SUNY Downstate Medical Center, Attending Physician, Lenox Hill Hospital | Northwell Health, 65 East 76th St, New York, NY, 10021, USA.
VU University Medical Center, Alzheimer's Center of VU University Medical Center, Amsterdam, the Netherlands.
Alzheimers Res Ther. 2018 Dec 19;10(1):122. doi: 10.1186/s13195-018-0455-y.
Alzheimer's disease is a heterogenous disorder with multiple phenotypes and genotypes, although they eventually converge to a final common clinicopathological endpoint. However, Alzheimer's disease drug trials do not account for the heterogeneity of the disease in trial design, impeding development of effective drugs.
Alzheimer's disease drug trials commonly have wide inclusion criteria that subsume multiple subtypes of the condition, with varying genotypes, phenotypes, and clinical courses. The outcome variables used in many trials may not be sensitive for the particular disease subtype and trials may not follow patients for the appropriate length of time necessary for the subtype of disease. Methods of stratifying treatment trial design to account for disease heterogeneity using algorithms incorporating demographics, neuroimaging, genetics, and clinical phenotypes, as well as more tailored outcome measures, are proposed to allow for personalized, precision medicine in Alzheimer's disease therapeutics development. Approaching Alzheimer's disease as a heterogenous disorder will likely improve yield in the search for effective treatments for the condition.
阿尔茨海默病是一种具有多种表型和基因型的异质性疾病，尽管它们最终会汇聚到一个共同的临床病理终点。然而，阿尔茨海默病药物试验在试验设计中并未考虑到疾病的异质性，从而阻碍了有效药物的开发。
阿尔茨海默病药物试验通常具有广泛的纳入标准，涵盖了该疾病的多种亚型，具有不同的基因型、表型和临床病程。许多试验中使用的结局变量可能对特定的疾病亚型不敏感，而且试验可能没有按照疾病亚型所需的适当时间长度来随访患者。为了在治疗试验设计中针对疾病异质性进行分层，提出了使用包含人口统计学、神经影像学、遗传学和临床表型的算法以及更针对性的结局测量方法的方法，以实现阿尔茨海默病治疗学的个性化、精准医学。将阿尔茨海默病视为一种异质性疾病可能会提高寻找该疾病有效治疗方法的效果。
