Relationship of the Japanese Old Stories Cognitive Scale With the Revised Hasegawa Cognitive Scale and Mini-Mental State Examination.

The Revised Hasegawa Dementia Scale (HDS-R) is the most widely used instrument to screen for dementia in Japan and is similar to the Mini-Mental State Examination (MMSE). The development of a quicker and simpler screening tool, the Japanese Old Stories Cognitive Scale (JOSS), was previously reported. A total of 953 new outpatients from 8 memory clinics in Japan completed the JOSS, HDS-R, and MMSE at first visit. We investigated the relationship of JOSS score with both the total and individual domain scores on the HDS-R and MMSE. We found a significant relation between JOSS score and total HDS-R and MMSE scores. In addition, JOSS score was significantly related to scores on 8 of the 9 HDS-R domains and 7 of the 11 MMSE domains. We obtained regression lines for JOSS score versus HDS-R and MMSE scores. JOSS score could be useful for predicting HDS-R and MMSE scores and thus in estimating cognitive functioning.

Attention to the domains of Revised Hasegawa Dementia Scale and Mini-Mental State Examination in patients with Alzheimer's disease dementia.

BACKGROUND: In Japan, Alzheimer's disease dementia (AD) is the most common cognitive disease, and the most widely used dementia screening tests are the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). This study sought to elucidate the relationships of the individual domains of these tests with age and duration of school education in a large group of patients with AD. METHODS: Participants were 505 new outpatients diagnosed with AD who completed the HDS-R and MMSE at the first visit. We investigated the relationships of total and individual domains of these tests with age and duration of school education using the least squares method. Next, we plotted regression lines of the individual domain scores against the total test scores. RESULTS: Younger age and longer duration of school education were significantly associated with higher total HDS-R and MMSE scores in AD. Domain-specific results indicated that younger age was significantly associated with a higher immediate memory score on both the HDS-R and MMSE and with a higher orientation (time), repetition score on the MMSE. Longer duration of school education was significantly associated with a higher working memory score on the HDS-R and with higher serial 7, repetition and writing scores on the MMSE. In addition, shorter duration of school education was significantly associated with higher naming score on the MMSE. The regression lines of orientation of time, remote memory, visual memory, and verbal frequency hit the bottom on the HDS-R (4/30, 8/30, 4/30, and 6/30, respectively) and of orientation of time, serial 7, remote memory, and writing also hit the bottom on the MMSE (8/30, 9/30, 11/30, and 8/30, respectively). CONCLUSIONS: We should pay attention to age, duration of school education, and the individual domains when using the HDS-R or MMSE to assess patients with AD.

Families of patients with Alzheimer's disease dementia notice progression from symptoms of disorientation and visual memory disturbance.

BACKGROUND: Alzheimer's disease dementia (ADD) is the most common cognitive disease, but patients' families may notice some symptoms yet not recognise that they indicate ADD. This study investigated the symptoms that families notice as ADD as the disease progresses. METHODS: New outpatients diagnosed with ADD (n = 315) at five memory clinics completed two cognitive assessments, the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). During an interview, family members completed the Functional Assessment Staging Test (FAST), an observational assessment tool that classifies ADD progression into seven stages. We then examined the relationship of the family-assessed FAST score with clinician-assessed HDS-R and MMSE domain scores by comparing between patients with FAST 1-3 and FAST 4-7. Next, we divided the FAST 4-7 group into the FAST 4-5 and FAST 6-7 subgroups and divided the FAST 1-3 group into the FAST 1-2 and FAST 3 subgroups. RESULTS: Surprisingly, half of the families did not recognise that the symptoms indicated ADD. Scores for orientation of time and place on the HDS-R and MMSE and for visual memory on the HDS-R were significantly related to family-assessed FAST score. Moreover, the orientation of time and place score on both scales and visual memory on the HDS-R were significantly worse in the FAST 4-7 group than in FAST 1-3 group. In the FAST 4-7 group, scores for age on the HDS-R and for reading and drawing on the MMSE were significantly worse in the FAST 6-7 subgroup. In the analysis of the FAST 1-3 group, there was no significant difference among the HDS-R and MMSE domains between the FAST 1-2 and FAST 3 subgroups. CONCLUSIONS: Family members of patients with ADD tend to notice the progression of ADD from the symptoms of disorientation and visual memory.

