Identification of salivary metabolic biomarker signatures for oral tongue squamous cell carcinoma.

OBJECTIVE: To identify the salivary metabolites associated with squamous cell carcinoma of the tongue to develop easy and non-invasive potential biomarkers for disease diagnosis. DESIGN: Initially, the study utilized untargeted metabolomics to analyze 20 samples of tongue squamous cell carcinoma and 10 control samples. The objective was to determine the salivary metabolites that exhibited differential expression in tongue squamous cell carcinoma. Then the selected metabolites were validated using targeted metabolomics in saliva samples of 100 patients diagnosed with squamous cell carcinoma of the tongue, as well as 30 healthy control individuals. RESULTS: From the analysis of untargeted metabolomics, 10 metabolites were selected as potential biomarkers. In the subsequent targeted metabolomics study on these selected metabolites, it was observed that N-Acetyl-D-glucosamine, L-Pipecolic acid, L-Carnitine, Phosphorylcholine, and Deoxyguanosine exhibited significant differences. The receiver operating characteristic curve analysis indicates a combination of three important metabolites such as N-Acetyl-D-glucosamine, L-Pipecolic acid and L-Carnitine provided the best prediction with an area under the curve of 0.901. CONCLUSIONS: The present result reveals that the N-Acetyl-D-glucosamine, L-Pipecolic acid and L-Carnitine are the signature diagnostic biomarkers for oral tongue squamous cell carcinoma. These findings can be used to develop a rapid and non-invasive method for disease monitoring and prognosis in oral tongue cancer.

Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland: Not so indolent a neoplasm?

A 58-year-old female, a known diabetic and hypertensive, presented with left-sided swelling on the anterior aspect of the neck of 1-year duration, which was rapidly increasing in size for the past 6 months. She was on Eltroxin for hypothyroidism for the past 1 year. Computed tomography study of the neck showed a nodule in the left lobe of thyroid which on fine-needle aspiration was suspicious for malignancy. Total thyroidectomy with left posterolateral lymph node dissection was done. Histopathological examination showed sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) of the thyroid gland with lymph node metastasis. SMECE of the thyroid was initially thought to be a low-grade malignancy with indolent clinical behavior. However, our case showed extra thyroidal spread with lymph node metastasis, necessitating adjuvant therapy for our patient. Such aggressive behavior has been noted in few earlier case reports also.

Significance of incidentally detected thyroid tissue in lymph nodes of neck dissections in patients with head and neck carcinoma.

BACKGROUND: The incidental discovery of thyroid tissue in lymph nodes of neck dissections performed for a separate primary head and neck cancer is an unusual clinical entity. Careful screening of large number of lymph nodes in the neck dissection specimens by the pathologist is critical in picking up such cases. There is controversy regarding clinical significance of such incidentally detected thyroid tissue in cervical nodes as to whether these represent benign inclusions or whether they represent metastatic focus of an underlying thyroid cancer. The appropriate clinical approach in such cases is less clear because it occurs in the context of another malignancy, usually squamous cell carcinomas with a more aggressive potential. MATERIALS AND METHODS: On reviewing the records of 1602 neck dissections done in patients with head and neck cancers over the years 2007-2011, this study identified 5 patients with incidentally detected thyroid tissue with features of malignancy in cervical lymph nodes. Subsequent thyroidectomies done in 4 cases showed primary thyroid cancer. CONCLUSION: The study's results emphasize the need for the clinician to do an accurate reevaluation and follow-up of patients with incidental occult metastasis for detection of primary thyroid tumor. A thorough sampling and screening of lymph nodes in neck dissection specimens by the pathologist is also essential. Incidentally discovered thyroid tissue in cervical lymph nodes need not always be benign inclusions. Aggressive therapy, however, may not be needed in all cases.

Dementia associated mental and behavioural disturbances in elderly people in the community: findings from the first Nakayama study.

OBJECTIVE: To determine the prevalence of mental and behavioural disturbances associated with dementia in elderly people living in the Japanese community of Nakayama. METHODS: A door to door three phase population survey was carried out on all persons aged 65 years and older living at home. The study included a psychiatric interview, neurological and neuropsychological examination, and cranial computed tomography. Participants with dementia were rated on the neuropsychiatric inventory. RESULTS: Of 1438 inhabitants, 1162 (81.0%) completed the protocol. The prevalence of dementia was 4.8%. Of the 60 participants with dementia (Alzheimer's disease 35%, vascular dementia 47%, and dementia from other causes 17%), 53 (88.3%) had shown one or more mental and behavioural disturbances. Apathy/indifference (56.7%), followed by agitation/aggression (35%), aberrant motor behaviour (31.7%), and irritability (31.7%) were the common symptoms. More productive (positive) symptoms such as delusions and aberrant motor behaviour were found in the Alzheimer group than in the vascular dementia group. CONCLUSIONS: A wide range of dementia associated mental and behavioural disturbances developed in the majority of community dwelling individuals with dementia. The findings suggest that a screening programme focusing on identifying these symptoms should be included in the physician's diagnostic tools for dementia.

