Integrin α6A (ITGA6A)-type Splice Variant in Extracellular Vesicles Has a Potential as a Novel Marker of the Early Recurrence of Pancreatic Cancer.

BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancers worldwide, with a poor prognosis. Owing to the difficulty of early diagnosis, the aim of this study was to isolate biomarkers from extracellular vesicles (EVs) that can lead to early diagnosis. MATERIALS AND METHODS: EVs in the culture supernatant were isolated from a pancreatic cancer cell line (PK-1) and expanded by using two-dimensional gel electrophoresis, and protein identification from each spot was performed by using matrix-assisted laser desorption ionization mass spectrometry. The identified proteins were classified and compared with previously reported results for EVs from murine pancreatic cancer PAN02 cells, and their expression specificity was examined using PDAC cell lines and patient-derived PDAC tissues. In addition, the significance of selected biomarker(s) was examined based on the changes in biomarkers in the blood EVs of PDAC patients after surgery. RESULTS: We found that the ITGA6A splice variant was predominantly expressed in several pancreatic cancer cell lines and blood EVs from patients with PDAC, whereas the ITGA6B splice variant was predominantly expressed in EVs from the blood of normal volunteers. In the expression pattern of ITGA6 in EVs from blood samples of two PDAC patients before and after resection surgery, the expression of ITGA6A in EVs significantly decreased after surgery and increased several months before clinical recurrence. Furthermore, the increased expression of ITGA6A in EVs occurred much earlier than that of CA19-9. CONCLUSION: Determination of ITGA6A expression in blood EVs in PDAC patients could be a useful blood marker for the early diagnosis of PDAC recurrence.

Patients with mild cognitive impairment diagnosed at dementia clinic display decreased maximum occlusal force: a cross-sectional study.

BACKGROUND: Previous research indicates that patients with mild cognitive impairment (MCI) are more likely to have poor oral health and impairments in oral functions, which may be due to few remaining teeth and impaired tongue and lip motor function. However, the oral health of those patients following comprehensive cognitive assessment by a dementia specialist has not been sufficiently investigated. Therefore, this study aimed to clarify the oral function of patients with MCI and the association between oral health and lower cognitive function. METHODS: This cross-sectional study included 96 participants (men: 35; women: 61; mean age: 73.3 ± 8.5 years) who visited a dementia clinic between December 2017 and January 2020. Participants' cognitive function was assessed by a dementia specialist using neuropsychological and hematological tests and neuroimaging immediately after enrollment. The participants were divided into the healthy and MCI groups according to comprehensive cognitive assessment. Participants' age, sex, body mass index, primary disease, education level, drinking habits, smoking habits, living environment, employment status, and exercise habits were evaluated. Moreover, oral outcomes, including the number of existing teeth, number of functional teeth (natural and prosthetic teeth which were occluded with antagonists), denture use, oral dryness, tongue and lip motor function, tongue pressure, occlusal force, masticatory ability, and swallowing ability were recorded. The Mann-Whitney U test, χ2, and Fisher's exact tests were used for between-group comparisons. Furthermore, logistic regression analysis using MCI diagnosis as the target variable was performed. RESULTS: A comprehensive evaluation of the cognitive function of the study participants by the dementia specialist revealed that 48 participants (mean age: 69.8 ± 8.8 years) were healthy and 48 (mean age: 76.9 ± 6.7 years) had MCI. MCI participants were significantly older (p < 0.001) and had significantly fewer existing teeth (p = 0.031) and lower maximum occlusal force (p = 0.019) than healthy participants. Age (odds ratio: 1.126, p = 0.002) and maximum occlusal force (odds ratio: 0.978, p = 0.048) were significantly associated with lower cognitive function. CONCLUSIONS: Patients with MCI had poorer oral health than healthy individuals. Decreased maximum occlusal force was independently associated with lower cognitive function, even when adjusted for age and sex.

