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 (Abeta42) 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 Abeta42 measured at baseline predicted which persons remained cognitively healthy (CH) and who developed AD 2.5 years later. The increase of plasma Abeta42 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 Abeta42 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 Abeta42 levels and rather no increase of homocysteine. In logistic regression analysis, the increase of plasma Abeta42 but not change of MTA significantly predicted the conversion from CH to MCI, and changes of MTA and homocysteine but not of plasma Abeta42 predicted the conversion from CH to AD. The increase of plasma Abeta42 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 Abeta42 alone is not suitable as a biomarker for AD, (2) in the course of cognitive deterioration of the AD-type the increase of plasma Abeta42 seems to be an initial event, (3) similar to cerebrospinal fluid, changes of plasma Abeta42 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.

Plasma amyloid beta protein 42 in non-demented persons aged 75 years: effects of concomitant medication and medial temporal lobe atrophy.

Plasma amyloid beta (Abeta42) levels increase with age and are elevated in some patients during the early stages of Alzheimer's disease (AD). Although plasma Abeta42 is not useful for diagnosis of AD, it might be a biological risk factor. In the elderly population a considerable variety of concomitant medication is used for the treatment of various disorders. How this co-medication might influence Abeta42 levels is still to be investigated. Through the Vienna Transdanube Aging study (VITA), the authors measured cross-sectional Abeta42 plasma levels during the initial examination of 526 individuals aged 75 years without dementia. The medication considered included: treatment with calcium channel blockers, digitalis, anticoagulants, antihistamines, ergotamine, histamine H(2) receptor antagonists, bronchodilators, pentoxyfilline, neuroleptics, insulin, oral antidiabetics, l-dopa, benzodiazepines, oestrogen, Gingko biloba, vitamins, piracetam, non-steroidal anti-inflammatory drugs (NSAIDs), and statins. Of the study population aged 75 years, 90% were users of some of the above-mentioned medication. Depending on their medial temporal lobe atrophy (MTA), users of insulin showed significantly increased levels of Abeta42, while users of gingko biloba for at least 2 years of drug intake had significantly decreased Abeta42 plasma levels, independent of their MTA. Users of NSAIDs showed a non-significant trend to reduced Abeta42 plasma levels, while users of biguanides showed an increase in Abeta42 plasma levels. In the multiple regression analysis considering possible interactions between various medications statin users showed a significant decrease of Abeta42; insulin users had again significantly higher and long-term gingko biloba users lower plasma Abeta42 levels. Persons with a low degree of MTA had significantly increased Abeta42 plasma levels. Considering the increase of Abeta42 plasma levels as a risk factor for AD, any changes induced by medication by long-term use in the peripheral and possibly also in the central compartment, could be of clinical relevance.