Dynamics of Interaction among Professionals, Informal Supporters, and Family Caregivers of People with Dementia along the Dementia Care Pathway: A Nationwide Survey in Japan.

This study aims to clarify the dynamics of information provision and human interaction to satisfy the needs of family caregivers. A questionnaire survey consisting of items on information received at and after diagnosis, persons and resources consulted, needs, and caregiver-oriented outcomes was conducted. Among the respondents, 2295 individuals who were caring for people with dementia were divided into quartiles by the time after diagnosis, and differences were statistically analyzed. The time after diagnosis in the first to fourth quartiles was 0.73 ± 0.4, 2.52 ± 0.49, 4.89 ± 0.73, and 10.82 ± 3.7 years, respectively. The number of persons consulted by family caregivers increased significantly from the first to the fourth quartiles (p < 0.001). During this time, attributes of professionals and informal supporters changed depending on the quartile. As time progressed, acceptance of the diagnosis increased, but so did its impact on the lives of family caregivers. These findings revealed differences over time in what family caregivers wanted and the dynamics of interactions that filled their needs. Informal supporters accounted for a significant proportion of the total resources. However, many family caregivers thought the information and support were insufficient. Thus, continuous reform of the care pathway is needed.

The Relationship between Restrictions on Going Out and Motor Imagery among Medical University Students in Japan-Research with Small Samples.

Motor imagery is often used as a training method to improve physical performance. Previous studies have often reported that reduced motor imagery is more likely to occur in older adults and stroke patients. However, it has also been reported that it is difficult to imagine exercises that cannot be performed. Therefore, we hypothesized that this may also have occurred in young people who were physically able to exercise but who were restricted by COVID-19 lockdowns, however, we could find no studies that investigated the impact of restricting outings. In this study, 83 healthy young people were measured for physical performance (maximum walking speed, grasp strength, Timed Up and Go test, imagined Timed Up and Go test, functional reach test, and five chair stand test). It was found that, while restricting outings did not influence physical performance in the subjects, it did influence motor imagery. Therefore, it should be borne in mind that training with motor imagery may not generate adequate actual motor imagery when restrictions are imposed on activities.

Living Arrangements and Education Duration Associated With Memory Clinic Attendance in Alzheimer's Disease.

Some new outpatients with mild cognitive impairment (MCI) or Alzheimer's disease (AD) do not regularly attend treatment appointments at memory clinics. To explore factors related to non-regular attendance, we divided new outpatients according to regular or non-regular attendance during the first 6 months of treatment and analyzed the relationship between individual patient factors and attendance. Approximately half of patients living alone did not regularly attend appointments. Living with family and longer duration of school education were significantly associated with regular attendance. Patients with mild or moderate AD attended appointments more regularly than patients with MCI or moderate-to-severe AD. Patients in Kyoto City had significantly better cognitive function than patients in satellite cities, and there were a significantly higher proportion of patients with MCI or AD at first visit in Kyoto City. Living arrangements and duration of education are important patient factors to consider to promote regular attendance at treatment appointments.

