Search

ABSTRACT Advances in diabetes medication and population aging are lengthening the lifespans of people with diabetes mellitus (DM). Older patients with diabetes mellitus often have multimorbidity and tend to have polypharmacy. In addition, diabetes mellitus is associated with frailty, functional decline, cognitive impairment, and geriatric syndrome. Although the numbers of patients with frailty, dementia, disability, and/or multimorbidity are increasing worldwide, the accumulated evidence on the safe and effective treatment of these populations remains insufficient. Older patients, especially those older than 75 years old, are often underrepresented in randomized controlled trials of various treatment effects, resulting in limited clinical evidence for this population. Therefore, a deeper understanding of the characteristics of older patients is essential to tailor management strategies to their needs. The clinical guidelines of several academic societies have begun to recognize the importance of relaxing glycemic control targets to prevent severe hypoglycemia and to maintain quality of life. However, glycemic control levels are thus far based on expert consensus rather than on robust clinical evidence. There is an urgent need for the personalized management of older adults with diabetes mellitus that considers their multimorbidity and function and strives to maintain a high quality of life through safe and effective medical treatment. Older adults with diabetes mellitus accompanied by frailty, functional decline, cognitive impairment, and multimorbidity require special management considerations and liaison with both carers and social resources.

AbstractTechnological advances of hand-held ultrasound devices and educational programmes for their use, such as point-of-care ultrasonography (POCUS) training, have contributed to the increasing application of these devices in clinical practice. With the greater impact of frailty and sarcopenia in aging societies, attention is being focused on the use of ultrasound for skeletal muscle assessment. In this narrative review, we discuss how ultrasound can be applied to skeletal muscle assessment, especially that of the quadriceps muscle, in clinical practice. Muscle thickness by ultrasound has been shown to have good reliability and validity for the evaluation of muscle size, and echo intensity has been used to evaluate muscle quality. Muscle ultrasound has not only been useful to diagnose sarcopenia in various settings, but has also been validated to predict health-related outcomes such as death and functional disability. Recommended methods for muscle ultrasound was published recently, and the results of future studies are expected to be comparable. Although several challenging issues with muscle ultrasound remain, if it could be incorporated into educational programmes such as POCUS training, more clinicians may be able to use ultrasound for skeletal muscle assessment in the future.KEY MESSAGESThe evolution of hand-held ultrasound devices enables physicians to perform ultrasound at the bedside as part of regular medical examinations.Muscle ultrasound is considered an effective tool for evaluating muscle size and quality, and has been studied in various settings.More clinicians may be able to evaluate skeletal muscle assessment with the development of educational programmes on muscle ultrasound in the future.

Abstract Reducing potentially inappropriate medications (PIMs) is a challenge in post-acute care hospitals. Some PIMs may be associated with patient characteristics and it may be useful to focus on frequent PIMs. This study aimed to identify characteristic features of PIMs by grouping patients as in everyday clinical practice. A retrospective review of medical records was conducted for 541 patients aged 75 years or older in a Japanese post-acute and secondary care hospital. PIMs on admission were identified using the Screening Tool for Older Person’s Appropriate Prescriptions for Japanese. The patients were divided into four groups based on their primary disease and reason for hospitalization: post-acute orthopedics, post-acute neurological disorders, post-acute others, and subacute. Approximately 60.8% of the patients were taking PIMs, with no significant difference among the four patient groups in terms of prevalence of PIMs (p = 0.08). However, characteristic features of PIM types were observed in each patient group. Hypnotics and nonsteroidal anti-inflammatory drugs were common in the post-acute orthopedics group, multiple antithrombotic agents in the post-acute neurological disorders group, diuretics in the post-acute others group, and hypnotics and diuretics in the subacute group. Grouping patients in clinical practice revealed characteristic features of PIM types in each group.

