Cortical hypometabolism on FDG-PET is a well-established neuroimaging biomarker of cognitive impairment in Parkinson’s disease (PD), but its pathophysiologic origins are incompletely understood. Cholinergic basal forebrain (cBF) degeneration is a prominent pathological feature of PD-related cognitive impairment and may contribute to cortical hypometabolism through cholinergic denervation of cortical projection areas. Here, we investigated in-vivo associations between subregional cBF volumes on 3T-MRI, cortical hypometabolism on [¹⁸F]FDG-PET, and cognitive deficits in a cohort of 95 PD participants with varying degrees of cognitive impairment. We further assessed the spatial correspondence of the cortical pattern of cBF-associated hypometabolism with the pattern of cholinergic denervation in PD as assessed by [¹⁸F]FEOBV-PET imaging of presynaptic cholinergic terminal density in a second cohort. Lower volume of the cortically-projecting posterior cBF, but not of the anterior cBF, was significantly associated with extensive neocortical hypometabolism [p(FDR) < 0.05], which mediated the association between cBF atrophy and cognitive impairment (mediated proportion: 43%, p < 0.001). In combined models, posterior cBF atrophy explained more variance in cortical hypometabolism (R² = 0.26, p < 0.001) than local atrophy in the cortical areas themselves (R² = 0.16, p = 0.01). Topographic correspondence analysis with the [¹⁸F]FEOBV-PET pattern revealed that cortical areas showing most pronounced cBF-associated hypometabolism correspond to those showing most severe cholinergic denervation in PD (Spearman’s ρ = 0.57, p < 0.001). In conclusion, posterior cBF atrophy in PD is selectively associated with hypometabolism in denervated cortical target areas, which mediates the effect of cBF atrophy on cognitive impairment. These data provide first-time in-vivo evidence that cholinergic degeneration represents a principle pathological correlate of cortical hypometabolism underlying cognitive impairment in PD.

FDG-PET 上的皮质代谢减退是帕金森病 （PD） 认知障碍的公认神经影像学生物标志物，但其病理生理学起源尚不完全清楚。胆碱能基底前脑 （cBF） 变性是 PD 相关认知障碍的一个突出病理特征，可能通过皮质投射区的胆碱能去神经支配导致皮质代谢减退。在这里，我们研究了 3T-MRI 上的亚区域 cBF 体积、[¹⁸F]FDG-PET 上的皮质代谢减退以及 95 名具有不同程度认知障碍的 PD 参与者队列中的认知缺陷之间的体内关联。我们进一步评估了 cBF 相关代谢减退的皮质模式与 PD 中胆碱能去神经支配模式的空间对应性，如在第二组中通过突触前胆碱能末端密度的 [¹⁸F]FEOBV-PET 成像评估的那样。皮质突出的后 cBF 体积较小，但前部 cBF 的体积较小，与广泛的新皮质代谢减退显着相关 [p（FDR） < 0.05]，介导 cBF 萎缩与认知障碍之间的关联 （介导比例：43%，p < 0.001）。在联合模型中，后 cBF 萎缩解释了皮质代谢减退的方差 （R² = 0.26，p < 0.001） 比皮质区域本身的局部萎缩 （R² = 0.16，p = 0.01） 更多。 与 [¹⁸F]FEOBV-PET 模式的地形对应分析显示，显示最明显的 cBF 相关代谢减退的皮质区域对应于 PD 中显示最严重的胆碱能去神经支配的区域 （Spearman 的 ρ = 0.57，p < 0.001）。 总之，PD 中的后 cBF 萎缩选择性地与去神经支配的皮质靶区代谢减退相关，这介导了 cBF 萎缩对认知障碍的影响。这些数据提供了首次体内证据，表明胆碱能变性代表了 PD 认知障碍潜在皮质代谢减退的主要病理相关性。