Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease

Abstract

Objective-Assess Aβ deposition longitudinally and explore its relationship with cognition and disease progression.Methods-Clinical follow-up was obtained 20 ± 3 months after [ 11 C]Pittsburgh compound B (PiB)-positron emission tomography in 206 subjects: 35 with dementia of the Alzheimer type (DAT), 65 with mild cognitive impairment (MCI), and 106 age-matched healthy controls (HCs). A second PiB scan was obtained at follow-up in 185 subjects and a third scan after 3 years in 57.Results-At baseline, 97% of DAT, 69% of MCI, and 31% of HC subjects showed high PiB retention. At 20-month follow-up, small but significant increases in PiB standardized uptake value Address correspondence to Dr Villemagne, Department of Nuclear Medicine and Centre for PET, Austin Health, 145 Studley Road, Heidelberg, Vic., 3084, Australia. villemagne@petnm.unimelb.edu.au. D.A. is Principle Investigator of the Australian Imaging, Biomarkers, and Lifestyle study of ageing.Additional Supporting Information can be found in the online version of this article. Potential Conflicts of InterestGE Healthcare holds a license agreement with the University of Pittsburgh based on the technology described in this article. W.E.K. and C.A.M. have received consultancy fees and royalties and have a grant pending from GE Healthcare. W.E.K. and C.A.M. are coinventors of PiB and, as such, have a financial interest in this license agreement. GE Healthcare provided no grant support for this study and had no role in the design or interpretation of results or preparation of the manuscript. All other authors have no conflicts of interest with this work, had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. NIH Public Access Author ManuscriptAnn Neurol. Author manuscript; available in PMC 2012 January 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript ratios were observed in the DAT and MCI groups, and in HCs with high PiB retention at baseline (5.7%, 2.1%, and 1.5%, respectively). Increases were associated with the number of apolipoprotein E ε4 alleles. There was a weak correlation between PiB increases and decline in cognition when all groups were combined. Progression to DAT occurred in 67% of MCI with high PiB versus 5% of those with low PiB, but 20% of the low PiB MCI subjects progressed to other dementias. Of the high PiB HCs, 16% developed MCI or DAT by 20 months and 25% by 3 years. One low PiB HC developed MCI.Interpretation-Aβ deposition increases slowly from cognitive normality to moderate severity DAT. Extensive Aβ deposition precedes cognitive impairment, and is associated with ApoE genotype and a higher risk of cognitive decline in HCs and progression from MCI to DAT over 1 to 2 years. However, cognitive decline is only weakly related to change in Aβ burden, suggesting that downstream factors have a more direct effect on symptom progression.In vivo amyloid imaging with positron emission tomography (PET) allows longitudinal study...

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