[en] [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.
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
Galli, Alice; Neurology Unit, Department of clinical and experimental sciences, University of Brescia, Brescia, 25123, Italy ; Laboratory of Digital Neurology and Biosensors, University of Brescia, Brescia, 25123, Italy
Inglese, Marianna; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, 0133, Italy
Presotto, Luca; Università degli Studi Milano-Bicocca, Milan, 20126, Italy
Di, Xin; Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA
Toschi, Nicola; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, 0133, Italy
Pilotto, Andrea; Neurology Unit, Department of clinical and experimental sciences, University of Brescia, Brescia, 25123, Italy ; Laboratory of Digital Neurology and Biosensors, University of Brescia, Brescia, 25123, Italy
Padovani, Alessandro; Neurology Unit, Department of clinical and experimental sciences, University of Brescia, Brescia, 25123, Italy ; Laboratory of Digital Neurology and Biosensors, University of Brescia, Brescia, 25123, Italy
Tassorelli, Cristina; IRCCS Mondino Foundation, 27100, Pavia, Italy ; Department of Brain and Behavioral Sciences, University of Pavia, 27100, Pavia, Italy
Perani, Daniela; IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
Sala, Arianna ✱; Université de Liège - ULiège > Département des sciences cliniques
Caminiti, Silvia Paola ✱; Department of Brain and Behavioral Sciences, University of Pavia, 27100, Pavia, Italy. silviapaola.caminiti@unipv.it ; University of Pavia, Viale Golgi 19, 27100, Pavia, Italy. silviapaola.caminiti@unipv.it
✱ These authors have contributed equally to this work.
Language :
English
Title :
Glucose metabolism in hyper-connected regions predicts neurodegeneration and speed of conversion in Alzheimer's disease.
Publication date :
October 2025
Journal title :
European Journal of Nuclear Medicine and Molecular Imaging
MIUR - Ministry of Education, University and Research
Funding text :
Study supported by #NEXTGENERATIONEU (NGEU) funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006) \u2013 A multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022), by the Belgian National Fund for Scientific Research (grant number 40001328 to A.S., Charg\u00E9e de Recherches F.R.S.-FNRS/Universit\u00E9 de Li\u00E8ge/Coma Science Group GIGA).CT has received personal fees for participating in advisory boards for Eli Lilly. APi has been supported by grants of Airalzh Foundation AGYR2021 Life-Bio Grant, The LIMPE-DISMOV Foundation Segala Grant 2021, the Italian Ministry of University and Research PRIN COCOON (2017MYJ5 TH) and PRIN 2021 RePlast (PRIN202039 WMFP), the H2020 IMI IDEA-FAST(ID853981), Italian Ministry of Health, Grant/Award Number: RF-2018-12366209 and PNRR-Health PNRR-MAD-2022-12376110. APa received grant support from the Italian Ministry of University and Research PRIN COCOON (2017MYJ5 TH) and PRIN 2021 RePlast (PRIN202039 WMFP), the H2020 IMI IDEA-FAST (ID853981), Italian Ministry of Health, Grant/Award Number: RF-2018-12366209, PNRR-Health PNRR-MAD-2022-12376110 and from CARIPLO Foundation.
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