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Aims/Introduction: To investigate the changes in the glycated hemoglobin (HbA1c) levels and the relative status of the glycemic control related to the new glycemic targets recommended by the Japan Diabetes Society/Japan Geriatrics Society Joint Committee in 2016 in patients with diabetes mellitus visiting a memory clinic from 2012 to 2020. Materials and Methods: This cross‐sectional study included 1,436 patients aged ≥65 years with diabetes. Patients were categorized into three categories as follows: category I, intact cognitive function and activities of daily living (ADL); category II, mild cognitive deficits or impaired instrumental ADL; and category III, moderate to severe cognitive impairment or impaired basic ADL. Trends in HbA1c levels, glycemic control status (optimally/poorly/excessively controlled) and proportion of individuals receiving drugs potentially associated with severe hypoglycemia among all patients and categories (I, II or III) from 2012 to 2020 were examined using linear, logistic and multinominal logistic regression models adjusted for confounding factors. Results: Between 2012 and 2020, the HbA1c levels, as well as the proportion of patients with poor glycemic control, increased, whereas the proportion of patients with excessive glycemic control and those receiving drugs potentially associated with severe hypoglycemia decreased. Conclusions: Increased levels of HbA1c and decreased proportions of individuals under excessive glycemic control might reflect recent treatment strategies that avoid hypoglycemia in older patients. Given the adverse complications associated with hyperglycemia, more flexible and individualized glycemic targets based on comprehensive assessments, including vascular complications and comorbidities, might be necessary. [ABSTRACT FROM AUTHOR]

Background: Gait disturbance and musculoskeletal changes are evident in persons living with Alzheimer's disease (AD). Because complex gait control requires the integration of neural networks, cerebral small vessel disease (SVD), which is highly prevalent in persons with AD, might have an additional impact on gait disturbance. This study investigated whether white matter hyperintensities (WMH) are more predominantly associated with gait disturbance in persons with AD than in individuals with mild cognitive impairment (MCI) and normal cognition (NC) and further identified the regional impact of WMH on specific gait changes. Methods: This study included 396 subjects (aged 65 to 86 years, 63.9% female) diagnosed with AD (n = 187), MCI (n = 118), or NC (n = 91). WMH, lacunes, perivascular spaces, and cerebral microbleeds were assessed as markers of SVD. The volume of WMH was quantified in each brain lobe (frontal, temporal, occipital, and parietal) and sublobar regions in the basal ganglia and thalamus. Gait function was assessed using an electronic walkway. We investigated the association between regional WMH and gait disturbance in individuals with AD, MCI, and NC, adjusted for classical and musculoskeletal confounders. Results: Among markers of SVD, WMH were most associated with gait disturbance. In AD subjects, periventricular WMH in the frontal and parietal lobes were associated with slow gait speed (rs = −0.21, P = 0.007 and rs = −0.18, P = 0.019, respectively). These lesions were also associated with changes in stride time, double‐leg support time, and walking angle (all rs > 0.20, P < 0.01). Lesions in the basal ganglia and thalamus were associated with slow gait speed (rs = −0.16, P = 0.034 and rs = −0.18, P = 0.023, respectively) and greater gait speed variability (rs = 0.16, P = 0.034 and rs = 0.20, P = 0.010, respectively). MCI subjects showed only associations between sublobar lesions and shorter stride length (rs = −0.24, P = 0.016) and increased walking angle (rs = 0.32, P = 0.002). NC subjects did not show associations between WMH and gait parameters. MCI and NC subjects were more affected by muscle weakness than WMH for global gait function (rs = 0.42, P < 0.001 and rs = 0.23, P = 0.046, respectively). Conclusions: Persons with AD showed a predominant association between WMH and gait disturbance compared with MCI and NC subjects, and regional WMH had a detrimental effect on specific gait changes. [ABSTRACT FROM AUTHOR]

