Makoto Sasaki

• MD PhD
• Professor at Iwate Medical University

Childhood obesity is a growing global health concern, contributing to numerous non-communicable diseases and long-term health complications. The prevalence of obesity in children and adolescents continues to rise, driven by complex interactions among various factors. The key risk factors include both environmental and genetic influences. Environmen...

Background and purpose: Post-carotid endarterectomy (CEA) cerebral hyperperfusion (CH) can cause intracerebral hemorrhage and cognitive decline. Alterations in susceptibility in response to acetazolamide (ACZ) on 7T MRI quantitative susceptibility mapping (QSM) detects elevated CBV occurring due to impaired cerebrovascular autoregulation. We explo...

Background: Enlarged perivascular spaces (PVS), a marker of cerebral small vessel disease (SVD), are considered to increase the risk of stroke. However, there is limited data on the benfits and harms of antithrombotic agents in patients with PVS. We assessed the association of PVS with the risk of hemorrhagic or ischemic events in patients receivin...

Objectives: Cortical superficial siderosis (cSS) has been implicated as a putative hemorrhagic MRI finding of cerebral small vessel disease (SVD) related to cerebral amyloid angiopathy. Few reports have examined the association between cSS and antithrombotic-related clinical events. The aim of this study is to investigate the association of cSS wit...

OBJECTIVE Plaque composition, but not degree of stenosis, may play a key role in the development of recurrent ischemic events in patients with symptomatic mild (< 50%) carotid artery stenosis. This multicenter prospective cohort study was aimed to determine their clinical and radiological features and to evaluate the benefits of carotid endarterect...

OBJECTIVE Studies have demonstrated the effectiveness of hydrogel-coated coils (HGCs) to achieve the composite endpoint of decreased recanalization rates and greater safety. Herein, the authors aimed to assess the true ability of second-generation HGCs to prevent recanalization. METHODS This randomized controlled study, the HYBRID (Hydrocoil Versu...

Background The association of Mini-Mental State Examination (MMSE) with microstructure of individual regions across the entire brain remains unexplored. Purpose To investigate the relationship between cognitive function and the microstructure of each brain region in the gray matter using diffusion kurtosis imaging (DKI) in older adults with mild c...

Obesity and overweight, fundamental components of the metabolic syndrome, predispose individuals to lifestyle-related diseases. The extent to which adopting healthy lifestyles can reduce obesity risk, even in those with a high genetic risk, remains uncertain. Our aim was to assess the extent to which lifestyle modifications can improve outcomes in...

Background and purpose: Quantitative susceptibility mapping (QSM) has been proposed to assess intraplaque hemorrhage (IPH) in the carotid artery. The purpose of this study was to compare the diagnostic accuracy of preoperative QSM with that of the conventional T1-weighed (T1W) three-dimensional (3D)-FSE sequence for detecting IPH in cervical ICA s...

BACKGROUND AND IMPORTANCE A double-layer micromesh stent is designed for the treatment of carotid artery stenosis that has been reported to potentially provide a flow diversion effect. However, the actual flow diversion effect of stents remains unclear. Here, we present a case of a growing saphenous vein graft (SVG) aneurysm treated with the placem...

Background and Purpose – Plaque composition, but not stenosis degree, may play a key role in the development of recurrent ischemic events in patients with symptomatic, mild (<50%) carotid stenosis. This multi-center prospective cohort study was aimed to determine their clinical and radiological features and to evaluate the benefits of carotid endar...

Background: Genetic epidemiological evidence for the kidney function traits in East Asian population including Japanese remain still relatively unclarified. Especially, the number of GWASs for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancest...

Fatigue of the muscles involved in swallowing is regarded as one of the factors that increase the risk of aspiration and choking. However, an objective method for assessing muscle fatigue in swallowing-related muscles during the act of swallowing, which consists of voluntary and involuntary reflexive movements and lasts about 1 s, has yet to be est...

Genetic testing is key in modern healthcare, particularly for monogenic disorders such as familial hypercholesterolemia. This Tohoku Medical Megabank Project study explored the impact of first-degree relatives’ dyslipidemia history on individual responses to familial hypercholesterolemia genomic results. Involving 214 participants and using Japan’s...

Although cognitive decline after carotid endarterectomy (CEA) is mainly related to postoperative cerebral hyperperfusion, approximately 30% of patients with cognitive decline do not have postoperative cerebral hyperperfusion. In patients with acute ischemic events, the development of cognitive decline after such events is associated with the presen...