Abstract Background Young bone marrow transplantation (YBMT) has been shown to stimulate vascular regeneration in pathological conditions, including ageing. Here, we investigated the benefits and mechanisms of the preventive effects of YBMT on loss of muscle mass and function in a senescence‐associated mouse prone 10 (SAMP10) model, with a special focus on the role of growth differentiation factor 11 (GDF‐11). Methods Nine‐week‐old male SAMP10 mice were randomly assigned to a non‐YBMT group (n = 6) and a YBMT group (n = 7) that received the bone marrow of 8‐week‐old C57BL/6 mice. Results Compared to the non‐YBMT mice, the YBMT mice showed the following significant increases (all P < 0.05 in 6–7 mice): endurance capacity (>61.3%); grip strength (>37.9%), percentage of slow myosin heavy chain fibres (>14.9–15.9%). The YBMT also increased the amounts of proteins or mRNAs for insulin receptor substrate 1, p‐Akt, p‐extracellular signal‐regulated protein kinase1/2, p‐mammalian target of rapamycin, Bcl‐2, peroxisom proliferator‐activated receptor‐γ coactivator (PGC‐1α), plus cytochrome c oxidase IV and the numbers of proliferating cells (n = 5–7, P < 0.05) and CD34+/integrin‐α7+ muscle stem cells (n = 5–6, P < 0.05). The YMBT significantly decreased the levels of gp91phox, caspase‐9 proteins and apoptotic cells (n = 5–7, P < 0.05) in both muscles; these beneficial changes were diminished by the blocking of GDF‐11 (n = 5–6, P < 0.05). An administration of mouse recombinant GDF‐11 improved the YBMT‐mediated muscle benefits (n = 5–6, P < 0.05). Cell therapy with young bone marrow from green fluorescent protein (GFP) transgenic mice exhibited GFP+ myofibres in aged muscle tissues. Conclusions These findings suggest that YBMT can prevent muscle wasting and dysfunction by mitigating apoptosis and proliferation via a modulation of GDF‐11 signalling and mitochondrial dysfunction in SAMP10 mice.

Objectives: We aimed to examine the association between intrinsic capacity (IC) and adverse outcomes of hospitalization. Design: A prospective observational cohort study. Setting and participants: We recruited patients aged 65 years or older who were admitted to the geriatric ward of an acute hospital between Oct 2019 and Sep 2022. Measurements: Each of the five IC domains (locomotion, cognition, vitality, sensory, and psychological capacity) was graded into three levels, and the composite IC score was calculated (0, lowest; 10, highest). Hospital-related outcomes were defined as in-hospital death, hospital-associated complications (HACs), length of hospital stay, and frequency of discharge to home. Results: In total, 296 individuals (mean age 84.7 ± 5.4 years, 42.7 % males) were analyzed. Mean composite IC score was 6.5 ± 1.8, and 95.6 % of participants had impairment in at least one IC domain. A higher composite IC score was independently associated with lower frequency of in-hospital death (odds ratio [OR] 0.59) and HACs (OR 0.71), higher frequency of discharge to home (OR 1.50), and shorter length of hospital stay (β = −0.24, p

Abstract Individuals with mild cognitive impairment (MCI) often make qualitative errors on the Clock Drawing Test (CDT), and these errors are reported to be associated with lower scores on neuropsychological assessments. Gait speed is also closely associated with cognitive dysfunction. However, the association between CDT errors and gait speed has not been investigated in individuals with MCI. Therefore, in this study, we explored the association between gait speed and qualitative errors on the CDT. Participants were 196 outpatients at a memory clinic with a clinical dementia rating of 0.5. The CDT was evaluated using the method of Cahn et al. The participants were divided into tertiles of normal and maximum gait speeds. The CDT error types of stimulus-bound response, conceptual deficit (CD), and planning deficit were found in 24.5%, 29.6%, and 30.1% of the participants, respectively. CD was found in 43.6% of the slowest tertile of maximum gait and in 22.2% of the fastest tertile. Multiple linear regression analysis gait speeds as objective continuous variables revealed that CD was significantly negatively associated with maximum gait, but not with normal gait. No other error types were associated with gait speeds. Only CD type error on the CDT was negatively associated with maximum gait speed, but not normal gait speed in the current study. The association between the qualitative error on the CDT and gait speed provides further basis of the clinical importance of qualitative assessments of CDT.

