Michel J. Grothe (Spain)
Instituto de Biomedicina de Sevilla (IBiS)
Movement Disorders Group
Dr. Grothe is a senior researcher leading the Neuroimaging section of the Movement Disorders Group (Dr. Pablo Mir) at the Instituto de Biomedicina de Sevilla (IBiS), Spain. He also holds a co-affiliation as Senior Research Associate in the Molecular Neuroimaging Group (Schöll Lab) at the Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden. His research focuses on the use of multimodal neuroimaging techniques for studying neurodegenerative disease pathology in-vivo, and he has published over 130 peer-reviewed research articles in this field over the last 12 years. While most of his work evolved around neuroimaging and biomarker research in Alzheimer’s disease, he recently also became interested in using these in-vivo techniques to study the pathologic correlates of cognitive decline and dementia associated with Lewy body disorders.

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FDG-PET IS SUPERIOR TO MRI FOR TRACKING NEURODEGENERATIVE CHANGES ASSOCIATED WITH EARLY STAGES OF NEUROFIBRILLARY TANGLE PATHOLOGY: AN IMAGING–PATHOLOGIC ASSOCIATION STUDY

Session Name
4330 - SYMPOSIUM: PET 01 (ID 117)
Session Type
SYMPOSIUM
Date
Sat, 01.04.2023
Session Time
08:40 - 10:40
Room
ONSITE - HALL G3
Presenter
Lecture Time
10:25 - 10:40

Abstract

Aims

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. We aimed to assess the relative sensitivities of FDG-PET-measured hypometabolism and MRI-measured gray matter (GM) atrophy to early stages of NFTp as assessed by post-mortem neuropathological examination.

Methods

We studied 64 individuals from the Alzheimer’s Disease Neuroimaging Initiative autopsy cohort who had Braak NFTp staging performed at autopsy and had FDG-PET and structural T1-MRI scans acquired before death (imaging-to-death 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 pair-wise comparisons between grouped Braak stages 0/I (N=7), II-IV (N=14), and V/VI (N=43).

Results

Higher Braak stages were significantly associated with lower FDG-PET SUVR in several temporo-parietal cortical regions typically affected by AD (Fig. 1A). 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. Although GM volume on MRI showed a similar regional association with Braak stages (Fig. 1B), effect sizes were considerably lower and differences to the Braak 0/I reference group were only significant for advanced Braak stages V/VI.

fig1.jpg

Conclusions

Glucose hypometabolism as measured by FDG-PET is a sensitive neuroimaging marker of the neurodegenerative changes that accompany progressive stages of neurofibrillary tangle pathology. Earliest NFTp-related neurodegenerative changes captured by FDG-PET hypometabolism appear to precede macrostructural gray matter atrophy as measured by MRI.

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