Background: The development of diagnostic tools to identify disease risk is critical to enable selection of suitable individuals for inclusion in clinical trials, cohort studies and ultimately to identify patients most likely to benefit from newly approved therapies. Cytox has developed and validated a polygenic risk scoring (PRS) algorithm, genoSCORETM, for predicting the Late Onset Alzheimer's disease (AD) based on the work pioneered by Escott‐Price, Williams et al 1. However, both training and testing has been performed in study populations containing primarily individuals with Caucasian ethnicity. To ensure that genoSCORE can equally be applicable to all ethnic groups, we have conducted an initial evaluation to understand predictive accuracy for the onset of AD in a Japanese population. Methods: The PRS approach used in this study is built from a sum of weighted contributions of over 100,000s SNPs associated with disease2. Due to the limited SNP coverage of existing genetic data, we only used 63,499 SNPs and utilized the core genoSCORE algorithm to calculate PRS in a cohort of 2,081 AD and 2,327 CN Japanese subjects from J‐ADNI3 and Niigata University. Results: The preliminary result shows an AUC of 0.659 (0.643‐0.675, 95% CI) between AD and CN subjects while PRS presents a bimodal distribution, but the main distribution trend is comparable to a normal distribution of PRS of the ADNI (US) subjects. Although this is significantly less than that seen for Caucasian individuals in the ADNI study, it compares well with the results generated when the reduced number of SNPs are used only in the ADNI cohort subjects (AUC = 0.691). Conclusions: The preliminary results show the potential use of genoSCORE in the Japanese population. However, the results are likely affected by the limited SNP coverage from the available genetic data for the Japanese population. To determine the true performance of the genoSCORE algorithm in a Japanese population, genotyping samples from this study using our proprietary variaTECTTM II array providing full SNP coverage is in progress. We will then determine the performance and make adjustments to the algorithm if required in a Japanese population of suitably characterized Alzheimer's disease patients and age‐matched healthy controls. [ABSTRACT FROM AUTHOR]

Bladder cancer is the 9th leading cause of cancer death worldwide. The major problem in bladder cancer is primarily the high recurrence rate after drug treatment and resection. Although conventional screening methods, such as cystoscopy, urinary cytology and ultrasound sonography, have become widely used in clinical settings, the diagnostic performance of these modalities is unsatisfactory due to low accuracy or high invasiveness. Because circulating micro RNA (miRNA) profiles have recently been reported as an attractive tool for liquid biopsy in cancer screening, here, we performed global miRNA profiling of 392 serum samples of bladder cancer patients with 100 non‐cancer samples and 480 samples of other types of cancer as controls. We randomly classified the bladder cancer and control samples into 2 cohorts, a training set (N = 486) and a validation set (N = 486). By comparing both controls, we identified specific miRNA, such as miR‐6087, for diagnosing bladder cancer in the training and validation sets. Furthermore, we found that a combination of 7 miRNA (7‐miRNA panel: miR‐6087, miR‐6724‐5p, miR‐3960, miR‐1343‐5p, miR‐1185‐1‐3p, miR‐6831‐5p and miR‐4695‐5p) could discriminate bladder cancer from non‐cancer and other types of tumors with the highest accuracy (AUC:.97; sensitivity: 95%; specificity: 87%). The diagnostic accuracy was high, regardless of the stage and grade of bladder cancer. Our data demonstrated that the 7‐miRNA panel could be a biomarker for the specific and early detection of bladder cancer. The present study selected 7 miRNA expression levels among bladder cancer, non‐cancer and other cancer samples. A diagnostic index was calculated and plotted in the dot plot among 12 different cancers. An index score ≥0 indicated the presence of bladder cancer and an index score <0 indicated the absence of bladder cancer. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA), which are stably present in serum, have been reported to be potentially useful for detecting cancer. In the present study, we examined the expression profiles of serum miRNA in several large cohorts to identify novel miRNA that can be used to detect early stage breast cancer. We comprehensively evaluated the serum miRNA expression profiles using highly sensitive microarray analysis. A total of 1280 serum samples of breast cancer patients stored in the National Cancer Center Biobank were used. In addition, 2836 serum samples were obtained from non-cancer controls, 451 from patients with other types of cancers, and 63 from patients with non-breast benign diseases. The samples were divided into a training cohort including non-cancer controls, other cancers and breast cancer, and a test cohort including non-cancer controls and breast cancer. The training cohort was used to identify a combination of miRNA that could detect breast cancer, and the test cohort was used to validate that combination. miRNA expressions were compared between patients with breast cancer and non-breast cancer, and a combination of five miRNA (miR-1246, miR-1307-3p, miR-4634, miR-6861-5p and miR-6875-5p) was found to be able to detect breast cancer. This combination had a sensitivity of 97.3%, specificity of 82.9% and accuracy of 89.7% for breast cancer in the test cohort. In addition, this combination could detect early stage breast cancer (sensitivity of 98.0% for Tis). [ABSTRACT FROM AUTHOR]

