Highly accurate colorectal cancer prediction model based on Raman spectroscopy using patient serum.

BACKGROUND: Colorectal cancer (CRC) is an important disease worldwide, accounting for the second highest number of cancer-related deaths and the third highest number of new cancer cases. The blood test is a simple and minimally invasive diagnostic test. However, there is currently no blood test that can accurately diagnose CRC. AIM: To develop a comprehensive, spontaneous, minimally invasive, label-free, blood-based CRC screening technique based on Raman spectroscopy. METHODS: We used Raman spectra recorded using 184 serum samples obtained from patients undergoing colonoscopies. Patients with malignant tumor histories as well as those with cancers in organs other than the large intestine were excluded. Consequently, the specific diseases of 184 patients were CRC (12), rectal neuroendocrine tumor (2), colorectal adenoma (68), colorectal hyperplastic polyp (18), and others (84). We used the 1064-nm wavelength laser for excitation. The power of the laser was set to 200 mW. RESULTS: Use of the recorded Raman spectra as training data allowed the construction of a boosted tree CRC prediction model based on machine learning. Therefore, the generalized R 2 values for CRC, adenomas, hyperplastic polyps, and neuroendocrine tumors were 0.9982, 0.9630, 0.9962, and 0.9986, respectively. CONCLUSION: For machine learning using Raman spectral data, a highly accurate CRC prediction model with a high R 2 value was constructed. We are currently planning studies to demonstrate the accuracy of this model with a large amount of additional data.

Possible roles of the dominant uncinate fasciculus in naming objects: a case report of intraoperative electrical stimulation on a patient with a brain tumour.

How the dominant uncinate fasciculus (UF) contributes to naming performance is uncertain. In this case report, a patient with an astrocytoma near the dominant UF was given a picture-naming task during intraoperative electrical stimulation in order to resect as much tumourous tissues as possible without impairing the dominant UF function. Here we report that the stimulations with the picture-naming task also provided some insights into how the dominant UF contributes to naming performance. The stimulation induced naming difficulty, verbal paraphasia, and recurrent and continuous perseveration. Moreover, just after producing the incorrect responses, the patient displayed continuous perseveration even though the stimulation had ended. The left UF connects to the inferior frontal lobe, which is necessary for word production, so that the naming difficulty appears to be the result of disrupted word production caused by electrical stimulation of the dominant UF. The verbal paraphasia appears to be due to the failure to select the correct word from semantic memory and the failure to suppress the incorrect word. The left UF is associated with working memory, which plays an important role in recurrent perseveration. The continuous perseveration appears to be due to disturbances in word production and a failure to inhibit an appropriate response. These findings in this case suggest that the dominant UF has multiple roles in the naming of objects.

Protein synthesis in the posterior cingulate cortex in Alzheimer's disease.

BACKGROUND: Neuroimaging studies using (18) F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and single photon emission computed tomography (SPECT) have shown that the posterior cingulate cortex (PCC) is the primary and most prominent area of cerebral metabolic and perfusional decrement in early Alzheimer's disease (AD). We carried out the present preliminary study to investigate whether a decline of cerebral blood flow (CBF) in the PCC in early to moderate AD was accompanied with that of cerebral protein synthesis (CPS). METHODS: We carried out both N-isopropyl-p-[123I] iodoamphetamine SPECT (IMP-SPECT) and L-[methyl-11C] methionine positron emission tomography (MET-PET) in eight AD patients with apolipoprotein E epsilon 4 allele in the early to moderate stage. We also carried out IMP-SPECT in eight healthy controls (HC). We located 32 regions of interest (ROI), and values of regional MET or IMP uptakes were averaged in five regions; the frontal lobe (FL), the parietal lobe (PL), the medial temporal lobe (MTL), PCC and the occipital lobe. Furthermore, the values in the FL, PL, MTL and PCC were divided by values in the occipital areas, and normalized values of regional CBF (rCBF) and CPS (rCPS) were calculated. Then, the rCBF in the FL, PL, MTL and PCC were compared between AD and HC. In addition, the rCBF and rCPS were compared in the FL, PL, MTL and PCC of AD. RESULTS: The rCBF in the PCC, but not in the other three regions, was significantly lower in AD than in HC. The rCBF was significantly lower than rCPS in the PCC, but rCBF and rCPS were comparable in the other three regions in AD. CONCLUSIONS: The CBF reduction in the PCC in AD was partly caused by neuronal loss in the PCC and partly supported the hypothesis that CBF reduction in the PCC was a result of functional deafferentation by neural degeneration in areas other than the PCC.

