Amyloid-ß prediction machine learning model using source-based morphometry across neurocognitive disorders.

Previous studies have developed and explored magnetic resonance imaging (MRI)-based machine learning models for predicting Alzheimer's disease (AD). However, limited research has focused on models incorporating diverse patient populations. This study aimed to build a clinically useful prediction model for amyloid-beta (Aß) deposition using source-based morphometry, using a data-driven algorithm based on independent component analyses. Additionally, we assessed how the predictive accuracies varied with the feature combinations. Data from 118 participants clinically diagnosed with various conditions such as AD, mild cognitive impairment, frontotemporal lobar degeneration, corticobasal syndrome, progressive supranuclear palsy, and psychiatric disorders, as well as healthy controls were used for the development of the model. We used structural MR images, cognitive test results, and apolipoprotein E status for feature selection. Three-dimensional T1-weighted images were preprocessed into voxel-based gray matter images and then subjected to source-based morphometry. We used a support vector machine as a classifier. We applied SHapley Additive exPlanations, a game-theoretical approach, to ensure model accountability. The final model that was based on MR-images, cognitive test results, and apolipoprotein E status yielded 89.8% accuracy and a receiver operating characteristic curve of 0.888. The model based on MR-images alone showed 84.7% accuracy. Aß-positivity was correctly detected in non-AD patients. One of the seven independent components derived from source-based morphometry was considered to represent an AD-related gray matter volume pattern and showed the strongest impact on the model output. Aß-positivity across neurological and psychiatric disorders was predicted with moderate-to-high accuracy and was associated with a probable AD-related gray matter volume pattern. An MRI-based data-driven machine learning approach can be beneficial as a diagnostic aid.

Decreased short-latency afferent inhibition in individuals with mild cognitive impairment: A TMS-EEG study.

TMS combined with EEG (TMS-EEG) is a tool to characterize the neurophysiological dynamics of the cortex. Among the TMS paradigms, short-latency afferent inhibition (SAI) allows the investigation of inhibitory effects mediated by the cholinergic system. The aim of this study was to compare cholinergic function in the DLPFC between individuals with mild cognitive impairment (MCI) and healthy controls (HC) using TMS-EEG with the SAI paradigm. In this study, 30 MCI and 30 HC subjects were included. The SAI paradigm consisted of 80 single pulse TMS and 80 SAI stimulations applied to the left DLPFC. N100 components, global mean field power (GMFP) and total power were calculated. As a result, individuals with MCI showed reduced inhibitory effects on N100 components and GMFP at approximately 100 ms post-stimulation and on ß-band activity at 200 ms post-stimulation compared to HC. Individuals with MCI showed reduced SAI, suggesting impaired cholinergic function in the DLPFC compared to the HC group. We conclude that these findings underscore the clinical applicability of the TMS-EEG method as a powerful tool for assessing cholinergic function in individuals with MCI.

Transcranial magnetic stimulation neurophysiology in patients with non-Alzheimer's neurodegenerative diseases: A systematic review and meta-analysis.

Non-Alzheimer's dementia (NAD) accounts for 30% of all neurodegenerative conditions and is characterized by cognitive decline beyond mere memory dysfunction. Diagnosing NAD remains challenging due to the lack of established biomarkers. Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that enables the investigation of cortical excitability in the human brain. Paired-pulse TMS paradigms include short- and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and short-latency afferent inhibition (SAI), which can assess neurophysiological functions of GABAergic, glutamatergic, and cholinergic neural circuits, respectively. We conducted the first systematic review and meta-analysis to compare these TMS indices among patients with NAD and healthy controls. Our meta-analyses indicated that TMS neurophysiological examinations revealed decreased glutamatergic function in patients with frontotemporal dementia (FTD) and decreased GABAergic function in patients with FTD, progressive supranuclear palsy, Huntington's disease, cortico-basal syndrome, and multiple system atrophy-parkinsonian type. In addition, decreased cholinergic function was found in dementia with Lewy body and vascular dementia. These results suggest the potential of TMS as an additional diagnostic tool to differentiate NAD.

Performance of plasma Aß42/40, measured using a fully automated immunoassay, across a broad patient population in identifying amyloid status.

