Dementia with Lewy bodies and Alzheimer’s disease show early degeneration of the cholinergic nucleus basalis of Meynert. However, how white matter projections between the nucleus basalis of Meynert and the cortex are altered in neurodegenerative disease is unknown. Tractography of white matter pathways originating from the nucleus basalis of Meynert was performed using diffusion-weighted imaging in 46 Alzheimer’s disease dementia, 48 dementia with Lewy bodies, 35 mild cognitive impairment with Alzheimer’s disease, 38 mild cognitive impairment with Lewy bodies, and 71 controls. Mean diffusivity of the resulting pathways was compared between groups and related to cognition, attention, functional EEG changes, and dementia conversion in the mild cognitive impairment groups. We successfully tracked a medial and a lateral pathway from the nucleus basalis of Meynert. Mean diffusivity of the lateral pathway was higher in both dementia and mild cognitive impairment groups than controls (all P < 0.03). In the patient groups, increased mean diffusivity of this pathway was related to more impaired global cognition (β=-0.22, P = 0.06) and worse performance on an attention task (β = 0.30, P = 0.03). In patients with mild cognitive impairment, loss of integrity of both nucleus basalis of Meynert pathways was associated with increased risk of dementia progression (hazard ratio [95% confidence interval], medial pathway: 2.51 [1.24–5.09]; lateral pathway: 2.54 [1.24–5.19]). Nucleus basalis of Meynert volume was reduced in all clinical groups compared to controls (all P < 0.001), but contributed less strongly to cognitive impairment and was not associated with attention or dementia conversion. EEG slowing in the patient groups as assessed by a decrease in dominant frequency was associated with smaller nucleus basalis of Meynert volumes (β = 0.22, P = 0.02) and increased mean diffusivity of the lateral pathway (β=-0.47, P = 0.003). We show that degeneration of the cholinergic nucleus basalis of Meynert in Alzheimer’s disease and dementia with Lewy bodies is accompanied by an early reduction in integrity of white matter projections that originate from this structure. This is more strongly associated with cognition and attention than the volume of the nucleus basalis of Meynert itself and might be an early indicator of increased risk of dementia conversion in people with mild cognitive impairment.

中文翻译：

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路易体痴呆和阿尔茨海默病中的胆碱能白质通路


路易体痴呆和阿尔茨海默氏病显示梅纳特胆碱能基底核的早期变性。然而，在神经退行性疾病中，Meynert 基底核和皮质之间的白质投射如何改变尚不清楚。使用扩散加权成像对 46 名阿尔茨海默病痴呆患者、48 名路易体痴呆患者、35 名阿尔茨海默病轻度认知障碍患者、38 名路易体轻度认知障碍患者和 71 名对照者进行了源自 Meynert 基底核的白质通路纤维束成像。 。比较各组之间产生的通路的平均扩散率，并与轻度认知障碍组的认知、注意力、功能性脑电图变化和痴呆转化相关。我们成功地追踪了从 Meynert 基底核开始的内侧和外侧通路。痴呆组和轻度认知障碍组的侧向通路平均扩散率均高于对照组（所有 P < 0.03）。在患者组中，该通路的平均扩散率增加与整体认知受损程度更高（β = -0.22，P = 0.06）和注意力任务表现较差（β = 0.30，P = 0.03）有关。在轻度认知障碍患者中，Meynert 通路的两个基底核完整性丧失与痴呆进展风险增加相关（风险比 [95% 置信区间]，内侧通路：2.51 [1.24–5.09]；外侧通路：2.54 [ 1.24–5.19]）。与对照组相比，所有临床组的 Meynert 基底核体积均减少（所有 P < 0.001），但对认知障碍的影响较小，并且与注意力或痴呆转化无关。 通过主频率降低评估，患者组中的脑电图减慢与 Meynert 体积较小的基底核 (β = 0.22，P = 0.02) 和侧向通路平均扩散率增加 (β = -0.47，P = 0.003) 相关。我们发现，阿尔茨海默病和路易体痴呆症中迈纳特胆碱能基底核的变性伴随着源自该结构的白质投射完整性的早期降低。与迈纳特基底核本身的体积相比，这与认知和注意力的相关性更强，并且可能是轻度认知障碍患者患痴呆症的风险增加的早期指标。