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. 2023 Feb;64(2):274-280.
doi: 10.2967/jnumed.122.264213. Epub 2022 Aug 25.

Differential Effects of Tau Stage, Lewy Body Pathology, and Substantia Nigra Degeneration on 18F-FDG PET Patterns in Clinical Alzheimer Disease

Jesús Silva-Rodríguez  1 , Miguel A Labrador-Espinosa  1   2   3 , Alexis Moscoso  4 , Michael Schöll  4   5 , Pablo Mir  6   2   3 , Michel J Grothe  6   2   4 ; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

Differential Effects of Tau Stage, Lewy Body Pathology, and Substantia Nigra Degeneration on 18F-FDG PET Patterns in Clinical Alzheimer Disease

Jesús Silva-Rodríguez et al. J Nucl Med. 2023 Feb.

Abstract

Comorbid Lewy body (LB) pathology is common in Alzheimer disease (AD). The effect of LB copathology on 18F-FDG PET patterns in AD is yet to be studied. We analyzed associations of neuropathologically assessed tau pathology, LB pathology, and substantia nigra neuronal loss (SNnl) with antemortem 18F-FDG PET hypometabolism in patients with a clinical AD presentation. Methods: Twenty-one patients with autopsy-confirmed AD without LB neuropathologic changes (LBNC) (pure-AD), 24 with AD and LBNC copathology (AD-LB), and 7 with LBNC without fulfilling neuropathologic criteria for AD (pure-LB) were studied. Pathologic groups were compared regarding regional and voxelwise 18F-FDG PET patterns, the cingulate island sign ratio (CISr), and neuropathologic ratings of SNnl. Additional analyses assessed continuous associations of Braak tangle stage and SNnl with 18F-FDG PET patterns. Results: Pure-AD and AD-LB showed highly similar patterns of AD-typical temporoparietal hypometabolism and did not differ in CISr, regional 18F-FDG SUVR, or SNnl. By contrast, pure-LB showed the expected pattern of pronounced posterior-occipital hypometabolism typical for dementia with LB (DLB), and both CISr and SNnl were significantly higher compared with the AD groups. In continuous analyses, Braak tangle stage correlated significantly with more AD-like, and SNnl with more DLB-like, 18F-FDG PET patterns. Conclusion: In autopsy-confirmed AD dementia patients, comorbid LB pathology did not have a notable effect on the regional 18F-FDG PET pattern. A more DLB-like 18F-FDG PET pattern was observed in relation to SNnl, but advanced SNnl was mostly limited to relatively pure LB cases. AD pathology may have a dominant effect over LB pathology in determining the regional neurodegeneration phenotype.

Keywords: 18F-FDG; AD; LBD; autopsy.

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Figures

FIGURE 1.
FIGURE 1.
(A) Hypometabolism patterns of pathologic groups compared with controls. (B) Patterns of limbic/neocortical and amygdala-predominant LB subgroups in AD-LB. (C) Direct comparisons between pathologic groups. Color represents effect size. White bars in color bars: P < 0.05 (FDR-corrected).
FIGURE 2.
FIGURE 2.
Comparison of MTL and occipital cortex 18F-FDG SUV ratios (SUVR) between different neuropathologic groups and the control group (CN).
FIGURE 3.
FIGURE 3.
(A) CISr comparisons between pathologic groups. Cases with high SNnl (≥ 2) are highlighted in orange. (B) Individual z score maps of 3 AD-LB cases with high SNnl.
FIGURE 4.
FIGURE 4.
Correlations of Braak tau stage and SNnl with regional 18F-FDG PET markers.
FIGURE 5.
FIGURE 5.
Voxel-wise correlations of Braak tau stage and SNnl with 18F-FDG uptake.
See this image and copyright information in PMC

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