J Nucl Med. 2007; 48 (Supplement 2):58P
Neurosciences: Neurology
Dementia, Amyloid and Beyond |
Aß burden correlates with memory impairment in non-demented subjects but plateaus in established Alzheimer’s disease: A PIB-PET cross sectional study
Christopher Rowe1,
Kerryn Pike2,
Steven Ng1,
Greg Savage2,
William Browne1,
Uwe Ackermann1,
Sylvia Gong1,
Gordon Chan1,
Graeme O'Keefe1,
Henri Tochon-Danguy1,
Colin Masters3 and
Victor Villemagne1
1 Centre for PET, Austin Hospital, Melbourne, Victoria, Australia; ;
2 School of Psychology, Psychiatry and Psychological Medicine, Monash University, Melbourne, Victoria, Australia; ;
3 Pathology, University of Melbourne, Melbourne, Victoria, Australia; ;
4 The Mental Health Research Institute of Victoria, Melbourne, Victoria, Australia
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Objectives: Mild cognitive impairment (MCI) carries a high risk of conversion to Alzheimer’s disease (AD). The relationship between amyloid (Aß) burden and severity of impairment in AD is controversial and has not been explored in MCI. We examined this relationship using PIB-PET. Methods: 34 healthy controls (HC) (age 71 ± 7; MMSE >28), 44 MCI subjects (age 72 ± 9; MMSE 26.6 ± 3) and 44 subjects with mild to moderate AD (age 73 ± 10; MMSE 21.3 ± 4) were studied. All subjects underwent cognitive assessment including MMSE and California Verbal Learning Test II long delay (CVLT). Aß burden was quantified using Standardized Uptake Value normalized to cerebellar cortex (SUVR) 40-70 min.PI. The mean of frontal, posterior cingulate, parietal, lateral temporal and occipital regions was used for analysis. Results: SUVR was 1.40 ± 0.33 in HC, 1.81 ± 0.59 in MCI and 2.39 ± 0.39 in AD and correlated negatively across all subjects with cognitive measures (MMSE r = -0.43, p<0.0001). When groups were examined separately, only the MCI cohort showed a correlation with cognition (CVLT r = -0.53, p < 0.001). MMSE did not correlate with PIB in any group. At a SUVR thresh-hold 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 +ve subjects performed worse than PIB -ve subjects on memory measures (CVLT 2.9 ± 0.9 vs 7.2 ± 1.1, p = 0.004). Correlation between Aß and memory impairment in MCI persisted after removing the PIB -ve subjects (CVLT r = -0.49, p = 0.01). Conclusions: Our data supports a pathogenic role for Aß accumulation in AD by showing a relationship to mild cognitive impairment. This relationship is lost in later stages of disease as dementia develops. These findings may have implications for anti-amyloid therapy.
Research Support (if any): Austin Hospital Medical Research Foundation, Neurosciences Victoria, University of Melbourne