Effect of Chlorogenic Acids on Cognitive Function in Mild Cognitive Impairment: A Randomized Controlled Crossover Trial.

BACKGROUND: Mild cognitive impairment (MCI) is a global-scale issue, due in large part to the rapidly growing elderly population. The main polyphenol contained in coffee beans, chlorogenic acid (CGA), improves attention in healthy individuals. The utility of CGAs for treating MCI, however, has not been evaluated. OBJECTIVE: To determine the effects of continuous CGA intake on cognitive function, especially attention, in patients diagnosed with MCI. METHODS: The study was a randomized controlled crossover trial including 34 patients with MCI. Participants were randomly divided into two groups: Those who first ingested a placebo beverage and those who first ingested an active beverage containing CGAs (553.6 mg/bottle) twice daily for 12 weeks. After a 4-week washout period, the subjects ingested the other beverage (i.e., placebo or active beverage) in the same manner. Endpoint measures included scores on the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive component (ADAS-cog) testing overall cognitive function, and the Japanese version of the Trail Making Test (TMT-A, TMT-B) testing attention, along with the results of blood tests to evaluate safety. RESULTS: In the TMT-B test, participants had a significantly reduced number of errors while ingesting the CGA beverage as compared with the placebo beverage (p < 0.05), although there was no difference in test completion time. Scores in the MMSE, ADAS-cog, and TMT-A did not differ significantly between conditions. CONCLUSION: Continuous intake of CGAs appears to improve attention and executive function among cognitive functions in MCI.

Identification of dementia using standard clinical assessments by primary care physicians in Japan.

AIM: The aim of the present study was to develop a way of identifying dementia using clinical assessments made by primary care physicians under the existing medical care system in Japan. METHODS: A total of 623 people aged ≥65 years underwent standard clinical assessments by primary care physicians under the long-term-care insurance program to determine their grade of activities of daily living related to dementia. To examine the validity of the diagnosis, neuropsychiatrists carried out further diagnosis of dementia for all the participants. We regarded the dementia patients who received care for disability under the long-term care insurance program as having disabling dementia. RESULTS: Multivariable odds ratio (95% confidence interval) in single-grade increments of the activity was 2.1 (1.7-2.5) for dementia and 2.8 (2.2-3.4) for disabling dementia. The grades ≥I and ≥IIa were near the upper-left corner in the receiver operating characteristic curves. Setting the cut-off point at grades ≥I or ≥IIa yielded a higher integrated discrimination improvement, suggesting a major improvement in reducing misclassification by using these cut-off points. When we used grades ≥I as the cut-off point, the sensitivity (95% confidence limits) was 65% (58-72%) and the specificity was 93% (91-96%) for dementia, and the corresponding values in grades ≥IIa were 54% (47-62%) and 96% (94-97%). The corresponding values for disabling dementia were 83% (76-90%), 92% (90-95%), 73% (65-80%) and 96% (94-97%). CONCLUSIONS: Our findings suggest that selection of grades ≥I or ≥IIa as the cut-off point would reduce instances of misclassification in the identification of dementia and disabling dementia. Geriatr Gerontol Int 2018; 18: 738-744.

A Validity and Reliability Study of the Japanese Version of the Geriatric Depression Scale 15 (GDS-15-J).

OBJECTIVE: The 15-item Geriatric Depression Scale (GDS-15) is one of the most widely used screening instruments for depression among the elderly. The aim of this study was to examine the validity and reliability of the Japanese version of the GDS-15 (GDS-15-J) in comparison with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for depression. METHODS: The study participants were 128 elderly outpatients (age range, 55 to 92 years) categorized into two groups (76 non-depressive patients, 52 depressive patients) based on the DSM-IV-TR criteria for depression. RESULTS: Logistic regression analysis showed that regardless of age and sex, the GDS-15-J score could be used to screen patients for depression (p < .001). The validity of the GDS-15-J for depression assessed against DSM-IV-TR criteria was excellent based on receiver operating characteristic analysis (optimal cutoff point: 6/7; sensitivity: .98; specificity: .86). The recommended optimal cutoff score when screening for depression is 6/7. To evaluate the constructive validity of the GDS-15-J, factor analysis was performed. Three factors were extracted. Cronbach's alpha reliability coefficient was .83 to the GDS-15-J scale, which indicated a high degree of internal consistency. CONCLUSION: The GDS-15-J is a clinically applicable screening instrument for depression. CLINICAL IMPLICATIONS: In this study this version of the GDS-15-J displayed excellent psychometric properties using a 6/7 cut off. Analyses suggest some items that might be removed in future studies of an abbreviated scale.