Abstract Background Mild hyponatremia (serum sodium 130–135 mEq/L) is a common electrolyte disorder in the elderly. However, its association with both sarcopenia and cognitive function remains to be clarified. Therefore, here we investigated the association of mild hyponatremia with skeletal muscle mass, physical function, and cognitive function in the elderly. Methods We enrolled 75 participants with mild hyponatremia and 2907 with normonatremia (serum sodium, 136–145 mEq/L) aged ≥70 years who visited the Memory Disorder Outpatient Center of Japan’s National Center for Geriatrics and Gerontology. Skeletal muscle mass index (SMI), grip strength (GS), walking speed (WS), one-leg standing (OLS) test times, and neuropsychological test scores were determined. Results One-way analysis of covariance showed that elderly participants with mild hyponatremia had lower SMI (7.1 ± 0.2, 7.2 ± 0.2 kg/m2, p = 0.04), weaker GS (19.1 ± 1.9 vs 21.4 ± 1.8 kg, p = 0.01), slower WS (0.9 ± 0.1 vs 1.1 ± 0.1 m/s, p = 0.001), and higher GDS- 15 score (6.4 ± 0.9 vs 5.2 ± 0.9, p = 0.002) than those with normonatremia. Multiple logistic regression analysis indicated that mild hyponatremia was independently associated with sarcopenia (odds ratio [OR]: 2.2, p = 0.02), slower WS (OR: 5.3, p = 0.04) and shorter OLS time (OR: 2.5, p = 0.02) as well as with severe depressive mood (OR: 2.6 p = 0.006) but not with SMI (OR: 1.6, p = 0.2) or GS (OR: 1.9, p = 0.09). Conclusions Our results suggest that elderly people with even mild hyponatremia had physical function impairment and depressive mood.

Abstract Background The use of home health care (HHC) is increasing worldwide. This may have an impact not only on patients and their caregivers’ health but on care resource utilization and costs. We lack information on the impact of HHC on the broader dimensions of health status and care resource utilization. More understanding of the longitudinal HHC impact on HHC patients and caregivers is also needed. Moreover, we know little about the synergy between HHC and social care. Therefore, the present study aims to observe longitudinal changes in health, care resource utilization and costs and caregiving burden among HHC recipients and their caregivers in Taiwan. Methods A prospective cohort study “Home-based Longitudinal Investigation of the Multidisciplinary Team Integrated Care (HOLISTIC)” will be conducted and 600 eligible patient-caregiver dyads will be recruited and followed with comprehensive quantitative assessments during six home investigations over two years. The measurements include physical function, psychological health, cognitive function, wellbeing, shared decision making and advance care planning, palliative care and quality of dying, caregiving burden, continuity and coordination of care, care resource utilization, and costs. Discussion The HOLISTIC study offers the opportunity to comprehensively understand longitudinal changes in health conditions, care resource utilization and costs and caregiving burden among HHC patients and caregivers. It will provide new insights for clinical practitioners and policymakers. Trial registration ClinicalTrials.gov Identifier is NCT04250103 which has been registered on 31st January 2020.

A growing body of evidence clearly indicates the beneficial effects of physical activity (PA) on cognition. The importance of PA is now being reevaluated due to the increase in sedentary behavior in older adults during the COVID-19 pandemic. Although many studies in humans have revealed that PA helps to preserve brain health, the underlying mechanisms have not yet been fully elucidated. In this review, which mainly focuses on studies in humans, we comprehensively summarize the mechanisms underlying the beneficial effects of PA or exercise on brain health, particularly cognition. The most intensively studied mechanisms of the beneficial effects of PA involve an increase in brain-derived neurotrophic factor (BDNF) and preservation of brain volume, especially that of the hippocampus. Nonetheless, the mutual associations between these two factors remain unclear. For example, although BDNF presumably affects brain volume by inhibiting neuronal death and/or increasing neurogenesis, human data on this issue are scarce. It also remains to be determined whether PA modulates amyloid and tau metabolism. However, recent advances in blood-based biomarkers are expected to help elucidate the beneficial effects of PA on the brain. Clinical data suggest that PA functionally modulates cognition independently of neurodegeneration, and the mechanisms involved include modulation of functional connectivity, neuronal compensation, neuronal resource allocation, and neuronal efficiency. However, these mechanisms are as yet not fully understood. A clear understanding of the mechanisms involved could help motivate inactive persons to change their behavior. More accumulation of evidence in this field is awaited.

