Dual Sensory Impairment Predicts an Increased Risk of Postdischarge Falls in Older Patients.

OBJECTIVES: The purpose of this study was to determine the associations of vision impairment, hearing impairment, and comorbid vision and hearing impairment [ie, dual sensory impairment (DSI)] on admission to hospital with falls within 3 months of discharge in older patients. DESIGN: This prospective multicenter study included patients admitted to and discharged from geriatric wards at 3 university hospitals and 1 national medical center in Japan between October 2019 and July 2023. SETTING AND PARTICIPANTS: Of 1848 individuals enrolled during the study period, 1141 were excluded, leaving 707 for inclusion in the analysis. METHODS: Participants' background factors were compared in terms of whether they had a fall during the 3 months postdischarge. Logistic regression analysis was then performed using the presence or absence of falls after discharge as the objective variable. Three models were created using vision impairment, hearing impairment, and DSI as covariates. Other covariates included physical function, cognitive function, and depression. In addition, logistic regression analysis was performed with falls during hospitalization as the objective variable. RESULTS: DSI was significantly more common in the falls group (P = .004). Logistic regression analysis showed that the risk of falls after discharge was higher in patients with DSI (odds ratio 3.432, P = .006) than in those with vision or hearing impairment alone. When adjusted for physical function, cognitive function, depression, and discharge location, DSI was significantly associated with an increased risk of falls after discharge (odds ratio 3.107, P = .021). The association between DSI and falls during hospitalization did not reach statistical significance, but a trend was observed. CONCLUSIONS AND IMPLICATIONS: This study is the first to show an association between DSI and falls after discharge. Simple interventions for patients with DSI may be effective in preventing falls, and we suggest that they be actively implemented early during hospitalization.

Prevalence of sleep disturbances in people with mild cognitive impairment: A systematic review and meta-analysis.

This review was performed to determine sleep disturbance prevalence in individuals with mild cognitive impairment (MCI). The MEDLINE, Embase, Cochrane Library, CINAHL, PsycINFO, and Web of Science databases were systematically searched from inception to January 20, 2024. Fifty-two studies fulfilling the eligibility criteria were included. However, six of these studies were excluded from data synthesis due to poor methodological quality. The subjective sleep disturbance prevalence among all individuals with MCI was 35.8 % (95 % CI: 31.9-39.7) across 44 studies, and the objective sleep disturbance prevalence was 46.3 % (95 % CI: 36.3-56.3) across 6 studies. Five studies examined TST and WASO, while three assessed SE. Among all potential objective assessments of sleep disturbance prevalence, only TST, WASO, and SE could be meta-analyzed in MCI because of the limited number of studies available. The estimated sleep disturbance prevalence differed significantly according to measurement method, geographical region, and research design. However, the data source did not significantly influence prevalence estimates. In meta-regression analysis, publication year, participant age, percentage of females, and study quality did not predict prevalence. As subjective and objective sleep disturbances are common in people with MCI, effective intervention strategies should be developed to alleviate them.

Impact of nurse-led interprofessional work in older patients with heart failure and multimorbidity: A retrospective cohort study.

Background: The number of patients with multimorbidity has increased due to the aging of the global population. Although the World Health Organization has indicated that multimorbidity will be a major medical problem in the future, the appropriate interventions for patients with multimorbidity are currently unknown. This study aimed to investigate whether nurse-led interprofessional work is associated with improved prognosis in heart failure patients with multimorbidity aged ≥65 years who were admitted in an acute care hospital. Methods: Patients who were admitted to the cardiovascular medicine ward of an acute care hospital in Osaka, Japan, and underwent nurse-led interprofessional work from April 1, 2017 to March 31, 2020, and from April 1, 2014 to March 31, 2016, were included in this retrospective cohort study. The patients were matched by age, sex, and New York Heart Association classification. The nurse-led interprofessional work was based on a three-step model that incorporates recommendations from international guidelines for multimorbidity. The primary outcome was all-cause mortality. Results: The mean age of the participants was 80 years, and 62 % were men. The nurse-led interprofessional work group showed a significant difference in all-cause mortality compared with the usual care group (hazard ratio, 0.45; 95 % confidence interval [CI], 0.29-0.69; P < 0.001). Compared with the usual care group, the nurse-led interprofessional work group exhibited a 7 % difference in mortality rate at 1-year post-discharge (P < 0.001). Conclusions: Nurse-led interprofessional work may reduce the all-cause mortality in older patients with heart failure and multimorbidity.

