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Doraiswamy PM, Sperling RA, Johnson K, Reiman EM, Wong TZ, Sabbagh MN, Sadowsky CH, Fleisher AS, Carpenter A, Joshi AD, Lu M, Grundman M, Mintun MA, Skovronsky DM, Pontecorvo MJ, AV45-A11 Study Group, AV45-A11 Study Group. Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study. Mol Psychiatry. 2014 Sep;19(9):1044-51. Epub 2014 Mar 11 PubMed.
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Mayo Clinic College of Medicine
This study represents the 36-month follow-up of a group of individuals in the AD spectrum who initially underwent Amyvid imaging as part of an Avid Pharmaceuticals-sponsored trial. As was expected from many studies using 11C PiB, the authors found that cognitively normal (CN) individuals who were amyloid positive (Aβ+) had a faster rate of cognitive decline than those who were amyloid negative (Aβ-). The authors did not report on whether Aβ+ CN participants had a higher rate of conversion to MCI, but presumably not (or they would have said so). Similarly, those with MCI had a higher rate of progression to AD dementia and a lower rate of regression to CN if Aβ+. These observations replicate many others that have been reported in MCI.
The authors also report that persons with dementia who were Aβ+, i.e., intermediate likelihood, or higher, AD dementia also worsened cognitively more than Aβ- dementia patients. It is of interest that in this cohort, presumably recruited and diagnosed by skilled clinicians, that the rate of Aβ+ was lower in both MCI (38 percent) and especially dementia (68 percent) than most other studies. This does not invalidate their findings, but it raises questions about the stringency of the diagnostic process at enrollment. The main weakness of this study is that it does not break much in the way of new ground, except to the extent that it shows that Amyvid behaves like PiB. In addition, the use of amyloid imaging alone, without biomarkers for neurodegeneration (ND), clearly gives an incomplete picture of prognosis. As in our work (Knopman et al., 2012; Petersen et al., 2013) and that of others (Prestia et al., 2013), the distinction between Aβ+ND- and Aβ+ND+ is quite relevant for prognosis.
References:
Knopman DS, Jack CR, Wiste HJ, Weigand SD, Vemuri P, Lowe V, Kantarci K, Gunter JL, Senjem ML, Ivnik RJ, Roberts RO, Boeve BF, Petersen RC. Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology. 2012 May 15;78(20):1576-82. PubMed.
Petersen RC, Aisen P, Boeve BF, Geda YE, Ivnik RJ, Knopman DS, Mielke M, Pankratz VS, Roberts R, Rocca WA, Weigand S, Weiner M, Wiste H, Jack CR. Criteria for mild cognitive impairment due to alzheimer's disease in the community. Ann Neurol. 2013 May 20; PubMed.
Prestia A, Caroli A, van der Flier WM, Ossenkoppele R, Van Berckel B, Barkhof F, Teunissen CE, Wall AE, Carter SF, Schöll M, Choo IH, Nordberg A, Scheltens P, Frisoni GB. Prediction of dementia in MCI patients based on core diagnostic markers for Alzheimer disease. Neurology. 2013 Mar 12;80(11):1048-56. Epub 2013 Feb 6 PubMed.
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