Background: The Japan-Multi-domain Intervention Trial for Prevention of Dementia in Older Adults with Diabetes (J-MIND-Diabetes) is an 18-month, multi-centered, open-labeled, randomized controlled trial designed to identify whether multi-domain intervention targeting modifiable risk factors for dementia could prevent the progression of cognitive decline among older adults with type 2 diabetes mellitus (T2DM). This manuscript describes the study protocol for the J-MIND-Diabetes trial.Materials and Methods: Subjects of this trial will comprise a total of 300 T2DM outpatients aged 70–85 years with mild cognitive impairment. Subjects will be centrally randomized into intervention and control groups at a 1:1 allocation ratio using the stratified permuted-block randomization methods. The intervention group will participate in multi-domain intervention programs aimed at: (1) management of metabolic and vascular risk factors; (2) physical exercise and self-monitoring of physical activity; (3) nutritional guidance; and (4) social participation. The control group will receive usual T2DM care and general instructions on dementia prevention. The primary and secondary outcomes will be assessed at baseline, at 6- and 18-month follow-up. The primary outcome is change from baseline at 18 months in a global composite score combining several neuropsychological domains, including global cognitive function, memory, attention, executive function, processing speed and language. Secondary outcomes include: (1) cognitive changes in neuropsychological tests; (2) changes in geriatrics assessments; (3) metabolic control and diabetic complications; (4) changes in blood and urinary markers.Discussion: This trial will be the first trial to demonstrate the effectiveness of multi-domain intervention in preventing cognitive decline in older adults with T2DM at increased risk of dementia in Japan.Trial Registration: UMIN000035911; Registered on the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) 18 February 2019. (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000040908).

Abstract Background The trajectories for health-related quality of life of patients receiving home-based primary care are not well identified. Our objective was to investigate changes in the quality of life (QOL) and factors that affected the QOL of patients receiving home-based primary care. Methods Our prospective cohort study, the Observational study of Nagoya Elderly with HOme MEdical (ONE HOME) study, recruited 184 patients undergoing home-based primary care with a 5-year follow-up period. Patients’ demographic data, socioeconomic status, physical diseases, medication use, feeding intake status, nutritional status, and functional status were measured annually. The 4-item quality of life index (QOL-HC [home care]) including self-perceived and family-reported QOL ratings that had been developed and previously validated in home care settings was used. Linear regression models were used for cross-sectional and longitudinal analyses. Results The participants’ mean age was 78.8 ± 10.8 years, and 55.9% of the sample was male. Most patients were frail, disabled, and/or malnourished. Self-perceived and family-reported QOL scores dropped sequentially on annual follow-ups. In the multivariate longitudinal analysis, patients who were divorced (β = 1.74) had high baseline QOL scores (β = 0.75) and reported higher QOL ratings. In addition, high functional dependency was associated with a low self-perceived QOL rating, with a β-value of − 1.24 in the pre-bedridden group and − 1.39 in the bedridden group. Given the family-reported QOL rating, the baseline QOL scores (β = 0.50) and Mini-Nutritional Assessment–Short-Form scores (β = 0.37) were found to have positive associations with the QOL rating. Conclusions For the disabled receiving home-based primary care, independent functional status and divorce were positively associated with better self-perceived QOL, whereas nutritional status was correlated with better family-reported QOL.

