基底前脑的纵向退化可预测帕金森病患者随后发生痴呆。
Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson's disease.
机构信息
Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden; Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmo, Sweden.
Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmo, Sweden; Memory Clinic, Skåne University Hospital, Malmo, Sweden.
出版信息
Neurobiol Dis. 2020 Jun;139:104831. doi: 10.1016/j.nbd.2020.104831. Epub 2020 Mar 5.
OBJECTIVES
Cholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD.
METHODS
We included 106 non-demented PD patients, 19 PD dementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing. After 4.2 ± 1.8 years, 20 non-demented PD patients were diagnosed with dementia (PD-dementia converters), whereas the rest of PD patients remained non-demented (stable-PD). We compared MRI volumes of the medial septum/diagonal band (Ch1/Ch2) and nucleus basalis of Meynert (Ch4) between groups. Cox regression analyses were applied to test whether Ch1/Ch2 or Ch4 atrophy could predict future dementia and linear mixed models assessed their association with cognitive decline.
RESULTS
Compared to controls, we found reduced Ch4 baseline volumes in PD-dementia converters (p = .003) and those who already had PDD (p < .001) but not in stable-PD. Over time, there was a greater loss in Ch1/Ch2 volumes in PD-dementia converters and PDD compared to the other groups (p = .004). Baseline and longitudinal Ch4 volumes were associated with cognition (p < .002) and longitudinal Ch4 atrophy predicted future dementia (p = .009).
CONCLUSIONS
Atrophy of Ch4 precedes and predicts future dementia in PD and is followed by changes in Ch1/Ch2, reflecting a posterior-anterior pattern of basal forebrain atrophy. This pattern could be used to track the spread of cholinergic degeneration and identify patients at risk of developing dementia.
目的
胆碱能功能障碍在帕金森病（PD）认知障碍中起着重要作用。本研究旨在评估基线和纵向基底前脑萎缩与 PD 认知下降和痴呆的关系。
方法
我们纳入了 106 名非痴呆 PD 患者、19 名 PD 痴呆（PDD）患者和 42 名具有纵向结构 MRI 和认知测试的对照者。4.2±1.8 年后，20 名非痴呆 PD 患者被诊断为痴呆（PD-痴呆转化者），而其余 PD 患者保持非痴呆（稳定-PD）。我们比较了各组间内侧隔/斜角带（Ch1/Ch2）和基底核（Ch4）的 MRI 体积。应用 Cox 回归分析来检验 Ch1/Ch2 或 Ch4 萎缩是否可以预测未来的痴呆，线性混合模型评估它们与认知下降的关系。
结果
与对照组相比，我们发现 PD-痴呆转化者和已经患有 PDD 的患者的 Ch4 基线体积减少（p=0.003 和 p<0.001），但稳定-PD 患者没有。随着时间的推移，PD-痴呆转化者和 PDD 患者的 Ch1/Ch2 体积损失更大（p=0.004）。基线和纵向 Ch4 体积与认知相关（p<0.002），纵向 Ch4 萎缩预测未来的痴呆（p=0.009）。
结论
Ch4 的萎缩先于并预测 PD 中的未来痴呆，并随后出现 Ch1/Ch2 的变化，反映了基底前脑萎缩的后前模式。这种模式可用于跟踪胆碱能退化的传播并识别有发生痴呆风险的患者。
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