Effect of Age Range on Power for a Clinical Trial Investigating the Effect of Intensive Systolic Blood Pressure Control on White Matter Hyperintensity Volume Accumulation

Abstract

AbstractBackgroundEpidemiological evidence has repeatedly demonstrated elevated systolic blood pressure (SBP) in midlife as a modifiable risk factor for Alzheimer’s Disease and Related Dementia (ADRD) later in life. Despite SBP being readily treatable with safe and inexpensive medications, no clinical intervention implementing a lower SBP goal (<120 mm Hg) in midlife to lower future ADRD risk has ever been attempted. Clinical outcomes are not practical in the age range of interest (45‐65 or 45‐70) during an initial trial period of 5 years however robust evidence demonstrates white matter hyperintensity volume (WMHV) as an MRI finding associated with and predictive of incident ADRD.MethodWe used four data sets (SPRINT, Wisconsin Registry for Alzheimer’s Prevention, Framingham, and UK Biobank) with longitudinal MRI data to examine the effect of age range on power for a clinical trial proposal investigating the effect of intensive SBP control on annualized rates of WMHV accumulation in persons starting in middle age. Analyses were conducted separately in each data set. We calculated mean, standard deviations, and annualized rates of WMHV accumulation (derived from T2 FLAIR MRI), using the linear rate of change for accumulation rate, first stratifying by SBP ( = 132 mm Hg vs <132mm Hg except in SPRINT where groups were stratified by goal SBP group) and then by various age ranges. Next, we examined the effect of age range on necessary sample size with 80% power and two‐tailed alpha of 0.05 for a prospective clinical trial.ResultAs expected, annualized WMHV accumulation rate is lower with younger age in all data sets. However, variability decreased (all four data sets) and the percent reduction achieved at lower SBPs is higher at younger ages (3/4 data sets), thus increasing power when excluding older individuals (e.g., >65 years old, Table 1).ConclusionRestricting age to individuals to = 65 years‐old may unexpectedly increase power in a clinical trial designed to investigate the effect of goal SBP<120 mm Hg on annualized WMHV accumulation rate. 45‐65 years‐old is a practical age range for the first ever clinical trial intended to investigate the effects of a lower SBP goal in middle age to reduce future ADRD risk.