CSF Aβ1–42 level is associated with cognitive decline in early Parkinson’s disease with rapid eye movement sleep behavior disorder

Abstract Background Rapid eye movement sleep behavior disorder (RBD) is associated with cognitive decline in early Parkinson’s disease (PD). However, the underlyling basis for this association remains unclear. Methods Parkinson’s Progression Marker’s Initiative (PPMI) subjects underwent baseline RBD testing with RBD sleep questionnaire (RBDSQ). Serial assessments included measures of motor symptoms, non-motor symptoms (NMS), neuropsychological assessment, blood and cerebrospinal fluid (CSF) biomarkers. Up to three years follow-up data were included. We stratified early PD subjects into PD with RBD (RBDSQ score > 5) and PD without RBD groups. Then, we evaluated baseline biomarkers in each group as a predictor of cognitive decline using Montreal Cognitive Assessment (MoCA) score changes over three years in regression models. Results Four hundred twenty-three PD subjects were enrolled at baseline, and a total of 350 PD subjects had completed 3 years of study follow-up with completely serial assessments. We found that at baseline, only CSF β-amyloid 1–42 (Aβ1–42) was significantly lower in PD subjects with RBD. On three years follow-up analysis, PD subjects with RBD were more likely to develop incident mild cognitive impairment (MCI) and presented greater cognitive decline in MoCA score. Lower baseline CSF Aβ1–42 predicted cognitive decline over 3 years only in PD subjects with RBD (β = − 0.03, P = 0.003). A significant interaction between Aβ1–42 and the 2 groups confirmed that this effect was indeed higher in PD with RBD than the other individual (β = − 2.85, P = 0.014). Conclusion These findings indicate that CSF Aβ1–42 level is associated with global cognitive decline in early PD with RBD. The addition of CSF Aβ1–42 to RBD testing increase the likelihood of identifying those at high risk for cognitive decline in early PD

Experimental study on the relationship between levodopa ⁃induced dyskinesia and phosphorylation of ERK in the striatum

Objective To explore the relationship between levodopa⁃induced dyskinesia (LID) and phosphorylated extracellular signal ⁃ regulated kinase (ERK, Thr202/Tyr204, ERK1/2) in striatum. Methods The hemiparkinsonian rat model was produced by stereotaxically injecting 6⁃hydroxydopamine (6⁃ OHDA) to right medial forebrain bundle (MFB). The hemiparkinsonian rats were intraperitoneally treated with levodopa (50 mg/kg) and benserazide (12.50 mg/kg) for 21 d and abnormal involuntary movement was evaluated. Immunofluorescent and Western blotting were used to observe the changes of phosphorylation of ERK1/2 in rat's striatum. Results Western blotting indicated that the 6 ⁃ OHDA lesion induced a significant downregulation of the phosphorylation of ERK1/2 to (68.28 ± 7.42)% in comparison with the sham⁃lesioned group [ (107.05 ± 3.81)% ; t = 0.109, P = 0.018]. Chronic treatment with levodopa significantly increased the phosphorylation of ERK1/2 to (160.37 ± 10.54)% , which was compared to the Parkinson's disease (PD) group (t = 0.109, P = 0.000). The study of immunofluorescent staining revealed that there were few phosphorylation of ERK1/2 in the lesion side of hemiparkinsonian rats, and most of them were expressed in dynorphin ⁃ negative neurons; levodopa administration increased the phosphorylation of ERK1/2 expression compared with the PD group (t = 5.121, P = 0.000), and the co⁃expression of the phosphorylation of ERK1/2 and dynorphin increased to (83.62 ± 1.46)％ compared with PD group (t = 11.263, P = 0.003). Conclusion These results suggest that the changes of ERK1/2 phosphorylation state in the strionigral neurons can play an important role in the over ⁃ excitation of the direct pathway medium⁃spiny neurons. DOI：10.3969/j.issn.1672-6731.2011.01.01

Headache Secondary to Isolated Sphenoid Sinus Fungus Ball: Retrospective Analysis of 6 Cases First Diagnosed in the Neurology Department

Fungal sphenoid sinusitis is easily misdiagnosed in clinic, particularly for patients with normal immunological status. Due to the anatomic characteristics of sphenoid sinus, patients presented with various nonspecific symptoms and complications. Headache is the most common presentation, but location of headache is not fixed. We intended to analyze 6 cases of headache secondary to the isolated sphenoid sinus fungus ball (SSFB) which were first diagnosed in the Neurology Department. There was significant female predominance with mean ages of 55 years. They had repeatedly headache history from months to years. The headache was unilateral and usually on the side of lesions. Medication of pain relievers worked well in the beginning of SSFB, but not in the late stage of disease. Notably, all patients did not present positive nervous systemic signs. A preoperative computed tomography (CT) scan or magnetic resonance imaging (MRI) demonstrated the inflammation in sphenoid sinus. Some cases showed calcification in soft tissue or bone lesions of sinus wall. All of 6 patients undertook transnasal endoscopic sphenoidotomy without antifungal therapy after operation. Characteristic fungus ball (FB) was detected after histopathological examination. No headache recurrence was found after average 15.5 months follow-up. Our results suggested that transnasal endoscopic sphenoidotomy is the treatment of choice to remove the FB in sphenoid sinus with a low rate of morbidity and recurrence

Neuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease

ObjectiveTo identify regional brain metabolic dysfunctions associated with neuropsychiatric symptoms (NPS) in preclinical Alzheimer disease (AD).MethodsWe stratified 115 cognitively normal individuals into preclinical AD (both amyloid and tau pathologies present), asymptomatic at risk for AD (either amyloid or tau pathology present), or healthy controls (no amyloid or tau pathology present) using [18F]florbetapir PET and CSF phosphorylated tau biomarkers. Regression and voxel-based regression models evaluated the relationships between baseline NPS measured by the Neuropsychiatric Inventory (NPI) and baseline and 2-year change in metabolism measured by [18F]fluorodeoxyglucose (FDG) PET.ResultsIndividuals with preclinical AD with higher NPI scores had higher [18F]FDG uptake in the posterior cingulate cortex (PCC), ventromedial prefrontal cortex, and right anterior insula at baseline. High NPI scores predicted subsequent hypometabolism in the PCC over 2 years only in individuals with preclinical AD. Sleep/nighttime behavior disorders and irritability and lability were the components of the NPI that drove this metabolic dysfunction.ConclusionsThe magnitude of NPS in preclinical cases, driven by sleep behavior and irritability domains, is linked to transitory metabolic dysfunctions within limbic networks vulnerable to the AD process and predicts subsequent PCC hypometabolism. These findings support an emerging conceptual framework in which NPS constitute an early clinical manifestation of AD pathophysiology