... so sorry, page-39

Dazed,

I think it is highly unlikely they were given incorrect pills.

I think it will be put down to the fact that PiB -PEt is imperfect for a number of reasons (some already hi-lighted in a previous post), and the decline seen in placebo reflects this.

"In one of the first multimodal imaging studies with longitudinal amyloid imaging in controls, MCI and AD (Jack et al., 2009), ventricular expansion rate measured with MRI differed between groups (controls 1.3 cm3/yr, MCI 2.5 cm3/yr, AD: 7.7 cm3/yr). This correlated with clinical decline (Jack et al., 2009). In contrast, in controls, MCI and AD, amyloid ligand retention only showed a small increase over time in the absence of between-group differences (Jack et al., 2009) and without any relationship to cognitive decline (Fouquet et al., 2009; Furst et al., 2012; Landau et al., 2011). In MCI in particular, there was a wide variability in the amount of increase in amyloid ligand retention and in some cases the rate of change was higher than in any of the two other groups (Jack et al., 2009). "


Won't bore you much further. But to illustrate how and why PiB PET may have been at fault, consider that studies have shown an increase in uptake of only 3-4% over 2 years in AD (to back this up: " For instance, in both AD and controls, a 3–4% increase in 11C-PIB uptake over a two-year period was restricted to medial frontal cortex (Scheinin et al., 2009). In a study with 3–5 years follow-up, 11C-PIB uptake increased in MCI but remained stationary in the AD group, be it with considerable inter-individual heterogeneity (Kadir and Nordberg, 2010)."

Combine this with a test-retest variability of 8% (again, evidence for this number: "Test–retest variability of the technique at a short interval must be known: Test–retest variability of 11C-PIB SUVR in AD is 8.0% (SD 7)(Tolboom et al., 2009b))."

So you can imagine that that if a patient actually increased insoluble amyloid accumulation by 2% over the trial, the variability in the test alone could show a 6% decrease in plaque! given the small number of patients in the placebo group, you can see how this may influence results!!

Also, are many other factors that may influence the PET readings or amyloid accumulation, such as what the baseline level was (they have shown a higher baseline level = more likely to accumulate - so called "amyloid accumulators"). [Were the 2 groups similar at baseline?]

Top it off with not great correlations of PET amyoloid and cognition and you have a recipe for misleading results!! Reassuringly, MRI volume indices are more reliable (less variability) and better correlated with cognition so the trends seen with hippocampal volumes is exciting, although not definitively proven yet.

Raw data is awaited with anticipation - we will all gain much insight from the actual numbers!

hope that makes sense and please again excuse the length of this post!

All IMO, dYor etc (all other acronyms for that stuff)