The Alzheimer's Prevention Initiative Composite Cognitive Test Score: Sample Size Estimates for the Evaluation of Preclinical Alzheimer's Disease Treatments in Presenilin 1 E280A Mutation Carriers

被引:57
作者
Ayutyanont, Napatkamon [1 ,3 ]
Langbaum, Jessica B. S. [1 ,3 ]
Hendrix, Suzanne B. [6 ]
Chen, Kewei [1 ,3 ,4 ]
Fleisher, Adam S. [1 ,3 ,7 ]
Friesenhahn, Michel [8 ]
Ward, Michael [8 ]
Aguirre, Camilo [9 ]
Acosta-Baena, Natalia [9 ]
Madrigal, Lucia [9 ]
Munoz, Claudia [9 ]
Tirado, Victoria [9 ]
Moreno, Sonia [9 ]
Tariot, Pierre N. [1 ,3 ,5 ]
Lopera, Francisco [9 ]
Reiman, Eric M. [1 ,2 ,3 ,5 ]
机构
[1] Banner Alzheimers Inst, Phoenix, AZ 85006 USA
[2] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA
[3] Arizona Alzheimers Consortium, Phoenix, AZ USA
[4] Arizona State Univ, Dept Math & Stat, Tempe, AZ USA
[5] Univ Arizona, Dept Psychiat, Tucson, AZ USA
[6] Pentara Corp, Salt Lake City, UT USA
[7] Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA
[8] F Hoffmann La Roche & Co Ltd, San Francisco, CA USA
[9] Univ Antioquia, Grp Neurociencias Antioquia, Medellin, Colombia
基金
美国国家卫生研究院;
关键词
PRESYMPTOMATIC TREATMENTS; CLINICAL-TRIALS; DECLINE; MEMORY; IMPAIRMENT; ONSET; OLDER; PERFORMANCE; PROGRESSION; BETA;
D O I
10.4088/JCP.13m08927
中图分类号
B849 [应用心理学];
学科分类号
040203 ;
摘要
Objective: To identify a cognitive composite that is sensitive to tracking preclinical Alzheimer's disease decline to be used as a primary end point in treatment trials. Method: We capitalized on longitudinal data collected from 1995 to 2010 from cognitively unimpaired presenilin 1 (PSEN1) E280A mutation carriers from the world's largest known early-onset autosomal dominant Alzheimer's disease kindred to identify a composite cognitive test with the greatest statistical power to track preclinical Alzheimer's disease decline and estimate the number of carriers age 30 years and older needed to detect a treatment effect in the Alzheimer's Prevention Initiative's (API) preclinical Alzheimer's disease treatment trial. The mean-to-standard-deviation ratios (MSDRs) of change over time were calculated in a search for the optimal combination of 1 to 7 cognitive tests/subtests drawn from the neuropsychological test battery in cognitively unimpaired mutation carriers during a 2- and 5-year follow-up period (n = 78 and 57), using data from noncarriers (n = 31 and 56) during the same time period to correct for aging and practice effects. Combinations that performed well were then evaluated for robustness across follow-up years, occurrence of selected items within top-performing combinations, and representation of relevant cognitive domains. Results: The optimal test combination included Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Recall, CERAD Boston Naming Test (high frequency items), Mini-Mental State Examination (MMSE) Orientation to Time, CERAD Constructional Praxis, and Raven's Progressive Matrices (Set A), with an MSDR of 1.62. This composite is more sensitive than using either the CERAD Word List Recall (MSDR = 0.38) or the entire CERAD-Col battery (MSDR = 0.76). A sample size of 75 cognitively normal PSEN1 E280A mutation carriers aged 30 years and older per treatment arm allows for a detectable treatment effect of 29% in a 60-month trial (80% power, P = .05). Conclusions: We have identified a composite cognitive test score representing multiple cognitive domains that, compared to the most sensitive single test item, has improved power to track preclinical Alzheimer's disease decline in autosomal dominant Alzheimer's disease mutation carriers and to evaluate preclinical Alzheimer's disease treatments. This API composite cognitive test score will be used as the primary end point in the first API trial in cognitively unimpaired autosomal dominant Alzheimer's disease carriers within 15 years of their estimated age at clinical onset. We have independently confirmed our findings in a separate cohort of cognitively healthy older adults who progressed to the clinical stages of late-onset Alzheimer's disease, described in a separate report, and continue to refine the composite in independent cohorts and compared with other analytic approaches. (C) Copyright 2014 Physicians Postgraduate Press, Inc.
