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

Blasko, Imrich; Jellinger, Kurt; Kemmler, Georg; Krampla, Wolfgang; Jungwirth, Susanne; Wichart, Ildigo; Tragl, Karl Heinz; Fischer, Peter

doi:10.1016/j.neurobiolaging.2006.09.002

« Previous Next »Neurobiology of Aging
Volume 29, Issue 1 , Pages 1-11, January 2008

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

Imrich Blasko
- Department of Psychiatry, Innsbruck Medical University, Austria
Kurt Jellinger
- Institute of Clinical Neurobiology, Vienna, Austria
Georg Kemmler
- Department of Psychiatry, Innsbruck Medical University, Austria
Wolfgang Krampla
- Ludwig Boltzmann Society, L. Boltzmann Institute of Digital Radiology and Interventional Radiology, Vienna, Austria
- Danube Hospital, Vienna, Austria
Susanne Jungwirth
- Ludwig Boltzmann Society, L. Boltzmann Institute of Aging Research, Vienna, Austria
Ildigo Wichart
- Institute of Clinical Neurobiology, Vienna, Austria
Karl Heinz Tragl
- Danube Hospital, Vienna, Austria
- Ludwig Boltzmann Society, L. Boltzmann Institute of Aging Research, Vienna, Austria
Peter Fischer
- Ludwig Boltzmann Society, L. Boltzmann Institute of Aging Research, Vienna, Austria
- Department of General Psychiatry, Medical University of Vienna, Austria
- Corresponding author at: Department of General Psychiatry, Medical University of Vienna, AKH, Waehringer Guertel 18-20, 1090 Vienna, Austria. Tel.: +43 1 40400 3543; fax: +43 1 40400 3099.

Received 18 May 2006; received in revised form 24 July 2006; accepted 6 September 2006. published online 23 October 2006.

Abstract

The changes of plasma amyloid beta (Aβ42) 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 Aβ42 measured at baseline predicted which persons remained cognitively healthy (CH) and who developed AD 2.5 years later. The increase of plasma Aβ42 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 Aβ42 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 Aβ42 levels and rather no increase of homocysteine. In logistic regression analysis, the increase of plasma Aβ42 but not change of MTA significantly predicted the conversion from CH to MCI, and changes of MTA and homocysteine but not of plasma Aβ42 predicted the conversion from CH to AD. The increase of plasma Aβ42 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 Aβ42 alone is not suitable as a biomarker for AD, (2) in the course of cognitive deterioration of the AD-type the increase of plasma Aβ42 seems to be an initial event, (3) similar to cerebrospinal fluid, changes of plasma Aβ42 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.

Keywords: Plasma Aβ42, Medial temporal lobe atrophy, Alzheimer's disease, Mild cognitive impairment, Homocysteine