KIBRA genetic polymorphism influences episodic memory in Alzheimer's disease, but does not show association with disease in a Japanese cohort.

BACKGROUND/AIMS: A single-nucleotide polymorphism (SNP) in the KIBRA gene, rs17070145, was reported to be significantly associated with episodic memory in cognitively normal cohorts. This observation has expanded genetic studies on KIBRA to Alzheimer's disease (AD). Importantly, the association between KIBRA and episodic memory in AD has never been addressed. In this study, we investigated whether the KIBRA rs17070145 SNP influences AD episodic memory and the disease in a Japanese cohort. METHODS: Blood samples from 346 AD patients and 375 normal cognitive controls were collected and genotyped for rs17070145. Episodic memory was measured in 32 AD patients, diagnosed for the first time, by use of the Rivermead Behavioral Memory Test (RBMT). RESULTS: We found that KIBRA C allele carriers scored significantly lower than KIBRA non-C carriers on both RBMT total profile score (p = 0.042, effect size = 0.84) and RBMT total screening score (p < 0.001, effect size = 1.42). The KIBRA gene did not show association with AD in our Japanese cohort. CONCLUSION: Our results evidence a strong association between the KIBRA gene and episodic memory impairment in AD, but show no influence on AD in our Japanese cohort. We propose that KIBRA might have an effect similar to cognitive reserve.

Global cerebral hypoperfusion in preclinical stage of idiopathic normal pressure hydrocephalus.

In patients with idiopathic normal pressure hydrocephalus (iNPH), ventriculomegaly and narrowed subarachnoid spaces at the high convexity appear in magnetic resonance (MR) images before the occurrence of objective symptoms. In addition, quantitative regional cerebral blood flow (rCBF) has been reported to be reduced in iNPH patients with objective symptoms. To determine whether reduced rCBF is responsible for the appearance of symptoms, we compared rCBF in patients with suspected iNPH with no objective triad symptoms (NOS), iNPH patients with apparent objective triad symptoms (AOS) and normal control subjects (NC). Regional CBF was quantified in 35 Regions-of-interest (ROIs) by 123I-IMP single photon emission computed tomography (SPECT) using the autoradiography (ARG) method. Multiple comparisons showed that, in all brain regions examined except for in the frontal white matter, rCBF in the NOS group was significantly lower than that in the NC group, but in all brain regions, not significantly different from that of the AOS group. These results suggest that factors other than rCBF in the resting state are responsible for the occurrence of objective symptoms of iNPH.

[Language and semantic memory impairment in a patient with motor neuron disease and semantic dementia: a case report].

We report the rare case of a 59-year-old man with motor neuron disease and semantic dementia (SD-MND); SD-MND was in a very early stage, and its clinical progression, especially with regard to language impairment, and abnormalities on neuroimages were evaluated for 3 years. The patient complained only of difficulties in recalling names of acquaintances and in writing kanji characters. After 1 year, he experienced difficulty in describing common objects. He developed two-way anomia only in some words, which varied from day to day. His anomia was not category-specific and was noted even with respect to words that describe color. In addition to experiencing difficulty in writing kanji characters, he experienced difficulty in writing kana characters. Muscle atrophy was observed, and he experienced weakness in his limbs, especially in the right upper limb; however, bulbar symptoms were not observed. At this point, he fulfilled the diagnostic criteria for MND. In the next year, semantic memory impairment became apparent, and he was subsequently diagnosed with SD. Deterioration in his ability to name objects in all categories, except body parts, was noted. Further, the ability of writing both kana and kanji characters was increasingly impaired. He developed bulbar symptoms and experienced increased muscle weakness. The characteristics of this patient differed from those of SD patients without MND with regard to the difficulty in writing kana characters and naming colors even though the SD-MND was in the early stage. Further, the pattern of brain hypoperfusion was different from that observed for SD patients without MND. In the case of this patient, brain hypoperfusion was found not only in the left anterior temporal lobe but also in the frontal lobe. The characteristics of his language symptoms might be related to the specific pattern of brain hypoperfusion, which might be commonly observed in patients with dementia and MND.

Neuroimaging studies in patients with Charles Bonnet Syndrome.

