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Ann Neurol. 2011 Jan;69(1):181-92. doi: 10.1002/ana.22248.

Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease.

Author information

  • 1Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Australia. villemagne@petnm.unimelb.edu.au

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 [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.

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 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.

Copyright © 2010 American Neurological Association.

PMID:
21280088
[PubMed - indexed for MEDLINE]
PMCID:
PMC3045039
Free PMC Article

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