BACKGROUND: Plasma biomarkers have emerged as promising screening tools for Alzheimer's disease (AD) because of their potential to detect amyloid ß (Aß) accumulation in the brain. One such candidate is the plasma Aß42/40 ratio (Aß42/40). Unlike previous research that used traditional immunoassay, recent studies that measured plasma Aß42/40 using fully automated platforms reported promising results. However, its utility should be confirmed using a broader patient population, focusing on the potential for early detection. METHODS: We recruited 174 participants, including healthy controls (HC) and patients with clinical diagnoses of AD, frontotemporal lobar degeneration, dementia with Lewy bodies/Parkinson's disease, mild cognitive impairment (MCI), and others, from a university memory clinic. We examined the performance of plasma Aß42/40, measured using the fully automated high-sensitivity chemiluminescence enzyme (HISCL) immunoassay, in detecting amyloid-positron emission tomography (PET)-derived Aß pathology. We also compared its performance with that of Simoa-based plasma phosphorylated tau at residue 181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). RESULTS: Using the best cut-off derived from the Youden Index, plasma Aß42/40 yielded an area under the receiver operating characteristic curve (AUC) of 0.949 in distinguishing visually assessed 18F-Florbetaben amyloid PET positivity. The plasma Aß42/40 had a significantly superior AUC than p-tau181, GFAP, and NfL in the 167 participants with measurements for all four biomarkers. Next, we analyzed 99 participants, including only the HC and those with MCI, and discovered that plasma Aß42/40 outperformed the other plasma biomarkers, suggesting its ability to detect early amyloid accumulation. Using the Centiloid scale (CL), Spearman's rank correlation coefficient between plasma Aß42/40 and CL was -0.767. Among the 15 participants falling within the CL values indicative of potential future amyloid accumulation (CL between 13.5 and 35.7), plasma Aß42/40 categorized 61.5% (8/13) as Aß-positive, whereas visual assessment of amyloid PET identified 20% (3/15) as positive. CONCLUSION: Plasma Aß42/40 measured using the fully automated HISCL platform showed excellent performance in identifying Aß accumulation in the brain in a well-characterized cohort. This equipment may be useful for screening amyloid pathology because it has the potential to detect early amyloid pathology and is readily applied in clinical settings.

Pneumonia Risk Increased by Dementia-Related Daily Living Difficulties: Poor Oral Hygiene and Dysphagia as Contributing Factors.

OBJECTIVE: Although pneumonia is the leading cause of death among patients with dementia, the specific underlying causes remain unclear. In particular, the potential connection between pneumonia risk and dementia-related daily living difficulties, such as oral hygiene practice and mobility impairment, and the use of physical restraint as a management practice, has not been extensively studied. METHODS: In our retrospective study, we included 454 admissions corresponding to 336 individual patients with dementia who were admitted to a neuropsychiatric unit due to behavioral and psychological symptoms. The admissions were divided into two groups: those who developed pneumonia while hospitalized (n=62) and those who did not (n=392). We investigated differences between the two groups in terms of dementia etiology, dementia severity, physical conditions, medical complications, medication, dementia-related difficulties in daily living, and physical restraint. To control potential confounding variables, we used mixed effects logistic regression analysis to identify risk factors for pneumonia in this cohort. RESULTS: Our study found that the development of pneumonia in patients with dementia was associated with poor oral hygiene, dysphagia, and loss of consciousness. Physical restraint and mobility impairment showed a weaker, nonsignificant association with the development of pneumonia. CONCLUSIONS: Our findings suggest that pneumonia in this population may be caused by two primary factors: increased pathogenic microorganisms in the oral cavity due to poor hygiene, and an inability to clear aspirated contents due to dysphagia and loss of consciousness. Further investigation is needed to clarify the relationship between physical restraint, mobility impairment, and pneumonia in this population.

A Case Series of Intermittent Theta Burst Stimulation Treatment for Depressive Symptoms in Individuals with Autistic Spectrum Disorder: Real World TMS Study in the Tokyo Metropolitan Area.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors. While the symptoms of ASD are present from early childhood, there has been an increase in the number of adults with ASD in recent years who visit healthcare professionals to seek the treatment of depression due to maladjustment resulting from the core symptoms and are eventually diagnosed with ASD. Currently, no treatment is available for the core symptoms of ASD, and pharmacotherapy and psychotherapy are often provided mainly for secondary disorders such as depression and anxiety. However, the effectiveness of these therapies is often limited in individuals with ASD compared to those with major depression. In this context, neuromodulation therapies such as transcranial magnetic stimulation (TMS) have gained increasing attention as potential treatments. In this case series, we retrospectively analyzed 18 cases with ASD from the TMS registry data who had failed to improve depressive symptoms with pharmacotherapy and were treated with intermittent theta burst stimulation (iTBS) therapy to the left dorsolateral prefrontal cortex (DLPFC). We also explored the relationship between treatment efficacy and clinical epidemiological profile. Our results indicated that, despite the limitations of an open-label preliminary case series, TMS therapy in the form of iTBS may have some beneficial therapeutic effects on depressive symptoms in individuals with ASD. The present findings warrant further validation through randomized, sham-controlled trials with larger sample sizes.

