Correlation between Amyloid Burden and Memory Impairment: A C-PIB PET Cross Sectional Study

Objectives: Mild cognitive impairment (MCI) carries a high risk of conversion to Alzheimer's disease (AD). The relationship between brain beta-amyloid (A ) burden and cognitive function has not been explored in subjects with MCI. We examined this relationship using in-vivo amyloid-imaging tracer C-PIB. Methods: 32 healthy controls (HC) (age 71 7; MMSE >28), 35 MCI subjects (age 71 9; MMSE 26.8 2) and 40 subjects with mild to moderate AD (age 74 10; MMSE 21.7 4) underwent 11C-PIB PET. All subjects underwent MMSE and California Verbal Learning Test II (CVLT II). A burden was quantified using Standardized Uptake Value normalized to cerebellar cortex (SUVR) 40-70 post-injection. The neocortical SUVR was used for analysis. Results: Neocortical SUVR was 1.40 0.33 in HC, 1.84 0.59 in MCI and 2.42 0.33 in AD and correlated negatively across all subjects with MMSE (r = -0.56, P < 0.001). When groups were analysed separately, only the MCI cohort showed a correlation with cognition (MMSE: r = -0.33, P < 0.05; CVLT: r = -0.53, P < 0.001). Cognitive performance did not correlate with level of PIB retention in other groups. At a SUVR threshold of 1.6 (the 75th percentile of HC), cortical PIB binding was present in 100% of AD, 60% of MCI and 23% of HC. In MCI, but not in HC, PIB positive subjects performed worse than PIB negative subjects on cognitive performance (CVLT II-long delay: 3.60 4.51 vs. 7.21 4.35; p= 0.026). Correlation between A and memory impairment in MCI persisted after excluding the PIB negative subjects (CVLT r = -0.49, P < 0.01). Conclusions: Our data supports a pathogenic role for A accumulation in AD by showing a relationship to mild cognitive impairment. This relationship is lost in later stages of disease as dementia develops suggesting a maximum or equilibrium level of A plaque can be reached early in the pathological a maximum or equilibrium level of A plaque can be reached early in the pathological A plaque can bereached early in the pathological plaque can be reached early in the pathological course of AD. These findings may have implications for anti-amyloid therapy. These findings may have implications for anti-amyloid therapy.