FDDNP PET in Mild Cognitive Impairment
Abstract & Commentary
By Brian Apatoff, MD, PhD, Director, Multiple Sclerosis Clinical Care and Research Center, Department of Neurology and Neuroscience, NewYork-Presbyterian Hospital, Cornell Campus. Dr. Apatoff is on the speaker's bureau for Biogen and Teva.
Synopsis: PET imaging using the novel radioligand FDDNP shows promise in the early diagnosis of Alzheimer's disease.
Source: Small Gary W, et al. PET of Brain Amyloid and Tau in Mild Cognitive Impairment. N Engl J Med. 355;2652-2663.
Pet imaging with FDDNP has been previously used to visualize amyloid plaque and neurofibrillary tangle pathology in the brains of living patients with Alzheimer's disease (AD). A recent study examined whether FDDNP could be used to distinguish normals and AD patients from persons with Mild Cognitive Impairment (MCI), who are at increased risk for developing AD. Gary Small and colleagues at UCLA used 18F-FDDNP as well as other imaging methods to scan 108 volunteers with self-reported memory problems, including 25 with Alzheimer's, 28 with MCI and 30 who were cognitively normal. Usable data was obtained in 83 cases. A subset of 12 subjects (9 normals and 3 MCI) were re-scanned after a period of 17-34 months.
The global levels of FDDNP uptake in the brain were highest in the AD patients, intermediate in MCI, and lowest in normals. The same pattern was observed when the analysis was focused on either the temporal, parietal or posterior cingulate regions. Two out of 3 individuals with MCI who were re-scanned after several months showed increased global FDDNP uptake compared to baseline. Five normal subjects had higher FDDNP uptake on their follow-up studies. Although none of the normals qualified for a diagnosis of MCI on follow-up, one with increased FDDNP uptake on the second scan showed worsening on memory test performance. One subject with AD who died during the study period underwent brain autopsy and was documented to have a significant numbers of plaques and tangles in regions that had shown high FDDNP uptake during life.
Although the mean values of FDDNP uptake differed between AD, MCI and normal groups in a statistically significant way, the individual values overlapped considerably across groups. Nevertheless, the authors concluded that FDDNP can be used to distinguish persons with MCI from normals and AD patients.
Commentary
FDDNP is a small lipophilic molecule that crosses the blood-brain barrier and binds to plaque and tangle pathology sufficiently to be visualized on PET scans. Very few centers outside of UCLA, where the radioligand was developed, have tested this approach to antemortem imaging of Alzheimer neuropathology. This study provides further evidence of the validity of FDDNP imaging to the extent that the PET findings correlated well with diagnoses by expert clinicians. The study also indicates that the technique is sensitive; pathology was detected in patients with very mild degrees of impairment. The study does not speak to clinical utility of FDDNP PET for a number of reasons. First, nearly 1/5 of those scanned were disqualified from the analyses, either due to non-AD diagnoses or movement artifacts. The test performed well in distinguishing AD from normal, but there was considerable overlap between these groups and MCI. In the present study, FDDNP has been shown to differentiate a group of AD patients from a group with MCI, but its application to diagnosis in individuals or in predicting which normals or MCI patients will develop AD remains uncertain. There is little information available about the specificity of the technique, which is an important issue from the standpoint of clinical applicability. Further studies will be needed to evaluate whether this technology, one of several promising PET techniques now under development, can contribute to clinical differential diagnosis of dementia in general and early diagnosis of AD in particular.
PET imaging using the novel radioligand FDDNP shows promise in the early diagnosis of Alzheimer's disease.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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