The assessment consisted of 12 sensi tive Dutch versions of widely used and well validated tests covering the major cognitive domains, that is, Learning Memory, Attention Concentration, Enzastaurin and Executive Functions. Tests in each domain were selected on the basis of cognitive theory and clinical validation stud ies and covered all relevant subdomains. First, within the domain Learning Memory, Working Memory was assessed by the subtests Digit Span Backwards and Letter Number Sequencing of the WAIS III, Episodic Memory was measured using the Rey Auditory Verbal Learning Test and the subtest Story Recall of the Rivermead Behavioural Memory Test and Semantic Memory was assessed by the Semantic Fluency Test.

As part of the domain Attention Concentration, Sustained Inhibitors,Modulators,Libraries At tention was assessed using the d2 Test, Alertness was measured by the WAIS III Digit Span Forward and the subtest Alertness from the computerized TAP 2. 1. In the domain Executive Functions the Controlled Oral Word Association Test was used to measure Response Generation. Response Inhibition was tapped by the Stroop Color Word test, Mental Flexibility by the sub test Flexibility of the TAP 2. 1 and Problem Solving by the Brixton Spatial Anticipation Test and Ravens Advanced Progressive Matrices. To estimate the level of premorbid intelligence the Dutch version of the National Adult Reading Test was ad ministered. Moreover, self report questionnaires were ad ministered to assess psychological well being, everyday cognitive fail ures, mood and Inhibitors,Modulators,Libraries fatigue. Biomarkers In the patient groups, blood samples were obtained on the day of the neuropsychological assessment.

Blood samples were analyzed for a full blood count, liver and renal function, and levels of testosterone, sex hormone binding globuline, estradiol, albumin, vitamin B12, thyroid function, glucose C reactive protein, erythrocyte sedimentation rate and lactate de hydrogenase. Free testosterone was calculated from the testosterone and SHBG Inhibitors,Modulators,Libraries values. Plasma VEGF and serum cytokine levels were measured. Levels of VEGF were measured by a specific ELISA as previous described. We used the Th1 Th2 11plex kit according to the manufacturers Inhibitors,Modulators,Libraries protocol to measure cytokines levels. The minimum detectable concentrations were estimated to be 4. 2 pg ml for IL 1B, 16. 4 pg ml for IL 2, 20. 8 pg ml IL 4, 1. 6 pg ml IL 5, 1. 2 pg ml IL 6, 0. 5 pg ml IL 8, 1.

9 pg ml IL 10, 1. 5 pg ml IL 12, 3. 2 pg ml TNF, 2. 4 pg ml TNFB and 1. 6 pg ml interferon gamma. Results were ex pressed as percentage of detectable values and as median values in both patient groups. Statistical analyses Inhibitors,Modulators,Libraries All neuropsychological tests were scored according to their manuals. For data reduction purposes and to enhance the comparability of cognitive AZD9291 molecular weight domains, standardized z scores were computed using the raw test results.