The paper by Agneta Nordberg and colleagues is a timely and important addition to the literature on amyloid imaging in several regards. It confirms that similar results can be obtained across multiple sites using different PET cameras and reconstruction techniques. It is impressive that PIB studies worldwide are so consistent in their findings. This is a testament to the robust nature of amyloid imaging with PIB. The paper also provides more evidence on the risk stratification power of amyloid imaging for progression of MCI to dementia due to Alzheimer's disease. However, while the data suggest that amyloid imaging provides powerful and useful prognostic information, this study does not compare this to other potential predictive features, such as severity of memory impairment, apolipoprotein E4 allele status, or MRI atrophy measures. Such comparisons are important when defining the appropriate and cost-effective use of amyloid imaging in clinical practice.

The authors found a low prevalence of positive PIB scans in the healthy control subjects. That is explained by the...  Read more

The paper by Agneta Nordberg and colleagues is a timely and important addition to the literature on amyloid imaging in several regards. It confirms that similar results can be obtained across multiple sites using different PET cameras and reconstruction techniques. It is impressive that PIB studies worldwide are so consistent in their findings. This is a testament to the robust nature of amyloid imaging with PIB. The paper also provides more evidence on the risk stratification power of amyloid imaging for progression of MCI to dementia due to Alzheimer's disease. However, while the data suggest that amyloid imaging provides powerful and useful prognostic information, this study does not compare this to other potential predictive features, such as severity of memory impairment, apolipoprotein E4 allele status, or MRI atrophy measures. Such comparisons are important when defining the appropriate and cost-effective use of amyloid imaging in clinical practice.

The authors found a low prevalence of positive PIB scans in the healthy control subjects. That is explained by the relatively young age of this cohort, as acknowledged by the authors in the discussion. Age and ApoE4 status are the strongest predictors of a positive amyloid scan in the healthy elderly population as shown by the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging and Washington University studies, which show a positive scan in 4, 10, 30, and >50 percent of people in their sixth, seventh, eighth, and ninth decades of life, respectively, and a risk at least three times higher in those with an ApoE4 allele than in those without. For example, in the seventh decade, positive amyloid prevalence is 5 percent in non-carriers versus 25 percent in carriers (Rowe et al., 2010).

Once again, this paper reports that the relationship between amyloid load and degree of memory impairment is weak in terms of a direct dose response, but strong if analyzed as present or not. This supports the amyloid cascade hypothesis that posits amyloid is a trigger, but downstream events then drive cognitive decline. This may have implications for anti-amyloid therapy, suggesting that a mild reduction in amyloid load in established clinical disease is unlikely to have a major effect on cognition.

References:
Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, Fripp J, Tochon-Danguy H, Morandeau L, O'Keefe G, Price R, Raniga P, Robins P, Acosta O, Lenzo N, Szoeke C, Salvado O, Head R, Martins R, Masters CL, Ames D, Villemagne VL. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010 Aug;31(8):1275-83. Abstract

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