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Background: Tau accumulation in the nucleus basalis of Meynert (nbM) has been documented in Alzheimer's disease (AD), but its relationship to neuropathological changes in other brain regions and cognitive deficits remains unclear, particularly between early-onset AD (EOAD) and late-onset AD (LOAD)., Objective: To evaluate tau accumulation patterns in the nbM and other brain regions in EOAD and LOAD using 18 F-florzolotau PET and examine correlations with cognitive function., Methods: Thirty-eight amyloid-positive AD patients (15 EOAD, 23 LOAD) and 46 healthy controls underwent 18 F-florzolotau PET. Tau levels were quantified in the nbM and Braak-staging regions. Postmortem brain samples were examined to assess 18 F-florzolotau binding to tau deposits., Results: EOAD showed a higher overall tau burden, including in the nbM, compared with LOAD. However, nbM tau levels correlated more strongly with cognitive decline in LOAD than EOAD. The relationship between nbM tau and neocortical tau differed between EOAD and LOAD. Histopathology revealed abundant 18 F-florzolotau labeling of neurofibrillary tangles (NFTs) and ghost tangles in AD nbM samples., Conclusions: This study provides the first in vivo PET evidence of differential nbM tau pathology between EOAD and LOAD, with higher accumulation but weaker correlation to cognition in EOAD. The distinct relationships between nbM and cortical tau in EOAD and LOAD suggest divergent pathological trajectories. 18 F-florzolotau PET successfully visualized NFTs and extracellular ghost tangles in the nbM across AD stages. These findings highlight the importance of considering age of onset when evaluating tau pathology and its clinical correlates in AD., Competing Interests: Declaration of conflicting interestsHitoshi Shimada, Ming-Rong Zhang, and Makoto Higuchi hold patents on compounds related to the present report (JP 5422782/EP 12 884 742.3/CA2894994/HK1208672). All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Phosphodiesterase 10 A (PDE10A), a pivotal element of the second messenger signaling downstream of the dopamine receptor stimulation, is conceived to be crucially involved in the mood instability of bipolar I disorder (BD-I) as a primary causal factor or in response to dysregulated dopaminergic tone. We aimed to determine whether striatal PDE10A availability is altered in patients with BD-I and assessed its relationship with the clinical characteristics of BD-I. This case-control study used positron emission tomography (PET) with 2-(2-(3-(4-(2-[ 18 F]fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([ 18 F]MNI-659), a radioligand that binds to PDE10A, to examine the alterations of the striatal PDE10A availability in the living brains of individuals with BD-I and their association with the clinical characteristics of BD-I. [ 18 F]MNI-659 PET data were acquired from 25 patients with BD-I and 27 age- and sex-matched healthy controls. Patients with BD-I had significantly lower PDE10A availability than controls in the executive (F = 8.86; P = 0.005) and sensorimotor (F = 6.13; P = 0.017) subregions of the striatum. Lower PDE10A availability in the executive subregion was significantly associated with a higher frequency of mood episodes in patients with BD-I (r = -0.546; P = 0.007). This study provides the first evidence of altered PDE10A availability in patients with BD-I. Lower PDE10A availability in the executive subregion of the striatum is associated with an increased recurrence risk, suggesting that PDE10A may prevent BD-I relapse. Further studies are required to elucidate the role of PDE10A in BD-I pathophysiology and explore its potential as a treatment target., (© 2024. The Author(s).)

In Alzheimer's disease (AD), reports on the association between false recognition and brain structure have been inconsistent. In dementia with Lewy bodies (DLB), no such association has been reported. This study aimed to identify brain regions associated with false recognition in AD and DLB by analyzing regional gray matter volume (rGMV). We included 184 patients with AD and 60 patients with DLB. The number of false recognitions was assessed using the Alzheimer's Disease Assessment Scale' word recognition task. Brain regions associated with the number of false recognitions were examined by voxel-based morphometry analysis. The number of false recognitions significantly negatively correlated with rGMV in the bilateral hippocampus, left parahippocampal gyrus, bilateral amygdala, and bilateral entorhinal cortex in patients with AD (p < 0.05, family-wise error [FEW] corrected) and in the bilateral hippocampus, left parahippocampal gyrus, right inferior frontal gyrus, right middle frontal gyrus, right basal forebrain, right insula, left medial and lateral orbital gyri, and left fusiform in those with DLB (p < 0.05, FWE corrected). Bilateral hippocampus and left parahippocampal gyrus were associated with false recognition in both diseases. However, we found there were regions where the association between false recognition and rGMV differed from disease to disease., (© 2024. The Author(s).)

Deposition of α-synuclein fibrils is implicated in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), while in vivo detection of α-synuclein pathologies in these illnesses has been challenging. Here, we have developed a small-molecule ligand, C05-05, for visualizing α-synuclein deposits in the brains of living subjects. In vivo optical and positron emission tomography (PET) imaging of mouse and marmoset models demonstrated that C05-05 captured a dynamic propagation of fibrillogenesis along neural pathways, followed by disruptions of these structures. High-affinity binding of 18 F-C05-05 to α-synuclein aggregates in human brain tissues was also proven by in vitro assays. Notably, PET-detectable 18 F-C05-05 signals were intensified in the midbrains of PD and DLB patients as compared with healthy controls, providing the first demonstration of visualizing α-synuclein pathologies in these illnesses. Collectively, we propose a new imaging technology offering neuropathology-based translational assessments of PD and allied disorders toward diagnostic and therapeutic research and development., Competing Interests: Declaration of interests M.O., M.-R.Z., and M. Higuchi filed a patent on compounds related to the present report (2019-034997, PCT/JP2020/002607)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its pathophysiological role remains unclear. This study aimed to assess astrocyte reactivity in vivo in patients with PSP. Furthermore, we investigated alterations in brain lactate levels and their relationship with astrocyte reactivity., Methods: We included 30 patients with PSP-Richardson syndrome and 30 healthy controls; in patients, tau deposition was confirmed through 18 F-florzolotau positron emission tomography. Myo-inositol, an astroglial marker, and lactate were quantified in the anterior cingulate cortex through magnetic resonance spectroscopy. We measured plasma biomarkers, including glial fibrillary acidic protein as another astrocytic marker. The anterior cingulate cortex was histologically assessed in postmortem samples of another 3 patients with PSP with comparable disease durations., Results: The levels of myo-inositol and plasma glial fibrillary acidic protein were significantly higher in patients than those in healthy controls (p < 0.05); these increases were significantly associated with PSP rating scale and cognitive function scores (p < 0.05). The lactate level was high in patients, and correlated significantly with high myo-inositol levels. Histological analysis of the anterior cingulate cortex in patients revealed reactive astrocytes, despite mild tau deposition, and no marked synaptic loss., Interpretation: We discovered high levels of astrocyte biomarkers in patients with PSP, suggesting astrocyte reactivity. The association between myo-inositol and lactate levels suggests a link between reactive astrocytes and brain energy metabolism changes. Our results indicate that astrocyte reactivity in the anterior cingulate cortex precedes pronounced tau pathology and neurodegenerative processes in that region, and affects brain function in PSP. ANN NEUROL 2024;96:247-261., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: Cosmetic behavior is an important daily activity, especially for women, because it increases visual attractiveness, self-confidence, and positive emotions. However, it is unknown whether a relationship exists between physiological measures and subjective experiences during the series of cosmetic behaviors., Methods: Electroencephalograms (EEG) and electrocardiograms (ECG) from thirty female participants who were asked to look in a mirror after applying skincare, as well as base, eye, cheek, and lip makeup were recorded. The price range of cosmetic products was also considered. Subjective evaluations of the skin surface, emotions, and self-confidence were equally measured after looking in the mirror at each step of the cosmetic behavior. Linear mixed models were fitted to examine whether the subjective experience could be explained by the variety of cosmetic products and/or physiological responses., Results: The subjective evaluation was summarized into the following three factors using a factor analysis: self-confidence, hedonic perception, and negative emotion. Each theta-band (4-6 Hz) power, alpha-band (8-13 Hz) power of the EEG, and heart rate variability measures were subjected to a principal component analysis separately. The linear mixed models indicated that the variation in the self-confidence score and the negative emotion score was explained only by the steps of cosmetic behaviors, that is, self-confidence increased while negative emotions decreased as the steps of cosmetic behaviors proceeded. On the other hand, the hedonic perception score was explained by the interaction of the steps of cosmetic behaviors and price, indicating that positive tactile perception and positive emotion were higher when luxury cosmetic products were applied than when affordable products were applied. Furthermore, the model indicated that the hedonic perception score was positively associated with the alpha-band power over occipital sites whereas sympathetic nervous system activity was negatively associated with the alpha-band power over lateral central sites., Discussion: These results suggest that positive perceptual and emotional experiences are associated with greater attention to somatosensory information than to visual information and sympathetic autonomic nervous system activities. The current results also emphasize the possibility of using physiological measurements as objective measures of cosmetic behavior., Competing Interests: Shiseido Co. Ltd., a company that manufactures cosmetics, took the lead in this research, formulated a plan, and commissioned research work, including experiments and analysis, to Centan Inc., a company that provides product development research and neuromarketing services. HM and TH were employed by Centan. Inc. as a researcher, while KT, AM, and TM were employed by Shiseido Co., Ltd. The present study was entirely funded by Shiseido Co., Ltd. The funder was involved in the study design, collection, analysis, interpretation of data, writing of this article, and the decision to submit it for publication., (Copyright © 2024 Moriya, Machida, Munakata, Herai and Tagai.)

