Enrichment and stratification for predementia Alzheimer disease clinical trials.
Enrichment and stratification for predementia Alzheimer disease clinical trials.
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DOI：
10.1371/journal.pone.0047739
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Holland D;McEvoy LK;Desikan RS;Dale AM;Alzheimer’s Disease Neuroimaging Initiative
The tau and amyloid pathobiological processes underlying Alzheimer disease (AD) progresses slowly over periods of decades before clinical manifestation as mild cognitive impairment (MCI), then more rapidly to dementia, and eventually to end-stage organ failure. The failure of clinical trials of candidate disease modifying therapies to slow disease progression in patients already diagnosed with early AD has led to increased interest in exploring the possibility of early intervention and prevention trials, targeting MCI and cognitively healthy (HC) populations. Here, we stratify MCI individuals based on cerebrospinal fluid (CSF) biomarkers and structural atrophy risk factors for the disease. We also stratify HC individuals into risk groups on the basis of CSF biomarkers for the two hallmark AD pathologies. Results show that the broad category of MCI can be decomposed into subsets of individuals with significantly different average regional atrophy rates. By thus selectively identifying individuals, combinations of these biomarkers and risk factors could enable significant reductions in sample size requirements for clinical trials of investigational AD-modifying therapies, and provide stratification mechanisms to more finely assess response to therapy. Power is sufficiently high that detecting efficacy in MCI cohorts should not be a limiting factor in AD therapeutics research. In contrast, we show that sample size estimates for clinical trials aimed at the preclinical stage of the disorder (HCs with evidence of AD pathology) are prohibitively large. Longer natural history studies are needed to inform design of trials aimed at the presymptomatic stage.
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影响因子：
4.2
作者：
Cardenas, V. A.;Chao, L. L.;Studholme, C.;Yaffe, K.;Miller, B. L.;Madison, C.;Buckley, S. T.;Mungas, D.;Schuff, N.;Weiner, M. W.
通讯作者：
Weiner, M. W.
影响因子：
11.2
作者：
Desikan, Rahul S.;McEvoy, Linda K.;Thompson, Wesley K.;Holland, Dominic;Roddey, J. Cooper;Blennow, Kaj;Aisen, Paul S.;Brewer, James B.;Hyman, Bradley T.;Dale, Anders M.
通讯作者：
Dale, Anders M.
DOI：
10.1016/j.jalz.2010.11.007
发表时间：
2011-01
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Brookmeyer R;Evans DA;Hebert L;Langa KM;Heeringa SG;Plassman BL;Kukull WA
通讯作者：
Kukull WA
影响因子：
9.9
作者：
Bakkour, Akram;Morris, John C.;Dickerson, Bradford C.
通讯作者：
Dickerson, Bradford C.
影响因子：
11.2
作者：
Becker, J. Alex;Hedden, Trey;Carmasin, Jeremy;Maye, Jacqueline;Rentz, Dorene M.;Putcha, Deepti;Fischl, Bruce;Greve, Douglas N.;Marshall, Gad A.;Salloway, Stephen;Marks, Donald;Buckner, Randy L.;Sperling, Reisa A.;Johnson, Keith A.
通讯作者：
Johnson, Keith A.