Impact of CSF storage volume on the analysis of Alzheimer's disease biomarkers on an automated platform.

OBJECTIVES: To assess the potential influence of the ratio between the storage tube surface area and the volume of cerebrospinal fluid (CSF) (surface/volume) on the quantifications of four Alzheimer's disease (AD) biomarkers on the Lumipulse G600II automated platform. METHODS: CSF samples of 10 consecutive patients were stored in 2 ml polypropylene tubes containing four different CSF volumes: 1.5 ml, 1 ml, 0.5 ml and 0.25 ml. Concentration of CSF Aß1-42, Aß1-40, t-Tau and p-Tau were measured in all aliquots using the LUMIPULSE G600II automated platform from Fujirebio. RESULTS: Levels of CSF Aß1-42 and Aß1-40 were lower in samples stored with lower volumes (higher surface/volume ratios). This decrease was partly compensated by using the ratio Aß1-42/Aß1-40. Quantification of t-Tau and p-Tau were not influenced by this pre-analytical condition. CONCLUSION: The surface/volume ratio can potentially influence the results of amyloid AD biomarkers. It appears essential to take into account the surface/volume ratio of the storage tubes when quantifying CSF biomarkers in clinical routine.

Importance and impact of preanalytical variables on Alzheimer disease biomarker concentrations in cerebrospinal fluid.

BACKGROUND: Analyses of cerebrospinal fluid (CSF) biomarkers (ß-amyloid protein, total tau protein, and hyperphosphorylated tau protein) are part of the diagnostic criteria of Alzheimer disease. Different preanalytical sample procedures contribute to variability of CSF biomarker concentrations, hampering between-laboratory comparisons. The aim of this study was to explore the influence of fractionated sampling, centrifugation, freezing temperature, freezing delay, and freeze-thaw cycles on CSF biomarker analyses. METHODS: We studied fractionated sampling in sequential aliquots of lumbar CSF. Centrifuged and noncentrifuged samples from the same fraction were compared. CSF samples were subjected to different protocols (liquid nitrogen, -80 °C, and -20 °C; 24 h at 2-8 °C; and 24 and 48 h at room temperature). To study the influence of freeze-thaw cycles, samples were thawed up to 4 times and refrozen at -80 °C. CSF was collected in polypropylene tubes. We measured CSF biomarker concentrations with commercially available single-analyte Innotest assays. RESULTS: CSF biomarker concentrations from non-blood-contaminated samples are not influenced by centrifugation or fractionated sampling. Freezing temperature and delayed storage can affect biomarker concentrations; freezing of CSF samples at -80 °C as soon as possible after collection is recommended. Consecutive freezing and thawing of CSF samples up to 3 times had little effect. CONCLUSIONS: Temperature of freezing, delay until freezing, and freeze-thaw cycles significantly influence CSF biomarker concentrations, stressing the need for standard operating procedures for preanalytical sample handling. The differences observed in this study are, however, relatively small, and the impact on the clinical value of these CSF biomarkers needs to be determined.

Is the geriatric depression scale a reliable screening tool for depressive symptoms in elderly patients with cognitive impairment?

OBJECTIVE: To determine the reliability of the 30-item Geriatric Depression Scale (GDS-30) for the screening of depressive symptoms in dementia and mild cognitive impairment (MCI) using the Cornell Scale for Depression in Dementia (CSDD) as the 'gold standard'. METHODS: Diagnosed according to strictly applied clinical diagnostic criteria, patients with MCI (n = 156) and probable Alzheimer's disease (AD) (n = 247) were included. GDS-30, CSDD, Mini Mental State Examination (MMSE) and Global Deterioration Scale were assessed in all patients at inclusion. The AD group was divided in three subgroups: mild AD (MMSE>or=18) (n = 117), moderate AD (MMSE< 18 and >or=10) (n = 89) and severe AD (MMSE<10) (n = 38). RESULTS: In MCI patients, moderate but highly significant correlations were found between GDS-30 and CSDD scores (Pearson: r = 0.565; p < 0.001). In mildly (r = 0.294; p = 0.001), moderately (r = 0.273; p = 0.010) and severely (r = 0.348; p = 0.032) affected AD patients, only weak correlations between GDS-30 and CSDD scores were calculated. ROC curve analysis showed that sensitivity and specificity values of respectively 95% and 67% were achieved when a GDS-30 cut-off score of 8 was applied in MCI patients. In AD patients, too low sensitivity and specificity values did not allow selecting an optimal cut-off score by means of ROC curve analysis. CONCLUSION: Using the CSDD as 'gold standard', we demonstrated that the GDS-30 is a reliable screening tool for depressive symptoms in MCI but not in AD patients.