Charles Bonnet Syndrome (CBS) is characterized by complex formed and recurrent visual hallucinations in psychologically normal people, and is often associated with eye pathology. Many psychiatrists have taken an interest in CBS because this syndrome could provide clues to the mechanisms underlying visual hallucinations. In the present paper, we review previous neuroimaging studies in patients with CBS and summarize the results of these studies. There could be a fundamental dysfunction in the primary and secondary visual cortices in some patients with CBS, and transient cortical activation occurs in the inferior lateral temporal cortex during the appearance of visual hallucinations in CBS patients. External visual stimuli are perceived in the retina and are transmitted to the primary visual cortex (Brodmann area (BA) 17). The stimuli are transmitted from BA 17 to the secondary visual cortex (BA 18) and then to the visual association cortices (BA 19 and BA 37). In general, our perception of external visual stimuli normally has an inhibitory effect on the endogenous activation of the visual cortex. Visual loss due to certain conditions, of which eye pathology is the most commonly postulated in CBS patients, produces a state of sensory deprivation that releases the visual cortex from regulation by external stimuli, resulting in visual hallucinations (cortical release phenomenon). The results of previous neuroimaging studies suggest that the cortical release phenomenon hypothesis for the occurrence of visual hallucinations in patients with CBS is plausible. In addition, the results indicate that not only eye pathology, but also dysfunction in the primary and secondary visual cortices could result in deprivation of external visual stimuli.

Association study of the G72 gene with schizophrenia in a Japanese population: a multicenter study.

G72 is one of the most widely tested genes for association with schizophrenia. As G72 activates the D-amino acid oxidase (DAO), G72 is termed D-amino acid oxidase activator (DAOA). The aim of this study is to investigate the association between G72 and schizophrenia in a Japanese population, using the largest sample size to date (1774 patients with schizophrenia and 2092 healthy controls). We examined eight single nucleotide polymorphisms (SNPs), which had been associated with schizophrenia in previous studies. We found nominal evidence for association of alleles, M22/rs778293, M23/rs3918342 and M24/rs1421292, and the genotype of M22/rs778293 with schizophrenia, although there was no association of allele or genotype in the other five SNPs. We also found nominal haplotypic association, including M15/rs2391191 and M19/rs778294 with schizophrenia. However, these associations were no longer positive after correction for multiple testing. We conclude that G72 might not play a major role in the risk for schizophrenia in the Japanese population.

Association between quality of life of demented patients and professional knowledge of care workers.

Professional knowledge about dementia and care methods is necessary for the appropriate care of demented people. In this study, the quality of life of 91 demented people staying at 12 care institutions was evaluated with the Quality of Life Questionnaire for Dementia (QOL-D). The amount of professional knowledge was evaluated in 140 staff members who took care of the patients using the professional knowledge test (PKT), and the mean PKT score was calculated for each institution (professional knowledge of institution). A positive significant correlation was observed between the QOL-D score and the professional knowledge of institution. The correlation remained significant when age, sex, and severity of dementia of demented patients were partialled out. This result indicated that the quality of life of demented people was better at institutions with staff members having more professional knowledge, indicating the importance of education of staff members and the possibility that such education improves the quality of life of the demented people.

Validation of grading scale for evaluating symptoms of idiopathic normal-pressure hydrocephalus.

BACKGROUND/AIMS: We developed an idiopathic normal-pressure hydrocephalus grading scale (iNPHGS) to classify a triad of disorders (cognitive impairment, gait disturbance and urinary disturbance) of iNPH with a wide range of severity. The purpose of this study was to assess the reliability and validity of this scale in 38 patients with iNPH. RESULTS: The interrater reliability of this scale was high. The iNPHGS cognitive domain score significantly correlated with the cognitive test scores, including the Mini-Mental State Examination (MMSE), the gait domain score with the Up and Go Test and Gait Status Scale scores, and the urinary domain score with the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. The MMSE, Gait Status Scale and ICIQ-SF scores significantly improved in patients whose iNPHGS scores improved after CSF tapping but not in those whose iNPHGS scores did not improve after CSF tapping. Fourteen of the 38 patients received shunt operations. In these 14 patients, changes in the iNPHGS cognitive and urinary domains after CSF tapping were significantly associated with the changes after the shunt operation.

Cognitive impairment in patients with idiopathic normal pressure hydrocephalus.

Cognitive impairment in patients with idiopathic normal pressure hydrocephalous (iNPH) has not been clearly documented. We performed standardized neuropsychological assessments of 21 patients with iNPH and of 42 patients with Alzheimer's disease (AD) matched to the patients with iNPH 2:1 by age, sex, and Mini-Mental State Examination score. Compared with the AD group, the iNPH group scored significantly higher on the orientation subtest of the Alzheimer's Disease Assessment Scale and on the general memory and delayed recall subtests of the Wechsler Memory Scale-Revised (WMS-R), and significantly lower on the attention/concentration subtest of the WMS-R and on the digit span, arithmetic, block design and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised. The impairment of frontal lobe functions is disproportionately severe and memory impairment is disproportionately mild in patients with iNPH compared with AD. Recognition of these features contributes to an early diagnosis, which can lead to a better prognosis.