Establishment of the MethyLight Assay for Assessing Aging, Cigarette Smoking, and Alcohol Consumption.

The environmental factors such as aging, smoking, and alcohol consumption have been reported to influence DNA methylation (DNAm). However, the versatility of DNAm measurement by DNAm array systems is low in clinical use. Thus, we developed the MethyLight assay as a simple method to measure DNAm. In the present study, we isolated peripheral blood DNA from 33 healthy volunteers and selected cg25809905, cg02228185, and cg17861230 as aging, cg23576855 as smoking, and cg02583484 as alcohol consumption biomarkers. The predicted age by methylation rates of cg25809905 and cg17861230 significantly correlated with chronological age. In immortalized B-cells, DNAm rates of two sites showed a younger status than the chronological age of donor. On the other hand, the predicted age of the patients with myocardial infarction (MI) was not accelerated. The methylation rate of cg23576855 was able to discriminate the groups based on the smoking status. The DNAm rate of cg02583484 was reduced in subjects with habitual alcohol consumption compared to that of subjects without habitual alcohol consumption. In conclusion, our MethyLight assay system reconfirms that aging, smoking, and alcohol consumption influenced DNAm in peripheral blood in the Japanese. This MethyLight system will facilitate DNAm measurement in epidemiological and clinical studies.

World Stem Cell Summit 2014. 3-5 December 2014, San Antonio, TX, USA.

Among the many international conferences in the field of stem cells and regenerative medicine, WSCS is distinct in focusing its efforts to serve as the meeting point by multisector communities of research, clinics, industry, regulation, policy making and ethics. All are aiming at advancing stem cell innovation and new therapies, under the banner of 'connect, collaborate and cure'. As same as past years, presenters and attendees included not only researchers but also clinicians, funding agencies, government officials, industries and patients. Thus, many sessions focused on the clinical translation from basic research. Another important agenda were industrial and social aspects, and problems to be solved before realization of practical and sustainable stem cell-based therapies.

[The Development of a Normal Database of Elderly People for Use with the Statistical Analysis Software Easy Z-score Imaging System with 99mTc-ECD SPECT].

We created a new normal database of elderly individuals (Tsukuba-NDB) for easy Z-score Imaging System (eZIS), a statistical imaging analysis software, comprised of 44 healthy individuals aged 75 to 89 years. The Tsukuba-NDB was compared with a conventional NDB (Musashi-NDB) using Statistical Parametric Mapping (SPM8), eZIS analysis, mean images, standard deviation (SD) images, SD values, specific volume of interest analysis (SVA). Furthermore, the association of the mean cerebral blood flow (mCBF) with various clinical indicators was statistically analyzed. A group comparison using SPM8 indicated that the t-value of the Tsukuba-NDB was lower in the frontoparietal region but tended to be higher in the bilateral temporal lobes and the base of the brain than that of the Musashi-NDB. The results of eZIS analysis by Musashi-NDB in 48 subjects indicated the presence of mild decreases in cerebral blood flow in the bilateral frontoparietal lobes of 9 subjects, precuneus and posterior cingulate gyrus of 5 subjects, lingual gyrus of 4 subjects, and near the left frontal gyrus, temporal lobe, superior temporal gyrus, and lenticular nucleus of 12 subjects. The mean images showed that there were no visual differences between both NDBs. The SD images intensities and SD values were lower in Tsukuba-NDB. Clinical case comparison and visual evaluation demonstrated that the sites of decrease in blood flow were more clearly indicated by the Tsukuba-NDB. Furthermore, mCBF was 40.87 ± 0.52 ml/100 g/min (mean ± SE), and tended to decrease with age. The tendency was stronger in male subjects than female subjects. Among various clinical indicators, the platelet count was statistically significantly correlated with CBF. In conclusion, our results suggest that Tsukuba-NDB, which is incorporated into a statistical imaging analysis software, eZIS, is sensitive to changes in cerebral blood flow caused by Cranial nerve disease, dementia and cerebrovascular accidents, and can provide precise diagnosis of these brain diseases in the rapidly aging Japanese population.