Introduction: There is a continuous consumer demand for ever superior cosmetic products. In marketing, various forms of sensory evaluation are used to measure the consumer experience and provide data with which to improve cosmetics. Nonetheless, potential downsides of existing approaches have led to the exploration of the use of neuroimaging methods, such as functional near-infrared spectroscopy (fNIRS), to provide addition information about consumers' experiences with cosmetics. The aim of the present study was to investigate the feasibility of a real-time brain-based product evaluation method which detects the incongruency between a product, in this case lipstick, and a consumer's expectations., Method: Thirty healthy, female, habitual lipstick users were asked to apply six different lipsticks varying in softness and to rate the softness of and their willingness to pay (WTP) for each lipstick. Cerebral hemodynamic responses in frontal areas were measured with fNIRS during lipstick application and analyzed using the general linear model (GLM). Incongruency scores between softness and expectation were calculated in order to understand how far removed each lipstick was from a participant's optimal softness preference. The correlation between brain activation (beta scores) during the application of each lipstick and the respective incongruency scores from each participant were acquired using semi-partial correlation analysis, controlling for the effects of WTP., Results: We revealed a significant intra-subject correlation between incongruency scores and activation in the right inferior frontal gyrus (IFG). This confirms that as the texture incongruency scores increased for the lipstick samples, activation in each individual's right IFG also increased., Conclusion: The correlation observed between incongruency perceived by participants and activation of the right IFG not only suggests that the right IFG may play an important role in detecting incongruity when there is a discrepancy between the perceived texture and the consumer's expectations but also that measuring activity in the IFG may provide a new objective measurement of the consumer experience, thus contributing to the development of superior cosmetics., Competing Interests: KH, KK, and KT are employed by Shiseido Global Innovation Center, Shiseido Co., Ltd., a company which manufactures cosmetics. KH, KK, KT, and ID are named inventors on a patent application covering the method disclosed in this research. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hirabayashi, Kawabata Duncan, Tagai, Kyutoku and Dan.)

Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and cognitive impairments in retired athletes with a long history of rmTBI. Overall, 27 retired athletes with a history of rmTBI (18 boxers, 3 kickboxers, 2 wrestlers, and 4 others; rmTBI group) and 23 age/sex-matched healthy participants (control group) were enrolled. MPRAGE on 3 T MRI was acquired and segmented. The TBV and TBV-adjusted regional brain volumes were compared between groups, and the relationship between the neuropsychological test scores and the regional brain volumes were evaluated. Total brain volume (TBV) and regional brain volumes of the mammillary bodies (MBs), hippocampi, amygdalae, thalami, caudate nuclei, and corpus callosum (CC) were estimated using the SPM12 and ITK-SNAP tools. In the rmTBI group, the regional brain volume/TBV ratio (rmTBI vs. control group, Mann-Whitney U test, p < 0.05) underwent partial correlation analysis, adjusting for age and sex, to assess its connection with neuropsychological test results. Compared with the control group, the rmTBI group showed significantly lower the MBs volume/TBV ratio (0.13 ± 0.05 vs. 0.19 ± 0.03 × 10 -3 , p < 0.001). The MBs volume/TBV ratio correlated with visual memory, as assessed, respectively, by the Rey-Osterrieth Complex Figure test delayed recall (ρ = 0.62, p < 0.001). In conclusion, retired athletes with rmTBI have MB atrophy, potentially contributing to memory impairment linked to the Papez circuit disconnection., (© 2024. The Author(s).)

Frontotemporal dementia refers to a group of neurodegenerative disorders with diverse clinical and neuropathological features. In vivo neuropathological assessments of frontotemporal dementia at an individual level have hitherto not been successful. In this study, we aim to classify patients with frontotemporal dementia based on topologies of tau protein aggregates captured by PET with 18 F-florzolotau (aka 18 F-APN-1607 and 18 F-PM-PBB3), which allows high-contrast imaging of diverse tau fibrils in Alzheimer's disease as well as in non-Alzheimer's disease tauopathies. Twenty-six patients with frontotemporal dementia, 15 with behavioural variant frontotemporal dementia and 11 with other frontotemporal dementia phenotypes, and 20 age- and sex-matched healthy controls were included in this study. They underwent PET imaging of amyloid and tau depositions with 11 C-PiB and 18 F-florzolotau, respectively. By combining visual and quantitative analyses of PET images, the patients with behavioural variant frontotemporal dementia were classified into the following subgroups: (i) predominant tau accumulations in frontotemporal and frontolimbic cortices resembling three-repeat tauopathies ( n = 3), (ii) predominant tau accumulations in posterior cortical and subcortical structures indicative of four-repeat tauopathies ( n = 4); (iii) amyloid and tau accumulations consistent with Alzheimer's disease ( n = 4); and (iv) no overt amyloid and tau pathologies ( n = 4). Despite these distinctions, clinical symptoms and localizations of brain atrophy did not significantly differ among the identified behavioural variant frontotemporal dementia subgroups. The patients with other frontotemporal dementia phenotypes were also classified into similar subgroups. The results suggest that PET with 18 F-florzolotau potentially allows the classification of each individual with frontotemporal dementia on a neuropathological basis, which might not be possible by symptomatic and volumetric assessments., Competing Interests: H.Shimada, M.-R.Z. and M.H. hold patents on compounds related to the present report (JP 5422782/EP 12 884 742.3/CA2894994/HK1208672). All authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Aim: Progressive supranuclear palsy (PSP) is a rapidly progressive neurodegenerative disorder characterized by Parkinsonism, supranuclear ophthalmoplegia, postural instability, and cognitive impairment., Patients: This case series describes three patients initially diagnosed with late-life mood disorders (depression and bipolar disorder) who were later diagnosed with PSP because of the development of typical neurological symptoms., Result: The diagnostic challenge of PSP is highlighted in this case report, particularly in the early stages, when characteristic symptoms may not be present. The importance of considering PSP in the differential diagnosis of late-life mood disorders, especially in the absence of response to standard antidepressant therapy, is also emphasized. The heterogeneity of PSP is described, with various subtypes and atypical variants presenting with different clinical features. The psychiatric symptoms of PSP include apathy, disinhibition, depression, and anxiety, whereas hallucinations and delusions are less frequent. Tau positron emission tomography imaging is discussed as a potential biomarker for atypical PSP., Conclusion: Early diagnosis and intervention are crucial for improved outcomes in PSP, necessitating further research to enhance the diagnostic and treatment strategies for PSP and other neurodegenerative diseases., Competing Interests: Keisuke Takahata is an Editorial Board member of Psychiatry and Clinical Neurosciences Reports and a co‐author of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication. The remaining authors declare no conflict of interest., (© 2024 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Aggression, a common symptom of Alzheimer's disease (AD), can impose a significant burden on caregivers, necessitating early institutionalization., Objective: The current study examined the neural basis of aggression and its expression mechanism, to advance the development of effective treatment strategies for aggression in patients with AD., Methods: The study sample included 257 patients; 180 were diagnosed with AD and 77 with amnestic mild cognitive impairment (aMCI). Factor analysis of the neuropsychiatric inventory (NPI) aggression scores was performed, and the correlation between each factor and cerebral blood flow (CBF) was examined via diagnosis of AD or aMCI using statistical parametric mapping., Results: Refusal of care was correlated with reduced CBF in the right hippocampus of patients with AD while no specific related regions could be identified in patients with aMCI. Violent behavior was associated with decreased CBF in the right temporal pole and medial frontal lobe of patients with AD and aMCI., Conclusions: These findings suggest that aggression, measured using NPI includes two distinct symptoms, refusal of care and violent behavior, having different underlying neural bases.