Imaging Biomarker for Early-Stage Alzheimer Disease: Utility of Hippocampal Histogram Analysis of Diffusion Metrics.

BACKGROUND AND PURPOSE: Biomarkers have been required for diagnosing early Alzheimer disease. We assessed the utility of hippocampal diffusion parameters for diagnosing Alzheimer disease pathology in mild cognitive impairment. MATERIALS AND METHODS: Sixty-nine patients with mild cognitive impairment underwent both CSF measurement and multi-shell diffusion imaging at 3T. Based on the CSF biomarker level, patients were classified according to the presence (Alzheimer disease group, n = 35) or absence (non-Alzheimer disease group, n = 34) of Alzheimer disease pathology. Neurite orientation dispersion and density imaging and diffusion tensor imaging parametric maps were generated. Two observers independently created the hippocampal region of interest for calculating histogram features. Interobserver correlations were calculated. The statistical significance of intergroup differences was tested by using the Mann-Whitney U test. Logistic regression analyses, using both the clinical scale and the image data, were used to predict intergroup differences, after which group discriminations were performed. RESULTS: Most intraclass correlation coefficient values were between 0.59 and 0.91. In the regions of interest of both observers, there were statistically significant intergroup differences for the left-side neurite orientation dispersion and density imaging-derived intracellular volume fraction, right-side diffusion tensor imaging-derived mean diffusivity, left-side diffusion tensor imaging-derived mean diffusivity, axial diffusivity, and radial diffusivity (P < .05). Logistic regression models revealed that diffusion parameters contributed the most to discriminating between the groups. The areas under the receiver operating characteristic curve for the regions of interest of observers A/B were 0.69/0.68, 0.69/0.68, 0.73/0.68, 0.71/0.68, and 0.68/0.68 for the left-side intracellular volume fraction (mean), right-side mean diffusivity (mean), left-side mean diffusivity (10th percentile), axial diffusivity (10th percentile), and radial diffusivity (mean). CONCLUSIONS: Hippocampal diffusion parameters might be useful for the early diagnosis of Alzheimer disease.

Expressed Emotion in Families of People With Dementia: A Review of Scale-Based Measures.

PURPOSE: Research on the concept of expressed emotion (EE) has expanded in recent years but its role in dementia still requires elucidation. Understanding the role of EE in the dementia context could help in the development of appropriate interventions. METHOD: The current review synthesized relevant literature to investigate the prevalence and correlates of EE status in families of people with dementia. A comprehensive search of four databases from inception to 2022 produced 2,683 papers; 18 studies met inclusion criteria. RESULTS: The use of EE criteria differed not only across cultural contexts, but even within the same cultural context. Overall, the prevalence of EE in families with dementia compared with other psychiatric conditions was not high. CONCLUSION: Specific changes in EE over time remain to be explored, and findings emphasize the need to carefully discriminate High EE status based on the cultural background of family members with dementia. [Journal of Gerontological Nursing, 50(2), 17-25.].

Effect of sleep report feedback using information and communication technology combined with health guidance on improving sleep indicators in community-dwelling older people: a pilot trial.

BACKGROUND: This study evaluated the preliminary effect of an integrated novel intervention comprising visualised sleep report feedback using information and communication technology and periodic health guidance on improving sleep indicators among community-dwelling older people. METHODS: The intervention was implemented among 29 older people in Sakai City, Japan, in a 3 months pilot trial. Non-worn actigraph devices were placed under participants' bedding to continuously measure their sleep state, and they received monthly sleep reports in writing. Sleep efficiency, total sleep time, sleep latency, and the number of times away from bed were recorded. A trained nurse expertly interpreted participants' sleep data and provided telephone health guidance. The first month's data were used as the baseline (T1), the second month provided data for the first intervention (T2), and the third month provided data for the second intervention (T3). Friedman tests and Wilcoxon signed-rank tests were used to examine differences in sleep outcomes between different time points. RESULTS: Participants' mean age was 78.97 ± 5.15 years, and 51.72% (15/29) were female. Comparison of T2 and T1 showed the intervention decreased participants' sleep latency at T2 (P = 0.038). Compared with T1, the intervention significantly decreased sleep latency (P = 0.004), increased total sleep time (P < 0.001), and improved sleep efficiency (P < 0.001) at T3. When T3 was compared with T2, only total sleep time was significantly increased (P < 0.001). There were no significant differences in the number of times away from bed across the three time points (P > 0.05). CONCLUSIONS: This visualised sleep report feedback and periodic health guidance intervention for community-dwelling older people showed promising, albeit small preliminary effects on sleep. A fully powered randomised controlled trial is required to verify the significance of this effect.