Background. We recently demonstrated that proliferin-1 (PLF-1) functions as an apoptotic cell-derived growth factor and plays an important role in vascular pathobiology. We therefore investigated its role in muscle regeneration in response to cardiotoxin injury. Methods and Results. To determine the effects of PLF-1 on muscle regeneration, we used a CTX-induced skeletal muscle injury model in 9-week-old male mice that were administered with the recombinant PLF-1 (rPLF-1) or neutralizing PLF-1 antibody. The injured muscles exhibited increased levels of PLF-1 gene expression in a time-dependent manner. On day 14 after injury, rPLF-1 supplementation ameliorated CTX-induced alterations in muscle fiber size, interstitial fibrosis, muscle regeneration capacity, and muscle performance. On day 3 postinjury, rPLF-1 increased the levels of proteins or genes for p-Akt, p-mTOR, p-GSK3α/β, p-Erk1/2, p-p38MAPK, interleukin-10, Pax7, MyoD, and Cyclin B1, and it increased the numbers of CD34+/integrin-α7+ muscle stem cells and proliferating cells in the muscles and/or bone marrow of CTX mice. An enzyme-linked immunosorbent assay revealed that rPLF-1 suppressed the levels of plasma tumor necrosis factor-α and interleukin-1β in CTX mice. PLF-1 blocking accelerated CTX-related muscle damage and dysfunction. In C2C12 myoblasts, rPLF-1 increased the levels of proteins for p-Akt, p-mTOR, p-GSK3α/β, p-Erk1/2, and p-p38MAPK as well as cellular functions; and these effects were diminished by the depletion of PLF-1 or silencing of its mannose-6-phosphate receptor. Conclusions. These findings demonstrated that PLF-1 can improve skeletal muscle repair in response to injury, possibly via the modulation of inflammation and proliferation and regeneration, suggesting a novel therapeutic strategy for the management of skeletal muscle diseases.

Background/Aims: Behavioral and psychological symptoms of dementia (BPSD) are exhibited in most patients with Alzheimer disease (AD). Although white matter hyperintensity (WMH) is often observed with AD, the precise role of WMH in BPSD remains unclear. The current study aimed to identify the impact of regional WMH on specific features of BPSD in persons with mild to moderate AD and amnestic mild cognitive impairment (aMCI). Methods: A sample of 256 female outpatients with AD (n = 217) and aMCI (n = 39) were recruited. We assessed BPSD using the Dementia Behavior Disturbance Scale. WMH and brain atrophy were evaluated using an automatic segmentation program. Regional WMH was evaluated as periventricular hyperintensity (PVH) and deep WMH in frontal, temporal, occipital, and parietal lobes. Results: Whole-brain WMH was associated with verbal aggressiveness. In multivariate analysis, PVH in the frontal lobe was independently associated with verbal aggressiveness after adjustment for brain atrophy and clinical confounders. Conclusion: The current results indicated that PVH in the frontal lobe was independently associated with verbal aggressiveness.

Abstract Background Pneumonia is a very common disease, especially among the elderly. Various drugs’ preventive effects against pneumonia have been reported. The antiplatelet drug cilostazol is used to prevent pneumonia, but the robustness of its efficacy is unclear. This review estimates the effectiveness of cilostazol for preventing pneumonia in elderly individuals. Methods The following databases were searched from the earliest record to January 2016, without language restriction (the secondary search was conducted on February 2017): MEDLINE, Cochrane Library, CINAHL, and Ichushi-Web. Studies were included if they were published randomized controlled trials investigating the preventive effect of cilostazol on pneumonia in the elderly. The outcome was the incidence of pneumonia. Results Two trials were identified that met the search criteria (1423 participants). Both trials compared cilostazol with no antiplatelet in patients with a history of cerebral infarction. A meta-analysis was not performed because of the small number of trials and the heterogeneity of the data. Both trials suggested that cilostazol reduced the incidence of pneumonia (risk ratio [RR] 0.40; 95% confidence interval [CI] 0.22–0.73 in one trial, RR 0.20; 95% CI 0.06–0.69 in the other) and the recurrence of cerebral infarction (0.43; 0.21–0.90, 0.53; 0.34–0.81, respectively). The quality of evidence provided by the trials was very low, mainly because of the high risk of bias. Conclusions It is difficult to draw conclusions on the basis of two trials. Moreover, in the two trials, cilostazol could have reduced the incidence of pneumonia via a reduction of the recurrence of cerebral infarction, which suggests that other antiplatelets could also have the same effects. Stronger evidence is required from large trials assessing the effectiveness of cilostazol for the prevention of pneumonia. Trial registration PROSPERO (CRD42016036724).