C-reactive protein levels and risk of disabling dementia with and without stroke in Japanese: the Circulatory Risk in Communities Study (CIRCS).

OBJECTIVE: Studies have shown that elevated high-sensitivity C-reactive protein (hs-CRP) predicts stroke, which is a risk factor for dementia. It remains, however, unclear whether hs-CRP increases risk of dementia. METHODS: A prospective nested case-control study of Japanese 40-69 years of age was conducted using frozen serum samples collected from approximately 7531men and women who participated in cardiovascular risk surveys from 1984 to 1994 in one community and 1989-1995 in another community under the Circulatory Risk in Communities Study (CIRCS). Two control subjects per case were matched by sex, age, community, and year of serum storage. The hs-CRP was measured using a latex particle-enhanced immunonephelometric assay. RESULTS: Between 1999 and 2013, we identified 275 disabling dementia cases (96 cases with history of stroke and 179 without it). There was a positive association between hs-CRP levels and risk of dementia with history of stroke. No significant association was observed between hs-CRP levels and risk of dementia without history of stroke. After adjustment for hypertension, diabetes and other confounding variables, the positive association remained statistically significant. The multivariable odds ratios associated with 1-SD increment of log hs-CRP were 1.02 (0.87-1.20) for total dementia, 1.35 (1.02-1.79) for dementia with history of stroke, and 0.89 (0.72-1.10) for dementia without history of stroke. CONCLUSION: Elevated hs-CRP levels were associated with increased risk of disabling dementia in individuals with history of stroke but not in those without it.

Combination of antioxidant supplements improved cognitive function in the elderly.

Although nutrients or agents with antioxidant properties were reported to show a preventive effect on cognitive decline in animal studies, epidemiologic data on select antioxidants have shown conflicting results. We investigated whether a combination of antioxidants from supplements is effective for the improvement of cognitive function of elderly. Forty-one subjects from a community dwelling aged 65 years and older took supplements containing n-3 polyunsaturated fatty acids (n-3 PUFA), lycopene, and Ginkgo biloba extracts (GE) daily for 3 years. The data of 622 subjects without supplement intake were used as control. We investigated the changes in cognitive function during a 3-year follow-up. We also investigated the influence of apolipoprotein E (APOE) genotype on the effect of antioxidants. We found that a combination of antioxidants improved cognitive function of aged persons after 3 years. Our present study also indicated this improvement in cognitive function with supplement intake in both APOE4 non-carrier (E4-) and APOE4 carrier (E4+) groups. Especially, in E4+, we found a large effect size of the improvement of cognition. When multiple antioxidants are used in combination, they protect against vulnerability to other agents and synergistically potentiate their antioxidant properties. These synergistically potentiated antioxidant effects of agents contribute to the improvement of cognitive function.

Role of the standardized uptake value of 18-fluorodeoxyglucose positron emission tomography-computed tomography in detecting the primary tumor and lymph node metastasis in colorectal cancers.