Introduction: While patients who experience improved cognition following carotid endarterectomy (CEA) typically demonstrate restored brain perfusion after the procedure, it is worth noting that less than 50% of patients in whom postoperative cerebral blood flow (CBF) restoration is achieved actually show improved cognition after postoperatively. T...

An East Asian–specific variant on aldehyde dehydrogenase 2 ( ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. Th...

Background: We investigated the clinical effect of intravenous thrombolysis using a magnetic resonance imaging (MRI)-guided approach in cardioembolic stroke (CE) patients with unknown time of onset. Methods and Results: This subanalysis of the THAWS trial assessed the efficacy and safety of alteplase 0.6 mg/kg in CE patients with unknown time of on...

Genome-wide association studies have been employed to develop numerous risk prediction models using polygenic risk scores (PRSs) for multifactorial diseases. However, healthcare providers lack confidence in their understanding of PRS risk stratification for multifactorial diseases, which underscores the need to assess the readiness of PRSs for clin...

Objective To determine the excess risk of antithrombotic‐related bleeding due to cerebral small vessel disease (SVD) burden. Methods In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline...

Modern medicine is increasingly focused on personalized medicine, and multi-omics data is crucial in understanding biological phenomena and disease mechanisms. Each ethnic group has its unique genetic background with specific genomic variations influencing disease risk and drug response. Therefore, multi-omics data from specific ethnic populations...

Flow diverters (FDs) are utilized for a wide range of aneurysms, but show safety issues such as adverse interactions with static magnetic fields (displacement force and torque) and radiofrequency-induced heating during magnetic resonance imaging (MRI). The present study aimed to assess these adverse interactions in a 7-tesla (7T) static magnetic fi...

Background Flow-mediated dilation (FMD) measures vascular endothelial function by evaluating the vasodilatory response of blood vessels to increased blood flow. Nevertheless, the association between FMD and stroke incidence in a general population remains unclear. This study investigated the association between vascular endothelial function and str...

Purpose: To develop a method for predicting amyloid positron emission tomography (PET) positivity based on multiple regression analysis of quantitative susceptibility mapping (QSM). Materials and methods: This prospective study included 39 patients with suspected dementia from four centers. QSM images were obtained through a 3-T, three-dimension...

Background and aim: Many patients have endoscopic evidence of recurrent Crohn's disease (CD) at one year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients. Methods: We retrospectively enrolled...

Background and Aims Japan has experienced 8 waves of the coronavirus disease 2019 (COVID-19) outbreak over the past 3 years, resulting in an increasing number of deaths and incidence of severe infections. This study aimed to analyze the data from the Japanese inflammatory bowel disease (IBD) patients with COVID-19 registry (J-COSMOS) up to the eigh...

Background Whether past disaster experiences affect the association between changes in social isolation and depressive symptoms is largely unknown. This study examined the association between changes in social isolation and depressive symptoms among survivors who experienced earthquake damage in the aftermath of the Great East Japan Earthquake (GEJ...

Observational studies suggest that abnormal glucose metabolism and insulin resistance contribute to colorectal cancer; however, the causal association remains unknown, particularly in Asian populations. A two-sample Mendelian randomisation analysis was performed to determine the causal association between genetic variants associated with elevated f...

Knowledge of genetics is essential for understanding the results of genetic testing and its implications. Recent advances in genomic research have allowed us to predict the risk of onset of common diseases based on individual genomic information. It is anticipated that more people will receive such estimates of risks based on their genomic data. Ho...

Oral care is key to maintaining overall health. Elderly people and people with disabilities who require nursing care can have difficulty in brushing their teeth effectively and may require the assistance of a caregiver. However, to date, an effective method for teaching toothbrushing skills to caregivers and a training system that can be implemente...

Xanthine oxidoreductase (XOR) and its products contribute to the development of chronic inflammation and oxidative stress. Excessive XOR activity is believed to promote inflammatory responses and atherosclerotic plaque formation, which are major cardiovascular risk factors. The mechanisms of XOR activity in the development and progression of cardio...

People who experience natural disasters have a high risk of developing cardiovascular diseases. We investigated the association between the extent of house collapse and urine sodium-to-potassium (UNa/K) ratio of 2011 Great East Japan Earthquake victims. We used the baseline survey data of the Tohoku Medical Megabank Project Community-Based Cohort S...

Objective: High density lipoprotein (HDL) exerts an anti-atherosclerotic effect via reverse cholesterol transport (RCT). Several phases of RCT are transcriptionally controlled by Liver X receptors (LXRs). Although macrophage LXRs reportedly promote RCT, it is still uncertain whether hepatic LXRs affect RCT in vivo. Approach and Results: To address...

