Etsuo Horikawa

Brain Microbleeds and Global Cognitive Function in Adults Without Neurological Disorder

Background and Purpose— Increasing attention has been paid to associations between cognitive dysfunction and brain microbleeds (MBs). Because all previous studies have investigated patients with neurological disorders, we examined subjects without neurological disorder in order to clarify pathogenic relationships. Methods— A total of 518 consecutive adults without neurological disorder who had undergone health-screening tests of the brain were studied prospectively. Gradient-echo T2*-weighted MRI using a 1.5-T system was used to detect MBs. The Mini-Mental State Examination (MMSE) was administered to determine cognitive functions. MMSE scores <27 or >1.5 SDs below the age-related mean were regarded as subnormal. Results— MBs were found in 35 subjects (6.8%). MMSE score <27 was found in 25 subjects (4.8%), with MMSE score >1.5 SDs below the age-related mean in 34 subjects (6.6%). Univariate analysis showed presence and number of MBs, short duration of education, and severe white matter hyperintensities as significantly associated with subnormal scores. In logistic regression analysis, presence of MBs (odds ratio [OR], 5.44; 95% CI, 1.83 to 16.19) and number of MBs (OR, 1.32; 95% CI, 1.04 to 1.68) still displayed significant associations with MMSE score <27. Logistic regression analysis revealed a significant relationship between presence (OR, 3.93; 95% CI, 1.44 to 10.74) and number (OR, 1.26; 95% CI, 1.01 to 1.59) of MBs and MMSE score >1.5 SDs below the age-related mean. Among MMSE subscores, “attention and calculation” was significantly lower in MB-positive subjects (P=0.017). Conclusions— MBs appear to be primarily associated with global cognitive dysfunction.

Trauma, depression, and resilience of earthquake/tsunami/nuclear disaster survivors of Hirono, Fukushima, Japan

A mega‐earthquake and tsunami struck the northeastern coast of Japan, and many survivors were forced to evacuate to temporary housing due to rising radiation levels. The aims of this study were to investigate the prevalence of symptoms of post‐traumatic stress disorder (PTSD), depression, and poor general health among survivors, to test the predictive roles of resilience on mental and physical health, and to examine the predictive sociodemographic factors on resilience.

Functional brain mapping of actual car driving using [18F]FDG-PET

AimsThis study aims at identifying the brain activation during actual car-driving on the road, and at comparing the results to those of previous studies on simulated car-driving.MethodsThirty normal volunteers, aged 20 to 56 years, were divided into three subgroups, active driving, passive driving and control groups, for examination by positron emission tomography (PET) and [18F]2-deoxy-2-fluoro-D-glucose (FDG). The active driving subjects (n = 10) drove for 30 minutes on quiet normal roads with a few traffic signals. The passive driving subjects (n = 10) participated as passengers on the front seat. The control subjects (n = 10) remained seated in a lit room with their eyes open. Voxel-basedt-statistics were applied using SPM2 to search brain activation among the subgroups mentioned above.ResultsSignificant brain activation was detected during active driving in the primary and secondary visual cortices, primary sensorimotor areas, premotor area, parietal association area, cingulate gyrus, the parahippocampal gyrus as well as in thalamus and cerebellum. The passive driving manifested a similar-looking activation pattern, lacking activations in the premotor area, cingulate and parahippocampal gyri and thalamus. Direct comparison of the active and passive driving conditions revealed activation in the cerebellum.ConclusionThe result of actual driving looked similar to that of simulated driving, suggesting that visual perception and visuomotor coordination were the main brain functions while driving. In terms of attention and autonomic arousal, however, it seems there was a significant difference between simulated and actual driving possibly due to risk of accidents. Autonomic and emotional aspects of driving should be studied using an actual driving study-design.

The Neural Correlates of Driving Performance Identified Using Positron Emission Tomography

Driving is a complex behavior involving multiple cognitive domains. To identify neural correlates of driving performance, [15O]H2O positron emission tomography was performed using a simulated driving task. Compared with the resting condition, simulated driving increased regional cerebral blood flow (rCBF) in the cerebellum, occipital, and parietal cortices. Correlations between rCBF and measurements of driving performance were evaluated during simulated driving. Interestingly, rCBF in the thalamus, midbrain, and cerebellum were positively correlated with time required to complete the course and rCBF in the posterior cingulate gyrus was positively correlated with number of crashes during the task. These brain regions may thus play roles in the maintenance of driving performance.

