TY - JOUR
T1 - Using baseline cognitive severity for enriching Alzheimer's disease clinical trials
T2 - How does Mini-Mental State Examination predict rate of change?
AU - Kennedy, Richard E.
AU - Cutter, Gary R.
AU - Wang, Guoqiao
AU - Schneider, Lon S.
N1 - Funding Information:
Funding acknowledgments: Funding for this reported was provided by NIH ( R01 AG 037561, P50 AG05142 ). Data used in the preparation of this study were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI, NIA [ U01 AG024904 ]) database ( www.loni.ucla.edu/ADNI ), and from the ADCS ( NIH AG10483 ). Study sponsorship or funding: Supported by NIH R01 AG037561 . Contributors. Conflict of interest statement. [During the 36 month window before submission] Disclosures of all authors' financial relationships deemed relevant to the manuscript: Dr. Lon S. Schneider reports being an editor on the Cochrane Collaboration Dementia and Cognitive Improvement Group, which oversees systematic reviews of drugs for cognitive impairment and dementia; receiving a grant from the Alzheimer's Association for a registry for dementia and cognitive impairment trials; within the past three years receiving grant or research support from NIA , Baxter , Eli Lilly , Forum , Genentech , Lundbeck , Merck , Novartis , Pfizer and Tau Rx ; and having served as a consultant for or receiving consulting fees from AC Immune, Allon, AstraZeneca, Avraham Pharmaceutical, Ltd, Baxter, Biogen Idec, Cerespir, Cytox, Elan, Eli Lilly, Forum, GlaxoSmithKline, Johnson & Johnson, Lundbeck, Merck, Pfizer, Roche, Servier, Takeda, Toyama, and Zinfandel.
Funding Information:
Dr. Richard E. Kennedy reports receiving grant support from NIA (R01 AG 037561, R01 AG015062), NINDS (U01 NS41588), NHLBI (T32 HL072757), NIDDK (P60 DK079626), and the Department of Education (H133A070039). Mr. Guoqiao Wang reports receiving grant support from NIA (R01 AG 037561). Dr. Gary R. Cutter reports receiving grant or research support from Participation of Data and Safety Monitoring Committees: All the below organizations are focused on medical research: Apotek, Biogen-Idec, Cleveland Clinic, Glaxo Smith Klein Pharmaceuticals, Gilead Pharmaceuticals, Modigenetech/Prolor, Merck/Ono Pharmaceuticals, Merck, Neuren, Revalesio, Sanofi-Aventis, Teva, Vivus, NHLBI (Bone Marrow Transplant Protocol Review Committee), NINDS, NMSS, NICHD (OPRU oversight committee). Consulting, Speaking fees & Adviosry Boards: Alexion, Allozyne, Bayer, Celgene, Coronado Biosciences, Consortium of MS Centers (grant), Diogenix, Klein-Buendel Incorporated, Medimmune, Novartis, Nuron Biotech, Receptos, Spiniflex Pharmaceuticals, Teva pharmaceuticals. Dr. Cutter is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc. a private consulting company located in Birmingham, AL.
Publisher Copyright:
© 2015 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
PY - 2015/10/14
Y1 - 2015/10/14
N2 - Background Post hoc analyses from clinical trials in Alzheimer's disease (AD) suggest that more cognitively impaired participants respond differently from less impaired on cognitive outcomes. We examined pooled clinical trials data to assess the utility of enriching trials using baseline cognition. Methods We included 2882 participants with mild to moderate AD in seven studies from a meta-database. We used mixed effects models to estimate the rate of decline in Alzheimer's disease Assessment Scale-cognitive (ADAS-Cog) scores among Mini-Mental State Examination (MMSE) groups. Findings Baseline MMSE category was associated with baseline scores and rate of decline on the ADAS-Cog, adjusting for age and education (both P <.001). Greater baseline cognitive impairment was associated with more rapid progression. Interpretations Although we found significant differences in rate of decline, most differences between individuals were from baseline ADAS-Cog values. Since enrichment based on MMSE would reduce the recruitment pool while adding only slightly to detecting differences in rate of progression, it is not advised.
AB - Background Post hoc analyses from clinical trials in Alzheimer's disease (AD) suggest that more cognitively impaired participants respond differently from less impaired on cognitive outcomes. We examined pooled clinical trials data to assess the utility of enriching trials using baseline cognition. Methods We included 2882 participants with mild to moderate AD in seven studies from a meta-database. We used mixed effects models to estimate the rate of decline in Alzheimer's disease Assessment Scale-cognitive (ADAS-Cog) scores among Mini-Mental State Examination (MMSE) groups. Findings Baseline MMSE category was associated with baseline scores and rate of decline on the ADAS-Cog, adjusting for age and education (both P <.001). Greater baseline cognitive impairment was associated with more rapid progression. Interpretations Although we found significant differences in rate of decline, most differences between individuals were from baseline ADAS-Cog values. Since enrichment based on MMSE would reduce the recruitment pool while adding only slightly to detecting differences in rate of progression, it is not advised.
KW - Alzheimer disease
KW - Alzheimer's Disease Assessment Scale
KW - Alzheimer's Disease Cooperative study (ADCS)
KW - Alzheimer's Disease Neuroimaging Initiative (ADNI)
KW - Clinical trials
KW - Clinical trials and methods
KW - Mini-Mental State Examination
KW - Simulations
UR - http://www.scopus.com/inward/record.url?scp=84944062096&partnerID=8YFLogxK
U2 - 10.1016/j.trci.2015.03.001
DO - 10.1016/j.trci.2015.03.001
M3 - Article
C2 - 27695707
AN - SCOPUS:84944062096
SN - 2352-8737
VL - 1
SP - 46
EP - 52
JO - Alzheimer's and Dementia: Translational Research and Clinical Interventions
JF - Alzheimer's and Dementia: Translational Research and Clinical Interventions
IS - 1
ER -