Longitudinal changes of CSF biomarkers in memory clinic patients.

OBJECTIVE: In Alzheimer disease (AD), longitudinal changes of beta-amyloid(1-42) (Abeta(1-42)), tau, and phosphorylated tau at threonine 181 (ptau-181) in CSF have been reported in small studies only. We evaluated the natural course of CSF biomarkers in patients with AD, subjective complaints, and mild cognitive impairment (MCI). METHODS: One hundred five patients (50 AD, 38 MCI, 17 subjective complaints) underwent two lumbar punctures, with a mean interval of 21 +/- 9 months. CSF levels of Abeta(1-42), tau, and ptau-181 were measured. RESULTS: CSF Abeta(1-42) and tau levels showed main effects for both diagnosis and time (all p < 0.05), with average increases of 47 +/- 72 and 49 +/- 143 pg/mL. The interaction terms were not significant, which implies a similar time effect for all diagnostic groups. CSF ptau-181 levels showed a main effect for diagnosis (p = 0.01) but not for time (p = 0.27, increase of 1.0 +/- 12 pg/mL). CONCLUSION: Levels of CSF beta-amyloid(1-42) and tau but not phosphorylated tau at threonine 181 increased over time in this memory clinic patient cohort with comparable change in all diagnostic groups. The cross-sectional difference between diagnostic groups, however, exceeded by far the longitudinal changes within individuals, suggesting that these biomarkers are not sensitive as markers of disease progression.

[Predictors of dementia, the construction of classification trees]. / Vroege predictoren van dementie, de constructie van beslisbomen.

In order to identify persons who are at risk for dementia in an early phase, two classification trees were developed. Data were used from the Longitudinal Aging Study Amsterdam (LASA). The prevalence of dementia in the whole sample was 4.0%. In the first tree age seemed to be the strongest predictor, with an increased risk for persons older than 75. In this group the positive predictive value reached a maximum of 33.3% when the persons had memory complaints and a score on the Mini Mental State Examination (MMSE) <24. In a second classification tree, age was excluded as a predictor because of high association with the other potential predictors. In this tree functional limitations seemed the strongest predictor. In the group of persons with at least one functional limitations, the positive predictive value reached a maximum of 28.8% when the persons had memory complaints and a score <24 on the MMSE. In persons without memory complaints, persons with cardiovascular diseases or diabetes were at increased risk of dementia. Further research is necessary before these classification trees can be implemented in general health care.

Propositional reasoning: the differential contribution of "rules" to the difficulty of complex reasoning problems.

In Experiment 1, complex propositional reasoning problems were constructed as a combination of several types of logical inferences: modus ponens, modus tollens, disjunctive modus ponens, disjunctive syllogism, and conjunction. Rule theories of propositional reasoning can account for how one combines these inferences, but the difficulty of the problems can be accounted for only if a differential psychological cost is allowed for different basic rules. Experiment 2 ruled out some alternative explanations for these differences that did not refer to the intrinsic difficulty of the basic rules. It was also found that part of the results could be accounted for by the notion of representational cost, as it is used in the mental model theory of propositional reasoning. However, the number of models as a measure of representational cost seems to be too coarsely defined to capture all of the observed effects.