Abstract Background Cathepsin K (CatK) is a widely expressed cysteine protease that has gained attention because of its enzymatic and non‐enzymatic functions in signalling. Here, we examined whether CatK‐deficiency (CatK−/−) would mitigate injury‐related skeletal muscle remodelling and fibrosis in mice, with a special focus on inflammation and muscle cell apoptosis. Methods Cardiotoxin (CTX, 20 μM/200 μL) was injected into the left gastrocnemius muscle of male wild‐type (CatK+/+) and CatK−/− mice, and the mice were processed for morphological and biochemical studies. Results On post‐injection Day 14, CatK deletion ameliorated muscle interstitial fibrosis and remodelling and performance. At an early time point (Day 3), CatK−/− reduced the lesion macrophage and leucocyte contents and cell apoptosis, the mRNA levels of monocyte chemoattractant protein‐1, toll‐like receptor‐2 and toll‐like receptor‐4, and the gelatinolytic activity related to matrix metalloproteinase‐2/‐9. CatK deletion also restored the protein levels of caspase‐3 and cleaved caspase‐8 and the ratio of the BAX to the Bcl‐2. Moreover, CatK deficiency protected muscle fibre laminin and desmin disorder in response to CTX injury. These beneficial muscle effects were mimicked by CatK‐specific inhibitor treatment. In vitro experiments demonstrated that pharmacological CatK inhibition reduced the apoptosis of C2C12 mouse myoblasts and the levels of BAX and caspase‐3 proteins induced by CTX. Conclusions These results demonstrate that CatK plays an essential role in skeletal muscle loss and fibrosis in response to CTX injury, possibly via a reduction of inflammation and cell apoptosis, suggesting a novel therapeutic strategy for the control of skeletal muscle diseases by regulating CatK activity.

Background Exposure to chronic psychosocial stress is a risk factor for atherosclerosis‐based cardiovascular disease. We previously demonstrated the increased expressions of cathepsin S (CatS) in atherosclerotic lesions. Whether CatS participates directly in stress‐related neointimal hyperplasia has been unknown. Methods and Results Male wild‐type and CatS‐deficient mice that underwent carotid ligation injury were subjected to chronic immobilization stress for morphological and biochemical studies at specific times. On day 14 after stress/surgery, stress enhanced the neointima formation. At the early time points, the stressed mice had increased plaque elastin disruption, cell proliferation, macrophage accumulation, mRNA and/or protein levels of vascular cell adhesion molecule‐1, angiotensin II type 1 receptor, monocyte chemoattractant protein‐1, gp91phox, stromal cell–derived factor‐1, C‐X‐C chemokine receptor‐4, toll‐like receptor‐2, toll‐like receptor‐4, SC35, galectin‐3, and CatS as well as targeted intracellular proliferating‐related molecules (mammalian target of rapamycin, phosphorylated protein kinase B, and p‐glycogen synthase kinase‐3α/β). Stress also increased the plaque matrix metalloproteinase‐9 and matrix metalloproteinase‐2 mRNA expressions and activities and aorta‐derived smooth muscle cell migration and proliferation. The genetic or pharmacological inhibition of CatS by its specific inhibitor (Z‐FL‐COCHO) ameliorated the stressed arterial targeted molecular and morphological changes and stressed aorta‐derived smooth muscle cell migration. Both the genetic and pharmacological interventions had no effect on increased blood pressure in stressed mice. Conclusions These results demonstrate an essential role of CatS in chronic stress–related neointimal hyperplasia in response to injury, possibly via the reduction of toll‐like receptor‐2/toll‐like receptor‐4–mediated inflammation, immune action, and smooth muscle cell proliferation, suggesting that CatS will be a novel therapeutic target for stress‐related atherosclerosis‐based cardiovascular disease.

