Douaud G, Menke RA, Gass A, Monsch AU, Rao A, Whitcher B, Zamboni G, Matthews PM, Sollberger M, Smith S. Brain microstructure reveals early abnormalities more than two years prior to clinical progression from mild cognitive impairment to Alzheimer's disease. J Neurosci. 2013 Jan 30;33(5):2147-55. PubMed.
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Karolinska Institutet
More and more, it is realized that the structural changes (volume losses) in the brain leading to Alzheimer's disease are preceded by more subtle but significant brain changes. Here, the authors show that, since stable MCI (sMCI) patients showed similar left hippocampal volume as MCI patients who progress to AD (pMCI), reduced gray matter (GM) volume was not sufficient to determine the progression toward AD. However, interestingly enough, pMCI showed lower mean diffusivity (MD) than sMCI. Cerebrospinal fluid showed similar to lower discrimination accuracies, with tau concentration providing the best marker of progression to AD. By combining GM volume, a composite of diffusion measures, and a composite of CSF biomarkers, the authors could classify pMCI patients with 85 percent sensitivity and 96 percent specificity. In a recent study (Choo et al., 2013), we also observed that a combination of 18F-fluorodeoxyglucose measures and CSF total tau improved AD prediction. These data indicate that a combination of biomarkers increases the predictive value. The authors speculate that the higher MD value in the left hippocampus could be a sign of reactive astrocytosis. It is, in this respect, interesting to note that increased astrocytosis has been reported in pMCI as compared to sMCI (with no fibrillar amyloid in brain) and in AD (Carter et al., 2012). It would be interesting to further analyze microstructural damage measured with MRI together with PET studies measuring increased astrocytosis with 11C-deprenyl PET.
References:
Choo IH, Ni R, Schöll M, Wall A, Almkvist O, Nordberg A. Combination of 18F-FDG PET and cerebrospinal fluid biomarkers as a better predictor of the progression to Alzheimer's disease in mild cognitive impairment patients. J Alzheimers Dis. 2013;33(4):929-39. PubMed.
Carter SF, Schöll M, Almkvist O, Wall A, Engler H, Långström B, Nordberg A. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med. 2012 Jan;53(1):37-46. PubMed.
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