Kadir A, Almkvist O, Forsberg A, Wall A, Engler H, Långström B, Nordberg A.
Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer's disease.
Neurobiol Aging. 2012 Jan;33(1):198.e1-14.
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Kadir et al. provide a valuable extension of our knowledge about longitudinal changes in amyloid deposition as measured by PIB-PET. Although the numbers are small in this study, several points emerge. First, amyloid-positive cognitively normal controls can remain cognitively normal for long periods of time. Although this is demonstrated with a single subject—first studied in 2002—it makes the point that much more follow-up for longer periods of time in much larger numbers will be necessary before we can make definite statements about the cognitive prognosis of amyloid-positive controls.
As mentioned in the original report of this subject in 2004, it is clear that this subject has cerebral β amyloidosis, but it is not yet clear whether he will ever progress to AD. The latter possibility remains a viable hypothesis, and may be foreshadowed by drops in full-scale IQ and episodic memory scores in this particular subject, but much more data is necessary in this regard. Second, the most consistent increases in amyloid burden (i.e., PIB retention) are seen prior to the clinical diagnosis of dementia, such as in the MCI phase (and probably the cognitively normal phase).
The findings of Kadir et al. are consistent with those of several other groups showing high rates of conversion from MCI to AD in amyloid-positive MCI patients in that AD-like changes in cerebral metabolism are common in the amyloid-positive MCI cases, but metabolism was stably normal in the single amyloid-negative MCI subject. Third, the changes in amyloid deposition in an AD population are highly variable and probably dependent on the stage of the disease. For example, the two AD patients with the highest baseline PIB retention were the only two to show convincing decreases in PIB retention. These same two subjects also showed the greatest drop in cognition over the five-year interval.
Since this data was not atrophy-corrected, one cannot determine how much the decrease in PIB retention reflects volume-averaging secondary to atrophy versus a true resorption of amyloid, possibly due to decreased production at advanced stages of neurodegeneration. Also, the two AD patients with the lowest baseline PIB retention showed the greatest increase over the five years. Fourth, the three subjects diagnosed with “AD” in 2004 but were found to be amyloid-negative then, remain amyloid negative with relatively little change in cerebral metabolism or cognition. This suggests that a negative amyloid PET scan at a time when clinical dementia is already present suggests that the etiology is a non-AD neurodegenerative disease and strongly argues against the possibility that PIB-PET is simply too insensitive to detect the first stages of amyloid deposition in these patients, since amyloid was still not detectable even five years later.