However, this kind of hypothesis can only be addressed by longitudinal studies. The relationship between amyloid burden as assessed by PET imaging and longitudinal change in cognitive function in cognitively normal and MCI populations is currently under examination in multiple trials, including the US ADNI Cabozantinib molecular weight study [40] (11C-PIB, phase 1, and florbetapir F 18, phase 2), the Australian Imaging, Biomarkers and Lifestyle Initiative (AIBL) initiative [43] (11C-PIB) and several ongoing longitudinal trials of aging [62,67], as well as in several trials with 18F-labeled agents that are either still ongoing (flutemetamol, NCT01028053; florbetaben, NCT01138111; ClinicalTrials.gov) or recently completed (florbetapir) [59]. First results, now coming into the literature, strongly suggest a relationship between amyloid burden and AD progression.

Four published studies have examined the potential of 11C-PIB PET amyloid imaging to predict progression from MCI to AD. Forsberg and colleagues [57] imaged 27 MCI subjects and reported that 7 who subsequently converted to AD had higher PIB retention than non-converting subjects. Okello and colleagues [56] studied 31 MCI subjects, 17 (55%) of whom were considered amyloid- positive on an 11C-PIB PET scan. Of these 17 subjects, 14 (82%) converted from MCI to AD in the follow-up period (up to 3 years). Only 1 of 14 (7%) amyloid-negative subjects converted in the same time period. A comparison of fast (<1 year) versus slower converters suggested that fast converters (within one year of scan; 8 of 17 amyloid-positive subjects) had higher 11C-PIB PET cortical to cerebellar uptake ratios than the slower converters, despite a similar mean age.

Notably, all fast converters for whom genotype was available carried an apolipoprotein E ??4 alleole, whereas only two of six slow converters with genotype information carried an apolipoprotein E ??4 alleole. Thus, the ??4 alleole may have contributed Anacetrapib to both the elevated amyloid burden (increased SUVR) and the more rapid conversion. Wolk and colleagues [68] similarly reported a higher rate of conversion in subjects classified as amyloid-positive (5 of 13, 38%) versus amyloid-negative (zero of 10) by 11C-PIB PET. Finally, Jack and colleagues [69] recently published the first report of follow-up results from the ADNI study.

Of 218 MCI subjects included in the analysis, 11C-PIB data were available for 53 subjects, and CSF A?? levels, but not sellekchem 11C-PIB, were available for 165. In order to increase power and to better draw conclusions regarding relationships between amyloid burden and disease progression, CSF data from subjects who did not undergo 11C-PIB imaging were transformed to facilitate a combined quantitative analysis. Over the observation period, 81 of 165 amyloid-positive versus 8 of 53 amyloid-negative MCI subjects progressed to AD. A Kaplin Meyer analysis estimated a significantly increased hazard ratio (3.