PURPOSE: To assess the role of positron emission tomography-computed tomography (PET-CT) and multidetector-row CT (MD-CT) in detecting the primary lesion and lymph node metastasis in patients with colorectal cancers. METHODS: A collective total of 80 lesions resected from 77 patients were examined pathologically. We analyzed the significance of the standardized uptake value (SUV) and its relationship with the clinicopathologic findings of primary lesions and lymph node metastasis. The detectability of primary lesions and lymph node metastases on PET-CT images was compared with that on MD-CT images. RESULTS: The detectability of primary lesions was better on PET-CT images than on MD-CT images (p = 0.0023). We observed no significant differences in the SUV with respect to staging, tumor grade, lymphatic or vessel invasion, and macroscopic type; however, primary tumor size analysis revealed that tumors larger than 3 cm had a higher SUV than those smaller than 3 cm. The sensitivity of PET-CT for detecting lymph node metastasis was lower than that of MD-CT, but the specificity of PET-CT was higher than that of MD-CT. CONCLUSIONS: The SUV of primary cancers tends to increase in proportion to tumor size. Although the value of PET-CT in detecting lymph node metastasis is limited, PET -positive lymph nodes can be considered metastatic.

Effect of parenteral hydration therapy based on the Japanese national clinical guideline on quality of life, discomfort, and symptom intensity in patients with advanced cancer.

CONTEXT: Although an evidence-based clinical guideline for parenteral hydration therapy was established in Japan, the efficacy of the guideline has not been assessed. OBJECTIVES: Our purpose was to explore the effect of parenteral hydration therapy based on this clinical guideline on quality of life (QoL), discomfort, symptoms, and fluid retention signs in patients with advanced cancer. METHODS: This multicenter, prospective, observational study included 161 patients with advanced abdominal cancer who received guideline-based hydration therapy. We evaluated the longitudinal changes of the global QoL (Item 30 of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30); the Discomfort Scale; the intensity of seven physical symptoms; and the severity of fluid retention signs. We also evaluated patient satisfaction and the feeling of benefit from hydration one week after the study commenced, and bronchial secretions, hyperactive delirium, communication capacity, and agitation 48 hours before a patient's death. RESULTS: The global QoL, the Discomfort Scale, and the intensities of all physical symptoms, except for vomiting and drowsiness, were stable throughout the study period. More than 80% of patients maintained all fluid retention signs. Patient global satisfaction was 76.4 (0-100) and feeling of benefit was 5.43 (range 0-7). CONCLUSION: Guideline-based parenteral hydration therapy contributed to maintaining global QoL and provided satisfaction and a feeling of benefit without increasing discomfort and worsening symptoms and fluid retention signs in patients with advanced cancer.

Rectal endometriosis masquerading as dissemination in a patient with rectal cancer: report of a case.

A 57-year-old woman was diagnosed as having rectal cancer. A barium enema study showed the apple-core sign at the rectosigmoid colon, and colonoscopy revealed an encircled ulcerated tumor. A laparoscope-assisted resection of the rectum was planned; however, the rectal cancer directly invaded the uterus body. The operation was converted to open surgery. An elastic hard tumor suspected of being peritoneal dissemination at the peritoneal reflection was detected and excised together with the rectum below the peritoneal reflection. A histological examination of this tumor revealed that cystic glands lined by nonmucinous columnar epithelial cells were seen on the serosal side and were embedded in the proper muscle of the rectum. This tumorous lesion was diagnosed as endometriosis.

Hyperperfusion in primary somatosensory region related to somatic hallucination in the elderly.

AIM: The purpose of the present study was to investigate the regional cerebral blood flow (rCBF) of patients with delusional disorder, somatic type (DDST) exhibiting somatic hallucination. METHODS: Five patients diagnosed with DDST, as well as 20 control subjects, were examined. All subjects underwent technetium-99m ethyl cysteinate dimer brain perfusion single-photon emission computed tomography. Statistical analysis was performed with SPM5, using a two-sample t-test model to test the regional population effect on rCBF. RESULTS: Patients with DDST had a significant increase in perfusion in the left post-central gyrus and the right paracentral lobule, both of which are involved in somatic sensory processing. CONCLUSION: Somatic hallucination might be associated with increased perfusion in the primary somatosensory regions.