In Alzheimer's disease (AD), aggregated abnormal proteins induce neuronal dysfunction. Despite the evidence supporting the association between tau proteins and brain atrophy, further studies are needed to explore their link to neuronal dysfunction in the human brain. To clarify the relationship between neuronal dysfunction and abnormal proteins in AD-affected brains, we conducted magnetic resonance spectroscopic imaging (MRSI) and assessed the neurofilament light chain plasma levels (NfL). We evaluated tau and amyloid-β depositions using standardized uptake value ratios (SUVRs) of florzolotau (18F) for tau and 11 C-PiB for amyloid-β positron emission tomography in the same patients. Heatmaps were generated to visualize Z scores of glutamate to creatine (Glu/Cr) and N-acetylaspartate to creatine (NAA/Cr) ratios using data from healthy controls. In AD brains, Z score maps revealed reduced Glu/Cr and NAA/Cr ratios in the gray matter, particularly in the right dorsolateral prefrontal cortex (rDLPFC) and posterior cingulate cortex (PCC). Glu/Cr ratios were negatively correlated with florzolotau (18F) SUVRs in the PCC, and plasma NfL levels were elevated and negatively correlated with Glu/Cr (P = 0.040, r = -0.50) and NAA/Cr ratios (P = 0.003, r = -0.68) in the rDLPFC. This suggests that the abnormal tau proteins in AD-affected brains play a role in diminishing glutamate levels. Furthermore, neuronal dysfunction markers including Glu/tCr and NAA/tCr could potentially indicate favorable clinical outcomes. Using MRSI provided spatial information about neural dysfunction in AD, enabling the identification of vulnerabilities in the rDLPFC and PCC within the AD's pathological context., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neuropsychiatric symptoms (NPS) in patients with dementia lead to caregiver burdens and worsen the patient's prognosis. Although many neuroimaging studies have been conducted, the etiology of NPS remains complex. We hypothesize that brain structural asymmetry could play a role in the appearance of NPS., Objective: This study explores the relationship between NPS and brain asymmetry in patients with Alzheimer's disease (AD)., Methods: Demographic and MRI data for 121 mild AD cases were extracted from a multicenter Japanese database. Brain asymmetry was assessed by comparing the volumes of gray matter in the left and right brain regions. NPS was evaluated using the Neuropsychiatric Inventory (NPI). Subsequently, a comprehensive assessment of the correlation between brain asymmetry and NPS was conducted., Results: Among each NPS, aggressive NPS showed a significant correlation with asymmetry in the frontal lobe, indicative of right-side atrophy (r = 0.235, p = 0.009). This correlation remained statistically significant even after adjustments for multiple comparisons (p < 0.01). Post-hoc analysis further confirmed this association (p < 0.05). In contrast, no significant correlations were found for other NPS subtypes, including affective and apathetic symptoms., Conclusions: The study suggests frontal lobe asymmetry, particularly relative atrophy in the right hemisphere, may be linked to aggressive behaviors in early AD. These findings shed light on the neurobiological underpinnings of NPS, contributing to the development of potential interventions.

Purpose: The topological distribution of dopamine-related proteins is determined by gene transcription and subsequent regulations. Recent research strategies integrating positron emission tomography with a transcriptome atlas have opened new opportunities to understand the influence of regulation after transcription on protein distribution. Previous studies have reported that messenger (m)-RNA expression levels spatially correlate with the density maps of serotonin receptors but not with those of transporters. This discrepancy may be due to differences in regulation after transcription between presynaptic and postsynaptic proteins, which have not been studied in the dopaminergic system. Here, we focused on dopamine D1 and D2/D3 receptors and dopamine transporters and investigated their region-wise relationship between mRNA expression and protein distribution., Methods: We examined the region-wise correlation between regional binding potentials of the target region relative to that of non-displaceable tissue (BP ND ) values of 11 C-SCH-23390 and mRNA expression levels of dopamine D1 receptors (D1R); regional BP ND values of 11 C-FLB-457 and mRNA expression levels of dopamine D2/D3 receptors (D2/D3R); and regional total distribution volume (V T ) values of 18 F-FE-PE2I and mRNA expression levels of dopamine transporters (DAT) using Spearman's rank correlation., Results: We found significant positive correlations between regional BP ND values of 11 C-SCH-23390 and the mRNA expression levels of D1R (r = 0.769, p = 0.0021). Similar to D1R, regional BP ND values of 11 C-FLB-457 positively correlated with the mRNA expression levels of D2R (r = 0.809, p = 0.0151) but not with those of D3R (r = 0.413, p = 0.3095). In contrast to D1R and D2R, no significant correlation between V T values of 18 F-FE-PE2I and mRNA expression levels of DAT was observed (r = -0.5934, p = 0.140)., Conclusion: We found a region-wise correlation between the mRNA expression levels of dopamine D1 and D2 receptors and their respective protein distributions. However, we found no region-wise correlation between the mRNA expression levels of dopamine transporters and their protein distributions, indicating different regulatory mechanisms for the localization of pre- and postsynaptic proteins. These results provide a broader understanding of the application of the transcriptome atlas to neuroimaging studies of the dopaminergic nervous system., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Increasing evidence suggests that reactive astrocytes are associated with Alzheimer's disease (AD). However, its underlying pathogenesis remains unknown. Given the role of astrocytes in energy metabolism, reactive astrocytes may contribute to altered brain energy metabolism. Astrocytes are primarily considered glycolytic cells, suggesting a preference for lactate production. This study aimed to examine alterations in astrocytic activities and their association with brain lactate levels in AD., Methods: The study included 30 AD and 30 cognitively unimpaired participants. For AD participants, amyloid and tau depositions were confirmed by positron emission tomography using [ 11 C]PiB and [ 18 F]florzolotau, respectively. Myo-inositol, an astroglial marker, and lactate in the posterior cingulate cortex were quantified by magnetic resonance spectroscopy. These magnetic resonance spectroscopy metabolites were compared with plasma biomarkers, including glial fibrillary acidic protein as another astrocytic marker, and amyloid and tau positron emission tomography., Results: Myo-inositol and lactate levels were higher in AD patients than in cognitively unimpaired participants (p < 0.05). Myo-inositol levels correlated with lactate levels (r = 0.272, p = 0.047). Myo-inositol and lactate levels were positively associated with the Clinical Dementia Rating sum-of-boxes scores (p < 0.05). Significant correlations were noted between myo-inositol levels and plasma glial fibrillary acidic protein, tau phosphorylated at threonine 181 levels, and amyloid and tau positron emission tomography accumulation in the posterior cingulate cortex (p < 0.05)., Interpretation: We found high myo-inositol levels accompanied by increased lactate levels in the posterior cingulate cortex in AD patients, indicating a link between reactive astrocytes and altered brain energy metabolism. Myo-inositol and plasma glial fibrillary acidic protein may reflect similar astrocytic changes as biomarkers of AD. ANN NEUROL 2023., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Increased excitatory neuronal tones have been implicated in autism, but its mechanism remains elusive. The amplified glutamate signals may arise from enhanced glutamatergic circuits, which can be affected by astrocyte activation and suppressive signaling of dopamine neurotransmission. We tested this hypothesis using magnetic resonance spectroscopy and positron emission tomography scan with 11 C-SCH23390 for dopamine D1 receptors in the anterior cingulate cortex (ACC). We enrolled 18 male adults with high-functioning autism and 20 typically developed (TD) male subjects. The autism group showed elevated glutamate, glutamine, and myo-inositol (mI) levels compared with the TD group (p = 0.045, p = 0.044, p = 0.030, respectively) and a positive correlation between glutamine and mI levels in the ACC (r = 0.54, p = 0.020). In autism and TD groups, ACC D1 receptor radioligand binding was negatively correlated with ACC glutamine levels (r =  - 0.55, p = 0.022; r =  - 0.58, p = 0.008, respectively). The enhanced glutamate-glutamine metabolism might be due to astroglial activation and the consequent reinforcement of glutamine synthesis in autistic brains. Glutamine synthesis could underly the physiological inhibitory control of dopaminergic D1 receptor signals. Our findings suggest a high neuron excitation-inhibition ratio with astrocytic activation in the etiology of autism., (© 2023. The Author(s).)