Factors associated with weight loss by age among community-dwelling older people.

BACKGROUND: Factors associated with weight loss in community-dwelling older people have been reported in several studies, but few studies have examined factors associated with weight loss by age groups. The purpose of this study was to clarify factors associated with weight loss by age in community-dwelling older people through a longitudinal study. METHODS: Participants in the SONIC study (Longitudinal Epidemiological Study of the Elderly) were community-dwelling people aged 70 or older. The participants were divided into two groups: 5% weight loss and maintenance groups, and compared. In addition, we examined factors affecting weight loss by age. The analysis method used was the χ2 test, and the t-test was used for comparison of the two groups. Factors associated with 5% weight loss at 3 years were examined using logistic regression analysis with sex, age, married couple, cognitive function, grip strength, and the serum albumin level as explanatory variables. RESULTS: Of the 1157 subjects, the proportions showing 5% weight loss after 3 years among all subjects, those aged 70 years, 80 years, and 90 years, were 20.5, 13.8, 26.8, and 30.5%, respectively. In logistic regression analysis, factors associated with 5% weight loss at 3 years by age were influenced by BMI of 25 or higher (OR = 1.90, 95%CI = 1.08-3.34, p = 0.026), a married couple (OR = 0.49, 95% = 0.28-0.86, p = 0.013), serum albumin level below 3.8 g/dL (OR = 10.75, 95% = 1.90-60.73, p = 0.007) at age 70, and the grip strength at age 90 (OR = 1.24, 95%CI = 1.02-1.51, p = 0.034), respectively. CONCLUSIONS: The results suggest that factors associated with weight loss by age in community-dwelling older people through a longitudinal study differ by age. In the future, this study will be useful to propose effective interventions to prevent factors associated with weight loss by age in community-dwelling older people.

Longitudinal association of hypertension and dyslipidemia with cognitive function in community-dwelling older adults: the SONIC study.

The associations among cognitive function, hypertension, and dyslipidemia in older adults are controversial. Therefore, we investigated the associations among cognitive decline, hypertension, dyslipidemia, and their combination in community-dwelling older people in their 70s, 80s, and 90s in the long-term observational Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians (SONIC) study. We administered the Montreal Cognitive Assessment Japanese version (MoCA-J) by trained geriatricians and psychologists, and conducted blood testing and blood pressure (BP) measuring by medical staff involving 1186 participants. We performed multiple regression analysis to assess the relationships among hypertension, dyslipidemia, their combination, and lipid and BP levels with cognitive function at the 3-year follow-up after adjusting for covariate factors. At the baseline, the percentage of the combination of hypertension and dyslipidemia was 46.6% (n = 553), hypertension was 25.6% (n = 304), dyslipidemia was 15.0% (n = 178), and that without hypertension or dyslipidemia was 12.7% (n = 151). Conducting multiple regression analysis, no significant correlation was found between the combination of hypertension and dyslipidemia and MoCA-J score. In the group with the combination, high high-density lipoprotein cholesterol (HDL) levels resulted in higher MoCA-J scores at the follow-up (ß = 0.06; P < 0.05) and high diastolic BP (DBP) also resulted in higher MoCA-J scores (ß = 0.08; P < 0.05). The results suggest that high HDL and DBP levels of individuals with HT & DL and high SBP levels of individuals with HT were associated with cognitive function in community-dwelling older adults. In the SONIC study, which is an epidemiological study of Japanese older persons aged 70 years or older, a disease-specific examination suggested that high HDL and DBP levels of individuals with hypertension & dyslipidemia and high SBP levels of individuals with hypertension were associated with maintaining cognitive function in community-dwelling older adults.

Antiepileptic Drugs Modulate Alzheimer-Related Tau Aggregation in a Neuronal Activity-Independent Manner.