[A case of recurrent gastric cancer during adjuvant chemotherapy with S-1, treated by S-1 combination chemotherapy].

A 59-year-old man was admitted to our hospital for the treatment of gastric cancer with synchronous and multiple metastatic liver tumors. After total gastrectomy in February 2005, partial resection of the posterior segment of the liver was carried out in the next month. Pathological study of both the resected specimens showed moderately differentiated adenocarcinoma. The postoperative treatment with S-1 was initiated without any evidence of recurrence. However, CT scans showed recurrent multiple liver tumors after 4 courses of treatment with S-1. Subsequently, a combination chemotherapy of S-1 (80 mg/m(2) over day 1-14 with a 2-week rest) and paclitaxel (PTX) (120 mg/m(2), day 1 and 15) was applied. After 3 courses, CT scans showed reduced liver metastases, judged as a partial response(PR)on Response Evaluation Criteria in Solid Tumors (RECIST). However, metastatic liver tumors showed progressive disease (PD) after 7 courses of treatment. The treatment was changed to combination chemotherapy with S-1 (80 mg/m(2) over day 1-21 with a 2-week rest) and CPT-11 (80 mg/m(2) day, day 1 and 15) for 6 courses, but the legions showed PD. He was then treated with combined chemotherapy with S-1 (70 mg/m(2) over day 1-14 with a 1-week rest)and cisplatin (CDDP) (10 mg/m(2), day 1 and 8). However, his condition became worse and he was treated at the palliative care unit. There were no adverse effects greater than grade 4 throughout the treatment period, and his treatment was continued as an outpatient for more than two years. This case suggests that after failure of S-1 therapy, S-1 combination chemotherapy might be an effective treatment for recurrent gastric cancer.

Multiseptate gallbladder: report of a case.

A 53-year-old Japanese female was referred to Miyazaki University hospital for the surgical treatment of gastric cancer. She had no symptoms and the presence of the complex cystic gallbladder with multiple and linear hyperechogenic septa was incidentally found by ultrasonography. Multicystic lesion of gallbladder was also observed on DIC-CT and MRCP. Neither the bile duct nor the pancreatic duct was dilated. The papilla of the Vater was of normal appearance endoscopically. Pathological study of the biopsy specimen from the type 3 tumor of the stomach showed poorly differentiated adenocarcinoma. Distal partial gastrectomy and cholecystectomy were performed. The gross examination of the gallbladder confirmed the presence of multiple thin septa with honeycomb appearance. Cancer cells were not observed histologically and final diagnosis was the multiseptate gallbladder. The postoperative course was uneventful. We herein report a rare case of multiseptate gallbladder showing the findings on DIC-CT and MRCP.

Cigarette smoking and risk of disabling dementia in a Japanese rural community: a nested case-control study.

BACKGROUND: Previous prospective cohort studies have examined the association between smoking and the risk of dementia, but the results were inconsistent. METHODS: A prospective, nested, case-control study was conducted to examine the association between cigarette smoking and risk of disabling dementia within the cohort of 6,343 men and women aged 35-85 years. Incident dementia was documented in 208 men and women (95 cases with and 113 cases without a history of stroke). Two control subjects per case were selected by matching for sex, age and year of examination. RESULTS: The multivariable odds ratios (95% CI) for current versus never smokers were 2.3 (1.1-4.7) for total dementia, 2.6 (0.8-8.2) for dementia with a history of stroke and 2.2 (0.8-5.7) for dementia without it, yielding no effect of stroke history on the smoking-dementia association. A dose-response relationship was noted between the years of cigarette smoking and the risk of total dementia, and a significant excess risk was found for smoking duration of >or=45 years. CONCLUSIONS: The present prospective study suggests that long-term cigarette smoking may raise the risk of disabling dementia.