Association between cognitive impairment and gait disturbance in patients with idiopathic normal pressure hydrocephalus.

We compared the scores of the Frontal Assessment Battery (FAB), initial fluency subtest, category fluency subtest and subtests of the Mini-Mental State Examination (MMSE) between patients with idiopathic normal pressure hydrocephalus (iNPH) and age-, sex- and MMSE-matched patients with Alzheimer's disease (AD). In patients with iNPH, the time and number of steps required to go and come back a 10-meter distance were measured (Walking test) and the associations between the scores of the cognitive tests and the performance of the Walking test were evaluated. The scores of the FAB and initial fluency subtest in patients with iNPH were significantly lower than those in patients with AD. The scores of the FAB, initial fluency subtest and serial 7 subtest of the MMSE significantly correlated with the two scores of the Walking test in patients with iNPH. The present results indicate that frontal lobe functions were impaired in patients with iNPH and that cognitive impairment was closely associated with gait disturbance in patients with iNPH.

Neural basis of fear conditioning induced by video clip: positron emission tomography study.

In patients with post-traumatic stress disorder (PTSD), re-experiencing the trauma is often induced by external cues in the environment. The cues, which were emotionally neutral for the patients before the traumatic event, become fearful ones after the event. This phenomenon is considered to be associated with fear conditioning. The paradigm was set up so that the emotionality changes in the patients with PTSD would be reproduced, and the regional cerebral blood flow (rCBF) measured with positron emission tomography (PET) was compared during exposure to the same stimuli before and after acquisition of fear conditioning. Ten healthy male subjects were asked to look at some emotionally neutral photos, then to watch a video with fearful content that also contained images similar to that presented in the photos, and afterwards to look at the photos again. Five of the 10 subjects felt that the object in the photos was more fearful after watching the video than before, and they were considered to have acquired fear conditioning. In those five subjects, the rCBF in the right amygdala and the left posterior cingulate gyrus after acquisition of fear conditioning significantly increased relative to the rCBF before conditioning. Thus, these regions seem to have a critical role in fear conditioning.

Everyday memory impairment of patients with mild cognitive impairment.

We evaluated everyday memory impairment in 24 patients with mild cognitive impairment (MCI) with the Rivermead Behavioral Memory Test (RBMT) and compared the scores with those of 48 age-, sex- and education-matched normal controls (NC) and 48 age-, sex- and education-matched Alzheimer disease (AD) patients. Overall everyday memory was impaired in MCI patients but the severity was milder than that in AD patients. The MCI patients showed impairment of everyday memory tasks requiring delayed recall. But they could normally perform tasks immediately after memorizing, except for recalling and retracing a simple new route. The total Profile score correctly classified 100% of the MCI patients and 91.7% of NC, thus demonstrating the usefulness of the RBMT for diagnosing MCI patients. Prospective memory tasks were not useful for detecting the patients with MCI.

Effectiveness of a clinical pathway for the diagnosis and treatment of dementia and for the education of families.

AIMS: Clinical pathways (CPs) are rarely used in the treatment of dementia. We established a CP for a series of medical practices (diagnosis, treatment, establishment of a care system, and caregiver education) for patients with dementia hospitalized for a three-week period, and evaluated its usefulness. METHODS: The length of hospital stay and hospital costs were compared between 23 consecutive patients with dementia hospitalized and treated using a CP and 20 controls treated by conventional medical practice without using a CP in a special ward for dementia patients. In the CP group, at the time of discharge, primary caregivers, physicians, and nurses were given a questionnaire to obtain their comments about the impression of treatment with the CP. RESULTS: The questionnaire survey indicated that the CP deepened the caregiver's understanding of the sequence of medical practices for the inpatient, the disorders of the inpatient, the treatment methods, and the methods for coping with the disorder. The CP was also useful for facilitating inpatient medical practice and promoting the establishment of a care system after discharge. The use of the CP significantly shortened the length of hospital stay and decreased hospital costs during hospitalization but increased the amount of work per day and made the medical staff feel that their freedom to choose medical procedures had been restricted. CONCLUSIONS: The CP was useful for execution of inpatient medical practices for patients with dementia.