Objectives One of the risk factors for cerebral hyperperfusion following carotid endarterectomy (CEA) is a chronic reduction in cerebral perfusion pressure due to internal carotid artery (ICA) stenosis, which is clinically detected as increased cerebral blood volume (CBV). The perfusion fraction (f) is one of the intra-voxel incoherent motion (IVIM...

Background: Centenarians and supercentenarians with exceptional longevity are excellent models for research towards improvements of healthy life expectancy. Extensive research regarding the maintenance and reduction of epigenetic age has provided insights into increasing healthy longevity. To this end, we explored the epigenetic signatures reflect...

Background: Cerebral small vessel disease (SVD) has received attention as a risk stratification tool for antithrombotic-related intracranial hemorrhage but may also be a predictor for bleeding in other organs. Purpose: To determine the excess risk of antithrombotic-related bleeding due to cerebral SVD burden. Methods: Patients with cerebrovascular...

Background: While type 2 diabetes (T2D) is a major risk for ischemic stroke, the associated vessel wall characteristics remain essentially unknown. This study aimed to clarify intracranial vascular changes on three-dimensional vessel wall imaging (3D-VWI) using fast spin echo by employing 7Tesla (7T) magnetic resonance imaging (MRI) in T2D patient...

Considerable effort has been spent on lowering and maintaining the epigenetic age. However, the extent to which epigenetic age fluctuates under normal conditions is poorly understood. Therefore, we analyzed methylation data from monocytes and peripheral blood mononuclear cells collected from two Japanese men. The ranges of the Pan-tissue, Skin and...

Flip angle (FA) measurements using the actual flip angle imaging (AFI) method may induce significant errors in ultrahigh fields. We aimed to develop a method for detecting errors in FA measurements using phase information at 7 tesla. We performed computer simulations to elucidate the relationship between the FA calculation errors and the phase diff...

Lecithin-cholesterol acyltransferase (LCAT) plays a significant role in the progression from premature to mature high-density lipoprotein (HDL) in circulation. Consequently, primary or secondary LCAT deletion or reduction naturally results in low serum HDL cholesterol levels. Recently, rare cases of acquired HDL deficiency with LCAT autoantibodies...

Decreased swallowing function increases the risk of choking and aspiration pneumonia. Videofluoroscopy and computed tomography allow for detailed observation of the swallowing movements but have radiation risks. Therefore, we developed a method using surface electromyography (sEMG) to noninvasively assess swallowing function without radiation expos...

Purpose : A meta-analysis suggests a relationship between abnormal glucose metabolism and primary open-angle glaucoma (POAG); however, the causal association between them remains controversial. We therefore conducted a Mendelian randomization (MR) study to assess the causal association between genetically predicted glycemic traits and the risk of P...

Elevated levels of circulating high-sensitivity cardiac troponin T (hs-cTnT) are associated with cardiovascular disease. This study aimed to examine whether hs-cTnT levels are associated with incident stroke in the elderly population. The Iwate Tohoku Medical Megabank Organization pooled participant data for a community-based cohort study (n = 15,0...

The associations between blood lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and low-density lipoprotein cholesterol (LDL-C), and colorectal cancer risk are controversial. We evaluated potential causal relationships between blood lipids and colorectal cancer risk. Using the baseline data from...

Background Bone metabolic dysregulation plays an important role in the pathogenesis of atherosclerosis; however, whether its markers contribute to coronary artery disease (CAD) risk in the general population remains unclear. Therefore, this study aimed to analyze the association between bone metabolic markers and CAD risk score in the general Japan...

The assessment of cerebral perfusion and metabolism is crucial in evaluating the indications for bypass surgery and other revascularization procedures in patients with chronic hemodynamic cerebral ischemia. In particular, it is necessary to detect misery perfusion(Powers' stage II), which is defined as an increased oxygen extraction fraction and in...

Background Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide, accounting for approximately 4% of all cancers. More than 70% of RCC are clear cell RCC (ccRCC). To date, no reliable biomarkers for the detection of ccRCC have been identified. The aim of this study was to identify blood-based DNA methylation (DNAm) markers for t...

Background Superficial siderosis is a rare neurodegenerative disease caused by hemosiderin deposition on the brain surface. Although the efficacy of the iron chelator—deferiprone—in superficial siderosis has recently been documented, a comparative study of patients who underwent surgical ablation of their bleeding source and subsequently received t...

This study aimed to investigate whether social isolation is associated with mortality, together with the effect of the Great East Japan Earthquake on mortality, due to the social isolation of community residents living in the affected areas, using data from the Tohoku Medical Megabank Project Community-Based Cohort Study. A total of 22,933 particip...

