Conversion from cognitive health to mild cognitive impairment and Alzheimer's disease: Prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine

The changes of plasma amyloid beta (A beta 42) protein, homocysteine and medial temporal lobe atrophy (MTA) were studied by the transition from cognitive health to mild cognitive impairment (MCI) and to Alzheimer's disease (AD) in a prospective cohort of individuals aged 75 years. MTA but not plasma A beta 42 measured. at baseline predicted which persons remained cognitively healthy (CH) and who developed AD 2.5 years later. The increase of plasma A beta 42 over time significantly distinguished between persons who remained CH on the one hand and MCI converters and AD converters out of cognitive health on the other (CH-to-MCI and CH-to-AD converters). Although both groups showed similar increase of A beta 42 levels, CH-to-AD converters had a higher increase of homocysteine compared to CH-to-MCI converters or to persons remaining CH. In comparison to all cognitive subgroups, the AD converters from MCI at baseline showed the smallest increase of A beta 42 levels and rather no increase of homocysteine. In logistic regression analysis, the increase of plasma A beta 42 but not change of MTA significantly predicted the conversion from CH to MCI, and changes of MTA and homocysteine but not of plasma A beta 42 predicted the conversion from CH to AD. The increase of plasma A beta 42 correctly allocated CH-to-MCI and CH-to-AD converters with low (63%) specificity (for both) and low (60%) sensitivity (54% for AD group). These results indicate that (1) plasma A beta 42 alone is not suitable as a biomarker for AD, (2) in the course of cognitive deterioration of the AD-type the increase of plasma A beta 42 seems to be an initial event, (3) similar to cerebrospinal fluid, changes of plasma A beta 42 may reflect the transition from cognitive health to AD, and (4) whether persons with MCI develop AD may depend on an accumulation of further toxic metabolites such as homocysteine. (C) 2006 Elsevier Inc. All rights reserved.