A biomarker combining imaging and neuropsychological assessment for tracking early Alzheimer’s disease in clinical trials

Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale-Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer’s disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcom-ponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer’s disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8+4.9% specificity at 80% sensitivity) that will evolve to Alzheimer’s disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

Original languageEnglish (US)
Pages (from-to)429-442
Number of pages14
JournalCurrent Alzheimer Research
Issue number5
StatePublished - 2018


  • Alzheimer's clinical trial
  • Alzheimer's disease assessment scale
  • Cerebral atrophy
  • Cognitive impairment
  • Latent variable modeling
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Medicine(all)


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