INTRODUCTION: A rapidly increasing number of patients with dementia present a serious social problem. Recently, the incidence of epilepsy in patients with Alzheimer's disease (AD) is increasing, drawing attention to the pathological relationship between the two conditions. Clinical studies have suggested the protective action of antiepileptic agents on dementia; however, the underlying mechanism remains unknown. We evaluated the effects of multiple antiepileptic drugs using tau aggregation assay systems to determine the effects of antiepileptic agents on tau aggregation, a major neuropathological finding associated with AD. METHODS: We evaluated the effects of seven antiepileptic agents on intracellular tau aggregation using a tau-biosensor cell-based high-throughput assay. Next, we tested these agents in a cell-free tau aggregation assay using thioflavin T (ThT). RESULTS: The assay results revealed that phenobarbital inhibited tau aggregation, whereas sodium valproate, gabapentin, and piracetam promoted tau aggregation. In the cell-free tau aggregation assay using ThT, we confirmed that phenobarbital significantly inhibited tau aggregation. CONCLUSION: Antiepileptic drugs may modify the tau pathology in AD in a neural activity-independent manner. Our finding may provide an important insight into the optimization of antiepileptic drug therapy in older adults with dementia.

Communication-related experiences of individuals in the early phase of semantic dementia and their families: an interview study.

BACKGROUND: Semantic dementia (SD), a subtype of frontotemporal dementia, manifests as verbal symptoms, including social and behavioural deficits, associated with focal atrophy of the frontotemporal lobes. This study aimed to clarify the experiences of individuals with early-onset SD receiving speech and language rehabilitation (hereafter referred to as 'rehabilitation'), with the intent of making it routine, as well as the experiences of their families. METHODS: Individual interviews were conducted with nine families with members who had adopted rehabilitation. Verbatim transcripts were used as data, and analyzed inductively according to the content analysis process. RESULTS: The family members realised the changes in the personality and behaviour of the individual with SD early, to the extent that they thought the individual with SD was different from before and were distressed by the loss of verbal communication. Nevertheless, the family members found a way to communicate by maintaining residual functions through rehabilitation and utilising their unique relationship with the individual with SD. CONCLUSIONS: It is important to carefully explain the characteristics of the disease and the long-term significance of rehabilitation to individuals with SD and their families in the early stages of the disease.

Lower cognitive function as a risk factor for anemia among older Japanese women from the longitudinal observation in the SONIC study.

AIM: The aging-related increase in the incidence of anemia potentially affects the mortality risk. Lower cognitive function is common among older adults, and anemia is one of the causes of cognitive decline. However, to the best of our knowledge, no study has investigated whether cognitive decline is a risk factor for anemia in older people. Therefore, in this study, we used a 3-year longitudinal evaluation to examine the association of cognitive function with anemia in community-dwelling older adults. METHODS: This longitudinal study enrolled participants without anemia (diagnosed based on the World Health Organization's criteria) at baseline. Cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment. Multiple logistic regression models were used to examine the association between cognitive function at baseline and the presence of anemia 3 years later. RESULTS: Participants were in the 69-71 and 79-81 years age groups, and 974 older people (48.6% men) were enrolled, of whom 126 (12.9%) had anemia after 3 years. After adjusting, cognitive function at baseline was associated with anemia in women, but not in men. CONCLUSIONS: Older Japanese women with lower cognitive function have an increased risk for anemia 3 years later. The adoption of a lifestyle that utilizes or improves cognitive function might be important to prevent anemia in older women. Geriatr Gerontol Int 2023; 23: 334-340.

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer's dementia in Japan.