Fractal analysis of cerebral blood flow distribution in Alzheimer's disease.

UNLABELLED: This study describes a method for quantifying cerebral blood flow (CBF) distribution in Alzheimer's disease (AD) from SPECT images obtained with (99m)Tc-hexamethylpropyleneamine oxime (HMPAO) by 3-dimensional fractal analysis (3D-FA). METHODS: HMPAO SPECT was performed on 68 patients with probable AD and 14 healthy control subjects. We delineated the CBF images using 4 cutoff levels (35%, 40%, 45%, and 50% of the maximal voxel radioactivity) and measured the total number of voxels in the areas surrounded by the contours obtained with each cutoff level. We calculated fractal dimensions from the relationship between the total number of voxels and the cutoff levels transformed into natural logarithms. RESULTS: The fractal dimensions (mean +/- SD) for patients with probable AD and healthy subjects were 0.74 +/- 0.33 and 0.52 +/- 0.09, respectively. A significant difference in the fractal dimension was found between groups (P = 0.001). Statistically significant correlations were obtained between the fractal dimension and the Mini-Mental State Examination score (r = -0.598; P < 0.0001) and between the fractal dimension and the AD Assessment Scale (r = 0.670; P < 0.0001). The fractal dimensions for subjects with clinical dementia rates (CDRs) of 0, 1, 2, and 3 were 0.52 +/- 0.09, 0.63 +/- 0.21, 0.77 +/- 0.23 (P < 0.05 vs. the group with a CDR of 1), and 1.43 +/- 0.49 (P < 0.0001 vs. the group with a CDR of 2), respectively. CONCLUSION: Quantification of CBF distribution on SPECT images in AD was possible using 3D-FA. The fractal dimension was well correlated with the cognitive impairment, as assessed in neuropsychologic tests. 3D-FA may be a useful method for objectively evaluating the progression of AD.

Frontotemporal lobar degeneration: a study in Japan.

Frontotemporal lobar degeneration is the most common form of cortical dementia occurring in the presenium after Alzheimer's disease. We analyzed two types of frontotemporal dementia (FTD) and semantic dementia (SD) selected from a consecutive series of outpatients based on neuropsychological symptoms, psychiatric symptoms and abnormal behavior. In our series of 134 patients with primary degenerative dementia, there were 16 cases of FTD and 6 cases of SD. Patients with subgroups of FTD and patients with SD were distinguishable only by the presence of aphasia in the latter group. They were not distinguishable from one another by other neuropsychological examinations, behavioral abnormalities or psychiatric symptoms assessed with the Neuropsychiatric Inventory.

Increased prevalence of vascular dementia in Japan: a community-based epidemiological study.

BACKGROUND AND OBJECTIVE: It has been suggested that there is a major difference in the ratio of AD to vascular dementia (VaD) between Japan and Western countries. To determine the type-specific prevalence of dementia in community-dwelling elderly from the Japanese community of Nakayama, all patients with dementing illness underwent a CT scan. METHODS: A door-to-door three-phase population survey was carried out on all persons aged 65 years and older residing at home on the prevalence day (January 1, 1997). The ascertainment of cases was made between January 1997 and March 1998. The study included a psychiatric interview; physical, neurologic, and neuropsychologic examinations; comprehensive laboratory tests; and cranial CT. A public health nurse also interviewed a person close to each subject. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, third edition-revised, criteria, AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association, and VaD according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, combined with information from the patient's neurologic history and CT scanning. RESULTS: Of 1438 inhabitants, 1162 (81.0%) completed the protocol. The prevalence of dementia was 4.8%. Of the 60 subjects with dementia, 35% had AD, 47% had VaD, and 17% had dementia resulting from other causes. CONCLUSIONS: The prevalence of dementia was similar to previous reports, but, contrary to results of virtually all studies conducted in developed countries and those recently conducted in Japan, almost half of the cases in the present study appeared to have VaD with neuroradiologic confirmation.

Alteration of rCBF in Alzheimer's disease patients with delusions of theft.

We investigated the neural substrate of the delusion of theft in patients with Alzheimer's disease (AD). Nine AD patients with only one type of delusion (delusions of theft) and nine age, cognitive function-matched AD patients without any type of delusions were selected from 334 consecutive outpatients of Ehime University Hospital. All subjects underwent (99m)Tc-HMPAO SPECT scanning, and SPECT images were analyzed by Statistical Parametric Mapping (SPM). AD patients with delusions of theft showed significant hypoperfusion in the right medial posterior parietal region compared to patients without delusions. Our data suggest that attention impairment or lack of awareness of illness caused by right parietal dysfunction might play a role in producing the delusion of theft.

