Association Between Gray Matter Microstructure and Glucose Metabolism in Older Adults With Cognitive Decline: A Multimodal Imaging Study
- 1IRCCS SYNLAB SDN Naples Italy
- 2Department of Advanced Medical Science University of Naples Federico II Naples Italy
Abstract
Cortical glucose hypometabolism is a well‐established early marker of neurodegeneration in dementia, mainly reflecting neuronal and synaptic dysfunction. Its relationship with underlying microstructural alterations remains unclear. Here, we combined multi‐shell diffusion microstructural and [18F]‐FDG PET data to investigate the possible association between regional cerebral glucose metabolism and microstructural integrity in patients with cognitive decline. Subjects from two independent datasets, an in‐house dataset of 65 cognitively impaired patients from a memory‐clinic cohort and a cognitively impaired cohort retrieved from the ADNI database (advanced ADNI3 protocol), underwent [18F]‐FDG PET and MRI scanning. Multiple linear regression models were used to evaluate regional associations between glucose metabolism and gray matter microstructure, as measured by NODDI‐derived metrics, namely neurite density index (NDI) and orientation dispersion index (ODI). Global spatial associations between metabolic and microstructural‐derived maps were investigated via spin tests. Regional analysis showed widespread significant positive associations between glucose consumption and ODI across the cortex and subcortex. In both datasets, the global spatial association between NODDI and metabolism showed the ODI being significantly correlated with glucose metabolism (ρ = 0.36, p spin < 0.001 for the in‐house dataset; ρ = 0.54, p spin < 0.001 for the ADNI dataset). Our findings provide new evidence that regional glucose metabolism in cognitive decline is positively associated with alterations in microstructural organization, as reflected by decreased neurite complexity. The significant association suggests that microstructural alterations may parallel the metabolic deficits characteristic of neurodegenerative diseases, pointing to a link between microstructural properties and neuronal metabolic dysfunction.
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BibTeX
@article{canna2026association,
title = {{Association Between Gray Matter Microstructure and Glucose Metabolism in Older Adults With Cognitive Decline: A Multimodal Imaging Study}},
author = {Antonietta Canna and Alessandro Pasquale De Rosa and Emanuele Nicolai and Elena Salvatore and Carlo Cavaliere and Angelica Di Cecca and Miriana Migliaccio and Vincenzo Alfano and Sabina Pappatà and Marco Aiello and Alzheimer's Disease Neuroimaging Initiative},
journal = {Human Brain Mapping},
year = {2026},
month = oct,
doi = {10.1002/hbm.70661},
url = {https://doi.org/10.1002/hbm.70661},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association Between Gray Matter Microstructure and Glucose Metabolism in Older Adults With Cognitive Decline: A Multimodal Imaging Study
AU - Antonietta Canna
AU - Alessandro Pasquale De Rosa
AU - Emanuele Nicolai
AU - Elena Salvatore
AU - Carlo Cavaliere
AU - Angelica Di Cecca
AU - Miriana Migliaccio
AU - Vincenzo Alfano
AU - Sabina Pappatà
AU - Marco Aiello
AU - Alzheimer's Disease Neuroimaging Initiative
PY - 2026
DA - 2026/10/27
JO - Human Brain Mapping
DO - 10.1002/hbm.70661
UR - https://doi.org/10.1002/hbm.70661
AB - Cortical glucose hypometabolism is a well‐established early marker of neurodegeneration in dementia, mainly reflecting neuronal and synaptic dysfunction. Its relationship with underlying microstructural alterations remains unclear. Here, we combined multi‐shell diffusion microstructural and [18F]‐FDG PET data to investigate the possible association between regional cerebral glucose metabolism and microstructural integrity in patients with cognitive decline. Subjects from two independent datasets, an in‐house dataset of 65 cognitively impaired patients from a memory‐clinic cohort and a cognitively impaired cohort retrieved from the ADNI database (advanced ADNI3 protocol), underwent [18F]‐FDG PET and MRI scanning. Multiple linear regression models were used to evaluate regional associations between glucose metabolism and gray matter microstructure, as measured by NODDI‐derived metrics, namely neurite density index (NDI) and orientation dispersion index (ODI). Global spatial associations between metabolic and microstructural‐derived maps were investigated via spin tests. Regional analysis showed widespread significant positive associations between glucose consumption and ODI across the cortex and subcortex. In both datasets, the global spatial association between NODDI and metabolism showed the ODI being significantly correlated with glucose metabolism (ρ = 0.36, p spin < 0.001 for the in‐house dataset; ρ = 0.54, p spin < 0.001 for the ADNI dataset). Our findings provide new evidence that regional glucose metabolism in cognitive decline is positively associated with alterations in microstructural organization, as reflected by decreased neurite complexity. The significant association suggests that microstructural alterations may parallel the metabolic deficits characteristic of neurodegenerative diseases, pointing to a link between microstructural properties and neuronal metabolic dysfunction.
SN - 1065-9471
SN - 1097-0193
ER -