Conference Coverage
Results were different among patients who progressed slowly, said Dr. Retout. “Among slow progressers, no exposure-response relationship could be observed, indicating that the slow disease progression over the two-year treatment period was probably limiting the detection of a drug effect,” she said.
Finding the Right Trial Population
Variability in progression, dropout rates, and potentially skewed clinical outcomes are difficult challenges for trials of drugs to treat Alzheimer’s disease, said Dr. Lasser. “This is likely to continue to surprise us if we still have 25% to 30% [of participants] in our trials who don’t decline over the course of treatment. There really aren’t any big differences at baseline that stand out so that you could create the inclusion criteria to minimize this population of patients.”
Amyloid imaging, which allows the recruitment of a population with pure Alzheimer’s disease, was not widely available when the SCARLET ROAD cohort was recruited. And although amyloid imaging helps to predict conversion from mild cognitive impairment to dementia, it is less useful as a tool for predicting progression. Taking baseline CSF tau levels into account did not improve the prediction of progression, said Dr. Lasser. APOE allele status was similarly unhelpful.
“We didn’t find very much difference among the allele groups; there was no consistent pattern, and the between-group differences were small. So, we’re beginning to hypothesize that while APOE is an excellent risk marker before cognitive decline develops, once it does start, allele status may not be as crucial in determining the patient’s eventual outcome.”
The only hints of progression speed at baseline were in the two functional measures of CDR-SOB and FAQ. Patients with rapid progression showed significantly more impairment on both of these scales at baseline than did patients with slow progression.
“Progression seems to be more likely in those who have functional decline already present as part of their prodromal presentation,” said Dr. Lasser. “At baseline, the most meaningful difference was not the MMSE, but the CDR-SOB. This indicates that functional impairment may be a critical factor to look at when you’re enrolling subjects.”
—Michele G. Sullivan