Effects of common genetic variants of human uridine diphosphate glucuronosyltransferase subfamilies on irinotecan glucuronidation.

The adverse effects (diarrhea and neutropenia) of irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin) are associated with genetic variants of uridine diphosphate glucuronosyltransferase 1A subfamilies (UGT1As). UGT1As are enzymes that metabolize the active form of irinotecan, 7-ethyl-10 hydroxycamptothecin (SN-38), by glucuronidation in the liver. They are widely known as predictive factors of severe adverse effects, such as neutropenia and diarrhea. Some studies have suggested that variants of UGT1As affect SN-38 glucuronidation activities, thus exerting severe adverse effects. We aimed to identify UGT1A isoforms that show SN-38 glucuronidation activity and determine the relationship between UGT1A variants and SN-38 glucuronidation in vitro. We found that UGT1A1 and UGT1A6-UGT1A10 displayed SN-38 glucuronidation activity. Among these, UGT1A1 was the most active. Furthermore, the variants of these isoforms showed decreased SN-38 glucuronidation activity. In our study, we compared the different variants of UGT1As, such as UGT1A1.6, UGT1A1.7, UGT1A1.27, UGT1A1.35, UGT1A7.3, UGT1A8.4, UGT1A10M59I, and UGT1A10T202I, to determine the differences in the reduction of glucuronidation. Our study elucidates the relationship between UGT1A variants and the level of glucuronidation associated with each variant. Therefore, testing can be done before the initiation of irinotecan treatment to predict potential toxicities and adverse effects.

Impact of Amyloid and Tau PET on Changes in Diagnosis and Patient Management.

BACKGROUND AND OBJECTIVES: Previous studies have evaluated the diagnostic effect of amyloid PET in selected research cohorts. However, these studies did not assess the clinical impact of the combination of amyloid and tau PETs. Our objective was to evaluate the association of the combination of 2 PETs with changes in diagnosis, treatment, and management in a memory clinic cohort. METHODS: All participants underwent amyloid [18F]florbetaben PET and tau PET using [18F]PI-2620 or [18F]Florzolotau, which are potentially useful for the diagnosis of non-Alzheimer disease (AD) tauopathies. Dementia specialists determined a pre- and post-PET diagnosis that existed in both a clinical syndrome (cognitive normal [CN], mild cognitive impairment [MCI], and dementia) and suspected etiology, with a confidence level. In addition, the dementia specialists determined patient treatment in terms of ancillary investigations and management. RESULTS: Among 126 registered participants, 84.9% completed the study procedures and were included in the analysis (CN [n = 40], MCI [n = 25], AD [n = 20], and non-AD dementia [n = 22]). The etiologic diagnosis changed in 25.0% in the CN, 68.0% in the MCI, and 23.8% with dementia. Overall changes in management between pre- and post-PET occurred in 5.0% of CN, 52.0% of MCI, and 38.1% of dementia. Logistic regression analysis revealed that tau PET has stronger associations with change management than amyloid PET in all participants and dementia groups. DISCUSSION: The combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia, and the second-generation tau PET has a strong impact on the changes in diagnosis and management in memory clinics. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia.

Investigation of Spatiotemporal Profiles of Single-Pulse TMS-Evoked Potentials with Active Stimulation Compared with a Novel Sham Condition.

