Diagnostic value of cerebrospinal fluid A? ratios in preclinical Alzheimer's disease.

ABSTRACT: In this study of preclinical Alzheimer's disease (AD) we assessed the added diagnostic value of using cerebrospinal fluid (CSF) A? ratios rather than A?42 in isolation for detecting individuals who are positive on amyloid positron emission tomography (PET).Thirty-eight community-recruited cognitively intact older adults (mean age 73, range 65-80 years) underwent (18)F-flutemetamol PET and CSF measurement of A?1-42, A?1-40, A?1-38, and total tau (ttau). (18)F-flutemetamol retention was quantified using standardized uptake value ratios in a composite cortical region (SUVRcomp) with reference to cerebellar grey matter. Based on a prior autopsy validation study, the SUVRcomp cut-off was 1.57. Sensitivities, specificities and cut-offs were defined based on receiver operating characteristic analysis with CSF analytes as variables of interest and (18)F-flutemetamol positivity as the classifier. We also determined sensitivities and CSF cut-off values at fixed specificities of 90 % and 95 %.Seven out of 38 subjects (18 %) were positive on amyloid PET. A?42/ttau, A?42/A?40, A?42/A?38, and A?42 had the highest accuracy to identify amyloid-positive subjects (area under the curve (AUC)???0.908). A?40 and A?38 had significantly lower discriminative power (AUC?=?0.571). When specificity was fixed at 90 % and 95 %, A?42/ttau had the highest sensitivity among the different CSF markers (85.71 % and 71.43 %, respectively). Sensitivity of A?42 alone was significantly lower under these conditions (57.14 % and 42.86 %, respectively).For the CSF-based definition of preclinical AD, if a high specificity is required, our data support the use of A?42/ttau rather than using A?42 in isolation.

SUBMITTER: Adamczuk K 

PROVIDER: S-EPMC4683859 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature