This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using ﬂorbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer’s disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ− ), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ− subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs −0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal ﬂuency test (Po0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal ﬂuency (Po0.05), whereas Aβ+ AD patients showed greater declines in verbal ﬂuency and the MMSE (Po0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (Po0.04), a global clinical assessment. Aβ+ subjects did not show signiﬁcantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these ﬁndings suggest that in CN, MCI and AD subjects, ﬂorbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ− subjects do.
Doraiswamy P.M., Sperling R.A., Johnson K., Reiman E.M., et al. “Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.” AV45-A11 Study Group; Mol Psychiatry, 19(9): 1044-51. doi: 10.1038/mp.2014.9. Epub, (2014).