. Correlation of longitudinal cerebrospinal fluid biomarkers with cognitive decline in healthy older adults. Arch Neurol. 2010 Feb;67(2):217-23. PubMed.

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  1. This is a study of 105 normal controls, 175 MCI, and 90 AD patients followed for on to two years. CSF biomarker and brain atrophy were used as predictive parameters for clinical changes in AD. Surprisingly the authors reported that MCI patients with CSF levels of Aβ42 comparable controls and of CSF tau below controls showed more atrophy than controls. The authors concluded that morphometry predicts cognitive progression better than CSF biomarkers. I think it would have been interesting to know the mean ages of these patients (only age range is given).

    CSF biomarkers, especially Aβ42, are considered to be (together with brain amyloid imaging by PET) comparable to atrophy changes. However, when studying the progression of the AD, disease atrophy as well as cerebral glucose metabolism better correlate with cognitive decline compared to CSF biomarkers. CSF Aβ42 could be considered as a biomarker to detect prodromal AD (preclinical AD), but there is no data so far that convincingly show changes in CSF Aβ levels with progression of the disease. Long-term follow-up of PIB amyloid imaging (we have data up to five years) show stable amyloid levels in AD and MCI. We still have to perform more studies to obtain a deeper understanding of how these different biomarkers, for example CSF Aβ42, could be used as early biomarkers.

    MCI patients with no changes in CSF Aβ42, but with atrophy, would have been interesting to study also with PIB imaging, and one can also question whether these MCI patients with atrophy but normal CSF Aβ42 could represent prodromal non-AD. I have examined several AD cases who have normal Aβ42 in CSF but high uptake of PIB in brain. These patients do very often show very little atrophy in the earlier stage of the disease.

    View all comments by Agneta Nordberg