Humans can communicate their emotions to others via volatile emissions from their bodies. Although there is now solid evidence for human chemical communication of fear, stress and anxiety, investigations of positive emotions remain scarce. In a recent study, we found that women's heart rate and performance in creativity tasks were modulated by body odors of men sampled while they were in a positive vs. neutral mood. However, inducing positive emotions in laboratory settings remains challenging. Therefore, an important step to further investigate the human chemical communication of positive emotions is to develop new methods to induce positive moods. Here, we present a new mood induction procedure (MIP) based on virtual reality (VR), that we assumed to be more powerful than videos (used in our previous study) to induce positive emotions. We hypothesized that, consequently, given the more intense emotions created, this VR-based MIP would induce larger differences between the receivers' responses to the positive body odor versus a neutral control body odor, than the Video-based MIP. The results confirmed the higher efficacy of VR to induce positive emotions compared with videos. More specifically, VR had more repeatable effects between individuals. Although positive body odors had similar effects to those found in the previous video study, especially faster problem solving, these effects did not reach statistical significance. These outcomes are discussed as a function of the specificities of VR and of other methodological parameters, that may have prevented the observation of such subtle effects and that should be understood more in-depth for future studies on human chemical communication., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest. This work results from a collaboration between the Lyon Neuroscience Research Center and the Shiseido company. The data collection and statistical analyses were exclusively led by the authors from the Lyon Neuroscience Research Center., (Copyright © 2023. Published by Elsevier Inc.)

Background and Hypothesis: Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. Therapeutic PDE10A inhibition effects on schizophrenia have been reported previously, but the status of this molecule in the living patients with schizophrenia remains elusive. Therefore, this study aimed to investigate the central PDE10A status in patients with schizophrenia and examine its relationship with psychopathology, cognition, and corticostriatal glutamate levels., Study Design: This study included 27 patients with schizophrenia, with 5 antipsychotic-free cases, and 27 healthy controls. Positron emission tomography with [18F]MNI-659, a specific PDE10A radioligand, was employed to quantify PDE10A availability by measuring non-displaceable binding potential (BPND) of the ligand in the limbic, executive, and sensorimotor striatal functional subregions, and in the pallidum. BPND estimates were compared between patients and controls while controlling for age and gender. BPND correlations were examined with behavioral and clinical measures, along with regional glutamate levels quantified by the magnetic resonance spectroscopy., Study Results: Multivariate analysis of covariance demonstrated a significant main effect of diagnosis on BPND (p = .03). A posthoc test showed a trend-level higher sensorimotor striatal BPND in patients, although it did not survive multiple comparison corrections. BPND in controls in this subregion was significantly and negatively correlated with the Tower of London scores, a cognitive subtest. Striatal or dorsolateral prefrontal glutamate levels did not correlate significantly with BPND in either group., Conclusions: The results suggest altered striatal PDE10A availability and associated local neural dysfunctions in patients with schizophrenia., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Patients with progressive supranuclear palsy (PSP) frequently exhibit apathy but the neuropathological processes leading to this phenotype remain elusive. We aimed to examine the involvement of tau protein depositions, oxidative stress (OS), and neuronal loss in the apathetic manifestation of PSP. Twenty patients with PSP and twenty-three healthy controls were enrolled. Tau depositions and brain volumes were evaluated via positron-emission tomography (PET) using a specific probe, 18 F-PM-PBB3, and magnetic resonance imaging, respectively. Glutathione (GSH) levels in the anterior and posterior cingulate cortices were quantified by magnetic resonance spectroscopy. Tau pathologies were observed in the subcortical and cortical structures of the patient brains. The angular gyrus exhibited a positive correlation between tau accumulations and apathy scale (AS). Although PSP cases did not show GSH level alterations compared with healthy controls, GSH levels in posterior cingulate cortex were correlated with AS and tau depositions in the angular gyrus. Marked atrophy was observed in subcortical areas, and gray matter volumes in the inferior frontal gyrus and anterior cingulate cortex were positively correlated with AS but showed no correlation with tau depositions and GSH levels. Path analysis highlighted synergistic contributions of tau pathologies and GSH reductions in the posterior cortex to AS, in parallel with associations of gray matter atrophy in the anterior cortex with AS. Apathetic phenotypes may arise from PET-visible tau aggregation and OS compromising the neural circuit resilience in the posterior cortex, along with neuronal loss, with neither PET-detectable tau pathologies nor OS in the anterior cortex., Competing Interests: Declaration of Competing Interest H.Sd., M.-R.Z., T.S., and M.H. hold patents on compounds related to the present report (JP 5422782/EP 12 884 742.3/CA2894994/HK1208672). All other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Deterioration of the oral environment is one of the risk factors for dementia. A previous study of an Alzheimer's disease (AD) model mouse suggests that tooth loss induces denervation of the mesencephalic trigeminal nucleus and neuroinflammation, possibly leading to accelerated tau dissemination from the nearby locus coeruleus (LC)., Objective: To elucidate the relevance of oral conditions and amyloid-β (Aβ) and tau pathologies in human participants., Methods: We examined the number of remaining teeth and the biofilm-gingival interface index in 24 AD-spectrum patients and 19 age-matched healthy controls (HCs). They also underwent positron emission tomography (PET) imaging of Aβ and tau with specific radiotracers, 11C-PiB and 18F-PM-PBB3, respectively. All AD-spectrum patients were Aβ-positive, and all HCs were Aβ-negative. We analyzed the correlation between the oral parameters and radiotracer retention., Results: No differences were found in oral conditions between the AD and HC groups. 11C-PiB retentions did not correlate with the oral indices in either group. In AD-spectrum patients, brain-wide, voxel-based image analysis highlighted several regions, including the LC and associated brainstem substructures, as areas where 18F-PM-PBB3 retentions negatively correlated with the remaining teeth and revealed the correlation of tau deposits in the LC (r = -0.479, p = 0.018) primarily with the hippocampal and neighboring areas. The tau deposition in none of the brain regions was associated with the periodontal status., Conclusions: Our findings with previous preclinical evidence imply that tooth loss may enhance AD tau pathogenesis, promoting tau spreading from LC to the hippocampal formation.