Background: 17 O-labeled water (PSO17) is a contrast agent developed to measure brain water dynamics and cerebral blood flow. Purpose: To evaluate the safety and feasibility of PSO17. Study type: Prospective study. Subjects: A total of 12 male healthy volunteers (23.1 ± 1.9 years) were assigned to three groups of four subjects: placebo (norm...

Purpose: Studies on quantitative susceptibility mapping (QSM) have reported an increase in magnetic susceptibilities in patients with Alzheimer's disease (AD). Despite the pathological importance of the brain surface areas, they are sometimes excluded in QSM analysis. This study aimed to reveal the efficacy of QSM analysis with brain surface corre...

Background The aim of this study was to determine the associations of cerebral small vessel disease (SVD) burden with renal dysfunction and albuminuria in patients taking oral antithrombotic agents. Methods and Results Patients who newly started or continued taking oral antiplatelets or anticoagulants were enrolled in a prospective, multicenter, o...

Aim: This study aimed to assess the potential effect of prior antithrombotic medication for thrombolysis in an unknown onset stroke. Methods: This was a predefined sub-analysis of the THAWS trial. Stroke patients with a time last known well ＞4.5 h who had a DWI-fluid-attenuated inversion recovery mismatch were randomly assigned (1:1) to receive...

Objectives: Voxel-based morphometry (VBM) is widely used to quantify the progression of Alzheimer's disease (AD), but improvement is still needed for accurate early diagnosis. We evaluated the feasibility of a novel diagnosis index for early diagnosis of AD based on quantitative susceptibility mapping (QSM) and VBM. Methods: Thirty-seven patient...

Background The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severit...

Background The spread of coronavirus disease 2019 (COVID-19) had a major impact on the health of people worldwide. The clinical background and clinical course of inflammatory bowel disease (IBD) among Japanese patients with COVID-19 remains unclear. Methods This study is an observational cohort of Japanese IBD patients diagnosed with COVID-19. Dat...

Background Tenecteplase has higher fibrin specificity with a longer half-life and the potential to achieve higher rates of recanalization than alteplase. A critical limitation of tenecteplase is no commercial use in Japan and no experience with its administration to Japanese patients. Hypothesis Tenecteplase is superior to alteplase in achieving r...

Previous genome-wide association studies (GWAS) of stroke, the second leading cause of death, have been conducted in populations of predominantly European ancestry.1,2 We undertook cross-ancestry GWAS meta-analyses of stroke and its subtypes in 110,182 stroke patients (33% non-European) and 1,503,898 control individuals of five ancestries from popu...

Background The severity of chronic cerebral ischemia can be assessed using cerebrovascular reactivity (CVR) to acetazolamide (ACZ) challenge, which is measured by single-photon emission computed tomography (SPECT); however, this is an invasive method. We investigated whether intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) can a...

Background One of the fundamental assumptions of DNA methylation in clinical epigenetics is that DNA methylation status can change over time with or without interplay with environmental and clinical conditions. However, little is known about how DNA methylation status changes over time under ordinary environmental and clinical conditions. In this s...

Background: High density lipoprotein (HDL) exerts anti-atherogenic functions including cholesterol efflux capacity and anti-oxidative activities. Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular disease via inflammation and oxidative stress. However, HDL functions in patients with OSA remains to be elucidated. We t...

Background and aims: Mosaic chromosomal alterations (mCAs) increase the risk for hematopoietic malignancies and may be risk factors for several other diseases. Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are associated with mCAs, and patients may be at risk for hematopoietic malignancy developmen...

Background The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. Aims This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. Methods In the primary sur...

Elevated serum uric acid (SUA)—hyperuricemia—is caused by overproduction of urate or by its decreased renal and/or intestinal excretion. This disease, which is increasing in prevalence worldwide, is associated with both gout and metabolic diseases. Several studies have reported relationships between apolipoprotein E ( APOE ) haplotypes and SUA leve...

Recently, dysphagia associated with aging has become more a serious concern. The current study therefore sought to develop a novel method for evaluating swallowing function that focused on changes in the movement of swallowing-related organs, which slightly occur depending on swallowing conditions, using surface electromyography (sEMG) signals from...

Background and aim: We determined to investigate the incidence and clinical impact of new cerebral microbleeds (CMBs) after intravenous thrombolysis (IVT) in patients with acute stroke. Methods: The THAWS was a multicenter, randomized trial to study the efficacy and safety of IVT with alteplase in patients with wake-up stroke or unknown onset st...