Background: Several medications have been applied to Alzheimer's dementia patients (AD) but their efficacies have been insufficient. The efficacy and safety of 4 weeks of repetitive transcranial magnetic stimulation (rTMS) in Japanese AD were evaluated in this exploratory clinical trial. Methods: Forty-two patients, aged 60-93 years (average, 76.4 years), who were taking medication (> 6 months) and had Mini-Mental State Examination (MMSE) scores ≤ 25 and Clinical Dementia Rating Scale scores (CDR-J) of 1 or 2, were enrolled in this single-center, prospective, randomized, three-arm study [i.e., 120% resting motor threshold (120% RMT), 90% RMT for the bilateral dorsolateral prefrontal cortex, and Sham]. Alzheimer's Disease Assessment Scale-Japanese Cognitive (ADAS-J cog), Montreal Cognitive Assessment (MoCA-J), Clinical Global Impression of Change (CGIC), Neuropsychiatric inventory (NPI), and EuroQOL 5 Dimensions 5-Level (EQ-5D-5L) were administered. The primary endpoint was the mean change from baseline in the MMSE score (week 4). An active rTMS session involved applying 15 trains bilaterally (40 pulses/train at 10 Hz; intertrain interval, 26 s). Participants received ≥ 8 interventions within the first 2 weeks and at least one intervention weekly in the 3rd and 4th weeks. Full Analysis set (FAS) included 40 patients [120% RMT (n = 15), 90% RMT (n = 13), and Sham (n = 12)]. Results: In the FAS, MMSE, ADAS-J cog, MoCA-J, CDR-J, CGIC, NPI, and EQ-5D-5L scores between the three groups were not significantly different. Two patients were erroneously switched between the 120% RMT and 90% RMT groups, therefore, "as treated" patients were mainly analyzed. Post hoc analysis revealed significant treatment efficacy in participants with MMSE scores ≥ 15, favoring the 120% RMT group over the Sham group. Responder analysis revealed 41.7% of the 120% RMT group had a ≥ 3-point improvement in the ADAS-J cog versus 0% in the Sham group (Fisher's exact test, p = 0.045). The MoCA-J showed the same tendency but was not significant. Efficacy disappeared in week 20, based on the ADAS-cog and MoCA-J. No intervention-related serious adverse events occurred. Conclusion: This paper is the first report of using rTMS in Japanese AD patients. The treatment seems safe and moderate-mild stage AD should be target population of pivotal clinical trial with 120% RMT rTMS.

Lower body mass index potentiates the association between skipping breakfast and prevalence of proteinuria.

Background: Proteinuria is an important predictor of cardiovascular disease and mortality. Several studies reported the association between skipping breakfast and the prevalence of proteinuria. Furthermore, skipping breakfast was associated with an increased risk of obesity. Although proteinuria is highly prevalent in obese individuals, the association between the prevalence of proteinuria and low body mass index (BMI) was reported in a previous cross-sectional study in asymptomatic individuals without known kidney diseases. The aim of this cross-sectional study was to assess the clinical impact of BMI on the association between skipping breakfast and the prevalence of proteinuria in normal renal function subjects. Methods: The present study included 26,888 subjects (15,875 males and 11,013 females) with an estimated glomerular filtration rate ≥60 ml/min/1.73 m2 and no history of kidney disease who underwent a health checkup in Sumitomo Hospital. The association between skipping breakfast and the prevalence of proteinuria (defined as dipstick proteinuria of ≥1+) was assessed using logistic regression models adjusted for clinically relevant factors. Results: Skipping breakfast was reported in 3,306 males (20.8%) and 1,514 females (13.8%). Multivariable adjusted logistic regression models showed that skipping breakfast was significantly associated with the prevalence of proteinuria above 1+. This association was evident in lower BMI subjects, even after adjusting for clinically relevant factors (adjusted odds ratios of males and females were 1.67 [1.17-2.38] and 1.92 [1.31-2.82], respectively), whereas this association was not evident in higher BMI subjects. Conclusion: Lower BMI subjects with proteinuria might need to be careful about skipping breakfast.

Novel pathophysiological roles of α-synuclein in age-related vascular endothelial dysfunction.

Although α-synuclein (SNCA) is a well-known pathological molecule involved in synucleinopathy in neurons, its physiological roles remain largely unknown. We reported that serum SNCA levels have a close inverse correlation with blood pressure and age, which indicates the involvement of SNCA in age-related endothelial dysfunction. Therefore, this study aimed to elucidate the molecular functions of SNCA in the endothelium. We confirmed that SNCA was expressed in and secreted from endothelial cells (ECs). Exogenous treatment with recombinant SNCA (rSNCA) activated the Akt-eNOS axis and increased nitric oxide production in ECs. Treatment with rSNCA also suppressed TNF-α- and palmitic acid-induced NF-κB activation, leading to the suppression of VCAM-1 upregulation and restoration of eNOS downregulation in ECs. As for endogenous SNCA expression, replicative senescence resulted in the attenuation of SNCA expression in cultured ECs, similar to the effects of physiological aging on mice aortas. The siRNA-mediated silencing of SNCA consistently resulted in senescent phenotypes, such as eNOS downregulation, increased ß-gal activity, decreased Sirt1 expression, and increased p53 expression, in ECs. Ex vivo assessment of endothelial functions using aortic rings revealed impaired endothelium-dependent acetylcholine-induced relaxation in SNCA knockout (KO) mice. Furthermore, SNCA KO mice, especially those on a high-fat diet, displayed elevated blood pressure compared with wild-type mice; this could be eNOS dysfunction-dependent because of the lower difference caused by L-NAME administration. These results indicate that exogenous and endogenous SNCA in ECs might physiologically maintain vascular integrity, and age-related endothelial dysfunction might be partially ascribed to loss-of-function of SNCA in ECs.

