Coffee intake and decreased amyloid pathology in human brain.

Several epidemiological and preclinical studies supported the protective effect of coffee on Alzheimer's disease (AD). However, it is still unknown whether coffee is specifically related with reduced brain AD pathologies in human. Hence, this study aims to investigate relationships between coffee intake and in vivo AD pathologies, including cerebral beta-amyloid (Aß) deposition, the neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH). A total of 411 non-demented older adults were included. Participants underwent comprehensive clinical assessment and multimodal neuroimaging including [11C] Pittsburgh compound B-positron emission tomography (PET), [18F] fluorodeoxyglucose PET, and magnetic resonance imaging scans. Lifetime and current coffee intake were categorized as follows: no coffee or <2 cups/day (reference category) and ≥2 cups/day (higher coffee intake). Lifetime coffee intake of ≥2 cups/day was significantly associated with a lower Aß positivity compared to coffee intake of <2 cups/day, even after controlling for potential confounders. In contrast, neither lifetime nor current coffee intake was not related to hypometabolism, atrophy of AD-signature region, and WMH volume. The findings suggest that higher lifetime coffee intake may contribute to lowering the risk of AD or related cognitive decline by reducing pathological cerebral amyloid deposition.

Preclinical anaylses of [18F]cEFQ as a PET tracer for imaging metabotropic glutamate receptor type 1 (mGluR1).

Metabotropic glutamate receptor type 1 (mGluR1) is related with various neurological and psychiatric diseases, such as anxiety, depression, epilepsy, Parkinson's disease, and neuropathic pain. Hence, mGluR1 is an important target for drug development and imaging. We synthesized [18F]cEFQ (3-ethyl-2-[18F]fluoroquinolin-6-yl cis-(4-methoxycyclohexyl)methanone) as a PET tracer for selective mGluR1 imaging and evaluated its properties in rodents. A chloroquinoline precursor was labeled by a nucleophilic substitution reaction, and the resulting [18F]cEFQ was obtained with high radiochemical purity (>99%) and specific activity (63-246 GBq/µmol). The log D value was 3.24, and the initial brain uptake at 10 min was over 4% of injected dose per gram in BALB/c mice. According to PET/CT and autoradiography in SD rats, [18F]cEFQ showed wide distribution in the whole brain and the highest uptake in the cerebellum. Pre-treatment with unlabeled cEFQ or the mGluR1-specific antagonist JNJ16259685 blocked the uptake of [18F]cEFQ. However, the uptake was not blocked by pre-treatment with the mGluR5-specific antagonist ABP688. The trans isomer [18F]tEFQ did not show high uptake in the mGluR1-rich region. [18F]cEFQ was straightforwardly prepared using a chloro-derivative precursor. Its feasibility as a specific and selective PET agent for imaging mGluR1 was proved by in vitro and in vivo experiments using rodents.

Transcranial direct current stimulation to lessen neuropathic pain after spinal cord injury: a mechanistic PET study.

BACKGROUND: It is suggested that transcranial direct current stimulation (tDCS) can produce lasting changes in corticospinal excitability and can potentially be used for the treatment of neuropathic pain. However, the detailed mechanisms underlying the effects of tDCS are unknown. OBJECTIVE: We investigated the underlying neural mechanisms of tDCS for chronic pain relief using [(18)F]-fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET). METHODS: Sixteen patients with neuropathic pain (mean age 44.1 ± 8.6 years, 4 females) due to traumatic spinal cord injury received sham or active anodal stimulation of the motor cortex using tDCS for 10 days (20 minutes, 2 mA, twice a day). The effect of tDCS on regional cerebral glucose metabolism was evaluated by [(18)F]FDG-PET before and after tDCS sessions. RESULTS: There was a significant decrease in the numeric rating scale scores for pain, from 7.6 ± 0.5 at baseline to 5.9 ± 1.8 after active tDCS (P = .016). We found increased metabolism in the medulla and decreased metabolism in the left dorsolateral prefrontal cortex after active tDCS treatment compared with the changes induced by sham tDCS. Additionally, an increase in metabolism after active tDCS was observed in the subgenual anterior cingulate cortex and insula. CONCLUSION: The results of this study suggest that anodal stimulation of the motor cortex using tDCS can modulate emotional and cognitive components of pain and normalize excessive attention to pain and pain-related information.

Effects of transcranial direct current stimulation (tDCS) on post-stroke dysphagia.

PURPOSE: Transcranial direct current stimulation (tDCS) combined with swallowing training might improve swallowing function in patients with post-stroke dysphagia. We investigate the effects of transcranial direct current stimulation (tDCS) combined with swallowing training on post-stroke dysphagia. METHODS: Sixteen patients with post-stroke dysphagia, diagnosed using video fluoroscopic swallowing (VFSS), were randomly assigned into two groups: (1) anodal tDCS group (1 mA for 20 min), or (2) sham group (1 mA for 30 s). Patients received anodal tDCS or sham over the pharyngeal motor cortex of the affected hemisphere during 30 min of conventional swallowing training for 10 days. Functional dysphagia scale (FDS) scores based on VFSS were measured at baseline and immediately and 3 months after the intervention. The effect of tDCS on dysphagia was analyzed using a generalized linear model (GLM) with repeated measures. RESULTS: After the intervention, FDS scores improved in both groups without significant differences. However, 3 months after the intervention, anodal tDCS elicited greater improvement in terms of FDS compared to the sham group (ß = -7.79, p = 0.041) after controlling for age, National Institutes of Health Stroke Scale (NIHSS) score, lesion size, baseline FDS score, and time from stroke onset. CONCLUSIONS: Anodal tDCS applied over the affected pharyngeal motor cortex can enhance the outcome of swallowing training in post-stroke dysphagia. Our results suggest that non-invasive cortical stimulation has a potential role as an adjuvant strategy during swallowing training in patients with post-stroke dysphagia.

Modafinil-induced hippocampal activation in narcolepsy.

This study was undertaken to investigate regional metabolic abnormalities and to determine the effects of modafinil in narcoleptics on cerebral glucose metabolism using [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET). Eight narcoleptic patients participated in the study. Two [(18)F] FDG PET scans were obtained before and after 2 weeks of modafinil treatment. To identify the effect of modafinil on regional cerebral abnormalities in narcoleptics, pre- and post-treatment PET scans were compared using paired t-statistics with voxel-wised manner. In narcolepsy patients, significant decreases in cerebral glucose metabolism were observed in the midbrain and upper pons, bilateral hypothalamus, posterior thalamus, hippocampus and right parahippocampus as compared with healthy subjects. After treatment, a significant increase in glucose metabolism in the left hippocampus was found in comparison with pre-treatment scan. This study demonstrated that modafinil activates the hippocampus which receives the afferents from hypothalamus, the center of sleep-wake rhythm.