Identifying genuine cortical stimulation-elicited electroencephalography (EEG) is crucial for improving the validity and reliability of neurophysiology using transcranial magnetic stimulation (TMS) combined with EEG. In this study, we evaluated the spatiotemporal profiles of single-pulse TMS-elicited EEG response administered to the left dorsal prefrontal cortex (DLPFC) in 28 healthy participants, employing active and sham stimulation conditions. We hypothesized that the early component of TEP would be activated in active stimulation compared with sham stimulation. We specifically analyzed the (1) stimulus response, (2) frequency modulation, and (3) phase synchronization of TMS-EEG data at the sensor level and the source level. Compared with the sham condition, the active condition induced a significant increase in TMS-elicited EEG power in the 30-60 ms time interval in the stimulation area at the sensor level. Furthermore, in the source-based analysis, the active condition induced significant increases in TMS-elicited response in the 30-60 ms compared with the sham condition. Collectively, we found that the active condition could specifically activate the early component of TEP compared with the sham condition. Thus, the TMS-EEG method that was applied to the DLPFC could detect the genuine neurophysiological cortical responses by properly handling potential confounding factors such as indirect response noises.

Reduced signal propagation elicited by frontal transcranial magnetic stimulation is associated with oligodendrocyte abnormalities in treatment-resistant depression.

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (dlPFC) has been established in patients with treatment-resistant depression (TRD), suggesting that alterations in signal propagation from the left dlPFC to other brain regions may be linked to the pathophysiology of TRD. Alterations at the cellular level, including dysfunction of oligodendrocytes, may contribute to these network abnormalities. The objectives of the present study were to compare signal propagation from the left dlPFC to other neural networks in patients with TRD and healthy controls. We used TMS combined with electroencephalography to explore links between cell-specific gene expression and signal propagation in TRD using a virtual-histology approach. METHODS: We examined source-level estimated signal propagation from the left dlPFC to the 7 neural networks in 60 patients with TRD and 30 healthy controls. We also calculated correlations between the interregional profiles of altered signal propagation and gene expression for 9 neural cell types derived from the Allen Human Brain Atlas data set. RESULTS: Signal propagation from the left dlPFC to the salience network was reduced in the θ and α bands in patients with TRD (p = 0.0055). Furthermore, this decreased signal propagation was correlated with cellspecific gene expression of oligodendrocytes (p < 0.000001). LIMITATIONS: These results show only part of the pathophysiology of TRD, because stimulation was limited to the left dlPFC. CONCLUSION: Reduced signal propagation from the left dlPFC to the salience network may represent a pathophysiological endophenotype of TRD; this finding may be associated with reduced expression of oligodendrocytes.

Restrictive type and infectious complications might predict nadir hematological values among individuals with anorexia nervosa during the refeeding period: a retrospective study.

BACKGROUND: Although hematological abnormalities in patients with anorexia nervosa have been documented, the mechanisms involved have not been fully clarified, especially during the refeeding period when hematological values further decrease after admission prior to improving. Here we address potential mechanisms underlying the hematological abnormalities of inpatients with anorexia nervosa during the refeeding period. METHODS: We recruited patients from 101 admissions corresponding to 55 individual patients with anorexia nervosa with severe malnutrition (body mass index, 13.4 ± 3.4) from the neuropsychiatry unit in Ashikaga Red Cross Hospital during the period from October 1999 to March 2018. We analyzed three hematological cell measures, i.e., hemoglobin, white cell count, and platelet count, to determine their levels at admission and their lowest levels during the refeeding period and calculated the percent decrease in those values from admission to the nadir levels. We analyzed each measure using a general mixed model with explanatory variables, including data upon admission and a treatment-related indicator, i.e., energy intake. RESULTS: The initial hemoglobin value of 12.1 ± 2.7 g/dl decreased by 22.3% to 9.4 ± 2.5 g/dl; the initial white cell count was 5387 ± 3474/µl, which decreased by 33.6% to 3576 ± 1440/µl; the initial platelet count of 226 ± 101 × 103/µl decreased by 24.3% to 171 ± 80 × 103/µl. All nadir levels were observed during the refeeding period from the fifth to tenth day of hospitalization. Significant correlations among the three hematological cell measures, particularly at the nadir levels, were found. Of note, 41.7% of our patients who received red blood cell transfusion during hospitalization showed normal hemoglobin levels upon admission. The anorexia nervosa restrictive type was associated with a lower nadir level of white blood cell count. Infectious complications were related to a lower nadir level of hemoglobin and a greater percent decrease in hemoglobin level as well as to the need for red blood cell transfusion. CONCLUSIONS: Nadir hematological cell measures of inpatients with anorexia nervosa might be predicted by the restrictive type and infectious complications. The anorexia nervosa restrictive type was associated with further decrease in hematological values during the refeeding period.

