This study suggests that amyloid load is significantly raised in over 80% of subjects with DLB, while amyloid pathology is infrequent in PDD. These in vivo PET findings suggest that the presence of amyloid in DLB could contribute to the rapid progression of dementia in this condition and that anti-amyloid strategies may be relevant.

[ 11 C](R)PK11195-PET measures upregulation of translocator protein, which is associated with microglial activation, [11 C]PIB-PET is a marker of amyloid, while [18 F]FDG-PET measures cerebral glucose metabolism (rCMRGlc). We hypothesize that microglial activation is an early event in the Parkinson's disease (PD) spectrum and is independent of the amyloid pathology. The aim of this study is to evaluate in vivo the relationship between microglial activation, amyloid deposition, and glucose metabolism in Parkinson's disease dementia (PDD) and PD subjects without dementia. Here, we evaluated 11 PDD subjects, 8 PD subjects without dementia, and 24 control subjects. Subjects underwent T1 and T2 MRI, 11 C]PIB uptake were interrogated using region of interest and SPM (statistical parametric mapping) analysis. The PDD patients showed a significant increase of microglial activation in anterior and posterior cingulate, striatum, frontal, temporal, parietal, and occipital cortical regions compared with the controls. The PD subjects also showed a statistically significant increase in microglial activation in temporal, parietal, and occipital regions. [11 C]PIB uptake was marginally increased in PDD and PD. There was a significant reduction in glucose metabolism in PDD and PD. We have also demonstrated pixel-by-pixel correlation between mini-mental state examination (MMSE) score and microglial activation, and MMSE score and rCMRGlc. In conclusion, we have demonstrated that cortical microglial activation and reduced glucose metabolism can be detected early on in this disease spectrum. Significant microglial activation may be a factor in driving the disease process in PDD. Given this, agents that affect microglial activation could have an influence on disease progression.

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The significant inverse correlations between cortical levels of microglial activation and rCMRGlc in AD and PDD suggest cortical neuroinflammation may drive neuronal dysfunction in these dementias.

Objective: To investigate striatal adenosine A2A receptor availability in patients with Parkinson disease (PD) with and without levodopa-induced dyskinesias (LIDs). While providing effective relief from the motor symptoms of PD, chronic levodopa use is associated with development of LIDs. A2A receptors are expressed on the bodies of indirect pathway medium spiny striatal neurons and on dopamine terminals and play a role in modulating dopamine transmission. A2A antagonists have antiparkinsonian activity by boosting levodopa efficacy. We aimed to study A2A receptor availability in patients with PD with and without LIDs using PET and [ 11 C]SCH442416, an A2A antagonist. Methods:Six patients with PD with and 6 without LIDs were studied withdrawn 12 hours from medication. Their PET findings were compared with 6 age-matched healthy controls. Using spectral analysis, [ 11 C]SCH442416 regional volumes of distribution (V T ) were computed for the caudate, putamen, and thalamus and binding potentials (BP ND ) reflecting the ratio of specific: nonspecific uptake were compared between groups.Results: A2A binding in the caudate and putamen of subjects with PD with LIDs was far higher (p ϭ 0.026 and p ϭ 0.036, respectively) than that of subjects with PD without LIDs, which lay within the control range. Thalamic A2A availability was similar for all 3 groups. Conclusion:Patients with PD with LIDs show increased A2A receptor availability in the striatum.This finding is compatible with altered adenosine transmission playing a role in LIDs and provides a rationale for a trial of A2A receptor agents in the treatment of these motor complications.

Levodopa-induced dyskinesias are a common complication of long-term therapy in Parkinson's disease. Although both pre- and post-synaptic mechanisms seem to be implicated in their development, the precise physiopathology of these disabling involuntary movements remains to be fully elucidated. Abnormalities in glutamate transmission (over expression and phosphorylation of N-methyl-D-aspartate receptors) have been associated with the development of levodopa-induced dyskinesias in animal models of Parkinsonism. The role of glutamate function in dyskinetic patients with Parkinson's disease, however, is unclear. We used (11)C-CNS 5161 [N-methyl-3(thyomethylphenyl)cyanamide] positron emission tomography, a marker of activated N-methyl-D-aspartate receptor ion channels, to compare in vivo glutamate function in parkinsonian patients with and without levodopa-induced dyskinesias. Each patient was assessed with positron emission tomography twice, after taking and withdrawal from levodopa. Striatal and cortical tracer uptake was calculated using a region of interest approach. In the 'OFF' state withdrawn from levodopa, dyskinetic and non-dyskinetic patients had similar levels of tracer uptake in basal ganglia and motor cortex. However, when positron emission tomography was performed in the 'ON' condition, dyskinetic patients had higher (11)C-CNS 5161 uptake in caudate, putamen and precentral gyrus compared to the patients without dyskinesias, suggesting that dyskinetic patients may have abnormal glutamatergic transmission in motor areas following levodopa administration. These findings are consistent with the results of animal model studies indicating that increased glutamatergic activity is implicated in the development and maintenance of levodopa-induced dyskinesias. They support the hypothesis that blockade of glutamate transmission may have a place in the management of disabling dyskinesias in Parkinson's disease.

Dietary arginine requirement of fingerling Indian major carp, Cirrhinus mrigala (4.20 ± 0.05 cm; 0.60 ± 0.02 g) was determined by conducting a 8‐week feeding trial with casein–gelatine‐based diets (400 g kg−1 crude protein; 17.90 kJ g−1, gross energy), containing crystalline amino acids with graded levels of l‐arginine (10, 12.5, 15, 17.5, 20 and 22.5 g kg−1, dry diet). Fish were randomly stocked, in triplicate groups, in 55‐L indoor polyvinyl flow through circular tanks and fed experimental diets at 5% of their body weight divided into two feedings at 08.00 and 16.00 hours. Live weight gain (321%) and feed conversion ratio (FCR 1.40) were significantly (P < 0.05) higher in fish fed diet containing 17.5 g kg−1dietary arginine compared with other diets. Second‐degree polynomial regression analysis of live weight gain, FCR and protein efficiency ratio data indicated requirements for dietary arginine at 18.7, 18.4 and 18.3 g kg−1 of the dry diet, respectively. Maximum carcass protein, and minimum moisture and fat contents were noticed at the requirement level. Carcass ash content remained insignificantly different among the treatments except at 17.5 g kg−1 dietary arginine showing significantly higher ash content. Based on the above results, it is recommended that the diet for fingerling C. mrigala should contain arginine at 18.4 g kg−1, dry diet, corresponding to 46 g kg−1 dietary protein for optimum growth and efficient feed utilization.

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