Neuropsychiatric Inventory Questionnaire Associated with Cognitive Function, Age, and Duration of Education in Patients with Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD) is the most common cognitive disease, and behavioral and psychological symptoms of dementia (BPSD) can place a heavy burden on families. The presence of these symptoms related to AD is commonly assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). This study sought to clarify the relationship between scores on the 12-domain NPI-Q and individual factors in patients with AD. METHODS: Participants were 218 new outpatients with AD at five memory clinics. Cognitive function was assessed using the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). We examined which individual factors were associated with the total NPI-Q score and the number of domains. We also examined which domains were associated with the factors identified. RESULTS: A higher total NPI score was significantly associated with lower scores on both cognitive assessments and a longer duration of education. Exhibiting symptoms on a greater number of domains was significantly associated with lower scores on both cognitive assessments, longer duration of education, and advanced age. The nighttime disturbances domain was significantly associated with lower scores on both cognitive assessments and advanced age. The delusions domain was significantly associated with lower education. CONCLUSIONS: BPSD may appear more easily with reduced quality of life and ongoing dissatisfaction. Effective individualized services are important for patients with AD, and therefore, we should account for age, cognitive function, and duration of education in the services provided.

Autologous Bilayered Adipose-Derived Mesenchymal Cell-Gelatin Sheets Reconstruct Ureters in Rabbits.

Repair of ureteral defects or strictures due to disease or trauma is usually dependent upon surgery that often requires either reoperation or an alternative treatment. By taking advantage of tissue engineering and regenerative techniques, it may be possible to define new approaches to ureteral repair. In this study, we fabricated autologous bilayered adipose-derived mesenchymal cell (AMC)-gelatin sheets and transplanted them into rabbits to replace surgically excised ureteral segments. AMCs harvested from abdominal adipose tissues of female New Zealand white rabbits were cultured on collagen-coated dishes and labeled with PKH26, a red fluorescent dye, for later identification. Monolayers of the cultured PKH26-labeled AMCs were detached and applied to gelatin hydrogel sheets. Two gelatin sheets were then united with the AMC monolayers apposed together, forming a bilayered AMC-gelatin sheet. Following each partial ureterectomy, a bilayered autologous AMC-gelatin sheet was transplanted, joining the proximal and distal ends of the remaining ureter (n = 9). Control animals underwent the same procedure except that the transplant was achieved with a bilayered acellular-gelatin sheet (n = 9). At 4 and 8 weeks after transplantation, the proximal regions of ureters treated with the control bilayered acellular-gelatin sheets exhibited flexures and dilations, which are not characteristic of unoperated ureters. In contrast, the bilayered AMC-gelatin sheet-transplanted rabbits did not have ureteral flexures or dilations. About midway between the proximal and distal ends, both the control and experimental reconstructed ureteral walls had smooth muscle layers; however, those in the experimental reconstructed ureteral walls were significantly thicker and better organized than those in the control reconstructed ureteral walls. Some AMCs differentiated into smooth muscle marker-positive cells. The experimental ureteral walls contained smooth muscle cells derived from the PKH26-labeled AMCs and others that were derived through migration and differentiation of cells from the remaining proximal and distal ends of the original ureter. In addition, the lumina of the 8-week reconstructed ureteral tissues in experimental rabbits did not show histological strictures as seen in the control ureters. These results suggest that the bilayered AMC-gelatin sheets have the potential to replace defective tissues and/or reconstruct damaged ureters. Impact Statement To reconstruct ureter tissues following partial ureterectomy, we fabricated bilayered adipose-derived mesenchymal cell (AMC)-gelatin sheets based on cell sheet engineering principles. The bilayered AMC-gelatin sheets were transplanted into rabbits to replace a surgically excised ureteral segment. At 4 and 8 weeks after, the ureters that received bilayered AMC-gelatin sheets did not exhibit severe flexures, dilations, or strictures. The experimental ureteral walls had smooth muscle marker-positive cells that were differentiated from the AMCs, and similar cells were present in the adjacent intact ureteral tissues. Therefore, the bilayered AMC-gelatin sheets have the potential to reconstruct ureters damaged through disease or trauma.

Performance evaluation of the new chemiluminescent intact FGF23 assay relative to the existing assay system.