Immunopathological Significance of Ovarian Teratoma in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Background: The clinical importance of ovarian teratoma in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been established, however investigations of ovarian teratoma in patients with anti-NMDAR encephalitis remain limited. Objective: To clarify differences in NMDAR distribution and lymphocyte infiltration in ovarian teratoma between patients with and without anti-NMDAR encephalitis. Methods: Participants initially comprised 26 patients with ovarian teratomas. NMDAR distribution and lymphocyte infiltration in ovarian teratomas were examined using immunopathological techniques. Clinical, laboratory, and radiological data were compared between patients showing the features of encephalitis. Anti-NMDAR antibodies in the serum and cerebrospinal fluid were also measured in encephalitis patients. Results: Neuronal tissues were obtained from ovarian teratomas in 22 patients (after excluding 4 patients who did not satisfy the inclusion criteria), and the presence of NMDA receptor subunits was revealed in all patients. Lymphocyte infiltration was more frequent in the encephalitis group (n = 3) than in the non-encephalitis group. In particular, dense B-lymphocyte infiltration near neural tissues was observed in the encephalitis group. Conclusions: Differences in lymphocyte infiltration in ovarian teratomas between anti-NMDAR encephalitis and non-encephalitis patients suggest the immunological importance of the ovarian teratoma as the site of antigen presentation in anti-NMDAR encephalitis.

The Control of Postural Stability during Standing is Decreased in Stroke Patients during Active Head Rotation

[Purpose] The aim of this study was to evaluate the effect of active head rotation on postural control in stroke patients during standing as compared with age-matched healthy subjects. [Subjects and Methods] In total, 46 stroke patients and 37 age-matched healthy subjects were recruited for the study. A stabilometer was used to assess postural stability in participants during standing, with or without active head rotation, and with their eyes open or closed. Subjects were asked to stand on a force plate while rotating their head in the yaw plane at a frequency of 1.0 Hz. A metronome was used to maintain the head rotation frequency, and the head rotation range was maintained at a total of 70° during the postural stability examinations. [Results] The control of postural stability during standing with active head rotation was significantly decreased in the stroke group as compared with the healthy group with both the eyes open and closed. No significant differences in relation to standing without head motion were observed between groups. [Conclusion] The findings suggest that postural instability is increased in stroke patients during active head rotation, and therefore, vestibular function in relation to head rotation might be reduced in stroke patients.

Greater Cervical Muscle Fat Infiltration Evaluated by Magnetic Resonance Imaging is Associated With Poor Postural Stability in Patients With Cervical Spondylotic Radiculopathy.

Study Design. A population-based, cross-sectional study. Objective. The aim of this study was to quantitatively evaluate the relationship between static postural stability and fat infiltration within cervical multifidus muscle in patients with cervical spondylotic radiculopathy (CSR). Summary of Background Data. CSR causes denervation by compression of nerve roots. This denervation is detected by fatty infiltration or results in fatty infiltration within muscles. Proprioceptive information in cervical multifidus muscle plays an important role in coordinated movement of postural stability; however, there have been few studies evaluating the relationship between postural stability and fat infiltration within cervical multifidus muscle among CSR patients. Methods. Sixteen CSR patients with C6 injuries and 25 age-matched healthy controls underwent magnetic resonance images to examine bilateral cervical multifidus muscle. For evaluation of fat within muscle, a muscle fat index (MFI) was calculated by using both measurement of cervical multifidus muscle and intermuscular fat. Participants’ postural stability at upright position with eyes-opened and eyes-closed for 60 seconds was examined by a platform. Two parameters, the total length and the area of the center of pressure (COP), were used for evaluation. Results. The CSR group showed significantly poorer postural stability than the control group (eyes-opened the total length; P < 0.05, eyes-closed the total length; P < 0.05, eyes-closed the area; P < 0.05). There were significant group differences at C4, C5, and C6 MFI (P < 0.05). In the CSR group, a correlation analysis demonstrated that the age, C4, C5, and C6 MFI values were significantly associated with the eyes-closed the total length of the COP (P < 0.05). Conclusions. Fat infiltration within muscle could lead to inhibition of normal activity of musculature. The present study suggests that fat within cervical multifidus muscle could directly cause postural instability in static standing, even though the proprioceptive information has normal lower limbs. Level of Evidence: 3

