Differential network‐based propagation of cortical thinning in atrophy subtypes in non‐demented individuals

Abstract Background Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages. Method From the AMYPAD‐PNHS cohort, we included a total of 1323 non‐demented individuals, including 1094 amyloid‐negative, and 229 amyloid‐positive participants (Table 1). Gray matter thickness in 100 regions of interest was measured using FreeSurfer. Global cortical amyloid burden was derived from amyloid PET scans in Centiloids (CL). Individuals were assigned to atrophy subtypes based on cortical thickness measures using Non‐Negative Matrix Factorization (Figure 1). Multinomial regression models were used to study differences between subtypes in age, sex, global CL and APOE E4 carriership. Linear regression models were used to investigate the effect of time on atrophy within each subtype. Coordinated deformation models (Figure 1, Shafiei et al. 2023) were used to estimate network‐based thickness changes in each region, by multiplying the effect of time in connected regions by the strengths of their connections. Connectivity strength was based on templates of functional, structural and morphometric similarity networks, and allowed us to evaluate differential mechanisms. Significance was tested using a permutation approach. Results Three significant subtypes of regional GM atrophy were identified:‘limbic predominant’, ‘typical AD’, and ‘diffuse cortical’ (Figure 2). Individuals assigned to the limbic predominant subtype were significantly older, while the typical AD subtype had more APOE E4 carriers compared to the others (all p<0.001). Both limbic predominant and typical AD subtypes had higher CL compared to the diffuse cortical atrophy subtype (all p<0.001). Significant longitudinal thickness changes per subtype are shown in Figure 2. In the typical AD subtype, all network architectures constrained longitudinal GM changes (p<0.001), while in the diffuse atrophy subtype, propagation was mostly determined by morphometric similarity (p<0.005). No significant prediction model was found for the limbic predominant subtype. Conclusion We show that atrophy subtypes can already be detected in non‐demented individuals. Progression of atrophy within subtypes is determined by network‐based mechanisms.

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Journal
Alzheimer s & Dementia
Published
2024-12-01
DOI
https://doi.org/10.1002/alz.093975
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
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article

Differential network‐based propagation of cortical thinning in atrophy subtypes in non‐demented individuals

Emma S. Luckett, Lyduine E. Collij, Rossella Gismondi, David Vállez García et al.
Alzheimer s & Dementia
Parkinson's Disease Mechanisms and Treatments
article

Differential network‐based propagation of cortical thinning in atrophy subtypes in non‐demented individuals

Emma S. Luckett, Lyduine E. Collij, Rossella Gismondi, David Vállez García, Isadora Lopes Alves, Andrew Stephens, Luigi Lorenzini, Mario Tranfa, Pieter Jelle Visser, Giuseppe Pontillo, Henk J. M. M. Mutsaerts, Christopher Buckley, Bernard Hanseeuw, Anouk den Braber, Merçé Boada, Giovanni Battista Frisoni, Mahnaz Shekari, Anja Mett, Frederik Barkhof, Frank Jessen, Juan Domingo Gispert, Daniele Altomare, Rik R. Vandenberghe, Alle Meije Wink, Karen A. Ritchie, Michael Schöll, Gill Farrar, Mara ten Kate, Cindy Birck, Leonard Pieperhoff, Marta Marquié
article en

Abstract

Abstract Background Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages. Method From the AMYPAD‐PNHS cohort, we included a total of 1323 non‐demented individuals, including 1094 amyloid‐negative, and 229 amyloid‐positive participants (Table 1). Gray matter thickness in 100 regions of interest was measured using FreeSurfer. Global cortical amyloid burden was derived from amyloid PET scans in Centiloids (CL). Individuals were assigned to atrophy subtypes based on cortical thickness measures using Non‐Negative Matrix Factorization (Figure 1). Multinomial regression models were used to study differences between subtypes in age, sex, global CL and APOE E4 carriership. Linear regression models were used to investigate the effect of time on atrophy within each subtype. Coordinated deformation models (Figure 1, Shafiei et al. 2023) were used to estimate network‐based thickness changes in each region, by multiplying the effect of time in connected regions by the strengths of their connections. Connectivity strength was based on templates of functional, structural and morphometric similarity networks, and allowed us to evaluate differential mechanisms. Significance was tested using a permutation approach. Results Three significant subtypes of regional GM atrophy were identified:‘limbic predominant’, ‘typical AD’, and ‘diffuse cortical’ (Figure 2). Individuals assigned to the limbic predominant subtype were significantly older, while the typical AD subtype had more APOE E4 carriers compared to the others (all p<0.001). Both limbic predominant and typical AD subtypes had higher CL compared to the diffuse cortical atrophy subtype (all p<0.001). Significant longitudinal thickness changes per subtype are shown in Figure 2. In the typical AD subtype, all network architectures constrained longitudinal GM changes (p<0.001), while in the diffuse atrophy subtype, propagation was mostly determined by morphometric similarity (p<0.005). No significant prediction model was found for the limbic predominant subtype. Conclusion We show that atrophy subtypes can already be detected in non‐demented individuals. Progression of atrophy within subtypes is determined by network‐based mechanisms.

Alzheimer s & DementiaVol. 20(S9)
University of Geneva (CH), Netherlands Institute for Neuroscience (NL), University of Cologne (DE), Lund University (SE), Pasqual Maragall Foundation (ES), Amsterdam Neuroscience (NL), Fundació ACE (ES), Amsterdam University Medical Centers (NL), University Hospital Cologne (DE), VIB-KU Leuven Center for Brain & Disease Research (BE), University of Naples Federico II (IT), Alzheimer Europe (LU), Vrije Universiteit Amsterdam (NL), University of Gothenburg (SE), University of Edinburgh (GB)
Openalex Percentile: Top 61%
Parkinson's Disease Mechanisms and Treatments
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