INTRODUCTION: This study assessed the performance of a new fully automated immunoassay for fibroblast growth factor (FGF) 23 (Determinar CL FGF23 CL) among healthy individuals and those with chronic hypophosphatemia compared with the previous assay (Kainos FGF23 KI). MATERIALS AND METHODS: A total of 380 serum samples from healthy participants were collected to determine the reference range of FGF23 levels with CL. A total of 200 serum samples from 22 hypophosphatemic patients were collected simultaneously to compare the difference in FGF23 levels between CL and KI. The Mann-Whitney U test and linear regression analysis were adopted to assess the differences and linearity between the two assays. RESULTS: The median FGF23 levels among healthy individuals was 31.7 (interquartile: 26.4-37.5) pg/mL. When the reference range was calculated as the mean ± 2 standard deviation (2SD), it was 16.1-49.3 pg/mL. A total of 363 individuals (96%) among normal cases fell in this range. Among 200 samples from patients with chronic hypophosphatemic disorder, the median FGF23 levels analyzed by CL and KI were 123.0 (90.2-237.7) and 172.5 (115.8-290.7) pg/mL. KI yielded significantly higher FGF23 values than CL (p < 0.001). A linear regression model revealed the correlation between KI (x) and CL (y), which had a slope of 0.76 with a y-intercept of -0.32 and high linearity (R2 = 0.99). CONCLUSION: The new measurement kit yielded lower FGF23 values when compared with the previous assay. Clinicians should consider this discrepancy when they assay intact FGF23 values with CL.

Age-Related Changes in Instrumental and Basic Activities of Daily Living Impairment in Older Adults with Very Mild Alzheimer's Disease.

BACKGROUND/AIMS: Age-related changes in impairments in activities of daily living (ADL) in older adults with very mild Alzheimer's disease (vmAD) have been scarcely explored. We clarified the characteristics of ADL impairment and examined how ADL impairments differed by age in such patients compared with community-dwelling cognitively normal older adults. METHODS: The participants were 107 older adults with vmAD (Mini-Mental State Examination [MMSE] score ≥24), all of whom were first-visit outpatients at the Dementia Clinic of the Department of Neuropsychiatry, Kumamoto University Hospital. The controls were 682 community-dwelling older adults who participated in the 3rd Nakayama Study with MMSE score ≥24. We examined the association of instrumental and basic ADL (IADL and BADL, respectively) independence with the odds of vmAD using multiple logistic regression analysis and determined differences in ADL impairment by age using age- and sex-matched analysis. RESULTS: Impairments in handling finances (OR 57.08), managing medication (OR 5.13), and dressing (OR 3.35; BADL) were associated with greater odds of vmAD. Among those aged 65 years and above, there were fewer patients with vmAD than healthy controls who could independently handle finances and medication. Among patients with vmAD, the percentages of those who could independently manage shopping, food preparation, and housekeeping only decreased after age 74. Age-related decreases in independence were observed in few BADL items; these, however, were temporary. CONCLUSIONS: Patients with vmAD show significantly decreased IADL independence from early old age.

Instrumental Activities of Daily Living: The Processes Involved in and Performance of These Activities by Japanese Community-Dwelling Older Adults with Subjective Memory Complaints.

Subjective memory complaints (SMCs) may predict the onset of dementia. The purpose of this study was to clarify characteristics of performance of activities of daily living (ADL) for older adults with SMCs and to offer support options that enable them to maintain their community-based lifestyle. A self-administered questionnaire was sent to 2000 randomly selected members of CO-OP Kagoshima, and 621 responded. 270 responders answered all questions were categorized into SMC (+) group and SMC (-) group (n = 133). Participants were evaluated the Process Analysis of Daily Activity for Dementia. A 2-sample t-test or the Chi-square test were used to compare the averages of continuous variables or the proportions of categorical variables. The results showed the SMC (+) group ranked significantly lower in ability to use the telephone, shop, cook, do housekeeping, manage finances, and manage medications compared with the SMC (-) group. In addition, the SMC (+) group was significantly less independent than the SMC (-) group in many processes requiring the use of tools, operation of machines, management of goods, selection of tools, and monitoring. To enable continued independence of older adults' experiencing SMCs, it may be important to analyze their performance of ADL and to develop plans for supporting their strengths.