Positron emission tomography (PET) with 18 F-PM-PBB3 ( 18 F-APN-1607, 18 F-Florzolotau) enables high-contrast detection of tau depositions in various neurodegenerative dementias, including Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). A simplified method for quantifying radioligand binding in target regions is to employ the cerebellum as a reference (CB-ref) on the assumption that the cerebellum has minimal tau pathologies. This procedure is typically valid in AD, while FTLD disorders exemplified by progressive supranuclear palsy (PSP) are characterized by occasional tau accumulations in the cerebellum, hampering the application of CB-ref. The present study aimed to establish an optimal method for defining reference tissues on 18 F-PM-PBB3-PET images of AD and non-AD tauopathy brains. We developed a new algorithm to extract reference voxels with a low likelihood of containing tau deposits from gray matter (GM-ref) or white matter (WM-ref) by a bimodal fit to an individual, voxel-wise histogram of the radioligand retentions and applied it to 18 F-PM-PBB3-PET data obtained from age-matched 40 healthy controls (HCs) and 23 CE, 40 PSP, and five other tau-positive FTLD patients. PET images acquired at 90-110 min after injection were averaged and co-registered to corresponding magnetic resonance imaging space. Subsequently, we generated standardized uptake value ratio (SUVR) images estimated by CB-ref, GM-ref and WM-ref, respectively, and then compared the diagnostic performances. GM-ref and WM-ref covered a broad area in HCs and were free of voxels located in regions known to bear high tau burdens in AD and PSP patients. However, radioligand retentions in WM-ref exhibited age-related declines. GM-ref was unaffected by aging and provided SUVR images with higher contrast than CB-ref in FTLD patients with suspected and confirmed corticobasal degeneration. The methodology for determining reference tissues as optimized here improves the accuracy of 18 F-PM-PBB3-PET measurements of tau burdens in a wide range of neurodegenerative illnesses., Competing Interests: Declaration of Competing Interest Hitoshi Shimada, Ming-Rong Zhang, and Makoto Higuchi hold patents on compounds related to the present report (JP 5422782/EP 12 884 742.3/CA2894994/HK1208672)., (Copyright © 2022. Published by Elsevier Inc.)

Background: We recently developed a positron emission tomography (PET) probe, [ 18 F]PM-PBB3, to detect tau lesions in diverse tauopathies, including mixed three-repeat and four-repeat (3R + 4R) tau fibrils in Alzheimer's disease (AD) and 4R tau aggregates in progressive supranuclear palsy (PSP). For wider availability of this technology for clinical settings, bias-free quantitative evaluation of tau images without a priori disease information is needed., Objective: We aimed to establish tau PET pathology indices to characterize PSP and AD using a machine learning approach and test their validity and tracer capabilities., Methods: Data were obtained from 50 healthy control subjects, 46 patients with PSP Richardson syndrome, and 37 patients on the AD continuum. Tau PET data from 114 regions of interest were subjected to Elastic Net cross-validation linear classification analysis with a one-versus-the-rest multiclass strategy to obtain a linear function that discriminates diseases by maximizing the area under the receiver operating characteristic curve. We defined PSP- and AD-tau scores for each participant as values of the functions optimized for differentiating PSP (4R) and AD (3R + 4R), respectively, from others., Results: The discriminatory ability of PSP- and AD-tau scores assessed as the area under the receiver operating characteristic curve was 0.98 and 1.00, respectively. PSP-tau scores correlated with the PSP rating scale in patients with PSP, and AD-tau scores correlated with Mini-Mental State Examination scores in healthy control-AD continuum patients. The globus pallidus and amygdala were highlighted as regions with high weight coefficients for determining PSP- and AD-tau scores, respectively., Conclusions: These findings highlight our technology's unbiased capability to identify topologies of 3R + 4R versus 4R tau deposits. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Purpose: Monoacylglycerol lipase (MAGL) regulates cannabinoid neurotransmission and the pro-inflammatory arachidonic acid pathway by degrading endocannabinoids. MAGL inhibitors may accordingly act as cannabinoid-potentiating and anti-inflammatory agents. Although MAGL dysfunction has been implicated in neuropsychiatric disorders, it has never been visualized in vivo in human brain. The primary objective of the current study was to visualize MAGL in the human brain using the novel PET ligand 18 F-T-401., Methods: Seven healthy males underwent 120-min dynamic 18 F-T-401-PET scans with arterial blood sampling. Six subjects also underwent a second PET scan with 18 F-T-401 within 2 weeks of the first scan. For quantification of MAGL in the human brain, kinetic analyses using one- and two-tissue compartment models (1TCM and 2TCM, respectively), along with multilinear analysis (MA1) and Logan graphical analysis, were performed. Time-stability and test-retest reproducibility of 18 F-T-401-PET were also evaluated., Results: 18 F-T-401 showed rapid uptake and gradual washout from the brain. Logan graphical analysis showed linearity in all subjects, indicating reversible radioligand kinetics. Using a metabolite-corrected arterial input function, MA1 estimated regional total distribution volume (V T ) values by best identifiability. V T values were highest in the cerebral cortex, moderate in the thalamus and putamen, and lowest in white matter and the brainstem, which was in agreement with regional MAGL expression in the human brain. Time-stability analysis showed that MA1 estimated V T values with a minimal bias even using truncated 60-min scan data. Test-retest reliability was also excellent with the use of MA1., Conclusions: Here, we provide the first demonstration of in vivo visualization of MAGL in the human brain. 18 F-T-401 showed excellent test-retest reliability, reversible kinetics, and stable estimation of V T values consistent with known regional MAGL expressions. PET with 18 F-T-401-PET is promising tool for measurement of central MAGL., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We examined differences in the severity of neuropsychiatric symptom (NPS) subsyndromes according to education level among patients with amnestic-mild cognitive impairment (a-MCI) with the aim of identifying patient demographics related to NPS subsyndromes., Methods: Overall, 140 patients with a-MCI were included. We divided the patients into three groups according to their educational level (primary education, middle education, and high education) and compared their demographics. To explore the severity of NPS subsyndromes according to educational level, we used the Neuropsychiatric Inventory (NPI) after adjustments for the Mini-Mental State Examination (MMSE) score. Finally, NPS subsyndromes that were identified as being related to educational level were further explored using a general linear model (GLM)., Results: Significant differences in several demographics were observed among the three groups. Among the NPS subsyndromes, the scores for aggressiveness were significantly higher in the primary and high education groups than in the middle education group, while the apathy/eating problem scores were significantly higher in the primary education group than in the other groups. The GLM analyses showed that aggressiveness was related to marital status and the Zarit Caregiver Burden Interview (ZBI-J) score, while apathy/eating problems were related to the instrumental activities of daily living (IADL) percentage, the ZBI-J score, and the education level in years., Conclusions: Among NPS subsyndromes, aggressiveness and apathy/eating problems differed according to education level in patients with a-MCI. A GLM analysis suggested that not only education level, but also various other factors should be considered when determining the need for NPS interventions., (© 2022 Japanese Psychogeriatric Society.)