Simple one-step extraction and cleanup by pressurized liquid extraction for gas chromatographic-mass spectrometric determination of pesticides in green leafy vegetables.

A simple one-step extraction and cleanup using a pressurized liquid extraction method was developed for the gas chromatographic-mass spectrometric determination of pesticides in vegetables. The pressurized liquid extraction conditions were optimized and cleanup agents were evaluated. The investigated pesticides included six insecticides, chlorpyrifos methyl, pirimiphos-methyl, malathion, chlorpyrifos, O-ethyl O-4-nitrophenylphenyl phosphonothioate (EPN) and permethrins, a fungicide, isoprothiolane, and a herbicides, thiobencarb. The cleanup agent and a mixture of the vegetable and anhydrous sodium sulfate were separately packed in an extraction vessel. A transparent and colorless extract was obtained using graphitized carbon as the cleanup agent. The overall recoveries were 71-103% and the relative standard deviations ranged from 5.6 to 24%. The limit of detection values were 3-8 microg kg(-1). This method was successfully applied to green leafy vegetables.

Incidence of dementia and associated risk factors in Japan: The Osaki-Tajiri Project.

The incidence of dementia and risk factors has not been fully investigated in Japan. Following a prevalence study in 1998, we investigated the incidence and associated factors in the same population in 2003 and 2005. Randomly selected 771 residents in Tajiri were targeted. The final participants included 204 (65.2%) healthy older adults (Clinical Dementia Rating, CDR 0) and 335 (73.1%) people with questionable dementia (CDR 0.5). We analyzed the incidence of dementia and dementing diseases, and possible risk factors. The risk factors included demographics, lifestyle-related factors, vascular risk factors, cognitive functions, and MRI findings. Overall, 3.9% of the CDR 0 and 37.0% of the CDR 0.5 participants developed dementia during the 5-year period, whereas 40.2% of the CDR 0.5 participants developed dementia during the 7-year period. Older adults had a higher incidence. Higher CDR Box scores had a higher incidence. Of the dementing diseases, 60.8% of participants developed Alzheimer' disease (AD), followed by vascular dementia (VaD), 17.9%. Logistic regression analyses showed that age, MMSE, cognitive functions such as recent memory, and generalized atrophy were significant predictors of progression to AD. Similarly, predictive factors for progression to VaD were age, MMSE, cognitive functions such as frontal function, and white matter lesions and cerebrovascular diseases. A comprehensive system including CDR, cognitive tests, and MRI, is recommended in community-based health policy planning.

Immunohistochemical and immunoblot analysis of Dopamine and cyclic AMP-regulated phosphoprotein, relative molecular mass 32,000 (DARPP-32) in the prefrontal cortex of subjects with schizophrenia and bipolar disorder.

Dopamine and cyclic adenosine 3':5'-monophosphate (AMP)-regulated phosphoprotein, relative molecular mass 32,000 (DARPP-32), plays an important role in modulating the functions of various neurotransmitter systems. To explore the alterations in DARPP-32 in subjects with schizophrenia and bipolar disorder, we employed immunohistochemical and Western blotting techniques and examined the distribution and expression of DARPP-32 in the postmortem dorsolateral prefrontal cortex (DLPFC) from 12 subjects with schizophrenia, 10 subjects with bipolar disorder, and 11 control subjects. Immunohistochemical study demonstrated that DARPP-32 immunolabeling in the neuronal soma from subjects with schizophrenia and bipolar disorder was lower than in that from the controls. The results of the immunoblot analysis were consistent with those of the immunohistochemistry, and the amount of DARPP-32 in subjects with schizophrenia and bipolar disorder was found to be lower than that in the control subjects. The present study suggests that DARPP-32 decreases in the DLPFC of patients with schizophrenia and bipolar disorder, and further suggests that this decrease is associated with dysfunction of dopaminoceptive neurons in the DLPFC of patients affected by these two mental disorders.