Richter Nils, Michel Anne, Onur Oezguer A, Kracht Lutz, Dietlein Markus, Tittgemeyer Marc, Neumaier Bernd, Fink Gereon R, Kukolja Juraj
Department of Neurology, University Hospital Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany.
Department of Neurology, University Hospital Cologne, Cologne, Germany; Gériatrie, CHU de Rouen, Rouen University Hospital, Rouen, Cedex, France.
Neurobiol Aging. 2017 May;53:27-35. doi: 10.1016/j.neurobiolaging.2017.01.012. Epub 2017 Jan 18.
In Alzheimer's disease (AD), white matter lesions (WMLs) are associated with an increased risk of progression from mild cognitive impairment (MCI) to dementia, while memory deficits have, at least in part, been linked to a cholinergic deficit. We investigated the relationship between WML load assessed with the Scheltens scale, cerebral acetylcholinesterase (AChE) activity measured with [C]N-methyl-4-piperidyl acetate PET, and neuropsychological performance in 17 patients with MCI due to AD and 18 cognitively normal older participants. Only periventricular, not nonperiventricular, WML load negatively correlated with AChE activity in both groups. Memory performance depended on periventricular and total WML load across groups. Crucially, AChE activity predicted memory function better than WML load, gray matter atrophy, or age. The effects of WML load on memory were fully mediated by AChE activity. Data suggest that the contribution of WML to the dysfunction of the cholinergic system in MCI due to AD depends on WML distribution. Pharmacologic studies are warranted to explore whether this influences the response to cholinergic treatment.
在阿尔茨海默病（AD）中，白质病变（WMLs）与轻度认知障碍（MCI）进展为痴呆的风险增加相关，而记忆缺陷至少部分与胆碱能缺陷有关。我们调查了用斯海尔滕斯量表评估的WML负荷、用[C]N-甲基-4-哌啶基乙酸PET测量的脑乙酰胆碱酯酶（AChE）活性与17例因AD导致MCI的患者及18名认知正常的老年参与者的神经心理学表现之间的关系。在两组中，仅脑室周围而非非脑室周围的WML负荷与AChE活性呈负相关。跨组的记忆表现取决于脑室周围和总的WML负荷。至关重要的是，AChE活性比WML负荷、灰质萎缩或年龄能更好地预测记忆功能。WML负荷对记忆的影响完全由AChE活性介导。数据表明，WML对因AD导致MCI的胆碱能系统功能障碍的影响取决于WML的分布。有必要进行药理学研究以探讨这是否会影响对胆碱能治疗的反应。
