TY - JOUR
T1 - Correlation between amyloid burden and memory impairment
T2 - A11C-PIB PET cross sectional study
AU - Ng, S.
AU - Villemagne, V. L.
AU - Pike, K.
AU - Savage, G.
AU - Browne, W.
AU - O'Keefe, G.
AU - Tochon-Danguy, H.
AU - Chan, G.
AU - Masters, C. L.
AU - Rowe, Christopher C.
PY - 2008/3
Y1 - 2008/3
N2 - Objectives: Mild cognitive impairment (MCI) carries a high risk of conversion to Alzheimer's disease (AD). The relationship between brain beta-amyloid (Aβ) burden and cognitive function has not been explored in subjects with MCI. We examined this relationship using in-vivo amyloid-imaging tracer 11C-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). Aβ 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 Aβ 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 Aβ 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 Aβ plaque can be reached early in the pathological course of AD. These findings may have implications for anti-amyloid therapy.
AB - Objectives: Mild cognitive impairment (MCI) carries a high risk of conversion to Alzheimer's disease (AD). The relationship between brain beta-amyloid (Aβ) burden and cognitive function has not been explored in subjects with MCI. We examined this relationship using in-vivo amyloid-imaging tracer 11C-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). Aβ 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 Aβ 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 Aβ 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 Aβ plaque can be reached early in the pathological course of AD. These findings may have implications for anti-amyloid therapy.
UR - http://www.scopus.com/inward/record.url?scp=54949156061&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:54949156061
SN - 1324-1435
VL - 39
SP - 1
EP - 7
JO - ANZ Nuclear Medicine
JF - ANZ Nuclear Medicine
IS - 1
ER -