[Factors associated with oral frailty among community-dwelling older people -A comparison between those <75 and ≥75 years old].

PURPOSE: This study investigated the factors associated with oral frailty among community-dwelling older adults. In particular, we compared the factors between individuals in the young-old and old-old groups and clarified the differences between the two groups. METHODS: We measured the basic attributes, body composition, grip strength, gait function, oral function, cognitive function, and daily living function using the Kihon checklist in older people living independently in T City, Aichi Prefecture. The risk of oral frailty was assessed using the Oral Frailty Screening and Evaluation Form (OFI-8), and the measurement results were compared between two groups: those with and those without risk. To identify the factors associated with oral frailty, we performed a multivariate analysis with the risk of oral frailty as the dependent variable and a univariate analysis separately for the young-old and old-old groups. RESULTS: The mean age of the 100 subjects was 76.6±4.6 years old. Forty-four subjects were at risk of oral frailty, and 55 subjects were not at risk. The high-risk group had significantly higher rates of polypharmacy, depression, and a slow walking speed than the no-risk group. The risk factors associated with oral frailty were living alone, polypharmacy, and depression. The risk factors for oral frailty were a poor ambulatory function in the young-old and a poor ambulatory function, decline in the cognitive function, and depression in the old-old. CONCLUSIONS: The results of this study suggest that the risk factors for oral frailty differ between older individuals in the young-old and old-old groups and that age-appropriate support is necessary to prevent oral frailty in older people.

Associations of polypharmacy with frailty severity and each frailty phenotype in community-dwelling older adults: Itabashi Longitudinal Study on Aging.

AIM: Although polypharmacy and frailty are concerns in older adults, there is limited understanding of their association, particularly regarding frailty severity and its phenotypes within this population. This study aimed to examine the association between polypharmacy and frailty severity or frailty phenotypes in community-dwelling older Japanese adults. METHODS: This cross-sectional study included 1021 older adults from the Itabashi Longitudinal Study on Aging. Men accounted for 45.4%, and the mean age (standard deviation) was 77.9 (5.1) years. Participants were classified into frail (n = 67), pre-frail (n = 543), and robust (n = 411) groups using the revised Japanese Cardiovascular Health Study criteria. Polypharmacy was defined as using five or more self-reported prescription drugs. Ordinal and binomial logistic regression analyses examined the association between polypharmacy and frailty severity or frailty phenotypes (weight loss, weakness, exhaustion, slowness, and low activity). These models were adjusted for age, sex, body mass index, number of comorbidities, living status, employment status, years of education, as well as drinking and smoking habits. RESULTS: The prevalence of frailty in participants with and without polypharmacy was 10.1% and 5.0%, respectively. Participants with polypharmacy were more likely to have frailty (adjusted odds ratio [95% confidence interval], 1.89 [1.40-2.57]), weight loss (1.81 [1.00-3.27]), weakness (1.50 [1.08-2.09]), and slowness (2.25 [1.29-3.94]) compared with the no-polypharmacy group. CONCLUSIONS: Polypharmacy was associated with frailty severity and three frailty phenotypes. Longitudinal studies are required to investigate whether polypharmacy can predict the development and progression of frailty. Geriatr Gerontol Int 2024; 24: 196-201.

[Possible relationship between prescription medications and urinary dysfunction in elderly home health care patients].

AIM: Although urinary incontinence (UI) in the elderly appears to be related to polypharmacy, it is unclear whether multiple medications elevate UI quantitatively or qualitatively. There have been few studies on the association of polypharmacy with each type of UI. The present survey aimed to clarify these issues. METHOD: The subjects were elderly home health care patients ≥65 years of age taking ≥5 prescription medications and not being treated with anti-cancer agent. The visiting nurses filled out a questionnaire based on their nursing and medication records. Types of UI were evaluated according to a UI checklist. RESULTS: A total of 167 subjects (97 women, 70 men, mean age of 83.8 years) were eligible for the data analysis. Subjects talking 5-9 prescription medications accounted for 59.3%, while those talking≥10 counted for 40.7%. Men talking ≥10 medications showed a slight but non-significant increased risk of UI. In women, α-adrenergic antagonists and benzodiazepines significantly increased the risk of stress UI and urge UI, respectively. Furthermore, α-adrenergic antagonists reduced the risk of functional UI, whereas acetylcholinesterase inhibitors elevated it. α-adrenergic antagonists in combination with benzodiazepines also significantly increased the risk of stress UI and urge UI, while α-adrenergic antagonists with acetylcholinesterase inhibitors increased the risk of stress UI. In men, there were no prescription medications that were particularly related to UI. CONCLUSIONS: The present results suggest that there are gender differences in prescription medications-induced UI. It is likely that the causing medications are different depending on the type of UI, and the combination of them significantly increase the risk of UI.

