Department of Neurology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, 59, Daesagwan-ro, Yongsan-gu, Seoul, 04401, Republic of Korea.
Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Republic of Korea.
Alzheimers Res Ther. 2024 Oct 2;16(1):210. doi: 10.1186/s13195-024-01580-y.
Cholinesterase inhibitors (ChEIs) are prescribed for Alzheimer's disease (AD) and sometimes for mild cognitive impairment (MCI) without knowing underlying pathologies and its effect on cognition. We investigated the frequency of ChEI prescriptions in amyloid-negative MCI and their association with cognitive changes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
We included participants with amyloid positron emission tomography (PET)-negative MCI from the ADNI. We analyzed the associations of ChEI use with cognitive changes, brain volume, and cerebrospinal fluid (CSF) total tau (t-tau), hyperphosphorylated tau (p-tau), and p-tau/t-tau ratio.
ChEIs were prescribed in 27.4% of amyloid PET-negative MCI and were associated with faster cognitive decline, reduced baseline hippocampal volume and entorhinal cortical thickness, and a longitudinal decrease in the frontal lobe cortical thickness.
The association between ChEI use and accelerated cognitive decline may stem from underlying pathologies involving reduced hippocampal volume, entorhinal cortical thickness and faster frontal lobe atrophy. We suggest that ChEI use in amyloid PET-negative MCI patients might need further consideration, and studies investigating the causality between ChEI use and cognitive decline are warranted in the future.
胆碱酯酶抑制剂（ChEIs）被用于治疗阿尔茨海默病（AD），有时也用于治疗轻度认知障碍（MCI），但并不了解潜在的病理及其对认知的影响。我们研究了在淀粉样蛋白阴性 MCI 中 ChEI 处方的频率及其与阿尔茨海默病神经影像学倡议（ADNI）队列中认知变化的关系。
我们纳入了 ADNI 中淀粉样蛋白正电子发射断层扫描（PET）阴性 MCI 的参与者。我们分析了 ChEI 使用与认知变化、脑体积以及脑脊液（CSF）总 tau（t-tau）、磷酸化 tau（p-tau）和 p-tau/t-tau 比值之间的关联。
ChEIs 在 27.4%的淀粉样蛋白 PET 阴性 MCI 中被处方，与认知衰退加速、基线海马体积和内嗅皮质厚度降低以及额叶皮质厚度进行性下降有关。
ChEI 使用与认知衰退加速之间的关联可能源于涉及海马体积、内嗅皮质厚度降低和额叶萎缩加速的潜在病理。我们建议，在淀粉样蛋白 PET 阴性 MCI 患者中使用 ChEI 需要进一步考虑，未来有必要研究 ChEI 使用与认知衰退之间的因果关系。
