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. Conclusion: 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.

目的：合并路易体 (LB) 病理学在 AD 中很常见。LB 共同病理学对 AD 中 FDG-PET 模式的影响仍有待研究。我们分析了临床 AD 患者中神经病理学评估的 tau 病理学、LB 病理学和黑质神经元丢失 (SNnl) 与生前 FDG-PET 代谢低下的关联。方法： 21 名尸检确诊的 AD 患者（“纯 AD”），24 名患者患有 AD 和 LB 共同病理（“AD-LB”），7 名患有 LB 但没有或很少有 AD 病理证据的患者（“纯 AD”） -LB')进行了研究。比较病理组的区域和体素 FDG-PET 模式、扣带岛符号比 (CISr) 和 SNnl 的神经病理学评级。其他分析评估了 Braak 缠结阶段和 SNnl 与 FDG-PET 模式的连续关联。结果：纯 AD 和 AD-LB 显示出高度相似的 AD 典型颞顶代谢低下模式，并且在 CISr、区域 FDG SUVR 或 SNnl 方面没有差异。相比之下，与 AD 组相比，纯 LB 显示出预期的 DLB 样模式，伴有明显的枕骨代谢减退以及 CISr 和 SNnl 升高。在连续分析中，Braak 缠结阶段与更多类似 AD 的模式显着相关，SNnl 与更多类似 DLB 的 FDG-PET 模式显着相关。结论：在尸检确诊的 AD 痴呆患者中，合并 LB 病理对局部 FDG-PET 模式没有显着影响。与 SNnl 相比，观察到更像 DLB 的 FDG-PET 模式，但晚期 SNnl 主要限于相对纯粹的 LB 病例。在确定区域神经变性表型方面，AD 病理学可能比 LB 病理学具有主导作用。