[Effects of drug treatment on the surviral-time in patients with dementia].

AIM: The effect of polypharmacy on the surviral-time in patients with dementia has never been fully elucidated. METHODS: A retrospective study was conducted in a hospital in Aichi, Japan, by reviewing the medical charts and autopsy reports. Patients were hospitalized and neuropathologically diagnosed with dementia. The data on medication was collected from the prescribed drugs taking right before the admission. Patients were divided into two groups according to the number of prescribed drugs: ≥ 5 drugs (polypharmacy) vs. ≤ 4 drugs (non-polypharmacy). "Drugs to be prescribed with special caution" were defined in accordance with the guidelines for medical treatment and its safety in the elderly (2015). RESULTS: Seventy-six patients were eligible, and 39.5% of patients had polypharmacy. The Kaplan-Meier method showed that the polypharmacy group tended to have a shorter survival-time than the non-polypharmacy group (p=0.067). A Cox proportional hazard model showed that the polypharmacy group tended to have a higher risk for a reduced survival-time than the non-polypharmacy group, and this tendency was more prominent after adjusting for sex and age at admission (adjusted hazard ratio, 1.631; 95% confidence interval, 0.991-2.683; p=0.054). "Drugs to be prescribed with special caution", including hypnotic-sedative drugs, antianxiety drugs, antipsychotics, and benzodiazepines, were not found to be risk factors for a reduced survival-time. CONCLUSIONS: The present study showed that polypharmacy in terminal patients with dementia tended to carry a risk for reducing their remaining lifespan. The results warrant further additional study.

Factors Associated with Pneumonia-caused Death in Older Adults with Autopsy-confirmed Dementia.

Objective A better understanding of risk factors for pneumonia-caused death may help to improve the clinical management of dementia. Methods A retrospective observational study was conducted by reviewing the medical charts and autopsy reports of 204 patients who were admitted to hospital, underwent a post-mortem examination, and who were neuropathologically diagnosed with dementia. The risk factors for pneumonia-caused death were examined both as underlying and immediate causes of death using logistic regression models. Results A high frequency of pneumonia-caused death was observed both in underlying- (37.3%) and immediate- (44.1%) cause of death, but varied according to the subtypes of dementia. The factors related to pneumonia-caused death (underlying) were subtypes of dementia; Alzheimer's disease (odds ratio [OR], 2.891; 95% confidence interval [CI], 1.459-5.730); argyrophilic grain disease (OR, 3.148; 95% CI, 0.937-10.577); and progressive supranuclear palsy (OR, 34.921; 95% CI, 3.826-318.775), dysphagia (OR, 2.045; 95% CI, 1.047-3.994), diabetes mellitus (OR, 3.084; 95% CI, 1.180-8.061) and conversely related with heart failure (OR, 0.149; 95% CI, 0.026-0.861). Factors relating to pneumonia-caused death (immediate) were incidence of pneumonia during hospitalizations (OR, 32.579; 95%CI, 4.308-246.370), gender-male (OR, 2.060; 95% CI, 1.098-3.864), and conversely related with malignant neoplasm (OR, 0.220; 95% CI, 0.058-0.840). Conclusion The different factors relating to the pneumonia-caused death were evaluated depending on whether pneumonia was the underlying- or immediate-cause of death. Strengthening clinical management on dysphagia and diabetes mellitus, and preventing incidence of pneumonia during hospitalization appear to be the important for the terminal stage of hospitalized patients with dementia.

Screening Tool for Older Persons' Appropriate Prescriptions for Japanese: Report of the Japan Geriatrics Society Working Group on "Guidelines for medical treatment and its safety in the elderly".

