Isolated Systolic Hypertension

In reply:-We appreciate Dr Schneider’s insightful analysis and comments, which provide compelling evidence that the Blessed Information Memory Concentration Test (IMC) has less variability associated with its annual rate of change than the MMSE. Regarding the issue of estimating clinical trial size, many compounds currently under development for Alzheimer’s Disease (AD) are anticipated to produce only modest slowing of the rate of progression. Thus, while a relatively small number of subjects would be needed to detect a 50% change in the rate of decline of the IMC over 1 year, 502 subjects would be needed to detect a 25% change in the rate of decline with 80% confidence (assuming the IMC declines by 4 f 4 points per year). During a clinical trial, the amount of variability associated with serial administration of cognitive tests can be further reduced by giving the test on more than two occasions, allowing statistical methods such as repeated-measures analysis to be brought into play. This would reduce the sample size required to detect a drug effect, making studies of drugs with effect sizes smaller than 50% feasible. In clinical practice, it is harder to interpret serial IMC or MMSE scores as an indicator of progression. For example, in early AD, where the clinical diagnosis is often equivocal, the clinician may be misled by finding very little or even no decline of test scores after following a patient for as long as a year. Although Dr Schneider has made a strong point in favor of the IMC as a measure of change, we would l i e to see efforts directed at developing new approaches or scales that have less noise or variability when used to tract cognitive progression in AD.