| Title: |
Glucose metabolism in hyper-connected regions predicts neurodegeneration and speed of conversion in Alzheimer's disease. |
| Authors: |
Galli, Alice; Inglese, Marianna; Presotto, Luca; Malito, Rachele; Di, Xin; Toschi, Nicola; Pilotto, Andrea; Padovani, Alessandro; Tassorelli, Cristina; Perani, Daniela; Sala, Arianna; Caminiti, Silvia Paola |
| Source: |
European Journal of Nuclear Medicine and Molecular Imaging, 52 (12), 4639 - 4651 (2025-10) |
| Publisher Information: |
Springer |
| Publication Year: |
2025 |
| Collection: |
University of Liège: ORBi (Open Repository and Bibliography) |
| Subject Terms: |
Glucose metabolism; Graph theory; Hyper-connectivity; Hypo-connectivity; Mild cognitive impairment; Prodromal; Glucose; Fluorodeoxyglucose F18; Humans; Male; Female; Aged; Positron-Emission Tomography; Disease Progression; Longitudinal Studies; Cognitive Dysfunction/metabolism; Cognitive Dysfunction/diagnostic imaging; Middle Aged; 80 and over; Alzheimer Disease/metabolism; Alzheimer Disease/diagnostic imaging; Alzheimer Disease/pathology; Glucose/metabolism; Brain/metabolism; Brain/diagnostic imaging; Alzheimer; Clustering analysis; Cognitive impairment; Connected region; Neurodegeneration |
| Description: |
peer reviewed ; [en] PURPOSE: Here, we combined a longitudinal design to assess whole-brain hyper- and hypo-connectivity in the different clinical phases of Alzheimer's disease (AD) with a multimodal approach to understand how such connectivity changes were related to glucose hypometabolism. METHODS: We selected a longitudinal cohort of N = 66 subjects with clinical, cerebrospinal fluid and FDG-PET assessments, from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. N = 31 AD individuals were assessed at three stages: mild cognitive impairment (AD-MCI, T0), early phase of dementia (mild-AD, T1) and dementia (AD-D, T2). We included N = 35 age/sex-matched healthy controls. We assessed longitudinal metabolic connectivity using Pearson's correlation, clustering analysis and graph theory metrics. RESULTS: In the MCI-AD stages, hypo- and hyper-connectivity coexisted. Data-driven, longitudinal clustering analysis identified specific pathological clusters: a default mode network cluster, with prevalent hypo-connectivity and severe, persistent hypometabolism; a limbic cluster showing hyper-connectivity and steeper metabolic decline. Metabolism in hyper-connected limbic regions showed a mediation effect on worsening of AD-like parieto-temporal hypometabolism and predicted faster conversion to dementia. CONCLUSION: Hypo- and hyper-connectivity, especially in early stages, may have different roles in AD neurodegenerative processes, with metabolism in hyper-connected regions acting as a mediator on the neurodegeneration of core regions of AD pathology. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1619-7070; 1619-7089 |
| Relation: |
https://link.springer.com/content/pdf/10.1007/s00259-025-07379-9.pdf; urn:issn:1619-7070; urn:issn:1619-7089; https://orbi.uliege.be/handle/2268/337117; info:hdl:2268/337117; info:pmid:40471318 |
| DOI: |
10.1007/s00259-025-07379-9 |
| Availability: |
https://orbi.uliege.be/handle/2268/337117; https://orbi.uliege.be/bitstream/2268/337117/1/s00259-025-07379-9.pdf; https://doi.org/10.1007/s00259-025-07379-9 |
| Rights: |
open access ; http://purl.org/coar/access_right/c_abf2 ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.7AD32895 |
| Database: |
BASE |