A neuropsychological test battery for use in Alzheimer disease clinical trials.
OBJECTIVE
To report the psychometric properties of an alternative instrument to the cognitive subscale of the Alzheimer's Disease Assessment Scale, a neuropsychological test battery (NTB) for measuring drug efficacy in Alzheimer disease clinical trials.


METHODS
The NTB was evaluated in a randomized, double-blind, placebo-controlled trial of AN1792(QS-21) (synthetic beta-amyloid plus an adjuvant) (300 patients) and isotonic sodium chloride solution (72 patients). The test-retest reliability of the NTB was examined, and the NTB was correlated with other cognitive (cognitive subscale of the Alzheimer's Disease Assessment Scale and Mini-Mental State Examination) and functional (Disability Assessment Scale for Dementia and Clinical Dementia Rating Sum of Boxes) measures. In addition, a factor analysis was performed on NTB components. Finally, the sensitivity of the NTB to change was assessed as a function of Mini-Mental State Examination performance.


RESULTS
The NTB had high test-retest reliability at 6 (Pearson product moment correlation [r] = 0.92) and 12 (r = 0.88) months. Internal consistency was high (Cronbach alpha = 0.84). The correlations between the NTB z score and scores on traditional measures of cognition and function were significantly different from 0 (P < .001). A factor analysis yielded "memory" and "executive function" factors. The NTB z score declined linearly over 1 year in patients receiving placebo and, in contrast to the Alzheimer's Disease Assessment Scale cognitive subscale, demonstrated similar declines in patients with high (21-26) and low (15-20) Mini-Mental State Examination scores at baseline.


CONCLUSIONS
The NTB exhibits excellent psychometric properties and seems to be a reliable and sensitive measure of cognitive change in patients with mild to moderate Alzheimer disease. The psychometric properties of the NTB suggest that it may have particular utility in evaluating drug efficacy in clinical trials in which patients with mild Alzheimer disease are included.
Harrison
John
J
CPC Pharma Services, PO Box 3223, Warminster, Wiltshire BA12 8XA, England. johncpc@btinternet.com
Minassian
Sonia L
SL
Jenkins
Lisa
L
Black
Ronald S
RS
Koller
Martin
M
Grundman
Michael
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003071:Cognition / Q000502:physiology; D004311:Double-Blind Method; D005163:Factor Analysis, Statistical; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D011939:Mental Recall / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D021641:Recognition, Psychology / Q000502:physiology; D015203:Reproducibility of Results; D014706:Verbal Learning; D014888:Wechsler Scales
C437846:AN-1792; D016229:Amyloid beta-Peptides