Our observations of significant relationships between higher PiB retention and greater cognitive decline in cognitively healthy individuals appear at first glance to conflict with our autopsy findings [11] showing similar longitudinal cognitive trajectories in older adults Erlotinib OSI-744 with and without AD pathology (Figure 1a, b). However, participants in imaging studies are younger and have not passed fully through the risk period for cognitive decline. Thus, cognitively healthy individuals with elevated A?? on imaging include those who are in a preclinical phase of AD as well as those who will be resilient and maintain cognitive health. Amyloid imaging and cognition in prediction of Alzheimer’s disease There are two ways that amyloid imaging may be useful in combination with cognition in prediction of the likelihood of developing AD.

The first involves using amyloid imaging to distinguish among mildly impaired individuals to predict who is likely to progress and who is more likely to remain stable. Table ?Table33 describes the results of initial attempts to use amyloid imaging in predicting outcomes in MCI. The second application combines information on longitudinal cognitive decline with A?? status to determine which cognitively healthy individuals are at highest risk for progression to impairment and AD. Table 3 Amyloid imaging and prediction of conversion to Alzheimer’s disease In MCI, A?? burden assessed by PiB PET has been helpful in distinguishing between individuals who will convert to AD and those who will remain stable [23-25] or develop other forms of dementia.

Rates of conversion to AD in MCI individuals with a positive amyloid imaging scan are substantially higher than those with a negative PiB scan, with the latter showing less than 10% rates of conversion over 3 years [24,25]. As described in Table ?Table3,3, MCI converters may also have different patterns of PiB amyloid deposition compared to MCI non-converters [24], with higher PiB retention in posterior cingulate [23,44] and frontal [44] regions. Okello and colleagues [24] identified a subset of PiB-positive MCI individuals Batimastat who rapidly progressed to AD. Compared to PiB-positive slower MCI converters and nonconverters, the rapid converters had higher PiB retention in anterior cingulate, frontal, and lateral temporal cortices.

In addition, the presence of the APOE ??4 allele in PiB-positive MCI individuals was associated with higher rates of conversion to AD [24]. In CN adults, consideration of A?? burden alone showed that risk for AD in PiB-positive individuals was 4.8 times that in PiB-negative CN individuals over a 2.4-year useful site follow-up [45] (Table ?(Table3).3). However, no studies to date have combined PET measures of A?? burden with cognitive performance for prediction of AD risk in CN individuals.