Application of the PredictAD decision support tool to a Danish cohort of patients with Alzheimer's disease and other dementias.

BACKGROUND: The diagnosis of Alzheimer's disease (AD) is based on an ever-increasing body of data and knowledge making it a complex task. The PredictAD tool integrates heterogeneous patient data using an interactive user interface to provide decision support. The aim of this project was to investigate the performance of the tool in distinguishing AD from non-AD dementia using a realistic clinical dataset. METHODS: We retrieved clinical data from a group of patients diagnosed with AD (n = 72), vascular dementia (VaD, n = 30), frontotemporal dementia (FTD, n = 25) or dementia with Lewy bodies (DLB, n = 14) at the Copenhagen Memory Clinic at Rigshospitalet. Three classification methods were applied to the data in order to differentiate between AD and a group of non-AD dementias. The methods were the PredictAD tool's Disease State Index (DSI), the naïve Bayesian classifier and the random forest. RESULTS: The DSI performed best for this realistic dataset with an accuracy of 76.6% compared to the accuracies for the naïve Bayesian classifier and random forest of 67.4 and 66.7%, respectively. Furthermore, the DSI differentiated between the four diagnostic groups with a p value of <0.0001. CONCLUSION: In this dataset, the DSI method used by the PredictAD tool showed a superior performance for the differentiation between patients with AD and those with other dementias. However, the methods need to be refined further in order to optimize the differential diagnosis between AD, FTD, VaD and DLB.

Added Diagnostic Value of (11)C-PiB-PET in Memory Clinic Patients with Uncertain Diagnosis.

INTRODUCTION: The added diagnostic value of (11)C-PiB-PET for the assessment of the accumulation of cortical beta-amyloid in memory clinic patients with uncertain diagnosis remains undetermined. METHODS: All patients who underwent PiB-PET at the Copenhagen Memory Clinic between March 2008 and November 2011 were included in this uncontrolled, retrospective study. The standard diagnostic evaluation program included physical and neurological examination, cognitive and functional assessment, a cranial CT or MRI, functional imaging and cerebrospinal fluid sampling. Based on anonymized case reports, three experienced clinicians reached a consensus diagnosis and rated their confidence in the diagnosis before and after disclosure of PiB-PET ratings. PiB-PET scans were rated as either positive or negative. RESULTS: A total of 57 patients (17 females, 30 males; age 65.7 years, range 44.2-82.6) were included in the study. Twenty-seven had a positive PiB-PET scan. At the first diagnostic evaluation, 16 patients were given a clinical Alheimer's disease diagnosis (14 PiB positive). Of the 57 patients, 13 (23%) were diagnostically reclassified after PiB-PET ratings were disclosed. The clinicians' overall confidence in their diagnosis increased in 28 (49%) patients. CONCLUSION: PiB-PET adds to the specialist clinical evaluation and other supplemental diagnostic investigations in the diagnostic classification of patients with uncertain diagnosis in a specialized memory clinic.

Effects of root exudate sorgoleone on photosynthesis.

The aim of this investigation was to determine if sorgoleone (SGL), ap-benzoquinone inSorghum bicolor root exudate, is a photosynthesis inhibitor. Assays usingGlycine max leaf disks showed concentrations as low as 10µM SGL inhibited oxygen evolution more than 50%. Tests conducted on chloroplasts isolated fromPisum sativum showed that SGL is a powerful inhibitor of CO2-dependent oxygen evolution. Using a chloroplast suspension equivalent to 80-100µg chlorophyll, the I50 was approximately 0.2µM SGL. These data indicate inhibition of photosynthesis is part of the explanation for growth reduction caused by this allelochemical.

Sorgoleone from root exudate inhibits mitochondrial functions.

The aim of this investigation was to determine if sorgoleone (SGL), a hydrophobic compound inSorghum bicolor (L.) Moench root exudate, interferes with mitochondrial functions. Tests were conducted on mitochondria isolated from etiolated soybean [Glycine max (L.) Merr.] and corn (Zea mays L.) seedlings. The data show SGL is a potent inhibitor of state 3 and state 4 respiration rates in both soybean and corn. Using either NADH, succinate, or malate as substrate, the I50 was about 0.5µM SGL for state 3 and 5.0µM for state 4 based on 0.3-0.5 mg mitochondrial protein. Absorption spectra indicate SGL blocks electron transport at theb-c 1 complex. These data show that disruption of mitochondrial function may be a mechanism of SGL-mediated growth inhibition previously reported and demonstrate a probable role of SGL inSorghum allelopathy.