Background: Converging evidence from autopsy, cerebrospinal fluid, and PET amyloid imaging studies suggests
that a substantial proportion of clinically normal, older individuals harbor amyloid-β pathology. The clinical
relevance of amyloid deposition in healthy older individuals remains to be fully elucidated, as neuropsychological studies in amyloid-positive older individuals have yielded variable results to date. In this study, we evaluated the relationship of amyloid burden and cognition in healthy control (HC) subjects recruited in a multicenter study of florbetapir F18 (18F-AV-45) PET amyloid imaging.
Methods: Seventy-eight HC subjects (CDR=0, MMSE>29, mean age 69.5±11.1) were assessed with a brief
cognitive test battery, including the Weschler memory immediate and delayed recall, digit-symbol substitution,
verbal fluency and ADAS-Cog. Subjects underwent PET amyloid imaging during a 10 min acquisition, 50 min
following i.v. injection of 10 mCi (370 MBq) of 18F-AV-45. SUVr were calculated from a combined set of 6 cortical
regions. Scans were also visually scored as amyloid+ or amyloid- by 3 blinded readers.
Results: Among the 78 HC subjects, SUVr was significantly related to both lower immediate (partial r=-0.33; p=0.003) and delayed recall scores (partial r=-0.28; p=0.017), controlling for both age and education. Digit-symbol substitution also demonstrated a relationship with SUVr (p=0.035), but this was no longer significant with age included in the model. On visual inspection, 11/78 (14%) of the HCs were rated as amyloid+. Performance on
immediate recall was significantly lower in the amyloid+ (11.9±3.99) compared with amyloid- HCs (14.0±2.94,
p=0.04); with a similar trend observed in delayed recall (p=0.061).
Conclusions: These results indicate that high amyloid burden is associated with decreased memory performance,
even within the range seen in clinically normal older subjects. Longitudinal follow-up is ongoing to determine if
18F-AV-45 is predictive of progressive cognitive decline in these individuals.