title_full_unstemmed | Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults |
| title_short | Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults |
| title_sort | longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults |
| topic | White Matter Hyperintensities Cortical Thickness Latent Growth Curve Model Longitudinal Modelling Structural Magnetic Resonance Imaging |
| url | https://doi.org/10.1186/s13195-024-01606-5 |
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