AIM: In 2005, the Japan Geriatrics Society published a list of potentially inappropriate medication that was an extract from the "Guidelines for medical treatment and its safety in the elderly 2005." The 2005 guidelines are due for a revision, and a new comprehensive list of potentially inappropriate medications is required. METHODS: A total of 15 diseases, conditions and special areas related to their clinical care were selected. We originated clinical questions and keywords for these 15 areas, carried out a systematic review using these search criteria, and formulated guidelines applying the Grading of Recommendations Assessment, Development and Evaluation system advocated by Minds2014. If we did not find good evidence despite the drug being clinically important, we looked for evidence of efficacy and for disease-specific guidelines, and incorporated them into our guidelines. RESULTS: We selected 2098 articles (140 articles per area), and extracted another 186 articles through a manual search. We further added guidelines based on disease entity and made two lists, one of "drugs to be prescribed with special caution" and the other of "drugs to consider starting," primarily considering individuals aged 75 years or older or those who are frail or in need of special care. CONCLUSIONS: New lists of potentially inappropriate medications and potential prescribing omissions called "Screening Tool for Older Person's Appropriate Prescriptions for Japanese" were constructed. We anticipate that future studies will highlight more evidence regarding the safety of high-quality drugs, further improving the provision of appropriate medical care for the elderly. Geriatr Gerontol Int 2016: 16: 983-1001.

Combination of antioxidant supplements improved cognitive function in the elderly.

Although nutrients or agents with antioxidant properties were reported to show a preventive effect on cognitive decline in animal studies, epidemiologic data on select antioxidants have shown conflicting results. We investigated whether a combination of antioxidants from supplements is effective for the improvement of cognitive function of elderly. Forty-one subjects from a community dwelling aged 65 years and older took supplements containing n-3 polyunsaturated fatty acids (n-3 PUFA), lycopene, and Ginkgo biloba extracts (GE) daily for 3 years. The data of 622 subjects without supplement intake were used as control. We investigated the changes in cognitive function during a 3-year follow-up. We also investigated the influence of apolipoprotein E (APOE) genotype on the effect of antioxidants. We found that a combination of antioxidants improved cognitive function of aged persons after 3 years. Our present study also indicated this improvement in cognitive function with supplement intake in both APOE4 non-carrier (E4-) and APOE4 carrier (E4+) groups. Especially, in E4+, we found a large effect size of the improvement of cognition. When multiple antioxidants are used in combination, they protect against vulnerability to other agents and synergistically potentiate their antioxidant properties. These synergistically potentiated antioxidant effects of agents contribute to the improvement of cognitive function.

Hyperperfusion in primary somatosensory region related to somatic hallucination in the elderly.

AIM: The purpose of the present study was to investigate the regional cerebral blood flow (rCBF) of patients with delusional disorder, somatic type (DDST) exhibiting somatic hallucination. METHODS: Five patients diagnosed with DDST, as well as 20 control subjects, were examined. All subjects underwent technetium-99m ethyl cysteinate dimer brain perfusion single-photon emission computed tomography. Statistical analysis was performed with SPM5, using a two-sample t-test model to test the regional population effect on rCBF. RESULTS: Patients with DDST had a significant increase in perfusion in the left post-central gyrus and the right paracentral lobule, both of which are involved in somatic sensory processing. CONCLUSION: Somatic hallucination might be associated with increased perfusion in the primary somatosensory regions.

[DARPP-32 in the patients with endogenous psychosis].

Dopamine- and cyclic AMP-regulated phosphoprotein with a relative molecular weight of 32 kDa (DARPP-32) plays an important role in integrating information of about several neurotransmitters arriving at dopaminoceptive neurons. DARPP-32 is phosphorylated by dopamine D1 receptor at threonine 34 and converted to an inhibitor of protein phosphatase I. It facilitates the phosphorylation of several neurotransmitter receptors, including N-methyl-D-aspartic acid (NMDA)- and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA)-type glutamate receptors and gamma-aminobutyric acid (GABA)A receptors. In contrast, D2 receptor stimulation induces dephosphorylation of DARPP-32, which results in dephosphorylation of the glutamate and GABAA receptors. Thus, phosphorylation and dephosphorylation of DARPP-32 regulates the functions of neurotransmitter systems. Recent studies from our laboratory and elsewhere have demonstrated that the amount of DARPP-32 in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia is lower than that in the DLPFC of control subjects. Thus, it is plausible that DARPP-32 is associated with the concurrent alterations in dopamine, glutamate, and GABA neurotransmitter systems in subjects with schizophrenia. We have also found reduced levels of DARPP-32 in the DLPFC of subjects with bipolar disorder. Thus, it is important to elucidate the role of DARPP-32 in the pathophysiology of schizophrenia and bipolar disorder.

