A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

Publisher: Bentham Science Publishers

E-ISSN: 1875-5828|15|5|429-442

ISSN: 1567-2050

Source: Current Alzheimer Research, Vol.15, Iss.5, 2018-03, pp. : 429-442

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Background: Combining optimized cognitive (Alzheimer#39;s Disease Assessment Scale-Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer#39;s disease for tracking progression inclinical trials may provide greater sensitivity than currently used methods, which have yielded negativeresults in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponentsyielded by cognitive and imaging testing, to address the symptomatic and anatomical variabilityof Alzheimer#39;s disease.

Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitiveimpairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer#39;sclinical trials that combines cognitive and atrophy markers.

Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitivedomains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivityin tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and areal world problem. The biomarker also improved the selection of MCI patients (78.8#177;4.9% specificityat 80% sensitivity) that will evolve to Alzheimer#39;s disease for clinical trials.

Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in themild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatmenteffects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.