To facilitate clinical trials of disease-modifying therapies for Alzheimer's disease, which are expected to be most efficacious at the earliest and mildest stages of the disease, supportive biomarker information is necessary. The only validated methods for identifying amyloid-β deposition in the brain-the earliest pathological signature of Alzheimer's disease-are amyloid-β positron-emission tomography (PET) imaging or measurement of amyloid-β in cerebrospinal fluid. Therefore, a minimally invasive, cost-effective blood-based biomarker is desirable. Despite much effort, to our knowledge, no study has validated the clinical utility of blood-based amyloid-β markers. Here we demonstrate the measurement of high-performance plasma amyloid-β biomarkers by immunoprecipitation coupled with mass spectrometry. The ability of amyloid-β precursor protein (APP)/amyloid-β (Aβ) and Aβ/Aβ ratios, and their composites, to predict individual brain amyloid-β-positive or -negative status was determined by amyloid-β-PET imaging and tested using two independent data sets: a discovery data set (Japan, n = 121) and a validation data set (Australia, n = 252 including 111 individuals diagnosed using C-labelled Pittsburgh compound-B (PIB)-PET and 141 using other ligands). Both data sets included cognitively normal individuals, individuals with mild cognitive impairment and individuals with Alzheimer's disease. All test biomarkers showed high performance when predicting brain amyloid-β burden. In particular, the composite biomarker showed very high areas under the receiver operating characteristic curves (AUCs) in both data sets (discovery, 96.7%, n = 121 and validation, 94.1%, n = 111) with an accuracy approximately equal to 90% when using PIB-PET as a standard of truth. Furthermore, test biomarkers were correlated with amyloid-β-PET burden and levels of Aβ in cerebrospinal fluid. These results demonstrate the potential clinical utility of plasma biomarkers in predicting brain amyloid-β burden at an individual level. These plasma biomarkers also have cost-benefit and scalability advantages over current techniques, potentially enabling broader clinical access and efficient population screening.

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BackgroundTo examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions.Methodology/Principal FindingsSubjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05).Conclusions/SignificanceThe results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI.Trial RegistrationUMIN-CTR UMIN000003662 ctr.cgi?function = brows&action = brows&type = summary&recptno = R000004436&language = J.

Social contact often initially depends on ascertaining the direction of the other person's gaze. We determined the brain areas involved in gaze monitoring by a functional neuroimaging study. Discrimination between the direction of gaze significantly activated a region in the left amygdala during eye-contact and no eye-contact tasks to the same extent. However, a region in the right amygdala was specifically activated only during the eye-contact task. Results confirm that the left amygdala plays a general role in the interpretation of eye gaze direction, and that the activity of the right amygdala of the subject increases when another individual's gaze is directed towards him. This suggests that the human amygdala plays a role in reading social signals from the face.

This study shows that ICG fluorescence imaging allows highly sensitive image-guided intraoperative SN mapping in cases of gastric cancer. Our data suggest that SN mapping guided by ICG fluorescence imaging might be useful for predicting the metastatic status in lymph nodes in cases of gastric cancer, especially those with cT1-stage cancer.

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By measuring regional cerebral blood flow using PET, we delineated the roles of the occipito-temporal regions activated by faces and scenes. We asked right-handed normal subjects to perform three tasks using facial images as visual stimuli: in the face familiar/unfamiliar discrimination (FF) task, they discriminated the faces of their friends and associates from unfamiliar ones; in the face direction discrimination (FD) task, they discriminated the direction of each unfamiliar face; in the dot location discrimination (DL) task, they discriminated the location of a red dot on a scrambled face. The activity in each task was compared with that in the control fixation (CF) task, in which they fixated on the centre of a display without visual stimuli. The DL task activated the occipital cortices and posterior fusiform gyri bilaterally. During the FD task, the activation extended anteriorly in the right fusiform gyrus and laterally to the right inferior temporal cortex. The FF task further activated the right temporal pole. To examine whether the activation due to faces was face-specific, we used a scene familiar/unfamiliar discrimination (SF) task, in which the subjects discriminated familiar scenes from unfamiliar ones. Our results suggest that (i) the occipital cortices and posterior fusiform gyri non-selectively respond to faces, scrambled faces and scenes, and are involved mainly in the extraction of physical features of complex visual images; (ii) the right inferior temporal/fusiform gyrus responds selectively to faces but not to non-face stimuli and is involved in the visual processing related to face perception, whereas the bilateral parahippocampal gyri and parieto-occipital junctions respond selectively to scenes and are involved in processing related to scene perception; and (iii) the right temporal pole is activated during the discrimination of familiar faces and scenes from unfamiliar ones, and is probably involved in the recognition of familiar objects.

It has been suggested that face recognition is primarily based on configural information, with featural information playing little or no role. We investigated this idea by comparing the prototype effect for face prototypes that emphasized either featural or configural processing. In Experiment 1, participants showed a tendency to commit false alarms in response to nonstudied prototypes, and this tendency was equivalent for featural and configural prototypes. Experiment 2 replicated this finding, and provided support for the assumption that the two types of prototypes differed in terms of featural and configural processing: Face inversion eliminated the prototype effect for configural prototypes but not for featural prototypes. These results suggest that both featural and configural processing make important contributions to face recognition, and that their effects are dissociable.