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Differential effects of tau stage, Lewy body pathology, and substantia nigra degeneration on FDG-PET patterns in clinical AD

Silva-Rodriguez, Jesus; Labrador-Espinosa, Miguel A; Moscoso, Alexis; Scholl, Michael; Mir, Pablo; Grothe, Michel; (2022) Differential effects of tau stage, Lewy body pathology, and substantia nigra degeneration on FDG-PET patterns in clinical AD. Journal of Nuclear Medicine 10.2967/jnumed.122.264213. (In press). Green open access

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Abstract

PURPOSE: Comorbid Lewy body (LB) pathology is common in AD. The effect of LB co-pathology on FDG-PET patterns in AD is yet to be studied. We analysed associations of neuropathologically-assessed tau pathology, LB pathology, and substantia nigra neuron loss (SNnl) with ante-mortem FDG-PET hypometabolism in patients with a clinical AD presentation. METHODS: Twenty-one patients with autopsy-confirmed AD (‘pure-AD’), 24 with AD and LB co-pathology (‘AD-LB’), and 7 with LB but no or low evidence of AD pathology (‘pure-LB’) were studied. Pathologic groups were compared on regional and voxel-wise FDG-PET patterns, the cingulate island sign ratio (CISr), and neuropathological ratings of SNnl. Additional analyses assessed continuous associations of Braak tangle stage and SNnl with FDG-PET patterns. RESULTS: Pure-AD and AD-LB showed highly similar patterns of AD-typical temporo-parietal hypometabolism and did not differ in CISr, regional FDG SUVR, or SNnl. By contrast, pure-LB showed the expected DLB-like pattern, accompanied by pronounced occipital hypometabolism and elevated CISr and SNnl compared to the AD groups. In continuous analyses, Braak tangle stage was significantly correlated with more AD-like, and SNnl with more DLB-like, FDG-PET patterns. CONCLUSIONS: In autopsy-confirmed AD dementia patients, comorbid LB pathology did not have a notable effect on the regional FDG-PET pattern. A more DLB-like 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.

Type: Article
Title: Differential effects of tau stage, Lewy body pathology, and substantia nigra degeneration on FDG-PET patterns in clinical AD
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.2967/jnumed.122.264213
Publisher version: https://doi.org/10.2967/jnumed.122.264213
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: AD, FDG, Image Processing, LBD, Neurology, PET, autopsy
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10155359
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