Deficiencies in components of the blood, such as a low red blood cell count, low white blood cell count, and low platelet numbers, are observed frequently in patients with anorexia nervosa, particularly those with severe malnutrition, and these deficiencies become manifest after hospitalization during the initial period when patients are reintroduced to food. Why this deterioration occurs even under medical care is not well understood. Here we analyzed the patient factors associated with these blood cell abnormalities. Patients with the restrictive type of anorexia nervosa, and infectious complications were more likely to have the lowest levels of hematological values during the refeeding period.

Differentiating autoimmune encephalitis from schizophrenia spectrum disorders among patients with first-episode psychosis.

BACKGROUND: Although differential diagnosis between autoimmune encephalitis and schizophrenia spectrum disorders is crucial for a good outcome, the psychiatric symptoms that distinguish these two conditions have not been identified even though psychiatric symptoms are often the main manifestation of autoimmune encephalitis. Also, there are many situations in clinical psychiatry in which laboratory testing and imaging studies are not available. Because no comparative study of the psychiatric symptoms between these two conditions has been carried out, we explored diagnostically useful psychiatric symptoms in a retrospective case-control study. METHODS: We recruited 187 inpatients with first-episode psychosis who were admitted to our psychiatric unit and categorized them into two groups: the autoimmune encephalitis group (n = 10) and the schizophrenia spectrum disorders group (n = 177). Differences in the symptoms and signs between the two groups were investigated. RESULTS: Schneider's first-rank symptoms (e.g., verbal commenting hallucinations and delusional self-experience) were observed only in the schizophrenia spectrum disorders group, whereas altered perception was found more frequently in the autoimmune encephalitis group. Functional status was worse in the autoimmune encephalitis group, and neurological and neuropsychological signs were revealed almost exclusively in this group. A history of mental illness was more frequently reported in the schizophrenia spectrum disorders group than in the autoimmune encephalitis group. CONCLUSIONS: The psychiatric symptoms, i.e., Schneider's first-rank symptoms and altered perception, together with neurological and neuropsychological signs, functional status, and past history, may help clinicians accurately differentiate these two conditions among patients with first-episode psychosis.

Symptom changes in patients with pre-existing psychiatric disorders in the initial phase of the COVID-19 pandemic: Vulnerability of female patients and patients with mood disorders.

How patients with pre-existing psychiatric disorders are responding to the COVID-19 pandemic remains unclear, and no comprehensive studies have yet been performed. To elucidate (1) which psychiatric disorders were exacerbated during the initial phase of the COVID-19 pandemic and (2) the contributing factors, we prospectively assessed psychiatric symptoms of 1592 psychiatric outpatients in a single-center study using the Global Assessment of Functioning (GAF) before the state of emergency was declared in Japan and during two months under the state of emergency (study period: April 8 to June 7, 2020). We conducted a chi-squared test for the relationship between psychiatric diagnostic category (ICD-10) and exacerbation. To control for confounders, we conducted a logistic regression analysis using sex, age, diagnostic category, and pre-pandemic GAF score as independent variables. Exacerbation rates of patients with mood disorders (F3) and neurotic disorders (F4) were 4.32% and 5.37%, respectively, and were significantly higher than those for patients with organic disorders (F0) and schizophrenic disorders (F2) (X2 (9, N = 1592) = 27.8, p < .01). Logistic regression analysis revealed that patients with F3 and female patients were significantly more affected than patients with other disorders or male patients, respectively (odds ratio (95% confidence interval) = 2.4 (1.2-4.6), p < .01 for F3; 3.1 (1.5-6.6), p < .01 for females). These findings suggest a need for careful management of patients with mood disorders and female psychiatric patients during a pandemic.

Hypokalemia in patients with anorexia nervosa during refeeding is associated with binge-purge behavior, lower body mass index, and hypoalbuminemia.