Effects of exercise on the nephron of Goto-Kakizaki rats: morphological, and advanced glycation end-products and inducible nitric oxide synthase immunohistochemical analyses

The current study aimed to examine how exercise affects morphology of the nephron, and localization of advanced glycation end-products (AGEs) and inducible nitric oxide synthase (iNOS) immunoreactivity in diabetic Goto-Kakizaki rats. Four groups of male rats were studied. WIS SED (Wistar rats; sedentary) group served as a control. Other groups were WIS EX (Wistar rats; exercise), GK SED (Goto-Kakizaki diabetic rats; sedentary) and GK EX (Goto-Kakizaki diabetic rats; exercise) groups. The rats in EX groups were subjected to 15weeks of treadmill running at a speed of 15m/min for a total of 30minutes, three times a week. Changes in the structure of renal corpuscles and in the distribution of AGEs- and iNOS-immunoreactive cells of the uriniferous tubules were evaluated. Every parameter of GK EX was significantly different from that of GK SED (area of Bowmans capsules: p<0.001, area of glomeruli: p<0.05 and the occupancy of a glomerulus: p<0.05). These findings suggest that exercise may ameliorate glomerular filtration rate (GFR). The localizations of AGEs and iNOS immunostaining in the uriniferous tubules were similar in each group. Immunohistochemical assays revealed that the number of the AGEs and iNOS immunopositive cells of the proximal tubule of cortico-deep layer in EX groups were markedly greater than those in SED groups and that iNOS expression in GK EX was significantly higher than GK SED (p<0.05). Exercise seems to normalize the GFR and glomerular filtrate absorption from the uriniferous tubules in Goto-Kakizaki diabetic rats with the recovered shape of renal corpuscles and may be involved in the absorption and catabolization of AGEs with iNOS-related reactions for reabsorption.

ELDERLY DRIVING BEHAVIOR AND COGNITIVE FUNCTIONS: Analysis of License Renewal Course Data

This paper describes a study which focused on analyzing the relationship between cognitive functions, driving conditions, and automobile driving behavior in elderly drivers. Data was obtained from elderly drivers who were attending driver license renewal courses at driving schools in order to renew their licenses. The data was drawn driving simulation tests, actual driving behavior assessments at the driving schools, a cognitive function test, and questionnaires.

Relationship between pulmonary function and elevated glycated hemoglobin levels in health checkups: A cross-sectional observational study in Japanese participants

Background Insulin resistance has been associated with cytokines, including interleukin-6 and tumor necrosis factor alpha soluble receptor, both of which are elevated in chronic obstructive pulmonary disease (COPD). Few studies have investigated the relationship between pulmonary function tests using spirometry (PFT) and fasting plasma glucose (FPG) or glycated hemoglobin (HbA1c) levels in Japanese participants. The purpose of this study was to clarify the relationship between PFT in Japanese people who had health checkups and their FPG or HbA1c levels. In the context of preventative medicine, we intend to connect early detection of COPD to an index of blood sugar. Methods From August 2013 through March 2014, 1019 participants underwent health checkups. PFT, FPG, and HbA1c measurements were conducted. HbA1c levels were measured according to National Glycohemoglobin Standardization Program guidelines. Results Participants with FPG ≥100 mg/dL and HbA1c ≥5.6% showed a significantly lower forced expiratory volume in 1 s:forced vital capacity ratio (FEV1/FVC) compared to participants with lower FPG and Hb1Ac levels. Prevalence of FEV1/FVC values <70% in PFT differed significantly depending on sex, age, body mass index, FPG, HbA1c, and smoking habits. Age (≥60 years), HbA1c (≥5.6%), and current or former smoking were associated with FEV1/FVC values <70%. Conclusion In Japan, HbA1c levels were higher in participants with FEV1/FVC values <70% in PFT than in those with FEV1/FVC ≥70%. In preventive medicine, PFT by spirometry should be performed in elderly participants with elevated HbA1c levels who are current or former smokers.