Predictors of placebo group decline in the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) in 24 week clinical trials of Alzheimer's disease.
One limitation of several recent 24 week Alzheimer's disease (AD) clinical trials was the lack of cognitive decline detected by the AD Assessment Scale-cognitive subscale (ADAS-cog) in the placebo groups, possibly obscuring true medication effects. Data from 733 individuals in the placebo arms of six AD clinical trials performed 1996-1997 were pooled to examine the relationship of clinical, demographic, and genetic characteristics with the 24 week change in ADAS-cog. Baseline cognitive and functional status and the screening-to-baseline change in ADAS-cog were the strongest independent predictors of the 24 week change in ADAS-cog. The ADAS-cog did not detect progression in patients with mild dementia (screening Mini-Mental State Exam, MMSE, >or=20). The change in ADAS-cog from screening to baseline was inversely correlated with the 24 week change score; it was more difficult to detect cognitive decline at 24 weeks if individuals markedly worsened from screening to baseline. The effects of baseline MMSE and screening-to-baseline change in ADAS-cog generalized to the placebo group (N=106) of another AD study performed in 2004-2005. Overcoming lack of placebo decline in AD clinical trials will require scales more sensitive to cognitive decline in mild AD and strategies to reduce within-person variability in outcome measures.
Irizarry
Michael C
MC
WW Epidemiology, GlaxoSmithKline, Harlow, UK. michael.c.irizarry@gsk.com
Webb
David J
DJ
Bains
Chanchal
C
Barrett
Steven J
SJ
Lai
Robert Y
RY
Laroche
Janette P
JP
Hosford
David
D
Maher-Edwards
Gareth
G
Weil
John G
JG
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D000077154:Rosiglitazone; D012720:Severity of Illness Index; D045162:Thiazolidinediones / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000627:therapeutic use
D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000077154:Rosiglitazone