Longitudinal Biomarker Study Research Articles

Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment

Objectives To longitudinally evaluate five cerebrospinal fluid (CSF) biomarkers in the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Methods A baseline and 2-year follow-up clinical and CSF study of 86 subjects, including 22 MCI patients that declined to AD (MCI-AD), 43 MCI that did not deteriorate (MCI-MCI) and 21 controls (NL-NL). All subjects were studied for total and phosphorylated tau (T-tau, P-tau 231), amyloid beta (Aβ) Aβ 42/Aβ 40 ratio, isoprostane (IP) as well as P-tau 231/Aβ 42/40 and T-tau/Aβ 42/40 ratios. Results At baseline and at follow-up MCI-AD showed higher levels P-tau 231, T-tau, IP, P-tau 231/Aβ 42/40 and T-tau/Aβ 42/40 ratios and lower Aβ 42/Aβ 40 than MCI-MCI or NL-NL. Baseline P-tau 231 best predicted MCI-AD (80%, p < 0.001) followed in accuracy by P-tau 231/Aβ 42/40 and T-tau/Aβ 42/40 ratios (both 75%, p's < 0.001), T-tau (74%, p < 0.001), Aβ 42/Aβ 40 (69%, p < 0.01), and IP (68%, p < 0.01). Only IP showed longitudinal effects ( p < 0.05). Conclusions P-tau 231 is the strongest predictor of the decline from MCI to AD. IP levels uniquely show longitudinal progression effects. These results suggest the use of CSF biomarkers in secondary prevention trials.

Longitudinal Study of Mercury Exposure Biomarkers Among Newborns and Their Mothers in the Brazilian Amazon

ISEE-131 Objective: Mercury (Hg) emissions by gold mining and deforestation have been contributing to increased human exposure to mercury by fish consumption in the Amazon. The aim of this study was to analyze the longitudinal pattern of mercury exposure in 3 different periods: 2000 to 2001 (1510 mothers and their 1510 newborns) and preliminary results of a sample from those persons in 2004 (254 mothers and 271 children) and 2006 (190 mothers and 180 children). Material and Methods: Data were obtained using a questionnaire and also from analysis of mercury concentration of blood samples from mothers, newborns (umbilical cord), and children according to the Brazilian ethical standards. Mercury analysis was carried out by a cold-vapor atomic absorption spectrophotometer. Results: Mercury of mother's blood in 2000 to 2001 was 11.53 ± 11.3 μg/L and newborn's umbilical cord blood reached 16.68 ± 17.1 μg/L. There was a strong and positive correlation among Hg levels in newborns and mothers with a significant model of linear regression (r = 0.8019; P = 0.000). In 2004, preliminary results pointed to similar mercury levels in mother's blood (10.19 ± 8.5 μg/L) and a significant decrease (t test 2.51; P < 0.006) in children's blood (9.51 ± 4.18 μg/L). At the last time point (2006) there was a significant decrease of these figures for both mothers (7.70 ± 5.9 μg/L and t test 3.45; P < 0.000) and children (5.27 ± 4.8 μg/L and t test 179; P < 0.000). Conclusions: The Hg levels found in mothers and newborns characterize an exposure profile that has been observed in this area. Decrease in mercury levels in children's blood should result after finishing Hg transfer through the placenta and Hg elimination during the first years of life. The result of Hg levels in mother's blood in 2006 could be explained, among others, by season type of fish consumption. Finally, special surveillance practices for preventing intrauterine accumulation of this metal in the Brazilian Amazon were discussed.

Commentary on “Diagnosis of Alzheimer's disease: Two decades of progress.” Central role of technology in the treatment and prevention of Alzheimer's disease

Commentary on “Diagnosis of Alzheimer's disease: Two decades of progress.” Central role of technology in the treatment and prevention of Alzheimer's disease

Specimen Allocation in Longitudinal Biomarker Studies: Controlling Subject-Specific Effects by Design

AbstractIt is important to understand specimen allocation factors that may impact the validity and reliability of results in longitudinal studies examining within-person changes in biomarker levels. Using data from a randomized clinical trial of an exercise intervention in 136 postmenopausal women, we determined the effect of assaying the baseline and follow-up samples of some subjects in different batches on the intervention effect estimates for serum concentrations of estrone, estradiol, testosterone, androstenedione, and dehydroepiandrosterone. Twenty-five subjects had their baseline and 3-month follow-up samples and 50 subjects had their baseline and 12-month samples assayed in different batches; all other subjects had their baseline, 3-month, and 12-month samples assayed in the same batch. Subjects with split samples were reassayed with all samples in the same batch. We compared the estimated regression coefficient for the intervention effect using the split sample data with one estimated excluding the split sample data and one estimated replacing the split sample data with the reassayed data. The median percentage difference in the intervention effect estimate was 59.6% between using versus excluding the split sample data and 74.6% between using the split sample versus using the reassayed data. In general, the coefficients from the model including the split sample data were closer to zero and statistically less significant than those from the models excluding the split sample data or using the reassayed data. These results suggest that bias can be artificially introduced into intervention effect estimates of longitudinal studies if samples from a subject are not assayed in the same batch.