Relationship between blood flow kinetics and severity of Alzheimer's disease: assessment of severity using a questionnaire-type examination, Alzheimer's disease assessment scale, cognitive sub-scale (ADAS(cog)).

We assessed hemokinetics associated with changes in Alzheimer's disease (AD) severity in 90 AD patients by researching the relationship between AD Assessment Scale, cognitive sub-scale (ADAS(cog)) scores and regional cerebral blood flow (rCBF). In the present study, we employed the questionnaire-type ADAS(cog) examination to accurately assess the severity of AD. Between five groups classified on the basis of ADAS(cog) score, significant differences were observed in parietal, lateral temporal and superior frontal rCBF. In addition, in parietal and lateral temporal regions, significant correlations were also observed between ADAS(cog) score and rCBF. In superior frontal rCBF, significant differences were noted only between group 5 (> or =40 ADAS(cog) points) and each of the other groups; there was no significant correlation between rCBF and ADAS(cog) score. Thus, we propose the following mechanism for blood flow kinetics associated with changed severity: In an early stage of AD, blood flow in the medial temporal cortex is impaired, and gradually involves the temporoparietal regions. While the medial temporal impairment of blood flow reaches a plateau, temporoparietal blood flow continues to be impaired well into a severe stage, at which point blood flow impairment in the frontal region is initiated.

Utility of (99m)Tc-HM-PAO SPECT hippocampal image to diagnose early stages of Alzheimer's disease using semiquantitative analysis.

OBJECTIVE: Examination of the utility of (99m)Tc-hexamethylpropylene amine oxide ((99m)Tc-HM-PAO) SPECT hippocampal image to diagnose early stages of Alzheimer's disease (AD) using semiquantitative analysis. SUBJECTS: 10 early-stage AD patients and 8 normal sex-matched elderly controls. SETTING: Outpatient division of the Ehime University Hospital. METHOD: We performed (99m)Tc-HM-PAO SPECT perfusion imaging in each subject. A semiquantitative method of assessing regional variation was used. The regions of interest for temporal regions were set at images parallel to the long axis of the hippocampal formation which were reconstructed at 30 degrees negative to the orbitomeatal line and those for other regions were set on ordinary transaxial images. RESULTS: The regional cerebral blood flow ratio of the bilateral medial temporal lobe at the hippocampal image was significantly lower in the AD subjects than in the normally aged controls without any other differences in ordinary transaxial images. CONCLUSION: This study suggests that (99m)Tc-HM-PAO SPECT hippocampal images might be a helpful tool for the diagnosis of very-early-stage AD.

The validity of the MMSE and SMQ as screening tests for dementia in the elderly general population-- a study of one rural community in Japan.

OBJECTIVE: To compare the validity of the Mini Mental State Examination (MMSE) and the Short-Memory Questionnaire (SMQ) as screening tests to detect dementia in the elderly general population. SUBJECTS: Six hundred and sixty-two subjects and their informants from the elderly general population sample who had completed these tests. SETTING: One rural community survey in Japan. METHOD: We used receiver-operating characteristic analysis to compare the performance of the MMSE and the SMQ with the clinical diagnosis of dementia according to DSM-III-R. RESULTS: The areas under the receiver-operating characteristic curve of the MMSE and the SMQ were 0.980 (SE = 0.006) and 0.982 (SE = 0.008), respectively. This differed from chance to a highly significant degree for both the MMSE and the SMQ, but the difference between the two scales was not statistically significant. CONCLUSION: As screening tests to detect dementia in the elderly general population, the SMQ which is assessed by informants demonstrates a statistically significant discriminating ability as well as the MMSE.

Validity of the Short-Memory Questionnaire in vascular dementia.

PURPOSE: To determine whether the Short-Memory Questionnaire (SMQ) being administered by caregivers to patients with Alzheimer's disease (AD) is also valid when given to patients with vascular dementia (VaD). METHODS: Subjects were 58 patients with VaD, 26 patients with cerebrovascular disorders free of cognitive deficit (CVD) and 62 healthy controls. All subjects received the Mini-Mental State Examination (MMSE), and their primary caregivers (or family members with same household) received the SMQ. RESULTS: In the VaD patients, the SMQ score was highly correlated with the MMSE score. When 39/40 was defined as a cutoff point based on the results of previous study, the SMQ properly classified 55 of the 58 VaD patients and 61 of the 62 controls, but only about half of the 26 CVD patients, as cases. CONCLUSION: The SMQ, a simple quantitative rating test for memory disturbance, is useful for the assessment and screening of VaD patients as well as AD patients, although careful attention should be paid to the assessment of CVD patients.

[Two cases of fronto-temporal dementia without remarkable lobar atrophy].

