Impaired synaptic function is linked to cognition in Parkinson's disease

OBJECTIVE: Cognitive impairment is frequent in Parkinson's disease, but the underlying mechanisms are insufficiently understood. Because cortical metabolism is reduced in Parkinson's disease and closely associated with cognitive impairment, and CSF amyloid‐β species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloid‐β release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloid‐β, and presynaptic deposits of α‐synuclein. We expect a correlation between hypometabolism, CSF amyloid‐β, and the synapse related‐markers CSF neurogranin and α‐synuclein. METHODS: Thirty patients with mild‐to‐moderate Parkinson's disease and 26 healthy controls underwent a clinical assessment, lumbar puncture, MRI, 18F‐fludeoxyglucose‐PET, and a neuropsychological test battery (repeated for the patients after 2 years). RESULTS: All subjects had CSF amyloid‐β 1‐42 within normal range. In Parkinson's disease, we found strong significant correlations between cortical glucose metabolism, CSF Aβ, α‐synuclein, and neurogranin. All PET CSF biomarker‐based cortical clusters correlated strongly with cognitive parameters. CSF neurogranin levels were significantly lower in mild‐to‐moderate Parkinson's disease compared to controls, correlated with amyloid‐β and α‐synuclein, and with motor stage. There was little change in cognition after 2 years, but the cognitive tests that were significantly different, were also significantly associated with cortical metabolism. No such correlations were found in the control group. INTERPRETATION: CSF Aβ, α‐synuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to Aβ and α‐synuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease

Improved Leakage Correction for Single-Echo Dynamic Susceptibility Contrast Perfusion MRI Estimates of Relative Cerebral Blood Volume in High-Grade Gliomas by Accounting for Bidirectional Contrast Agent Exchange

Background and purposeContrast agent extravasation through a disrupted blood-brain barrier potentiates inaccurate DSC MR imaging estimation of relative CBV. We explored whether incorporation of an interstitial washout rate in a leakage-correction model for single-echo, gradient-echo DSC MR imaging improves relative CBV estimates in high-grade gliomas.Materials and methodsWe modified the traditional model-based postprocessing leakage-correction algorithm, assuming unidirectional contrast agent extravasation (Boxerman-Weisskoff model) to account for bidirectional contrast agent exchange between intra- and extravascular spaces (bidirectional model). For both models, we compared the goodness of fit with the parent leakage-contaminated relaxation rate curves by using the Akaike Information Criterion and the difference between modeled interstitial relaxation rate curves and dynamic contrast-enhanced MR imaging by using Euclidean distance in 21 patients with glioblastoma multiforme.ResultsThe bidirectional model had improved Akaike Information Criterion versus the bidirectional model in >50% of enhancing tumor voxels in all 21 glioblastoma multiformes (77% ± 9%; P < .0001) and had reduced the Euclidean distance in >50% of enhancing tumor voxels for 17/21 glioblastoma multiformes (62% ± 17%; P = .0041). The bidirectional model and dynamic contrast-enhanced-derived kep demonstrated a strong correlation (r = 0.74 ± 0.13). On average, enhancing tumor relative CBV for the Boxerman-Weisskoff model exceeded that for the bidirectional model by 16.6% ± 14.0%.ConclusionsInclusion of the bidirectional exchange in leakage-correction models for single-echo DSC MR imaging improves the model fit to leakage-contaminated DSC MR imaging data and significantly improves the estimation of relative CBV in high-grade gliomas

Hogback

Materials: Wood, Cotton, and Resin Dimensions: 75 x 37 x 57 Project Advisor: Rob Neilson Year of Graduation: 2014https://lux.lawrence.edu/artgallery_se2014/1024/thumbnail.jp

Hogback: Installation View

Materials: Wood, Cotton, and Resin Dimensions: 75 x 37 x 57 Project Advisor: Rob Neilson Year of Graduation: 2014https://lux.lawrence.edu/artgallery_se2014/1043/thumbnail.jp

Hogback (Detail)

Materials: Wood, Cotton, and Resin Dimension: 75 x 37 x 57 Project Advisor: Rob Neilson Year of Graduation: 2014https://lux.lawrence.edu/artgallery_se2014/1026/thumbnail.jp

Hogback (3/4 View)

Materials: Wood, Cotton, and Resin Dimensions: 75 x 37 x 57 Project Advisor: Rob Neilson Year of Graduation: 2014https://lux.lawrence.edu/artgallery_se2014/1025/thumbnail.jp

Voxel-Wise Perfusion Assessment in Cerebral White Matter with PCASL at 3T; Is It Possible and How Long Does It Take?

Neuro Imaging Researc