Biomarkers and cognitive endpoints to optimize trials in Alzheimer's disease

被引：28

作者：

Insel, Philip S. ^{[1
,2
]}

Mattsson, Niklas ^{[1
,2
,3
]}

Mackin, R. Scott ^{[1
,4
]}

Kornak, John ^{[5
]}

Nosheny, Rachel ^{[1
]}

Tosun-Turgut, Duygu ^{[1
,2
]}

Donohue, Michael C. ^{[6
,7
]}

Aisen, Paul S. ^{[7
]}

Weiner, Michael W. ^{[1
,2
]}

机构：

[1] Ctr Imaging Neurodegenerat Dis, Dept Vet Affairs Med Ctr, San Francisco, CA 94121 USA

[2] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA

[3] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden

[4] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA

[5] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[6] Univ Calif San Diego, Dept Family & Prevent Med, Div Biostat & Bioinformat, San Diego, CA 92103 USA

[7] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA

来源：

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY | 2015年 / 2卷 / 05期

关键词：

CEREBROSPINAL-FLUID; AMYLOID-BETA; SENILE PLAQUES; CSF BIOMARKERS; DECLINE; DEPOSITION; ACCUMULATION; ASSOCIATION; IMPAIRMENT; CORRELATE;

D O I：

10.1002/acn3.192

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: To find the combination of candidate biomarkers and cognitive endpoints to maximize statistical power and minimize cost of clinical trials of healthy elders at risk for cognitive decline due to Alzheimer's disease. Methods: Four-hundred and twelve cognitively normal participants were followed over 7 years. Nonlinear methods were used to estimate the longitudinal trajectories of several cognitive outcomes including delayed memory recall, executive function, processing speed, and several cognitive composites by subgroups selected on the basis of biomarkers, including APOE-epsilon 4 allele carriers, cerebrospinal fluid biomarkers (A beta(42), total tau, and phosphorylated tau), and those with small hippocampi. Results: Derived cognitive composites combining Alzheimer's Disease Assessment Scale (ADAS)-cog scores with additional delayed memory recall and executive function components captured decline more robustly across biomarker groups than any measure of a single cognitive domain or ADAS-cog alone. Substantial increases in power resulted when including only participants positive for three or more biomarkers in simulations of clinical trials. Interpretation: Clinical trial power may be improved by selecting participants on the basis of amyloid and neurodegeneration biomarkers and carefully tailoring primary cognitive endpoints to reflect the expected decline specific to these individuals.

引用

页码：534 / 547

页数：14

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