BACKGROUND: Hypokalemia is frequently found in patients with anorexia nervosa and sometimes leads to life-threatening conditions. Although their serum potassium levels are considered to further decrease during refeeding, no previous studies have addressed actual changes in the serum potassium levels and potential mechanisms underlying hypokalemia during the refeeding period of patients with anorexia nervosa. In this study, we investigated factors associated with hypokalemia during refeeding of patients with anorexia nervosa. METHODS: We recruited 52 independent patients from 89 admissions with anorexia nervosa (body mass index, 13.0 ± 3.3) from the psychiatry unit in Ashikaga Red Cross Hospital during the period from April 2003 to March 2018 and analyzed serum potassium levels at admission. Of the 89 admissions, 66 admissions with > 1-week hospitalization were recruited to determine the lowest potassium levels during the refeeding period. We analyzed these levels with multiple linear regression analysis with explanatory variables, including data upon admission and treatment-related indicators. RESULTS: The initial serum potassium level of 3.6 ± 0.9 mg/dl decreased to 3.1 ± 0.7 mg/dl at nadir hypophosphatemia, which was observed an average of 2.5 days after admission. A lower serum potassium level at admission and a lower nadir potassium level during refeeding were associated with a lower body mass index, hypoalbuminemia, and binge-purge behavior. Similar results were obtained when the analysis included restrictive or binge-purge types as well as the independent patient group. CONCLUSIONS: Lower body mass index, hypoalbuminemia, and binge-purge behavior might be used as indicators to guide clinical approaches for controlling serum potassium levels in patients with anorexia nervosa during refeeding. Hypokalemia, low levels of serum potassium, in patients with anorexia nervosa sometimes leads to life-threatening conditions. Thus, it is of great importance to predict the risk of hypokalemia in patients with anorexia nervosa during the refeeding period. Our study found that hypokalemia in patients with anorexia nervosa during refeeding is associated with a lower body mass index and hypoalbuminemia (low levels of serum albumin), in addition to binge-purge behavior.

Association between resilience and cortical thickness in the posterior cingulate cortex and the temporal pole in Japanese older people: A population-based cross-sectional study.

BACKGROUND: Resilience is a crucial factor preventing the onset of mental illness and contributing to the well-being and healthy longevity, whose neural bases are not fully elucidated in older people. The present study aimed to identify the cortical thickness associating with resilience in older adults. METHODS: This is a part of the cross-sectional Arakawa geriatric cohort study for people aged 65 years or older, consisting of 1001 individuals. A Self-Reported Resilience Scale (RS), neuropsychological batteries, face-to-face interviews for diagnosis, and a three-dimensional T1-weighted magnetic resonance imaging were conducted. Cortical thickness was computed by the FreeSurfer. The relationships among cortical thickness, total RS score, and clinico-demographic data were investigated using univariate and multivariable regression analyses. RESULTS: The total RS score was correlated with age, education, and scores of the Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS) in univariate analyses. The total RS score was associated with cortical thicknesses in the left posterior cingulate (ß [95 % CI of B] = 0.07 [0.16-14.84]) and the left temporal pole (ß [95 % CI of B] = 0.08 [0.63-9.93]) after adjusting sex, age, imaging acquisition site, education, MMSE and GDS scores, hypertension, hyperlipidemia, diabetes mellitus, Barthel index, BMI, and living situation in multivariable regression analyses. CONCLUSION: The present analyses suggest that the resilience capacity may be related to the cortical thickness in the posterior cingulate and temporal cortices in older adults. Our findings warrant further longitudinal studies to confirm the causal relationship between stress events, resilience, and brain structures.

"Case series: ischemic stroke associated with dehydration and arteriosclerosis in individuals with severe anorexia nervosa".

BACKGROUND: Numerous reports have indicated that patients with anorexia nervosa (AN) are at a relatively high risk of developing vascular diseases, including cardiovascular events and venous thromboembolism. However, there have been no previous reports of the development of ischemic stroke during refeeding therapy in patients with severe AN. This report is aimed at reporting the characteristics of an ischemic stroke in patients with AN. CASE PRESENTATIONS: Our study included 29 admissions by independent 19 female patients cases (19 patients), who received thorough medical, neurological, and psychiatric examinations. Two patients were diagnosed as having developed ischemic stroke; the first patient showed multiple infarctions in the brain, while the second showed symptomatic focal infarction. Our findings suggest that dehydration and arteriosclerosis, in association with severe malnutrition, could predispose to the development of ischemic stroke in patients with severe AN. CONCLUSIONS: Development of ischemic stroke in patients with AN might be overlooked. Watching out for neurological signs would help in early diagnosis of ischemic stroke in patients with AN during refeeding. Specific etiology could induce ischemic stroke in patients with AN even if they have no common risk factors of ischemia.

Body mass index and blood urea nitrogen to creatinine ratio predicts refeeding hypophosphatemia of anorexia nervosa patients with severe malnutrition.

