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Title: Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease.
Austin Authors: Villemagne, Victor L ;Pike, Kerryn E;Chételat, Gaël;Ellis, Kathryn A;Mulligan, Rachel S ;Bourgeat, Pierrick;Ackermann, Uwe ;Jones, Gareth;Szoeke, Cassandra;Salvado, Olivier;Martins, Ralph N;O'Keefe, Graeme J;Mathis, Chester A;Klunk, William E;Ames, David;Masters, Colin L ;Rowe, Christopher C 
Affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 1-Jan-2011
Publication information: Annals of Neurology; 69(1): 181-92
Abstract: Assess Aβ deposition longitudinally and explore its relationship with cognition and disease progression.Clinical follow-up was obtained 20 ± 3 months after [¹¹C]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.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 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.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.
DOI: 10.1002/ana.22248
Journal: Annals of Neurology
Type: Journal Article
Subjects: Aged
Alzheimer Disease.diagnosis.pathology.radionuclide imaging
Amyloid beta-Peptides
Aniline Compounds.diagnostic use
Brain.pathology.radionuclide imaging
Cognition Disorders.diagnosis
Disease Progression
Follow-Up Studies
Longitudinal Studies
Magnetic Resonance Imaging
Neuropsychological Tests
Plaque, Amyloid.diagnosis.pathology.radionuclide imaging
Polymorphism, Genetic
Positron-Emission Tomography
Severity of Illness Index
Thiazoles.diagnostic use
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