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Background: Mild cognitive impairment (MCI) has attracted considerable interest as a potential predictor of Alzheimer’s disease (AD). Both the apolipoprotein E (ApoE) Ε4 allele and vascular factors have been associated with a higher risk for AD, recently they have also been linked to the risk of MCI. Objectives: To estimate the incidence of MCI among cognitively healthy elderly subjects during a 3-year follow-up, and to evaluate the impact of demographic and vascular factors as well as the ApoE Ε4 allele on the conversion to MCI. Methods: At baseline, the cognitive abilities of 806 out of 1,150 eligible subjects (aged 60–76 years) from a population-based sample were examined. Cognitively intact subjects (n = 747) were followed for an average of 3 years. Results: 66 subjects (8.8%) had converted to MCI. The global incidence rate of MCI was 25.94/1,000 person-years. Persons with higher age (OR 1.08, 95% CI 1.01–1.16), ApoE Ε4 allele carriers (OR 2.04, 95% CI 1.15–3.64) and persons with medicated hypertension (OR 1.86, 95% CI 1.05–3.29) were more likely to convert to MCI than those individuals of lower age and without an ApoE Ε4 allele or medicated hypertension. Persons with high education (OR 0.79, 95% CI 0.70–0.89) were less likely to convert to MCI than persons with low or no education. In subjects with both the ApoE Ε4 allele and medicated hypertension, the crude OR for conversion was 3.92 (95% CI 1.81–8.49). In subjects with cardiovascular disease, the crude OR for conversion was 2.13 (95% CI 1.26–3.60). Gender, elevated blood pressure, diabetes or cerebrovascular disease had no significant effect on the conversion to MCI. Conclusion: Higher age, the presence of at least one ApoE Ε4 allele and medicated hypertension are independent risk factors, but high education is a protective factor for MCI. The results suggest that vascular factors may have an important role in the pathogenesis of MCI.

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BackgroundSingle measurements of plasma Aβ are not useful in the diagnostics of Alzheimer's disease (AD). However, changes in plasma Aβ levels during repeated testing may be helpful in the prediction and evaluation of progression of the incipient AD or mild cognitive impairment.ObjectiveTo examine the relation of baseline and serial plasma Aβ levels to cognitive change in follow-up.Methods269 subjects (52 cognitively impaired and 217 controls) from a population-based cohort were clinically followed up from 3 to 6 years. Serial plasma samples were available from 70 subjects who were followed up for 3 years and 43 subjects followed for 6 years. The plasma Aβ levels were measured using ELISA.ResultsSubjects who declined cognitively during the follow-up had lower levels of plasma Aβ42 at the baseline. Plasma Aβ42 and the Aβ42/Aβ40 ratio decreased (−2.4 pg/ml for Aβ42 in 6 years) in those who declined in follow-up, whereas Aβ42 and the Aβ42/Aβ40 ratio increased in the subjects who remained cognitively stable or improved in follow-up. Subjects using acetylsalicylic acid, dipyridamole, antidiabetic or anticoagulant drugs as well as subjects with coronary heart disease had higher levels of Aβ40.ConclusionsLow or decreasing plasma Aβ42 during the follow-up is associated with cognitive decline. Serial measurement of plasma Aβ42 may be useful in the detection of the subjects who are at risk for cognitive decline.