AIM: To investigate development of refeeding hypophosphatemia during the refeeding period and the extent of the decrease in the serum phosphorus level among anorexia nervosa patients with severe malnutrition. OBJECTIVE: The accurate prediction of the severity of refeeding hypophosphatemia in patients with anorexia nervosa during acute treatment is of great importance. Although some predictors were found in previous reports, these studies used binominal data-the presence or absence of hypophosphatemia-as an outcome indicator but not the extent of serum phosphorus level decrease. It is crucial in clinical settings to predict the extent of the serum phosphorus level decrease as well as development of refeeding hypophosphatemia, in particular, for patients with severe malnutrition, who has a higher risk of death. METHODS: We investigated 63 admissions from 37 patients with anorexia nervosa who had severe malnutrition (admission body mass index 11.5 ± 1.6) and carried out a linear discriminant regression analysis for the development of refeeding hypophosphatemia. The extent of the decrease in the serum phosphorus level were investigated using multiple linear regression analysis. Explanatory variables included data upon admission (age, sex, body mass index, blood urea nitrogen to creatinine ratio, albumin, initial serum phosphorus level, anorexia nervosa type, i.e., restrictive or binge-purge) as well as treatment-related indicators (calorie intake, amount of phosphate administered, and rate of weight gain). RESULTS: Development of refeeding hypophosphatemia and a change in serum phosphorus levels were predicted by body mass index and elevated blood urea nitrogen to creatinine ratio. CONCLUSIONS: Our study found that refeeding hypophosphatemia among patients with severe malnutrition was predicted by a lower body mass index and elevated blood urea nitrogen to creatinine ratio.

Neurophysiological biomarkers using transcranial magnetic stimulation in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis.

Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that enables the investigation of cortical excitability in the human brain. Paired-pulse TMS paradigms include short- and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and short-latency afferent inhibition (SAI), which can assess neurophysiological functions of GABAergic, glutamatergic, and cholinergic neural circuits, respectively. We conducted the first systematic review and meta-analysis to compare these TMS indices among patients with AD, mild cognitive impairment (MCI), and healthy controls (HC). Our meta-analyses indicated that RMT, SAI, SICI, and LICI were significantly lower in patients with AD, while ICF did not show a difference in patients with AD compared with HC. In patients with MCI, RMT and SAI were significantly lower than in HC. In conclusion, motor cortical excitability was increased, while cholinergic function was decreased in AD and MCI in comparison with HC and patients with AD had decreased GABAergic and glutamatergic functions compared with HC. Our results warrant further studies to differentiate AD, MCI, and HC, employing multimodal TMS neurophysiology.

Dissociation in Pharmacokinetic Attenuation Between Central Dopamine D2 Receptor Occupancy and Peripheral Blood Concentration of Antipsychotics: A Systematic Review.

OBJECTIVE: The objective of this study was to examine the extent of possible dissociation in pharmacokinetic decay between central dopamine D2 receptor occupancy with antipsychotics and their peripheral blood concentrations. DATA SOURCES: MEDLINE and Embase were searched using the following keywords: (positron emission tomography OR PET OR single-photon emission computed tomography OR SPECT) AND (dopamine OR D2) AND (receptor* OR occupanc*) AND antipsychotic*, with a limitation of English language (last search: December 14, 2019). STUDY SELECTION: The search identified 18 studies that met the following criteria: (1) including patients with schizophrenia spectrum disorders and/or healthy subjects, (2) using positron emission tomography or single-photon emission computed tomography, and (3) examining the time courses of D2 occupancy with antipsychotics and their blood concentrations. DATA EXTRACTION: The ratios of D2 occupancy reduction rate (%) from peak to blood concentration reduction rate (%) from peak (relative attenuation ratio) were calculated. RESULTS: Among the studies, oral risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perospirone, haloperidol, sulpiride, and clozapine and long-acting injectable risperidone and haloperidol were included. Relative attenuation ratios were less than 1, indicating a slower central versus peripheral attenuation, across the time points for all antipsychotic types and doses with only a few exceptions. The ratio decreased in a dose-dependent as well as a peak D2 occupancy-dependent fashion. It contrarily increased in a time-dependent manner. CONCLUSIONS: The findings indicate pharmacokinetic attenuation of antipsychotics was generally slower at the central versus the peripheral level and pose a critical challenge to the current dosing strategy that primarily relies on peripheral pharmacokinetics of antipsychotics.