Front-temporal dementia (FTD), advocated by Lund and Manchester groups, includes Pick type corresponding to the conventional frontal Pick's disease, motor-neuron type associated with neural symptoms, and frontal lobe degeneration type. In Japan, however, there have been few case reports of the frontal lobe degeneration type. Here we examined clinical characteristics and imaging findings of 2 cases of FTD frontal lobe degeneration type. Neurological examinations were normal. CT and MRI scans revealed no obvious frontal lobar atrophy, while HMPAO-SPECT scans demonstrated remarkable hypoperfusion in anterior hemisphere. Neuropsychological examination revealed frontal symptoms, including personality change, stereotypes, and disinhibition. These symptoms can not be distinguished from the cases of FTD Pick type, because those cases of FTD Pick type have obvious lobar atrophy.

[Japanese version of the Short-Memory Questionnaire and Mini-Mental State Examination in relation to demographic variables: community survey of elderly healthy residents in Nakayama, Japan].

BACKGROUND AND PURPOSE: The Short-Memory Questionnaire (SMQ) developed by Koss et al. is a standardized, validated reliable informant-based scale to assess everyday memory problems. In the previous study, we prepared its Japanese version and validated the reliability in assessing patients with Alzheimer Disease. In the present study, we examined the relations between the performance evaluated by the Japanese version of the SMQ combined with the Mini-Mental State Examination (MMSE) and demographic variables (age, sex, and education). SUBJECTS AND METHODS: Subjects were a total of 613 elderly healthy individuals living in the rural residency of Nakayama, Japan. They consisted of 287 males and 326 females and ranged from 65 to 94 years in age and from 0 to 16 years in education. The MMSE was conducted by neuropsychiatrists to assess the severity of cognitive impairment, and the SMQ was conducted by public health nurses, who asked a family member of each subject. The effects of age, sex and education on the MMSE and SMQ scores were analyzed by analysis of variance (ANOVA) using post-hoc Scheffé test. RESULTS: The mean MMSE and SMQ scores (+/- SD) were 27.6 (+/- 2.5) and 44.5 (+/- 2.1), respectively. The post-hoc Scheffé test revealed significantly higher MMSE scores for individuals with 8 years or more in education than for those with less than 8 education years. Between males, no significant differences were observed in MMSE score; however, among females, significantly higher scores were noted in those aged 69 or younger than in those aged 70-74 or those aged 80 or older. Of individuals aged 80 or older, males showed significantly higher scores than females, whereas no significant differences were observed between sex in other age groups. As to the SMQ, higher scores were shown by persons with longer education years and by females than males. CONCLUSION: Low MMSE scores were related to low education level and older females. Low SMQ scores were not related to aging, but linked to low education level and males. Both the MMSE and SMQ, which can be easily administered, are affected by education years and sex. In addition, MMSE score depends on age. Therefore, careful consideration should be paid to age, education level and sex for future execution of the MMSE and SMQ.

[Japanese version of the Short-Memory Questionnaire: memory evaluation in Alzheimer's disease].

BACKGROUND AND PURPOSE: Memory deficit is a common sign of Alzheimer's disease (AD), which appeared generally in the early stage of the disease. Therefore, evaluation of memory is important for management of patients and for clinical research of AD. The Short-Memory Questionnaire (SMQ), an easily administered, informant-based scale, which was developed by Koss et al. (1993), is a standardized, validated, and reliable tool to assess everyday memory problems. In the present study, we prepared a Japanese version of the SMQ and examined its reliability and validity in assessing AD patients. SUBJECTS AND METHODS: The subjects consisted of 42 patients with NINCDS-ADRDA probable AD whose diagnosis was made on the basis of the results of comprehensive examinations including cranial CT/MRI and SPECT and age- and education-matched 53 healthy controls. Patients had no history of stroke, head injury, or any other prior neurological events. Patients and controls were between the ages of 51 and 90 years, and they had from 6 to 16 years education. The Japanese version of the SMQ was given to a family member by either neuropsychiatrist, public nurse or case worker. To evaluate test-retest reliability of the test, interview was repeated in 16 randomly selected patients by two different examiners (neuropsychiatrist and another) in two weeks interval. The Mini-Mental State Examination (MMSE) was used to assess the severity of cognitive impairment. RESULT: The test-retest reliability was acceptably high with intraclass correlation coefficients. There was a high correlation between scores of SMQ and MMSE. The SMQ had excellent specificity and sensitivity in discriminating patients from controls. Caregiver appraisals of memory deficits significantly correlated with generalized cognitive dysfunction. CONCLUSIONS: Similarly to the original version, the present Japanese version of the SMQ is a reliable and valid tool in assessing memory function in AD, which can be effectively used in clinical settings and epidemiologic studies to screen out persons with memory problems.