BACKGROUND:Although potentially inappropriate medications (PIMs) have been linked to poor health outcomes, country-specific PIM criteria have not been compared. Thus, we compared the identification of PIMs between the Screening Tool for Older Person's Appropriate Prescriptions for Japanese (STOPP-J) and the 2015 American Geriatrics Society Beers Criteria in elderly patients receiving home-based medical services. METHODS:A 5-year prospective cohort study was conducted with 196 patients receiving home-based medical services. Data were collected using questionnaires and chart reviews and included detailed information on prescription medication. STOPP-J and the Beers Criteria were used to categorize PIM and non-PIM recipients. All-cause mortality and first hospitalization were compared using a multivariate Cox regression model. RESULTS:PIMs were detected in 132 patients (67.3%) by STOPP-J and in 141 patients (71.9%) by the Beers Criteria, and the mean numbers of PIMs were 1.3 ± 1.3 and 1.2 ± 1.1, respectively. The three most frequently prescribed STOPP-J PIMs were hypnotics (26.8%), diuretics (25.6%), and NSAIDs (12.6%), compared with proton pump inhibitors (PPIs) (29.8%), hypnotics (26%), and NSAIDs (8.1%) according to the Beers Criteria. STOPP-J PIMs were associated with all-cause mortality (HR 3.01, 95% CI 1.37-6.64) and hospitalization (HR 1.91, 95% CI 1.17-3.09); neither was associated with Beers Criteria PIMs. Using a modified Beers Criteria (excluding PPIs), PIMs were correlated with first hospitalization (HR 1.91, 95% CI 1.17-3.09). CONCLUSIONS:PIMs categorized by STOPP-J are associated with hospitalization and mortality in Japanese patients receiving home-based medical services. PPIs, commonly used for acid-related diseases, do not seem to have deleterious effects on health outcomes. Country-oriented, medication-specific criteria would be of considerable clinical utility.

Background/Aims: We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients. Methods: We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD) in 66 diabetic patients. Results: During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR), albuminuria, and being an ApoE ε4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders. Conclusion: Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy.

Chronic dehydration mainly occurs due to insufficient fluid intake over a lengthy period of time, and nursing home residents are thought to be at high risk for chronic dehydration. However, few studies have investigated chronic dehydration, and new diagnostic methods are needed. Therefore, in this study, we aimed to identify risk factors for chronic dehydration by measuring serum osmolality in nursing home residents and also to evaluate whether examining the inferior vena cava (IVC) and determining the IVC collapsibility index (IVC-CI) by ultrasound can be helpful in the diagnosis of chronic dehydration. A total of 108 Japanese nursing home residents aged ≥65 years were recruited. IVC measurement was performed using a portable handheld ultrasound device. Fifteen residents (16.9%) were classified as having chronic dehydration (serum osmolality ≥295 mOsm/kg). Multivariate logistic regression analysis showed that chronic dehydration was associated with dementia (odds ratio (OR), 6.290; 95% confidential interval (CI), 1.270–31.154) and higher BMI (OR, 1.471; 95% CI, 1.105–1.958) but not with IVC or IVC-CI. Cognitive function and body weight of residents should be considered when establishing a strategy for preventing chronic dehydration in nursing homes.

Type 2 diabetes mellitus is associated with neurodegeneration and cerebrovascular disease. However, the precise mechanism underlying the effects of glucose management on brain abnormalities is not fully understood. The differential impacts of glucose alteration on brain changes in patients with and without cognitive impairment are also unclear. This cross-sectional study included 57 older type 2 diabetes patients with a diagnosis of Alzheimer’s disease (AD) or normal cognition (NC). We examined the effects of hypoglycemia, postprandial hyperglycemia and glucose fluctuations on regional white matter hyperintensity (WMH) and brain atrophy among these patients. In a multiple regression analysis, postprandial hyperglycemia was independently associated with frontal WMH in the AD patients. In addition, postprandial hyperglycemia was significantly associated with brain atrophy, regardless of the presence of cognitive decline. Altogether, our findings indicate that postprandial hyperglycemia is associated with WMH in AD patients but not NC patients, which suggests that AD patients are more susceptible to postprandial hyperglycemia associated with WMH.

