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

Comorbid Lewy body (LB) pathology is common in Alzheimer disease (AD). The effect of LB copathology on F-18-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 F-18-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 F-18-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 F-18-FDG SUVR, or SNnl. By contrast, pure-LB showed the expected pattern of pronounced posterior-occipital hypo -metabolism 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, F-18-FDG PET patterns. Conclusion: In autopsy-confirmed AD dementia patients, comorbid LB pathology did not have a notable effect on the regional F-18-FDG PET pattern. A more DLB-like F-18-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 determin-ing the regional neurodegeneration phenotype.