Creation of haemoglobin A1c direct oxidase from fructosyl peptide oxidase by combined structure-based site specific mutagenesis and random mutagenesis.

The currently available haemoglobin A1c (HbA1c) enzymatic assay consists of two specific steps: proteolysis of HbA1c and oxidation of the liberated fructosyl peptide by fructosyl peptide oxidase (FPOX). To develop a more convenient and high throughput assay, we devised novel protease-free assay system employing modified FPOX with HbA1c oxidation activity, namely HbA1c direct oxidase (HbA1cOX). AnFPOX-15, a modified FPOX from Aspergillus nidulans, was selected for conversion to HbA1cOX. As deduced from the crystal structure of AnFPOX-15, R61 was expected to obstruct the entrance of bulky substrates. An R61G mutant was thus constructed to open the gate at the active site. The prepared mutant exhibited significant reactivity for fructosyl hexapeptide (F-6P, N-terminal amino acids of HbA1c), and its crystal structure revealed a wider gate observed for AnFPOX-15. To improve the reactivity for F-6P, several mutagenesis approaches were performed. The ultimately generated AnFPOX-47 exhibited the highest F-6P reactivity and possessed HbA1c oxidation activity. HbA1c levels in blood samples as measured using the direct assay system using AnFPOX-47 were highly correlated with the levels measured using the conventional HPLC method. In this study, FPOX was successfully converted to HbA1cOX, which could represent a novel in vitro diagnostic modality for diabetes mellitus.

Morphological and clinical evaluation of prostatic urethra using modified sonourethrography with retrograde jelly injection.

OBJECTIVE: Using modified sonourethrography (mSUG) with retrograde jelly injection to precisely measure the morphological characteristics of the prostatic urethra, we assessed prostatic urethral morphology associated with clinical parameters of benign prostatic hyperplasia (BPH). METHODS: BPH patients (n = 43) and control patients with localized prostate cancer (PC; n = 57) were imaged by mSUG before surgery. Using the seminal colliculus as a landmark, prostatic urethral angulation (PUA), sagittal urethral diameter, and anterior or posterior prostatic urethral length were measured. The International Prostatic Symptoms Score (IPSS) was also evaluated in all patients. The Bladder Outlet Obstruction Index (BOOI) was measured in BPH patients that could void in a pressure-flow study. Parameters were compared between BPH and PC patients, and correlations among morphological and clinical parameters were evaluated. RESULTS: Prostatic urethras were clearly observed in all patients by mSUG. PUA, sagittal urethral diameter, and posterior urethral length were all greater in BPH than PC patients (P < .05). Among all parameters examined, PUA had the strongest correlation with IPSS (r = 0.56). Longitudinal urethral diameter showed the strongest correlation with BOOI, whereas PUA was not correlated with BOOI. CONCLUSIONS: Prostatic urethral morphology can be imaged precisely by mSUG. Morphometric measurements showed that increased PUA was strongly correlated with problematic urinary symptoms, and a flattened shape of the posterior urethra, such as extension of the sagittal urethral diameter, was correlated with urinary tract obstruction by BPH.

Preanesthetic severe postural hypotension following 5-aminolevulinic acid pretreatment in patients for photodynamic diagnosis-assisted urological surgery.

BACKGROUND: 5-Aminolevulinic acid (5-ALA) is utilized for photodynamic diagnosis-assisted (PDD) surgery. However, it has been associated with vasodilation, hence, occasional hypotension. CASE PRESENTATION: We encountered two patients who had severe postural hypotension following 5-ALA pretreatment prior to an operation. They were scheduled for urological PDD surgery, but upon standing to walk to the operation room, they felt sick because of severe hypotension. One of them underwent the surgery after recovery, but the other surgery was canceled due to a prolonged hypotension that lasted for more than a day. CONCLUSIONS: Severe postural hypotension may develop as a result of the high concentration of porphyrin precursors, which may affect the nervous system. Severe postural hypotension may be due to 5-ALA-induced autonomic dysfunction as well as vasodilative action of 5-ALA. These observations suggest that in addition to the careful monitoring of patients' vital signs, standing should be avoided following 5-ALA pretreatment.

