| Autor: |
Vernhet, Paul, Bilgel, Murat, Durrleman, Stanley, Resnick, Susan M., Johnson, Sterling C., Jedynak, Bruno Michel |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2020 Supplement S11, Vol. 16 Issue 11, p1-3, 3p |
| Abstrakt: |
Background: Accumulation of beta‐amyloid plaques, an early hallmark neuropathology of Alzheimer's disease (AD), begin more than a decade prior to the onset of clinical symptoms. Understanding the temporal progression of early amyloid accumulation is important for predicting who will become amyloid‐positive and when. Based on observations from several longitudinal amyloid positron emission tomography (PET) studies that the rate of overall amyloid burden is closely associated with baseline level of amyloid, we develop a formal mathematical model capturing this phenomenon and use it to (i) align temporal trajectories of amyloid accumulation across individuals, (ii) create a fine‐grained timeline of amyloid accumulation, and (iii) estimate the age at onset of amyloid positivity per individual. Method: We used (PiB) PET scans from the Wisconsin Registry for Alzheimer's Prevention (WRAP) and the Baltimore Longitudinal Study of Aging (BLSA) to assess global amyloid burden cDVR, see Figure 1. A first‐order autonomous model for the slope of cDVR as a function of cDVR was fit to the data. We used Bayesian modeling with a Gaussian process (GP) prior and independent homoscedastic noise. Result: The best fit was obtained with a quadratic GP kernel (Figure 2). Since the system is autonomous, the trajectories are parallel and thus can be registered by translation. The progression of the Amyloid burden is thus visualized as a function of the time (in years) from PIB positivity in Figure 3. The estimated age when the PIB cDVR becomes positive is estimated. This age depends on APOE status, with a significant difference between the APOE groups [3,3] and [3,4]. p‐value=.008 in WRAP, p‐value=.054 In BLSA. Conclusion: Large studies on aging allow studying the time‐progression of the amyloid burden. We found that an autonomous ordinary differential equation allows for a good explanatory model of the PIB‐DVR data in the WRAP as well as in the BLSA studies. Still, a few participants do not fit the data closely. It remains to understand if this is due to noisy measurements or to specific conditions. Also, alternative dynamical systems, including Hamiltonian, still need to be investigated and compared. [ABSTRACT FROM AUTHOR] |
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