Introduction: Corticobasal degeneration (CBD) is the most common neuropathological substrate for clinically diagnosed corticobasal syndrome (CBS), while identifying CBD pathology in living individuals has been challenging. This study aimed to examine the capability of positron emission tomography (PET) to detect CBD-type tau depositions and neuropathological classification of CBS., Methods: Sixteen CBS cases diagnosed by Cambridge's criteria and 12 cognitively healthy controls (HCs) underwent PET scans with 11 C-PiB, 11 C-PBB3, and 18 F-FDG, along with T1-weighted magnetic resonance imaging. Amyloid positivity was assessed by visual inspection of 11 C-PiB retentions. Tau positivity was judged by quantitative comparisons of 11 C-PBB3 binding to HCs., Results: Sixteen CBS cases consisted of two cases (13%) with amyloid and tau positivities indicative of Alzheimer's disease (AD) pathologies, 11 cases (69%) with amyloid negativity and tau positivity, and three cases (19%) with amyloid and tau negativities. Amyloid(-), tau(+) CBS cases showed increased retentions of 11 C-PBB3 in the frontoparietal areas, basal ganglia, and midbrain, and reduced metabolism in the precentral gyrus and thalamus relative to HCs. The enhanced tau probe retentions in the frontal gray and white matters partially overlapped with metabolic deficits and atrophy and correlated with Clinical Dementia Rating scores., Conclusions: PET-based classification of CBS was in accordance with previous neuropathological reports on the prevalences of AD, non-AD tauopathies, and others in CBS. The current work suggests that 11 C-PBB3-PET may assist the biological classification of CBS and understanding of links between CBD-type tau depositions and neuronal deteriorations leading to cognitive declines., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives : We examined the clinicodemographic and psychosocial factors that relate to the presentation and severity of delusions of theft among female patients with amnestic mild cognitive impairment (a-MCI) and Alzheimer's disease (AD). Methods : We enrolled a total of 177 female patients with a-MCI or AD, of whom 40 presented with delusions of theft. We compared the differences in clinicodemographic and psychosocial factors of the 40 patients (delusions of theft group) with 50 age- and Mini-Mental State Examination (MMSE)-matched controls without delusions (control group). Furthermore, we identified the factors associated with the presentation of delusions of theft using a general linear model (GLM). The severity of delusions of theft was calculated using the Neuropsychiatric Inventory Questionnaire, and correlations between the clinicodemographic and psychosocial factors were examined. Results : Between the two groups, the delusions of theft group had lower scores on the Physical Self-Maintenance Scale and instrumental activities of daily living (IADL) and higher scores on the Japanese version of the Zarit Caregiver Burden Interview (ZBI-J) than the control group. GLM analysis revealed that the IADL score was related to the presentation of delusions of theft. The severity of delusions of theft correlated with the MMSE and the ZBI-J scores in the delusions of theft group. Conclusions : The two groups had several differences regarding clinicodemographic and psychosocial factors. Furthermore, lower IADL scores were related to symptom presentation. Symptom severity correlated with cognitive functioning and caregiver burden. Clinical Implications : In the determination of treatment or care, differences in these factors should be considered.

Emotions can be communicated in social contexts through chemosignals contained in human body odors. The transmission of positive emotions via these signals has received little interest in past research focused mainly on negative emotional transmission. Furthermore, how the use of perfumed products might modulate this transmission remains poorly understood. To investigate human positive chemical communication, we explored the autonomic, verbal, and behavioral responses of receivers exposed to body odors of donors having undergone a within-subject positive or neutral mood induction procedure. These responses were compared with those obtained after exposure to the same body odors with added fragrance. Our findings suggest that positive emotions can be transmitted through body odor. They not only induced modifications at the physiological (heart rate) and verbal levels (perceived intensity and familiarity) but also at the behavioral level, with an improved performance on creativity tasks. Perfume did not modulate the physiological effects and had a synergistic effect on the positive body odor ratings (increased perceived differences between the neutral and positive body odor)., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Understanding consumer preferences and behavior is a major goal of consumer-oriented companies. The application of neuroscience to this goal is a promising avenue for companies. Previously, we observed a positive correlation during actual cosmetic use between the right dorsolateral prefrontal cortex (dlPFC) activity, measured by functional near-infrared spectroscopy (fNIRS), and the associated willingness-to-pay (WTP) values. However, we were unable to find any consistent group differences in the right dlPFC between different powdery foundations. Thus, the main objective of this study was to replicate the previous study and in addition, we aimed to refine the method of the previous study to increase the chance that a difference in valuation between different products can be detected. Twenty-five frequent lipstick using females were asked to apply six different lipsticks to their lips and to record how much they were willing to pay. To maximize the variation of the subjective experience of the products and the associated brain activity, the most preferred color lipstick and a less preferred color lipstick were chosen for each participant, and each color of lipstick had three different textures ( Lo, Mid , and Hi ). The time series was analyzed with the general linear model (GLM) and the correlation between the right dlPFC beta scores for the lipsticks and their respective WTP values conducted for each participant. This revealed a significant positive correlation and replicated our previous study. Surprisingly, the lipstick color and the texture manipulations did not result in any consistent differences in WTP and similarly no consistent group differences in brain activations. This study replicates our previous study extending it to a different type of cosmetic. The right dlPFC activity during the use of cosmetics may be a potential brain-based personalization or product selection process biomarker., Competing Interests: KH, KK, and KT are employed by Shiseido Global Innovation Center, Shiseido Co., Ltd., a company which manufactures cosmetics. KH, TT, KK, KT, and ID are named inventors on a patent application covering the method disclosed in this research. This study received funding from Shiseido Global Innovation Center. The funder was involved in the study design, collection, analysis, interpretation of data, the writing of this article and the decision to submit it for publication. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hirabayashi, Tokuda, Nishinuma, Kawabata Duncan, Tagai and Dan.)

Fluctuations of neuronal activities in the brain may underlie relatively slow components of neurofunctional alterations, which can be modulated by food intake and related systemic metabolic statuses. Glutamatergic neurotransmission plays a major role in the regulation of excitatory tones in the central nervous system, although just how dietary elements contribute to the tuning of this system remains elusive. Here, we provide the first demonstration by bimodal positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) that metabotropic glutamate receptor subtype 5 (mGluR5) ligand binding and glutamate levels in human brains are dynamically altered in a manner dependent on food intake and consequent changes in plasma glucose levels. The brain-wide modulations of central mGluR5 ligand binding and glutamate levels and profound neuronal activations following systemic glucose administration were further proven by PET, MRS, and intravital two-photon microscopy, respectively, in living rodents. The present findings consistently support the notion that food-associated glucose intake is mechanistically linked to glutamatergic tones in the brain, which are translationally accessible in vivo by bimodal PET and MRS measurements in both clinical and non-clinical settings.