[Sleep disturbance in elderly patients with dementia at home and the factors associated with its identification: An observational study].

AIMS: The purpose of this study was to objectively quantify the sleep of elderly patients with dementia at home using a device and to investigate the factors associated with its identification. METHODS: Sixteen patients (6 males [37.5%], 84.1±4.7 years old; and 10 patients with mild dementia [62.5%]) and their family caregivers who were using outpatient memory clinics and home-visiting nursing station in Japan were included. Demographic and clinical data of the patients and their family caregivers, subjective perceptions of patients' sleep, family caregivers' Zarit care burden, and whether or not they were aware of patients' sleep problems were determined. Nighttime sleep parameters were collected for one week using a non-wearable actigraph. Sleep parameters were compared with patients' subjective views and family caregivers' observations to investigate factors indicative of sleep disturbance. RESULTS: Nighttime sleep parameters for 1 week (mean) were follows: sleep efficiency, 77.2%±9.3%; asleep time, 442.3±99.9 minutes; sleep latency, 18.2±15.8 minutes; awake time, 105.1±69.7 minutes; and number of times leaving the bed, 4.6±3.8 (maximum of 29/night). A significant positive correlation was found between sleep efficiency and duration of dementia (r=0.53, p=0.046), while no correlation was found with dementia severity or Zarit care burden score. The agreement between the patients' complaints about sleep and sleep efficiency (75%) was 30.7%, and family caregivers' awareness of patients' nighttime awakening and bed-leaving was significantly associated with patients' incontinence (p=0.024) and a greater dementia severity (p=0.027). CONCLUSIONS: Elderly dementia patients experienced sleep disturbance at home, such as nighttime awakening and associated bed-leaving; however, it might be difficult to identify these patients at an early stage based on their own complaints and observations by family caregivers. Identifying sleep problems at an early stage may thus require the use of objective measurement devices.

Self-Monitoring Home Blood Pressure in Community-Dwelling Older People: Age Differences in White-Coat and Masked Phenomena and Related Factors-The SONIC Study.

Some studies reported that home blood pressure (HBP) monitoring was conducted by community-dwelling older people themselves, but there have been few studies on HBP including very old populations aged over 90 years old. Thus, the aim of the present study was to clarify the current situation of white-coat and masked phenomena defined by on-site and home BP measurements in community-dwelling old and oldest-old populations. The study subjects were 380 participants from the SONIC study, a cohort study of a community-dwelling old population, who measured their HBP in a series of 3-5 days by themselves and brought their HBP records to the venue on the survey day. Study participants' characteristics were as follows: female, 185 (48.7%); male, 195 (51.3%); 70s, 95 (25.0%); 80s, 245 (64.5%); and 90s, 40 (10.5%). A total of 344 (90.5%) participants had hypertension. A total of 291 (76.6%) hypertensive participants taking antihypertensive medication were analyzed in the present study. Regarding the types of hypertension defined by home and on-site BP, they showed white-coat phenomenon, 183 (48.2%); masked phenomenon, 115 (30.3%); sustained hypertension, 130 (34.2%); and normotension, 82 (21.6%). On comparison of age groups, there was a tendency for the white-coat phenomenon to be common in young-old people in their 70s and the masked phenomenon to be common in very old people in their 90s. Therefore, since the detection of white-coat and masked phenomena is closely associated with appropriate BP management, it is very important for community-dwelling older populations to self-monitor HBP.

A novel chronic dural port platform for continuous collection of cerebrospinal fluid and intrathecal drug delivery in free-moving mice.

