Performance testing of a fully automated, Chemiluminescent, beta ...

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Judes Poirier2, David Fontaine2, Pedro Rosa-Neto2, Natasha Rajah2,. 1McGill University and ... Shari Jackson2, Karen Ackles2, Anne Tweedie2, Daniel Kozo5,.
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Poster Presentations: P1

into three groups: dementia, cognitive impairment not dementia (CIND), and those without cognitive impairment (WCI). One year later 199 participants without dementia agreed to be reevaluated according to the same protocol. Results: Multiple regression analysis in the reevaluation sample disclosed no associations between baseline laboratory data and worsening performance in any cognitive tests or functional measurement. In the CIND group, cortisol levels correlated with MMSE (rho¼ -0,33; p¼0,015) and Functional Assessment Questionnaire decline (rho¼-0,30 ; p¼0,038). sTNFR1 levels correlated with worsening category fluency test performance (rho¼0,31 ; p¼0,029). Conclusions: Even though the magnitude of the associations was generally weak, in the CIND group we did found significant relationships between cortisol and sTNFR1 levels, and prospective cognitive and functional outcomes, which might encourage further research in the field. P1-160

OLFACTORY IDENTIFICATION AS A POTENTIAL MARKER OF PRESYMPTOMATIC ALZHEIMER’S DISEASE

Marie-Elyse Lafaille-Magnan1, John Breitner2, Pierre Etienne2, Judes Poirier2, David Fontaine2, Pedro Rosa-Neto2, Natasha Rajah2, 1 McGill University and Centre for Studies on Prevention of Alzheimer’s Disease, Douglas Mental Health University Institute Research Centre, Montreal, Quebec, Canada; 2Centre for Studies on Prevention of Alzheimer’s Disease, Douglas Mental Health University Institute Research Centre, Montreal, Quebec, Canada. Contact e-mail: marie-elyse. [email protected] Background: Several studies suggest that olfactory dysfunction is an early symptom of Alzheimer’s disease (AD). The olfactory bulb and entorhinal cortex are among the first brain structures affected in AD pathology. Therefore, changes in olfactory function may serve as a marker for the progress of pre-symptomatic AD. We have begun a program to explore olfaction as an endpoint for trials of interventions that may arrest or delay pre-symptomatic AD, and thus serve as potential agents for prevention of AD dementia. As a first step in this research we examined (baseline) olfactory abilities in relation to cognitive functions in a group of older dementiafree subjects at risk of AD. Methods: 73 adults aged 55 and older, with a first degree family history of AD, were enrolled in a pilot clinical trial of an agent with potential for mitigation of pre-symptomatic AD progression. At baseline, these persons were evaluated cognitively using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and their sense of smell was evaluated using the University of Pennsylvania Smell Identification Test (UPSIT). Here we report the association of these two measures. Results: 62 % of the sample were female. Mean age was 65.6 6 s.d. 5.0 yrs, and mean education 15.4 6 s.d. 3.3 years. Baseline UPSIT score was significantly associated with score on the RBANS immediate memory sub-scale (Pearson r ¼ 0.350, P < 0.002), and showed a trend toward association with overall RBANS score (r ¼ 0.229, P ¼ 0.051). Participants will now be followed to observe change over time in UPSIT and/or RBANS scores, as well as several imaging and other potential biomarkers. Conclusions: In cognitively intact older adults, a lower score on the

smell identification test is associated with reduced ability in immediate memory, and possibly with other cognitive functions. Future work will examine whether olfactory testing may serve as a marker of progression in pre-symptomatic AD. P1-161

PERFORMANCE TESTING OF A FULLY AUTOMATED, CHEMILUMINESCENT, BETA-AMYLOID 42 ASSAY

Irina Baburina1, Paul Contestable2, George Green3, Holly Soares4, Shari Jackson2, Karen Ackles2, Anne Tweedie2, Daniel Kozo5, Jodi Courtney6, Salvatore Salamone7, 1Saladax Biomedical Inc., Bethlehem, Pennsylvania, United States; 2Ortho Clinical Diagnostics, Rochester, New York, United States; 3Bristol Myers Squibb, Princeton, New Jersey, United States; 4Bristol Myers Squibb, Wallingford, New Jersey, United States; 5Saladax Biomedical, Bethlehem, Pennsylvania, United States; 6Saladax Biomedical Inc, Bethlehem, Pennsylvania, United States; 7 Saladax Biomedical, Inc, Bethlehem, Pennsylvania, United States. Contact e-mail: [email protected] Background: Evaluation of cerebrospinal fluid (CSF) biomarkers in Alzheimer’s disease (AD) is increasingly more important for improving the certainty of ante-mortem diagnosis of AD, ensuring proper patient management. Use of such markers for clinical purposes, in conjunction with potential disease-modifying therapies, requires assays that can deliver high analytical and clinical performance. Two biomarkers, beta amyloid 1-42 (Ab42) and tau, correlate with disease progression and a number of research use only (RUO) tests are available. The VITROS Ò Immunodiagnostic Products Amyloid Beta 42 Assay(AB-42)1 is an accurate and robust assay under development for Ab42 that shows a marked improvement in precision, linearity and reproducibility when compared to currently available tests. Methods: VITROS AB-42 assay is being developed for the VITROS Immunodiagnostic Systems and analytical performance was evaluated following CLSI guidelines using two VITROS AB-42 assay reagent lots, 3 CSF pools, and 3 controls. Linearity was tested with 11 admixtures of endogenous Ab42 in CSF and synthetic Ab42 in buffer. Interference testing included commonly prescribed drugs, other Ab peptides, and endogenous substances. Limit of detection (LoD) and lower limit of quantitation were confirmed with 20 replicates per day on 3 days. Results: The median within-laboratory coefficient of variation (CV) for the 3 CSF pools was 3.95% with a range of 1.3%V‘8.2%. The controls’ within-laboratory CV was 2.9%. Repeatability CVs were 3.4% for CSF pools and 1.2% for controls. The assay showed good linearity across the measuring range (0-2,500pg/mL) with the admixture of endogenous and synthetic peptide. Bias introduced by commonly prescribed drugs at high levels was