Taste function in early stage treated and untreated Parkinson’s disease

Since brain stem regions associated with early Parkinson’s disease (PD) pathology encroach upon those involved in taste function, the ability to taste may be compromised in PD. However, studies on this point have been contradictory. We administered well-validated wholemouth and regional taste tests that incorporated multiple concentrations of sucrose, citric acid, caffeine, and sodium chloride to 29 early stage PD patients and 29 age-, sex-, and race-matched controls. Electrogustometry was also performed on the anterior tongue. The PD cohort was tested both on and off dopamine-related medications in counterbalanced test sessions. While whole-mouth taste identification test scores for all stimuli were, on average, nominally lower for the PD patients than for the controls, a trend in the opposite direction was noted for the intensity ratings at the lower stimulus concentrations for all stimuli except caffeine. Moreover, regional testing found that PD subjects tended to rate the stimuli, relative to the controls, as more intense on the anterior tongue and less intense on the posterior tongue. No significant associations were evident between taste test scores and UPDRS scores, L-DOPA medication equivalency values, or [99mTc]TRODAT-1 SPECT imaging of dopamine transporter uptake within the striatum and associated regions. Our findings suggest that suprathreshold measures of taste function are influenced by PD and that this disease differentially influences taste function on anterior (CN VII) and posterior (CN IX) tongue regions. Conceivably PD-related damage to CN IX releases central inhibition on CN VII at the level of the brainstem, resulting in enhanced taste intensity on the anterior tongue

Axonal Dynamics of Excitatory and Inhibitory Neurons in Somatosensory Cortex

Electrophysiology-delivery of fluorescent viral vectors-and two-photon microscopy were used to demonstrate the rapidity of axonal restructuring of both excitatory and inhibitory neurons in rodent cortical layer II/III following alterations in sensory experience

[¹⁸F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson’s Disease

Neuroinflammation is implicated as a key pathologic mechanism in many neurodegenerative diseases and is thought to be mediated in large part by microglia, native phagocytic immune cells of the CNS. Abnormal aggregation of the protein α-synuclein after phagocytosis by microglia is one possible neuropathophysiological mechanism driving Parkinson’s disease (PD). We conducted a human pilot study to evaluate the feasibility of targeting the inducible isoform of nitric oxide synthase using the [18F]NOS radiotracer to measure neuroinflammation in idiopathic PD. Ten adults consisting of 6 PD patients and 4 healthy controls (HC) underwent one hour of dynamic [18F]NOS positron emission tomography (PET) brain imaging with arterial blood sampling. We observed increased [18F]NOS whole brain distribution volume (VT) in PD patients compared to age-matched healthy controls (p p = 0.72). These findings suggest elevated oxidative stress, a surrogate marker of inflammation, is present in early-stage idiopathic PD and indicate that [18F]NOS PET imaging is a promising, non-invasive method to measure neuroinflammation

The role of resting myocardial blood flow and myocardial blood flow reserve as a predictor of major adverse cardiovascular outcomes.

Cardiac perfusion PET is increasingly used to assess ischemia and cardiovascular risk and can also provide quantitative myocardial blood flow (MBF) and flow reserve (MBFR) values. These have been shown to be prognostic biomarkers of adverse outcomes, yet MBF and MBFR quantification remains underutilized in clinical settings. We compare MBFR to traditional cardiovascular risk factors in a large and diverse clinical population (60% African-American, 35.3% Caucasian) to rank its relative contribution to cardiovascular outcomes. Major adverse cardiovascular events (MACE), including unstable angina, non-ST and ST-elevation myocardial infarction, stroke, and death, were assessed for consecutive patients who underwent rest-dipyridamole stress 82Rb PET cardiac imaging from 2012-2015 at the Hospital of the University of Pennsylvania (n = 1283, mean follow-up 2.3 years). Resting MBF (1.1 ± 0.4 ml/min/g) was associated with adverse cardiovascular outcomes. MBFR (2.1 ± 0.8) was independently and inversely associated with MACE. Furthermore, MBFR was more strongly associated with MACE than both traditional cardiovascular risk factors and the presence of perfusion defects in regression analysis. Decision tree analysis identified MBFR as superior to established cardiovascular risk factors in predicting outcomes. Incorporating resting MBF and MBFR in CAD assessment may improve clinical decision making

Molecular imaging of pulmonary inflammation in electronic and combustible cigarette users: a pilot study.

Electronic cigarette (EC) use has increased dramatically, particularly among adolescents and young adults, which, like cigarette use, can cause pulmonary inflammation and increase the risk of lung disease. This preliminary study used positron emission tomography with F-6-(1/2)(2-fluoro-propyl)-4-methylpyridin-2-amine (F-NOS) to quantify inducible nitric oxide synthase (iNOS) expression to characterize oxidative stress and inflammation in the lungs in vivo in three age- and sex-matched groups: (1) 5 EC users, (2) 5 cigarette smokers, and (3) 5 never smoke/vape controls. EC users showed greater F-NOS non-displaceable binding potential (BPND) than cigarette smokers ( = 0.03) and never smoke/vape controls ( = 0.01); whereas BPND in cigarette smokers did not differ from controls (p> 0.1). F-NOS lung tissue delivery and iNOS distribution volume did not significantly differ between groups. Although there were no group differences in peripheral inflammatory biomarker concentrations, F-NOS BPND correlated with the pro-inflammatory cytokine tumor necrosis factor-α concentrations (rs= 0.87, = 0.05) in EC users. Additionally, when EC users and cigarette smokers were pooled together, vaping episodes/cigarettes per day correlated with interleukin-6 levels (rs= 0.86, = 0.006). This is the first PET imaging study to compare lung inflammation between EC and cigarette users in vivo. We found preliminary evidence EC users had greater pulmonary inflammation than cigarette smokers and never smoke/vape controls, with a positive association between pulmonary and peripheral measures of inflammation