Certain large genome cohort studies attempt to return the individual genomic results to the participants; however, the implementation process and psychosocial impacts remain largely unknown. The Tohoku Medical Megabank Project has conducted large genome cohort studies of general residents. To implement the disclosure of individual genomic results,...

Early reperfusion after endovascular thrombectomy is associated with an improved outcome in ischemic stroke patients; however, the time dependency in elderly patients remains unclear. We investigated the time–outcome relationships in different age subgroups. Of 2420 patients enrolled in the RESCUE-Japan Registry 2 study, a study based on a prospect...

An East Asian-specific variant on aldehyde dehydrogenase 2 ( ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis in up to 40,679 individuals from Japanese populations to uncover additional loci associated with alcohol consumption in an rs671...

Several basic experimental studies have demonstrated that statins have beneficial effects for intracranial aneurysm (IA). Clinical studies on unruptured IAs, however, remain limited to four retrospective studies that have reached different conclusions. This study was the first open-label, multicenter, randomized controlled trial to assess the preve...

Purpose It is unclear what kind of modifiable lifestyle factors are associated with long-time weight gain in adulthood. To clarify the lifestyle behavior related to body weight gain since the age of 20 years, we explored the lifestyle risk factor, independently associated with excessive weight gain after 20 years of age as compared to those in subj...

Background: Social isolation and mental health issues have become a severe problem in disaster areas in the Great East Japan Earthquake. This study examined whether the combination of the house damage and social isolation or the combination of the death of family members and social isolation is associated with depressive symptoms among survivors u...

Background Anti-tumour necrosis factor (TNF) agents are the mainstay of long-term treatment for refractory ulcerative colitis. However, long-term use of anti-TNF therapy might lead to an increased risk of malignancy or infection. To date, no randomised controlled trial has evaluated whether anti-TNF agents can be safely discontinued in patients wit...

A correction to this paper has been published: https://doi.org/10.1007/s10157-021-02053-4

Purpose: To reveal effects of improvement of masseter muscle activity on brain function in elderly people wearing complete dentures. Methods: Subjects were 14 edentulous patients with a chief complaint of the inconvenience of their complete dentures. The surface electromyographic (EMG) activity of the masseter muscles was measured. Brain activities...

We investigated the spatial and temporal variations of flip-angle (FA) distributions in the human brain from multiple scans, using an eight-channel parallel transmission (pTx) system at 7T. Nine healthy volunteers were scanned in five sessions using three radiofrequency excitation techniques each time: circular polarization (CP), static pTx, and dy...

Background and purpose: To assess the potential effect of prior antithrombotic medication for thrombolysis using alteplase at 0.6mg/kg in unknown onset stroke. Methods: This was a prespecified sub-analysis of a THAWS trial (an investigator-initiated, multicenter, randomized, open, blinded-endpoint trial). Stroke patients with a time last-known-well...

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two‐sample Mendelian randomization (MR) study was performed using 68 single nucleotide polymor...

The purpose of this study was to investigate the association between xanthine oxidoreductase (XOR) activity and a high risk of cardiovascular disease (CVD) in a general Japanese population. The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture. The cardiova...

Background Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called “mesalamine allergy,” which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the gen...

Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a s...

Formalin‐fixed paraffin‐embedded (FFPE) tissues are promising biological resources for genetic research. Recent improvements in DNA extraction from FFPE samples allowed the use of these tissues for multiple sequencing methods. However, fundamental research addressing the application of FFPE‐derived DNA for targeted‐bisulfite sequencing (TB‐seq) is...

Background and Purpose We determined to identify patients with unknown onset stroke who could have favorable 90-day outcomes after low-dose thrombolysis from the THAWS (Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg) database. Methods This was a subanalysis of an investigator-initiated, multicenter, randomized...

Background Studies on quantitative susceptibility mapping (QSM) have reported increased susceptibility in the brain of Alzheimer’s disease patients, reflecting the pathological accumulation of iron in Aβ plaques. Previously, we revealed moderate correlation between increased magnetic susceptibility in QSM and Aβ deposition in PET by using a region...

Background Cardiovascular disease (CVD) is a major cause of mortality worldwide. High-sensitivity cardiac troponin T (hs-cTnT) is released into the bloodstream due to cardiomyocyte damage and is associated with a high CVD risk. This study aimed to investigate hs-cTnT-related genetic variation and to examine whether this is an associated risk factor...

In the Tohoku Medical Megabank project, genome and omics analyses of participants in two cohort studies were performed. A part of the data is available at the Japanese Multi Omics Reference Panel (jMorp; https://jmorp.megabank.tohoku.ac.jp) as a web-based database, as reported in our previous manuscript published in Nucleic Acid Research in 2018. A...