Depression is one of the common psychiatric disorders in old age. Major depressive disorder (MDD) has been identified as a risk factor or prodrome for neurodegenerative dementias, suggesting neuropathological overlaps and a continuum between MDD and neurodegenerative disorders. In this study, we examined tau and amyloid-β (Aβ) accumulations in the brains of MDD and healthy controls using positron emission tomography (PET) to explore pathological substrates of this illness. Twenty MDD and twenty age-matched, healthy controls were examined by PET with a tau radioligand, [ 11 C]PBB3, and an Aβ radioligand, [ 11 C]PiB. Radioligand retentions were quantified as a standardized uptake value ratio (SUVR). We also assessed clinical manifestations of the patients using the 17-item Hamilton Depression Scale, the Geriatric Depression Scale, and psychotic symptoms. Mean cortical [ 11 C]PBB3 SUVRs in MDD patients were significantly higher than those of healthy controls. These values were higher in MDD patients with psychotic symptoms than in those without any. The present findings indicate that tau depositions may underlie MDD, and especially in patients with psychotic symptoms. PET detection of tau accumulations may provide mechanistic insights into neuronal dysfunctions in these cases and could serve as predictions of their clinical consequences., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: Patients with severe behavioral and psychological symptoms of dementia (BPSD) are often admitted to mental hospitals, while, inpatient care could also lead to prolonged hospital stay. The present study aims to survey clinical profiles of patients who required inpatient treatment for BPSD, and then establish the criteria for introducing inpatient treatment through assessment by certified psychiatrists., Methods: We performed a prospective survey about clinical characteristics of people with dementia who required treatment of BPSD at 12 mental medical institutions. All patients were assessed by certified psychiatrists to determine the optimal treatment settings: outpatient or inpatient. The multivariate logistic regression analysis was performed to specify factors contributed to the judgement of clinicians. Subsequently, the receiver operating characteristic curve analysis was conducted to explore a score derived from the Neuropsychiatric Inventory to divide patients into outpatient or inpatient groups., Results: The present study included 386 patients, of which 242 were admitted to mental hospitals. BPSD were classified into four domains, and aggressive BPSD was significantly associated with assessment for inpatient treatment; the adjusted odds ratio was approximately 2 regardless of dementia severity. Furthermore, the composite score of agitation, irritability and aberrant behavior showed the highest area under the curve value (=0.706), which differentiated inpatients from outpatients with a sensitivity of 76% and a specificity of 54%., Conclusions: Aggressive BPSD was the risk factor for inpatient treatment. The composite score of the Neuropsychiatric Inventory subdomain-related aggressive BPSD could be a screening tool to introduce inpatient treatment for BPSD. Geriatr Gerontol Int 2021; 21: 825-829., (© 2021 Japan Geriatrics Society.)

Self-grooming of the antennae is frequently observed in ants. This antennal maintenance behavior is presumed to be essential for effective chemical communication but, to our knowledge, this has not yet been well studied. When we removed the antenna-cleaning apparatuses of the Japanese carpenter ant ( C. japonicus ) to limit the self-grooming of the antennae, the worker ants demonstrated the self-grooming gesture as usual, but the antennal surface could not be sufficiently cleaned. By using scanning electron microscopy with NanoSuit, we observed the ants' antennae for up to 48 h and found that the antennal surfaces gradually became covered with self-secreted surface material. Concurrently, the self-grooming-limited workers gradually lost their behavioral responsiveness to undecane-the alarm pheromone. Indeed, their locomotive response to the alarm pheromone diminished for up to 24 h after the antenna cleaner removal operation. In addition, the self-grooming-limited workers exhibited less frequent aggressive behavior toward non-nestmate workers, and 36 h after the operation, approximately half of the encountered non-nestmate workers were accepted as nestmates. These results suggest that the antennal sensing system is affected by excess surface material; hence, their proper function is prevented until they are cleaned.

Purpose: Phosphodiesterase 7 (PDE7) is an enzyme that selectively hydrolyses cyclic adenosine monophosphate, and its dysfunction is implicated in neuropsychiatric diseases. However, in vivo visualization of PDE7 in human brains has hitherto not been possible. Using the novel PET ligand 11 C-MTP38, which we recently developed, we aimed to image and quantify PDE7 in living human brains., Methods: Seven healthy males underwent a 90-min PET scan after injection of 11 C-MTP38. We performed arterial blood sampling and metabolite analysis of plasma in six subjects to obtain a metabolite-corrected input function. Regional total distribution volumes (V T s) were estimated using compartment models, and Logan plot and Ichise multilinear analysis (MA1). We further quantified the specific radioligand binding using the original multilinear reference tissue model (MRTM O ) and standardized uptake value ratio (SUVR) method with the cerebellar cortex as reference., Results: PET images with 11 C-MTP38 showed relatively high retentions in several brain regions, including in the striatum, globus pallidus, and thalamus, as well as fast washout from the cerebellar cortex, in agreement with the known distribution of PDE7. V T values were robustly estimated by two-tissue compartment model analysis (mean V T  = 4.2 for the pallidum), Logan plot, and MA1, all in excellent agreement with each other, suggesting the reversibility of 11 C-MTP38 binding. Furthermore, there were good agreements between binding values estimated by indirect method and those estimated by both MRTM O and SUVR, indicating that these methods could be useful for reliable quantification of PDE7. Because MRTM O and SUVR do not require arterial blood sampling, they are the most practical for the clinical use of 11 C-MTP38-PET., Conclusion: We have provided the first demonstration of PET visualization of PDE7 in human brains. 11 C-MTP38 is a promising novel PET ligand for the quantitative investigation of central PDE7.

Objective: Facial attractiveness has been reported to be influenced by visual features such as facial shape and the colour and texture of the skin. However, no empirical studies have examined the effects of facial skin radiance on facial attractiveness. The present study investigated whether types of skin reflection (i.e. radiant, oily and shiny, and matte) and the position of the reflection on the face influence facial attractiveness and other affective impressions., Methods: A total of 160 female participants (1) estimated the ages and (2) evaluated attractiveness and other impressions of unfamiliar female faces in a total of seven skin reflection conditions. These conditions incorporated three types of reflection (i.e. radiant, oily and shiny, and matte) and three positions of the reflection on the face (i.e. entire facial skin, only cheeks, and only T-zone)., Results: The facial images of radiance on entire faces were rated as appearing younger than the facial images of oily shine on entire faces and the matte faces. Attractiveness ratings and other positive impressions increased in the order of the matte (ranked lowest), the oily shine on entire face, and the radiance on entire face (ranked highest) conditions. The reflection position also influenced facial attractiveness: attractiveness ratings and other positive impressions were higher in the radiance on entire face condition than in the radiant cheeks and the radiant T-zone conditions. Interestingly, the radiant cheek faces were rated more radiant and healthier but less feminine and less bright than the radiant T-zone faces., Conclusion: These results suggest that facial radiance enhances facial attractiveness and conveys a wide variety of positive impressions on the observer. The magnitude of the effects of cheek radiance and T-zone radiance differs across various affective impressions. Nevertheless, the results demonstrate that cheek and the T-zone radiance both contribute to higher attractiveness and other positive impressions of the radiance on entire faces. We believe that our findings can contribute as a guide to the enhancement of positive facial impressions by means of skin radiance, thereby leading to a better understanding of the value of skincare and base makeup., (© 2020 Shiseido Global Innovation Center. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Facial attraction has a great influence on our daily social interactions. Previous studies have mainly focused on the attraction from facial shape and expression. We recently found that faces with radiant skin appear to be more attractive than those with oily-shiny or matte skin. In the present study, we conducted functional magnetic resonance imaging (fMRI) and psychological experiments to determine the human brain activity that reflects facial attractiveness modulated by these skin reflection types. In the fMRI experiment, female subjects were shown successive images of unfamiliar female faces with matte, oily-shiny, or radiant skin. The subjects compared each face with the immediately preceding face in terms of attractiveness, age, and skin reflection, all based on the skin. The medial part of the orbitofrontal cortex (mOFC) was significantly more active when comparing attractiveness than when comparing skin reflection, suggesting that the mOFC is involved in processing facial attractiveness from skin reflection. In the psychological experiment, attractiveness rating was highest for radiant skin, followed by oily-shiny, and then matte skin. Comparison of the results of these experiments showed that mOFC activation level increased with attractiveness rating. These results suggest that the activation level of the mOFC reflects facial attractiveness from skin reflection.