Aim Lower urinary tract symptoms often limit activities of daily life and impair quality of life in the elderly. The purpose of the present study was to determine whether regional white matter hyperintensity ( WMH) can predict lower urinary tract symptoms in elderly with amnestic mild cognitive impairment or Alzheimer's disease. Methods The participants were 461 patients aged 65-85 years diagnosed with amnestic mild cognitive impairment or Alzheimer's disease. Patients and their caregivers were asked about symptoms of lower urinary tract symptoms (urinary difficulty, frequency and incontinence). Cognition, behavior and psychological symptoms of dementia and medication were evaluated. WMH and brain atrophy were analyzed using an automatic segmentation program. Regional WMH was evaluated in the frontal, parietal, temporal and occipital lobes. Results Patients with urinary incontinence showed significantly greater volume of WMH. WMH increased with age, especially in the frontal lobe. WMH in the frontal lobe was closely associated with urinary incontinence after adjustment for brain atrophy and classical confounding factors. Conclusions Frontal WMH was a predictive factor for urinary incontinence in older adults with amnestic mild cognitive impairment or Alzheimer's disease. Urinary incontinence in demented older adults is not an incidental event, and careful insight into regional WMH on brain magnetic resonance imaging might greatly help in diagnosing individuals with a higher risk of urinary incontinence. Geriatr Gerontol Int 2016; 16: 167-174. [ABSTRACT FROM AUTHOR]

The article presents a study on the analysis of white matter hyperintensity (WMH), a common finding in the aging brain, which highlights the accuracy of the newly developed modified Rotterdam visual rating scale. The cubed values of the scale are found to have a good correlation with the WMH. WHM is also noted to be involved with the development of various geriatric conditions and it increases with age.

Background and aims: The localized occlusion of bile ducts by intrahepaticlithiasis and intrahepatic neoplasms dose not cause severe jaundice, although the reason is unclear. The aim of this study was to clarify the molecular change of the liver in partial cholestasis, especially with respect to transporter expression (Mrp2, Mrp3, Bsep, P-gps) and membrane fluidity. Methods and results: After 3 days of selective bile duct ligation in Sprague–Dawley rats, the obstructed lobe (OL) and non-OL were analyzed. Canalicular and sinusoidal membrane fluidity were decreased in the OL compared with the non-OL. Mrp2 protein expression was significantly lower in the OL (by 62.9±6.9%) when compared with the non-OL. Mdr1b and Mdr2 mRNA were up-regulated in the OL when compared with the non-OL. Interestingly, Mrp3 protein and mRNA were induced in both the non-OL and OL of rats without hyperbilirubinemia. Conclusions: It seems that the reduction of membrane fluidity in the OL is a local response to localized cholestasis, while the induction of Mrp3 observed in both the OL and non-OL may be a response of the whole liver to localized impairment of bile secretion, although the regulatory mechanism is yet to be established. [Copyright &y& Elsevier]

Background: Late‐onset Alzheimer's disease (LOAD) is a neurodegenerative disease characterized by cognitive impairment and has a high heritability of 60%–80%. The genetic factor, with the strongest influence identified to date, that is associated with the increased risk of LOAD is the APOE ε4 allele. However, the APOE alleles only explain approximately 6% of LOAD phenotypic variance, and other genetic factors may be responsible for the remainder. The polygenic model explains complex traits, including diseases based on multiple single nucleotide polymorphisms (SNPs) with weak effects as well as several dozen SNPs identified by genome‐wide association studies (GWASs). Recent studies have reported that the polygenic risk score (PRS), which is an index that quantifies polygenic effects, increased the ability to discriminate LOAD patients and correlated with the amount of amyloid β in cerebrospinal fluid. In this study, we calculated PRSs for approximately 2,000 Japanese people using the European LOAD GWAS statistics provided by a previous study. To examine the discrimination ability for LOAD patients, we compared ones between PRSs calculated using the LOAD GWAS statistics and PRSs computed using the GWAS statistics in other diseases. Additionally, we also compared the discrimination ability by LOAD PRS with that of APOE ε4 variation only. Method: PRS was calculated for each individual as the weighted linear sum of the genotypes of SNPs and the GWAS statistics, including the p‐values or the odds ratios. In this study, we utilized the GWAS statistics from psychiatric disorders, including schizophrenia, and non‐psychiatric disorders, including type 2 diabetes. We performed bootstrapping to evaluate the discrimination ability for LOAD patients and simulation analysis to discuss the differences between populations. Result: The predictive powers of LOAD were significantly higher than those from other diseases. With GWAS statistics of the same population, the accuracy prominently increased. Conclusion: We demonstrated the polygenic effects of LOAD in the Japanese population. Our simulation analysis suggested that PRS constructed based on LOAD GWAS statistics in the same population increased the discrimination ability for LOAD patients. [ABSTRACT FROM AUTHOR]