Cross-sectional association between high-sensitivity C-reactive protein and cognitive function in community-dwelling older adults: the SONIC study.

BACKGROUND: A decline in cognitive function is associated with inflammatory processes. However, the association between high-sensitivity C-reactive protein (hs-CRP) levels and cognitive decline in the Japanese population remains inconclusive. Thus, this study aimed to determine whether hs-CRP is associated with low cognitive function in 70- and 80-year-old community-dwelling Japanese individuals. METHODS: The participants in this cross-sectional study were 872 Japanese residents aged 70 and 80 years who voluntarily participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study between 2010 and 2011. Blood sample collection, cognitive assessment, and other measurements were performed at the venue. Low cognitive function was defined as a score of 25 points or lower on the Japanese version of the Montreal Cognitive Assessment. The odds ratio (OR) and 95% confidence interval (95% CI) for each hs-CRP quartile were calculated using logistic regression analysis. RESULTS: A total of 288 (69.9%) parsons in the 70-year-old group and 372 (80.9%) in the 80-year-old group exhibited low cognitive function. The association between hs-CRP levels and low cognitive function was significant among 70- and 80-year-old Japanese community-dwelling adults. In particular, the fourth quartile of hs-CRP (0.727-7.420 mg/L) in the 70-year-old group and the second and fourth quartiles (0.214-0.404 and 0.911-9.890 mg/L) in the 80-year-old group were associated with low cognitive function. Furthermore, the third quartile (0.409-0.892 mg/L) in the 80-year-old group was closely associated with low cognitive function. CONCLUSIONS: High hs-CRP levels were associated with lower cognitive function in 70- and 80-year-old Japanese community-dwelling individuals, suggesting that high hs-CRP levels may influence cognitive function.

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.].

Appropriateness of Nursing Home to Emergency Department Transitional Care for Older Adults With Dementia: A Scoping Review.

PURPOSE: To systematically identify knowledge patterns and gaps in the appropriateness of nursing home (NH) to emergency department (ED) transitional care for older adults with dementia. METHOD: A systematic search of multiple information sources was performed from July to August 2023 using predesigned search strategies. RESULTS: From 13 articles, 54 identified pieces of specific care evidence were grouped into six major care domains: (1) Resource Support for Assessing Transfer Needs and Patient Status; (2) Resource Support, Shared Decision Making, and Early Advance Care Planning; (3) Standardized Multimodal Information Transfer; (4) Designated ED and NH Transition Coordinators; (5) Enhanced Interfacility Collaboration; and (6) Appropriate Transitional Care Education, Research, and Policy Beyond the Transfer Interface. CONCLUSION: A comprehensive, consensus-based body of evidence is lacking. Despite person-centered, standardized, and professional resources supporting transitional care, reorienting NH cultural models remains unclear. Gaps include evidence tailored to diverse participants and contexts. Thus, a focus on policies, education, and research is required. [Journal of Gerontological Nursing, 50(9), 37-45.].

Exploring expressed emotion and its influencing factors among family caregivers of dementia people: a 3-month study in Japan.

BACKGROUND: Family caregivers of dementia patients face significant challenges, including managing their own emotional responses. Understanding factors influencing expressed emotion (EE) is crucial for effective support interventions. The aim of this study was to explore and describe changes in EE among family caregivers of dementia and its associated factors at different time points over 3 months. METHODS: A 3-month observational study was conducted in Japan. We collected demographically detailed data on family caregivers currently providing care, including care burden, relationship closeness, and depression. We assessed EE using the validated Family Attitude Scale (FAS). After adjustment for multiple confounding factors, multivariate linear regression analysis was performed to assess factors affecting EE at various time points. Linear regression analysis with generalised estimating equations was used to assess associations between 3-month time-varying EE and burden, intimacy, and depression. RESULTS: Fifty-six family caregivers completed the study. Changes in FAS scores did not show statistical differences over 3 months. It is worth noting that the degree of relationship closeness and care burden are important influencing factors of EE in both cross-sectional analysis and longitudinal analysis. CONCLUSIONS: Early identification of risk factors can aid in developing interventions aimed at preventing high levels of EE in the dementia family, thereby mitigating their detrimental effects. Tailored interventions are essential to enhance caregiver well-being and cultivate positive caregiver-patient relationships.

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.

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.

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.

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.

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.

A pressor dose of angiotensin II has no influence on the angiotensin-converting enzyme 2 and other molecules associated with SARS-CoV-2 infection in mice.

In the early phase of the Coronavirus disease 2019 (COVID-19) pandemic, it was postulated that the renin-angiotensin-system inhibitors (RASi) increase the infection risk. This was primarily based on numerous reports, which stated that the RASi could increase the organ Angiotensin-converting enzyme 2 (ACE2), the receptor of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in rodents. RASi can theoretically antagonize the potential influence of angiotensin II (Ang II) on ACE2. However, while Ang II decreases the ACE2 levels in cultured cells, there is little evidence that supports this phenomenon in living animals. In this study, we tested whether Ang II or Ang II combined with its antagonist would alter the ACE2 and other molecules associated with the infection of SARS-CoV-2. Male C57BL6/J mice were administered vehicle, Ang II (400 ng/kg/min), or Ang II with losartan (10 mg/kg/min) for 2 weeks. ACE2 knockout mice were used as a negative control for the ACE2 assay. We found that both Ang II, which elevated blood pressure by 30 mm Hg, and Ang II with losartan, had no effect on the expression or protein activity of ACE2 in the lung, left ventricle, kidney, and ileum. Likewise, these interventions had no effect on the expression of Transmembrane Protease Serine 2 (TMPRSS2) and Furin, proteases that facilitate the virus-cell fusion, and the expression or activity of Tumor Necrosis Factor α-Convertase (TACE) that cleaves cell-surface ACE2. Collectively, physiological concentrations of Ang II do not modulate the molecules associated with SARS-CoV-2 infection. These results support the recent observational studies suggesting that the use of RASi is not a risk factor for COVID-19.