The Memory Disorders Center and the Division of Geriatric Psychiatry at the New York State Psychiatric Institute, New York, NY, USA.
Department of Neurology and the Taub Institute for Research in Alzheimer's disease at Columbia University Medical Center, New York, NY, USA.
J Alzheimers Dis. 2020;75(3):845-854. doi: 10.3233/JAD-200021.
Anticholinergic challenge can induce odor identification impairment that indicates Alzheimer's disease (AD) pathology, and short-term change in odor identification impairment with cholinesterase inhibitor (CheI) treatment may predict longer term cognitive outcomes.
In patients with mild cognitive impairment (MCI) treated prospectively with donepezil, a CheI, for 52 weeks, to determine if 1) acute decline in odor identification ability with anticholinergic challenge can predict cognitive improvement, and 2) change in odor identification over 8 weeks can predict cognitive improvement.
MCI was diagnosed clinically without AD biomarkers. At baseline, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge. Donepezil was started at 5 mg daily, increased to 10 mg daily if tolerated, and this dose was maintained for 52 weeks. Main outcomes were ADAS-Cog total score and Selective Reminding Test (SRT) total immediate recall score measured at baseline, 26 and 52 weeks.
In 100 study participants, mean age 70.14 (SD 9.35) years, atropine-induced decrease in UPSIT score at baseline was not associated with change in ADAS-Cog or SRT scores over 52 weeks. Change in UPSIT score from 0 to 8 weeks did not show a significant association with change in the ADAS-Cog or SRT measures over 52 weeks.
These negative findings in a relatively large sample of patients with MCI did not replicate results in much smaller samples. Change in odor identification with anticholinergic challenge, and over 8 weeks, may not be useful predictors of cognitive improvement with CheI in patients with MCI.
抗胆碱能挑战可引起嗅觉识别障碍，这表明存在阿尔茨海默病（AD）病理，而胆碱酯酶抑制剂（CheI）治疗后嗅觉识别障碍的短期变化可能预测更长期的认知结局。
在接受前瞻性多奈哌齐治疗的轻度认知障碍（MCI）患者中，确定 1）抗胆碱能挑战时嗅觉识别能力的急性下降是否可预测认知改善，以及 2）8 周内嗅觉识别的变化是否可预测认知改善。
MCI 的临床诊断不依赖于 AD 生物标志物。在基线时，在接受抗胆碱能阿托品鼻喷雾剂挑战之前和之后，进行宾夕法尼亚大学嗅觉识别测试（UPSIT）。多奈哌齐起始剂量为 5mg/天，如果耐受可增加至 10mg/天，此剂量维持 52 周。主要结局为基线、26 周和 52 周时的 ADAS-Cog 总分和选择性提醒测试（SRT）总即刻回忆评分。
在 100 名研究参与者中，平均年龄为 70.14（9.35）岁，基线时 UPSIT 评分的阿托品诱导下降与 52 周时 ADAS-Cog 或 SRT 评分的变化无关。0 至 8 周时 UPSIT 评分的变化与 52 周时 ADAS-Cog 或 SRT 测量值的变化没有显著关联。
在 MCI 患者的较大样本中，这些阴性发现未能复制在较小样本中的结果。抗胆碱能挑战后以及 8 周内的嗅觉识别变化可能无法作为 CheI 治疗 MCI 患者认知改善的有用预测指标。