引用
收藏
页码:652 / 660
页数:9
相关论文
共 43 条
[1]   Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study [J].
Acosta-Baena, Natalia ;
Sepulveda-Falla, Diego ;
Mario Lopera-Gomez, Carlos ;
Cesar Jaramillo-Elorza, Mario ;
Moreno, Sonia ;
Camilo Aguirre-Acevedo, Daniel ;
Saldarriaga, Amanda ;
Lopera, Francisco .
LANCET NEUROLOGY, 2011, 10 (03) :213-220
[2]   Report of the task force on designing clinical trials in early (predementia) AD [J].
Aisen, P. S. ;
Andrieu, S. ;
Sampaio, C. ;
Carrillo, M. ;
Khachaturian, Z. S. ;
Dubois, B. ;
Feldman, H. H. ;
Petersen, R. C. ;
Siemers, E. ;
Doody, R. S. ;
Hendrix, S. B. ;
Grundman, M. ;
Schneider, L. S. ;
Schindler, R. J. ;
Salmon, E. ;
Potter, W. Z. ;
Thomas, R. G. ;
Salmon, D. ;
Donohue, M. ;
Bednar, M. M. ;
Touchon, J. ;
Vellas, B. .
NEUROLOGY, 2011, 76 (03) :280-286
[3]   Prodromal Alzheimer's Disease: Successive Emergence of the Clinical Symptoms [J].
Amieva, Helene ;
Le Goff, Melanie ;
Millet, Xavier ;
Orgogozo, Jean Marc ;
Peres, Karine ;
Barberger-Gateau, Pascale ;
Jacqmin-Gadda, Helene ;
Dartigues, Jean Francois .
ANNALS OF NEUROLOGY, 2008, 64 (05) :492-498
[4]  
[Anonymous], DRAFT GUID
[5]  
Arango Lasprilla Juan Carlos, 2003, Am J Alzheimers Dis Other Demen, V18, P137
[6]  
Ashford JW, 2011, HDB IMAGING ALZHEIME
[7]  
Ayutyanont N, 2011, ALZHEIMERS DEMENT, V7, pS608
[8]   Gaining precision on the Alzheimer's Disease Assessment Scale-cognitive: A comparison of item response theory-based scores and total scores [J].
Balsis, Steve ;
Unger, Alexis A. ;
Benge, Jared F. ;
Geraci, Lisa ;
Doody, Rachelle S. .
ALZHEIMERS & DEMENTIA, 2012, 8 (04) :288-294
[9]   Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease [J].
Bateman, Randall J. ;
Xiong, Chengjie ;
Benzinger, Tammie L. S. ;
Fagan, Anne M. ;
Goate, Alison ;
Fox, Nick C. ;
Marcus, Daniel S. ;
Cairns, Nigel J. ;
Xie, Xianyun ;
Blazey, Tyler M. ;
Holtzman, David M. ;
Santacruz, Anna ;
Buckles, Virginia ;
Oliver, Angela ;
Moulder, Krista ;
Aisen, Paul S. ;
Ghetti, Bernardino ;
Klunk, William E. ;
McDade, Eric ;
Martins, Ralph N. ;
Masters, Colin L. ;
Mayeux, Richard ;
Ringman, John M. ;
Rossor, Martin N. ;
Schofield, Peter R. ;
Sperling, Reisa A. ;
Salloway, Stephen ;
Morris, John C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (09) :795-804
[10]   The ADAS-cog in Alzheimer's disease clinical trials: psychometric evaluation of the sum and its parts [J].
Cano, Stefan J. ;
Posner, Holly B. ;
Moline, Margaret L. ;
Hurt, Stephen W. ;
Swartz, Jina ;
Hsu, Tim ;
Hobart, Jeremy C. .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2010, 81 (12) :1363-1368