BACKGROUND:Instrumental activities of daily living (IADL) start to decline during the progression of amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD). Cognitive and physical decline are involved in the loss of functional independence. However, little is known about AD-related neural change that leads to IADL impairment. The purpose of this study was to clarify the effects of regional white matter hyperintensity (WMH) on IADL impairment in persons with AD and aMCI. METHODS:The participants were 347 female subjects aged 65-85 years diagnosed with AD (n = 227), aMCI (n = 44) or normal cognition (n = 76). IADL was assessed by the Lawton Index. Cognition, mood and mobility function were evaluated by comprehensive geriatric assessment batteries. WMH and brain atrophy were analyzed with brain magnetic resonance imaging, using an automatic segmentation program. Regional WMH was measured in the frontal, temporal, occipital and parietal lobes. RESULTS:Ability to carry out IADL of shopping, food preparation, mode of transportation, responsibility for own medication, and ability to handle finances was obviously impaired in the early stage of AD. Frontal WMH was specifically associated with disability to do shopping and food preparation even after adjusting for several confounders including brain atrophy. CONCLUSIONS:IADL subcategories were differentially impaired along with cognitive status in persons with AD and aMCI. Frontal WMH was an important predictor of impaired ability to do shopping and food preparation. A preventive strategy for WMH might lead to suppression of IADL disability and slow the progression of AD.

Background/Aims: In recent years, the relationship between chronic kidney disease (CKD) and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD) is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years) were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR 2). SVD was evaluated by the presence and severity of silent brain infarcts (SBIs) and white matter lesions (WMLs) on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017) and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026) after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.

Background/Aims: Although recent evidence has indicated that type 2 diabetes mellitus (T2DM) in the elderly is a risk factor for cognitive dysfunction or dementia, few studies have prospectively observed this potential cognitive decline. In the current study, we performed cognitive assessments at baseline and after 3 years in the same patient group in an attempt to reveal the contributions of diabetes-related factors to the increased decline in cognitive function in elderly patients with T2DM. Methods: We recruited 55 consecutive T2DM patients with a Mini-Mental State Examination (MMSE) score ≧24 from the Diabetic Center at the Chubu Rosai Hospital. These patients ranged in age from 65 to 85 years. Cognitive and clinical assessments, including brain MRI, were performed at baseline and at the 3-year follow-up. Results: The higher plasma insulin and HbA1c levels observed at baseline were significantly associated with a worse cognitive performance at baseline and a more neurocognitive decline at the follow-up visit. Conclusion: The current prospective study suggests that higher insulin and glycohemoglobin levels may be associated with diabetes-related cognitive dysfunction.

As the Japanese population continues to age steadily, the number of older adults requiring healthcare has increased. Evidence demonstrates that hospitalization for acute care has a negative impact on the health outcomes of older adults. Frail older adults tend to have multifactorial conditions collectively known as "geriatric syndromes." When those with these premorbid conditions are hospitalized for acute care, they tend to develop new problems such as delirium and new functional impairments. Adverse consequences of hospitalization include the risk of loss of functional independence and chronic disability. In 2019, the new concept of "hospital-associated complications" (HACs) was proposed to describe these new problems. HACs comprise five conditions: hospital-associated falls, delirium, functional decline, incontinence, and pressure injuries. This review discusses the important issues of HACs in relation to their classification, prevalence, risk factors, prevention, and management in older adults hospitalized for acute care. Robust prevention and management are imperative to address the serious consequences and escalating medical costs associated with HACs, and a multidimensional and multidisciplinary approach is key to achieving this goal. Comprehensive geriatric assessment (CGA) is the cornerstone of geriatric medicine and offers a holistic approach involving multidisciplinary and multidimensional assessments. Considerable evidence is accumulating regarding how CGA and coordinated care can improve the prognosis of hospitalized older adults. Further research is needed to understand the occurrence of HACs in this population and to develop effective preventive measures. [ABSTRACT FROM AUTHOR]