Overactive bladder.

Overactive bladder (OAB) is a storage symptom complex that includes urinary urgency with or without urge incontinence, urinary frequency and nocturia. OAB is common symp- tom complex and its morbidity is high and increased with age. Although many factors cause OAB, we can classify them as neurogenic or non-neurogenic. To diagnose OAB, we need to ask a patient about his condition using Overactive Bladder Symptom Score (OABSS), exam- ine physical findings and urinalysis. And we also need to exclude other urinary tract diseases that make bladder irritation. Pharmacotherapy and behavior therapy are useful for improving OAB symptoms. Anticholinergic agents are utilized for OAB treatment but we need to pay attention to the adverse effects.

Plasma levels of natriuretic peptides and development of chronic kidney disease.

BACKGROUND: Plasma levels of atrial and brain natriuretic peptides (ANP and BNP) are increased in patients with chronic kidney disease (CKD) complicated with deteriorated kidney function, but the relationship between the plasma level of ANP or BNP and the future development of CKD is unclear. METHODS: We measured the plasma ANP and BNP levels of 294 local residents without CKD in a Japanese community (56.5 ± 10.4 years, mean ± S.D.), who were followed up for the development of CKD over the next 7 years. RESULTS: Sixty-three residents developed CKD during the follow-up period, and the baseline level of plasma ANP of these residents was significantly higher than in those without CKD development. Kaplan-Meier analysis showed that the residents with higher ANP than the median value developed CKD more frequently than those with lower ANP. The association between plasma ANP level and CKD development was found to be independent of baseline estimated glomerular filtration rate by a Cox proportional hazards model, while this association became insignificant when adjusted by age; plasma ANP was significantly correlated with age. Compared with ANP, the relationship between plasma BNP and CKD development was unclear in these analyses. CONCLUSIONS: Age-related elevation of plasma ANP levels preceded the development of CKD in the general population of Japan, raising a possibility for ANP being involved in the development of CKD.

Intervention for several behavioural disorders in Alzheimer's-type dementia.

In Alzheimer's-type dementia, significant nerve cell degeneration is seen in the medial temporal lobe, including the hippocampal region, and in the temporoparietal association area. As symptoms progress, impairments in various behaviours begin to occur in daily life. In particular, higher brain dysfunction, including parietal association area dysfunction, are major impediments to providing care or rehabilitation. Herein, we explain behavioural disorders stemming from higher brain dysfunction and discuss the methodology in providing specific care and appropriate rehabilitation. To provide appropriate rehabilitation, it is important to properly assess the causes of behavioural disorder by organizing the characteristics of symptoms, the person and the environment.

Purification and characterization of paralytic shellfish toxin-transforming enzyme, sulfocarbamoylase I, from the Japanese bivalve Peronidia venulosa.

The Japanese bivalve Peronidia venulosa contains paralytic shellfish toxin (PST)-transforming enzymes that convert the weakly toxic C-toxins to the more potent decarbamoyl toxins. The enzyme was purified 154-fold with a yield of 0.26% and was named sulfocarbamoylase I. It was found to be a protein with an estimated molecular weight of 300 kDa by gel filtration column chromatography. Observation of a single band equivalent to 150 kDa on SDS-PAGE with or without reducing agents suggested it to be a homodimer with ionically bound subunits. The enzyme catalyzes the hydrolysis of the carboxyl bond in the N-sulfocarbamoyl moiety of PSP-toxins. The sulfonyl moiety in the carbamoyl side chain of substrates is essential for enzyme recognition. The N-terminal amino acid sequences of nine tryptic peptides were determined by the Edman degradation method. In a database search using the BLAST program, no protein that shows remarkable homology was retrieved. Several characteristics of the enzyme were also compared with those of another PST-transforming enzyme, carbamoylase I, which was previously isolated from the Japanese clam Mactra chinensis.