Cerebrospinal fluid pro-inflammatory cytokines differentiate parkinsonian syndromes.

INTRODUCTION: Neuroinflammation has been established to be part of the neuropathological changes in Parkinson's disease (PD) and atypical parkinsonism (APD). Activated microglia play a key role in neuroinflammation by release of cytokines. Evidence of the disparity, if any, in the neuroinflammatory response between PD and APD is sparse. In this study, we investigated CSF cytokine profiles in patients with PD, multiple system atrophy (MSA), or progressive supranuclear palsy (PSP). METHODS: On a sensitive electrochemiluminescence-based platform (Quickplex, Meso Scale Discovery®), we examined a panel of C-reactive protein (CRP) and eight selected cytokines, IFN-γ, IL-10, IL-18, IL-1ß, IL-4, IL-6, TGF-ß1, and TNF-α, among patients with PD (n = 46), MSA (n = 35), and PSP (n = 39) or controls (n = 31). Additionally, CSF total tau protein levels were measured as a marker of nonspecific neurodegeneration for correlation estimates. RESULTS: CRP and the pro-inflammatory cytokines TNF-α, IL-1ß, and Il-6 were statistically significantly elevated in MSA and PSP patients compared to PD patients but not compared to control patients. No analytes differed statistically significantly between MSA and PSP patients. The best diagnostic discrimination, evaluated by ROC curve (AUC 0.77, p = 007, 95% CI 0.660-0.867), between PD and MSA patients was seen for a subset of analytes: CRP, TNF-α, IL-1ß, and IFN-γ. CONCLUSION: Among the investigated cytokines and CRP, we found a statistically significant increase of microglia-derived cytokines in MSA and PSP patients compared to PD patients.

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.

Potentially reversible conditions in 1000 consecutive memory clinic patients.

OBJECTIVES: To investigate the prevalence and classification of potentially reversible conditions in a prospective memory clinic cohort of younger and elderly patients with cognitive symptoms. PATIENTS: 1000 consecutive patients referred during a period of 54 months to a university hospital multidisciplinary memory clinic based in neurology. METHODS: All patients were referred for diagnostic evaluation and treatment of cognitive symptoms. The multidisciplinary staff prospectively established a standardised consensus report for each patient based on the results of clinical and ancillary investigations with classification of cognitive profile, primary underlying cause, and concomitant conditions. RESULTS: The mean age of the patients was 66.1 years (range 17-98) and 43% met diagnostic criteria for dementia. A potentially reversible primary aetiology for cognitive symptoms was identified in 19% and a potentially reversible concomitant condition in 23% of all patients. In the subgroup of patients with dementia, 4% had a potentially reversible primary aetiology. Careful clinical examination, routine laboratory tests, and cranial computed tomography identified most of these conditions. CONCLUSIONS: Reversible conditions are most often encountered in patients with mild cognitive disturbances. Although treatment may not always result in full reversal of cognitive symptoms, potentially reversible conditions should be identified in the diagnostic evaluation of the patient.

Effects of juglone on growth, photosynthesis, and respiration.

The impacts of juglone on plant growth and several other physiological functions were evaluated in this study. Juglone inhibitedLemna minor growth, chlorophyll content, and net photosynthesis at treatments between 10 and 40µM. Soybean leaf disks vacuum infiltrated with as little as 10µM juglone had reduced photosynthesis. Oxygen evolution by chloroplasts isolated fromPisum sativum was inhibited by juglone with an I50 of 2µM. Micromolar treatments of juglone stimulated oxygen uptake in mitochondria isolated fromGlycine max. These data suggest perturbations of chloroplast and mitochondrial functions may contribute to plant growth reductions observed in juglone-mediated allelopathy.

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.

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.