BACKGROUND: Cerebrospinal fluid (CSF) provides a close representation of pathophysiological changes occurring in the central nervous system (CNS); therefore, it has been employed in pathogenesis research and biomarker development for CNS disorders. CSF obtained from valid mouse models relevant to CNS disorders can be an important resource for successful biomarker and drug development. However, the limited volume of CSF that can be collected from tiny intrathecal spaces and the technical difficulties involved in CSF sampling has been a bottleneck that has hindered the detailed analysis of CSF in mouse models. METHODS: We developed a novel chronic dural port (CDP) method without cannulation for CSF collection of mice. This method enables easy and repeated access to the intrathecal space in a free-moving, unanesthetized mouse, thereby enabling continuous long-term CSF collection with minimal tissue damage and providing a large volume of high-quality CSF from a single mouse. When combined with chemical biosensors, the CDP method allows for real-time monitoring of the dynamic changes in neurochemicals in the CSF at a one-second temporal resolution in free-moving mice. Moreover, the CDP can serve as a direct access point for the intrathecal injection of CSF tracers and drugs. RESULTS: We established a CDP implantation and continuous CSF collection protocol. The CSF collected using CDP was not contaminated with blood and maintained physiological concentrations of basic electrolytes and proteins. The CDP method did not affect mouse's physiological behavior or induce tissue damage, thereby enabling a stable CSF collection for up to four weeks. The spatio-temporal distribution of CSF tracers delivered using CDP revealed that CSF metabolism in different brain areas is dynamic. The direct intrathecal delivery of centrally acting drugs using CDP enabled real-time behavioral assessments in free-moving mice. CONCLUSIONS: The CDP method enables the collection of a large volume of high-quality CSF and direct intrathecal drug administration with real-time behavioral assessment in free-moving mice. Combined with animal models relevant to CNS disorders, this method provides a unique and valuable platform for biomarker and therapeutic drug research.

Alcohol drinking patterns have a positive association with cognitive function among older people: a cross-sectional study.

BACKGROUND: The relationship between moderate alcohol drinking or other alcohol drinking patterns such as frequency, beverage type, and situation of drinking and cognitive function is not sufficiently clear in older people. The purpose of this study was to investigate the association between alcohol drinking patterns and cognitive function in community-dwelling Japanese people aged 75 and over. METHODS: This study was a cross-sectional design based on a prospective cohort study called the SONIC study. Subjects were older people aged 75-77 or 85-87 who voluntarily participated in 2016-2017. Drinking information was collected for daily drinking frequency, daily drinking intake, beverage type, and non-daily drinking opportunity. Cognitive function was measured using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Other potential confounding factors evaluated were age, sex, medical factors, and psychosocial factors. An analysis of covariance was performed to evaluate the MoCA-J score relative to drinking frequency or alcohol intake. Multiple regression analysis was performed to investigate the association between beverage type or non-daily drinking opportunity and the MoCA-J score. RESULTS: The final number of participants analyzed was 1,226. The MoCA-J score for participants who reported drinking alcohol 1-6 days/week was significantly higher than that for those who reported drinking none or every day. No significant difference in the MoCA-J score was observed relative to daily alcohol intake. In terms of beverage type, wine was associated positively with the MoCA-J score. Non-daily drinking opportunity was also associated positively with the MoCA-J score. CONCLUSIONS: Moderate-frequency drinking, wine consumption, and non-daily drinking opportunities were associated with higher cognitive function in community-dwelling Japanese aged 75 and over. Further longitudinal studies are needed to clarify the causal relationships.

Association between protein intake and changes in renal function among Japanese community-dwelling older people: The SONIC study.

AIM: The aim of this study was to clarify the association between dietary protein intake and decline in the estimated glomerular filtration rate (eGFR) among Japanese older adults. METHODS: We used the data of the Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC) study, an ongoing narrow-age range cohort study: 69-71 years, 79-81 years and 89-91 years. The outcome variable, change in eGFR, was estimated from serum creatinine measured at the baseline and 3-year follow up, and the exposure variable, protein intake, was calculated using the brief-type self-administered diet history questionnaire at the baseline. Associations between eGFR change and protein intake were determined by multiple linear regression analysis. RESULTS: The mean eGFR change per year was -1.89 mL/min/1.73 m2 . The mean protein intake was 1.50 g/kg/day. The results of this study showed that there was no significant association between protein or animal protein intake and change in eGFR per year in the entire population of participants, including the very elderly, but there was a significant positive association in those whose renal function fell into chronic kidney disease stage G3 or G4. CONCLUSIONS: Protein intake among community-dwelling older adults was not associated with lower eGFR, and for older chronic kidney disease patients, protein and animal protein intakes were more beneficial in maintaining eGFR. The results provide evidence that protein intake should not be restricted for older patients with chronic kidney disease, including the very elderly. Geriatr Gerontol Int 2022; 22: 286-291.