Immunohistochemical and immunoblot analysis of Dopamine and cyclic AMP-regulated phosphoprotein, relative molecular mass 32,000 (DARPP-32) in the prefrontal cortex of subjects with schizophrenia and bipolar disorder.

Dopamine and cyclic adenosine 3':5'-monophosphate (AMP)-regulated phosphoprotein, relative molecular mass 32,000 (DARPP-32), plays an important role in modulating the functions of various neurotransmitter systems. To explore the alterations in DARPP-32 in subjects with schizophrenia and bipolar disorder, we employed immunohistochemical and Western blotting techniques and examined the distribution and expression of DARPP-32 in the postmortem dorsolateral prefrontal cortex (DLPFC) from 12 subjects with schizophrenia, 10 subjects with bipolar disorder, and 11 control subjects. Immunohistochemical study demonstrated that DARPP-32 immunolabeling in the neuronal soma from subjects with schizophrenia and bipolar disorder was lower than in that from the controls. The results of the immunoblot analysis were consistent with those of the immunohistochemistry, and the amount of DARPP-32 in subjects with schizophrenia and bipolar disorder was found to be lower than that in the control subjects. The present study suggests that DARPP-32 decreases in the DLPFC of patients with schizophrenia and bipolar disorder, and further suggests that this decrease is associated with dysfunction of dopaminoceptive neurons in the DLPFC of patients affected by these two mental disorders.

Changes in hippocampal GABABR1 subunit expression in Alzheimer's patients: association with Braak staging.

Alterations in the gamma-aminobutyric acid (GABA) neurotransmitter and receptor systems may contribute to vulnerability of hippocampal pyramidal neurons in Alzheimer's disease (AD). The present study examined the immunohistochemical localization and distribution of GABA(B) receptor R1 protein (GBR1) in the hippocampus of 16 aged subjects with a range of neurofibrillary tangle (NFT) pathology as defined by Braak staging (I-VI). GBR1 immunoreactivity (IR) was localized to the soma and processes of hippocampal pyramidal cells and some non-pyramidal interneurons. In control subjects (Braak I/II), the intensity of neuronal GBR1 immunostaining differed among hippocampal fields, being most prominent in the CA4 and CA3/2 fields, moderate in the CA1 field, and very light in the dentate gyrus. AD cases with moderate NFT pathology (Braak III/IV) were characterized by increased GBR1-IR, particularly in the CA4 and CA3/2 fields. In the CA1 field of the majority of AD cases, the numbers of GBR1-IR neurons were significantly reduced, despite the presence of Nissl-labeled neurons in this region. These data indicate that GBR1 expression changes with the progression of NFT in AD hippocampus. At the onset of hippocampal pathology, increased or stable expression of GBR1 could contribute to neuronal resistance to the disease process. Advanced hippocampal pathology appears to be associated with decreased neuronal GBR1 staining in the CA1 region, which precedes neuronal cell death. Thus, changes in hippocampal GBR1 may reflect alterations in the balance between excitatory and inhibitory neurotransmitter systems, which likely contributes to dysfunction of hippocampal circuitry in AD.

[Incidence of adverse drug reactions in geriatric wards of university hospitals].

Adverse drug reactions (ADR) in elderly people, which have been shown to increase with age, are often attributed to functional decline and polypharmacy. A multi-institutional retrospective survey was undertaken to investigate the current status of ADR in geriatric wards of university hospitals. The inpatient database from 2000 to 2002 in 5 university hospitals was studied, and a total of 1,289 patients were analyzed. The incidence of ADR, as determined by attending physicians, was 9.2% on the whole but varied from 6.3% to 15.8% among the institutions. The factors significantly related to ADR were number of diagnoses, number of geriatric syndromes, number of prescribed drugs, increase of more than two drugs during admission, longer hospital stay, emergency admission, depression and apathy. These results are mostly consistent with previous reports and will provide important information on pharmacotherapy in elderly people.