A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of 18 F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of 18 F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of 18 F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis., Competing Interests: Declaration of Interests H. Shimada, M.-R.Z., T.S., and M.H. hold patents on compounds related to the present report (JP 5422782/EP 12 884 742.3/CA2894994/HK1208672)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Behavioral and psychological symptoms of dementia (BPSD) cause a heavy burden for both patient and caregivers. These symptoms are diverse, and their mechanism is still unclear. Agitation is the most common and difficult to treat among BPSD. In recent years, while changes in DNA methylation levels have been receiving attention as a biomarker of aging and dementia, associations with BPSD have not been examined., Objective: Focusing on agitation, the objective of the present study was to identify a region where changes in DNA methylation levels are associated with agitation., Methods: Using genome-wide DNA methylation analysis data for 7 dementia subjects with agitation, 5 dementia subjects without agitation, and 4 normal elderly controls, we determined a signaling pathway in the WNT5A gene promoter region to be associated with agitation. Based on this result, we measured DNA methylation levels in this region for 26 dementia subjects with agitation and 82 dementia subjects without agitation by means of methylation-sensitive high-resolution melting (MS-HRM) analysis., Results: The WNT5A DNA methylation level in dementia subjects with agitation was significantly lower than in those without agitation (p = 0.001). Changes in WNT5A DNA methylation levels were not influenced by age, sex, body mass index, APOE ɛ4, medication, or inflammatory cytokines., Conclusion: Our results suggested an association of agitation with Wnt signaling, in particular with changes in WNT5A DNA methylation levels, which could be a potentially useful biomarker for predicting the appearance of agitation. It may contribute to the elucidation of the mechanism of BPSD.

Although previous studies have suggested the involvement of dopamine (DA) and noradrenaline (NA) neurotransmissions in the autism spectrum disorder (ASD) pathophysiology, few studies have examined these neurotransmissions in individuals with ASD in vivo. Here, we investigated DA D1 receptor (D1R) and noradrenaline transporter (NAT) binding in adults with ASD (n = 18) and neurotypical controls (n = 20) by utilizing two different PET radioligands, [11C]SCH23390 and (S,S)-[18F]FMeNER-D2, respectively. We found no significant group differences in DA D1R (striatum, anterior cingulate cortex, and temporal cortex) or NAT (thalamus and pons) binding. However, in the ASD group, there were significant negative correlations between DA D1R binding (striatum, anterior cingulate cortex and temporal cortex) and the "attention to detail" subscale score of the Autism Spectrum Quotient. Further, there was a significant positive correlation between DA D1R binding (temporal cortex) and emotion perception ability assessed by the neurocognitive battery. Associations of NAT binding with empathic abilities and executive function were found in controls, but were absent in the ASD group. Although a lack of significant group differences in binding might be partly due to the heterogeneity of ASD, our results indicate that central DA and NA function might play certain roles in the clinical characteristics of ASD., (© The Author(s) 2020. Published by Oxford University Press.)

Early diagnosis of dementia including Alzheimer's disease (AD) is an urgent medical and welfare issue. However, to date, no simple biometrics have been available. We reported that blood DNA methylation levels of the COASY gene, which encodes coenzyme A synthase, were increased in individuals with AD and amnestic mild cognitive impairment (aMCI). The present study sought to replicate these findings with larger numbers of samples. Another objective was to clarify whether COASY methylation is associated with neurodegeneration through a comparison of AD, AD with cardiovascular disease (CVD), and vascular dementia (VaD). We measured blood COASY methylation levels in normal controls (NCs) (n = 200), and individuals with aMCI (n = 22), AD (n = 151), and VaD (n = 21). Compared with NCs, they were significantly higher in individuals with aMCI and AD. Further, they were significantly higher in AD patients without cardiovascular diseases compared to AD patients with them. These findings suggest that COASY methylation levels may be related to neurodegeneration in AD.

Aim: In patients with Alzheimer's disease (AD), cognitive impairments cause a progressive reduction in Activities of Daily Living (ADL). Neuropsychiatric symptoms (NPS) also appear in most patients; however, the association between NPS and reductions in ADL remains unclear. The present study evaluated whether NPS influence such reductions using two different ADL measures in patients with AD., Methods: Among 546 consecutive outpatients who visited the memory clinic at the Jikei University Kashiwa Hospital, we recruited 208 patients with AD and investigated the correlations between either the Physical Self-Maintenance Scale (PSMS) score or the Instrumental ADL (IADL) level, and each of the Behavioral Pathology in AD (Behave-AD) subscales. To clarify the causal relationships of these correlations, we then verified the associations between statistically significant demographic variables and the Behave-AD subscales as well as the two ADL scales (PSMS score and IADL percentage) using a general linear model., Results: Neither the PSMS nor the IADL results were significantly influenced by the aberrant motor behaviors score. However, the IADL was significantly influenced by the Mini-Mental State Exam (MMSE) score. Furthermore, diurnal rhythm disturbances and the interaction between diurnal rhythm disturbances score and the MMSE score significantly influenced the PSMS results., Conclusion: Basic ADL reductions may be influenced by diurnal rhythm disturbances, in addition to cognitive impairments in patients with AD. Furthermore, the interaction between the diurnal rhythm disturbances score and cognitive function may also influence basic ADL. Geriatr Gerontol Int 2020; ••: ••-••., (© 2020 Japan Geriatrics Society.)

Alzheimer's disease (AD) is a neurodegenerative disease characterised by neurocognitive impairments, especially memory impairment, as core symptoms linked to reductions in activities of daily life. As marginal symptoms, neuropsychiatric symptoms (NPSs) appear during the progressive course of the disease. A lack of self-awareness (anosognosia) of cognitive and functional impairments is often seen in patients with AD, and associations between anosognosia and other NPSs have been previously reported. To account for anosognosia pathogenesis neurocognitively, the cognitive awareness model (CAM) has been helpful for explaining the stream of events from sensory input to behavioural/affective and metacognitive outputs. According to CAM, there are three types of anosognosia: (i) primary anosognosia, (ii) executive anosognosia, and (iii) mnemonic anosognosia. These types of anosognosia are generated from different neurocognitive modulations leading to metacognitive outputs or behavioural/affective regulations. Primary anosognosia is considered to be caused by deficits in the metacognitive awareness system (MAS). While preserved MAS function is associated with milder depression and anxiety in AD, a severer depressive mood in patients with mild AD can inversely cause self-underestimation. The modulation of executive anosognosia is thought to be associated with dangerous/disinhibition behaviours and apathy among NPS sub-symptoms, via impairments of comparator mechanism (Cm) within the central executive system. Other neurobehavioral reactions linked to self-awareness include 'denying' and 'confabulation', and each of these reactions is thought to be affected by the MAS and a Cm. Denial of one's own memory impairments appears as a defensive reaction to protect against dysphoric feelings, and the confabulatory comment is instantly reaction constructed by fabrications according to misinterpretations of memory information about oneself. Similarly, the innovative development of a theoretical model (CAM) has contributed to explaining the mechanism of anosognosia and some neurobehavioral outputs from a neurocognitive perspective., (© 2020 Japanese Psychogeriatric Society.)

Objectives: We examined differences in the severity of neuropsychiatric symptoms (NPS) according to sex and identified NPS-related clinico-demographic and psychosocial factors among community-living patients with amnestic-mild cognitive impairment (a-MCI) or mild Alzheimer's disease (AD). Method: Overall, 111 patients (44 males, 67 females) with mild a-MCI (n = 64) or mild AD (n = 47) were included. We divided the patients according to sex and compared their clinico-demographic and psychosocial factors, explored the severity of NPS using the subscales from the Neuropsychiatric Inventory-Questionnaire (NPI-Q), and further identified variables related to NPS. Results : Significant differences in several clinico-demographic and psychosocial characteristics were observed between the sexes. The severity of delusions was higher among females (mean, 0.48; SD, 1.60) than males (mean, 0.23; SD, 1.07; p = .02), while the severity of irritability was higher among males (mean, 0.97; SD, 1.92) than females (mean, 0.49; SD, 1.40; p = .03). The severity of delusions among females was related to the duration of cognitive decline (B = 0.37, p = .03), while the severity of irritability among males was related to general cognition (B = -0.40, p = .003). Conclusion: The severity of NPS among patients with a-MCI or mild AD differed according to sex. We identified NPS-related clinico-demographic factors among these patients. Sex differences should be considered when determining the need for NPS interventions.