Small Gary W
Department of Psychiatry and Biobehavioral Sciences and the Center on Aging, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA.
Adv Drug Deliv Rev. 2002 Dec 7;54(12):1561-6. doi: 10.1016/s0169-409x(02)00151-5.
The neuropathological and cognitive changes preceding Alzheimer's disease appear to begin subtly decades before symptoms of the disease make the clinical diagnosis obvious. Clinical trials have begun to focus on preventive treatments designed to slow age-related cognitive decline and delay the onset of Alzheimer's disease in people with only mild memory complaints. Because people with few cognitive deficits represent a heterogeneous population, prevention studies require large samples in order to detect active drug effects. To address such challenges, recent neuroimaging studies have focused on middle-aged and older adults with only mild memory complaints and evaluated results according to the major known genetic risk for Alzheimer's disease, the apolipoprotein E-4 (APOE-4) allele. In studies using positron emission tomography during mental rest and functional magnetic resonance imaging during memory task performance, brain patterns differ according to genetic risk and are useful in predicting future decline measures and following disease progression in clinical trials.
阿尔茨海默病出现之前的神经病理学和认知变化似乎在该疾病症状使临床诊断变得明显的几十年前就已悄然开始。临床试验已开始聚焦于预防性治疗,旨在减缓与年龄相关的认知衰退,并延缓仅有轻微记忆问题的人群中阿尔茨海默病的发病。由于认知缺陷较少的人群构成了一个异质性群体,预防研究需要大样本才能检测到药物的有效作用。为应对此类挑战,近期的神经影像学研究聚焦于仅有轻微记忆问题的中老年人,并根据已知的阿尔茨海默病主要遗传风险因素——载脂蛋白E-4(APOE-4)等位基因来评估结果。在静息状态下使用正电子发射断层扫描以及在记忆任务执行过程中使用功能磁共振成像的研究中,脑图谱因遗传风险而异,并且有助于在临床试验中预测未来的衰退指标以及追踪疾病进展。