FDG-PET Outperforms MRI in Monitoring Early Neurodegenerative Changes Tied to Neurofibrillary Tangle Pathology: An Imaging-Pathology Study

Sep 30, 2026

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Background: Neurofibrillary tangle pathology (NFTp) in Alzheimer’s disease is linked to neurodegeneration measurable in vivo by structural MRI or FDG-PET. This study compares the sensitivities of FDG-PET hypometabolism and MRI gray-matter atrophy for early and advanced NFTp stages using post-mortem neuropathology. Methods: 88 ADNI autopsy participants with Braak staging and pre-death FDG-PET and T1-MRI were analyzed with brain-wide Spearman correlations and paired Braak-stage comparisons. Conclusion: FDG-PET hypometabolism detects NFTp-related neurodegenerative change earlier than MRI atrophy.

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Abstract

Background

Method

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DOI: 10. 1002/alz70856_106413 BIOMARKERS POSTER PRESENTATION NEUROIMAGING FDG-PET Outperforms MRI in Monitoring Early Neurodegenerative Changes Tied to Neurofibrillary Tangle Pathology: An Imaging-Pathology Study Orfeas Vourkas Linda Zhang Alberto Rabano Pascual Sanchez-Juan Jesús Silva-Rodríguez Michel J. Grothe CIEN Foundation, Reina Sofia Alzheimer Center, ISCIII, Madrid, Madrid, Spain Correspondence OrfeasVourkas, CIEN Foundation, Reina Sofia Alzheimer Center, ISCIII, Madrid, Madrid, Spain. [Email:](Email: ovourkas@fundacioncien.es)[ ovourkas@fundacioncien.es](Email: ovourkas@fundacioncien.es) Abstract Background: Neurofibrillary tangle pathology (NFTp) in Alzheimer’s disease (AD) is closely related to neurodegeneration, which can be measured in vivo using structural MRI or FDG-PET. While several studies have assessed this correlation using in vivo markers of NFTp (i.e., tau PET), very few studies to date have compared MRI and FDG-PET with respect to neuropathological assessments of NFTp. Here, we aimed to assess the relative sensitivities of FDG-PET-measured hypometabolism and MRImeasured gray matter(GM)atrophy, to early and advanced stages of NFTp, as assessed by post-mortem neuropathological examination. Method: We studied 88 individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) autopsy cohort who had Braak NFTp staging performed at autopsy and had FDG-PET and structural T1-MRI scans acquired before death (imaging-todeath interval: 3.4±2. 3 years). Associations of Braak stages with regional FDG-PET SUVRs and GM volumes on MRI were assessed in exploratory brain-wide Spearman correlation analyses across 52 cortical and subcortical brain regions. For regions showing a significant association (p <0.05, FDR-corrected), we then performed pairwise comparisons between grouped Braak stages 0/I (N = 18), II-IV (N = 14), and V-VI (N = 56). Result: Higher Braak stages were significantly associated with lower FDG-PET SUVRin several tempero-parietal cortical regions typically affected by AD. Compared to the Braak 0/I reference group, most of these regions showed significant and pronounced (Cohen’s d>0. 9) hypometabolism in early Braak stages II-IV, and severity of hypometabolism further increased in Braak stages V/VI (Figure 1A). Although GM volume on MRI showed a similar regional association with Braak stages, effect sizes This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e106413. [https://doi.org/10.1002/alz70856_106413](https://doi.org/10.1002/alz70856_106413) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of2 BIOMARKERS were considerably lower and differences to the Braak 0/I reference group were only significant for advanced Braak stages V/VI (Figure 1B). Conclusion: Glucose hypometabolism as measured by FDG-PET is a sensitive neuroimaging marker of the neurodegenerative changes that accompany progressive stages of neurofibrillary tangle pathology in AD. Earliest NFTp-related neurodegenerative changes captured by FDG-PET hypometabolism appear to precede macrostructural gray matter atrophy as measured by MRI.

FAQs

What was the study’s main goal?

To compare how sensitively FDG-PET hypometabolism and MRI gray-matter atrophy reflect early versus advanced neurofibrillary tangle pathology stages using post-mortem neuropathology.

How were associations between NFTp and imaging signals tested?

Braak NFTp stages were related to regional FDG-PET SUVRs and MRI gray-matter volumes using exploratory brain-wide Spearman correlations, followed by pairwise comparisons for Braak stage groupings when associations were significant.

Which imaging modality detected neurodegenerative changes earlier?

FDG-PET hypometabolism showed sensitivity to the earliest NFTp-related neurodegenerative changes, preceding macrostructural gray-matter atrophy detected by MRI.

Sep 30, 2026

Uploaded by Aria