Changes in Polypharmacy and Potentially Inappropriate Medications in Homebound Older Adults in Japan, 2015-2019: a Nationwide Study.

BACKGROUND: With rising worldwide population aging, the number of homebound individuals with multimorbidity is increasing. Improvement in the quality of home medical care (HMC), including medications, contributes to meeting older adults' preference for "aging in place" and securing healthcare resources. OBJECTIVE: To evaluate the changes in drug prescriptions, particularly potentially inappropriate medications (PIMs), among older adults receiving HMC in recent years, during which measures addressing inappropriate polypharmacy were implemented, including the introduction of clinical practice guidelines and medical fees for deprescribing. DESIGN: A cross-sectional study. PARTICIPANTS: Using data from the national claims database in Japan, this study included older adults aged ≥ 75 years who received HMC in October 2015 (N = 499,850) and October 2019 (N = 657,051). MAIN MEASURES: Number of drugs, prevalence of polypharmacy (≥ 5 regular drugs), major drug categories/classes, and PIMs according to Japanese guidelines were analyzed. Random effects logistic regression models were used to evaluate the differences in medications between 2015 and 2019, considering the correlation within individuals who contributed to the analysis in both years. KEY RESULTS: The number of drugs remained unchanged from 2015 to 2019 (median: 6; interquartile range: 4, 9). The prevalence of polypharmacy also remained unchanged at 70.0% in both years (P = 0.93). However, the prescription of some drugs (e.g., direct oral anticoagulants, new types of hypnotics, acetaminophen, proton pump inhibitors, and ß-blockers) increased, whereas others (e.g., warfarin, vasodilators, H2 blockers, acetylcholinesterase inhibitors, and benzodiazepines) decreased. Among the frequently prescribed PIMs, benzodiazepines/Z-drugs (25.6% in 2015 to 21.1% in 2019; adjusted odds ratio: 0.52) and H2 blockers (11.2 to 7.3%; 0.45) decreased, whereas diuretics (23.8 to 23.6%; 0.90) and antipsychotics (9.7 to 10.5%; 1.11) remained unchanged. CONCLUSIONS: We observed some favorable changes but identified some continuous and new challenges. This study suggests that continued attention to medication optimization is required to achieve safe and effective HMC.

Palliative home care for older patients with respiratory disease in Japan: Practices and opinions of physicians.

AIM: Older adults at the end-of-life stage receiving home visits from physicians often experience symptoms such as dyspnea, pain and fatigue, among others. This study aimed to investigate the practices and opinions of physicians providing home visits regarding palliative care for older adults with respiratory symptoms due to non-malignant diseases in Japan. METHODS: A nationwide questionnaire survey on home palliative care for non-cancer chronic respiratory diseases was sent to 2988 home-care physicians in 2020 through postal mail and/or email. The questions focused on their background, their use of rating scales to evaluate the intensity of dyspnea, and their practices and opinions regarding home palliative care for respiratory diseases or symptoms. RESULTS: Valid responses were collected from 592 physicians (19.8%). A total of 251 participants (43.1%) used a rating scale to evaluate the intensity of dyspnea. While 87.8%, 86.6%, 67.3%, and 60.0% of physicians considered pulmonary rehabilitation, morphine, sedative medications, and non-invasive positive pressure ventilation (NPPV), respectively, as effective in relieving respiratory distress, 73.0%, 66.9%, 57.3%, and 55.2% of those physicians, respectively, used each modality to relieve respiratory distress. Frequently involved physicians in the aforementioned care prescribed morphine or sedative medications and used NPPV more frequently. CONCLUSIONS: This study found a discrepancy between the proportion of physicians who considered palliative care as effective and those who prescribed it. Geriatr Gerontol Int 2022; 22: 943-949.

Drug prescribing changes in the last year of life among homebound older adults: national retrospective cohort study.

OBJECTIVES: This study aimed to evaluate the prescription patterns of drugs during the last year of life in homebound older adults who received home medical care. METHODS: We used a nationwide claims database in Japan and selected older adults aged ≥75 years who received home medical care services from ≥12 months before their death. We evaluated medications prescribed 12 months before death (month 12), 3 months before death (month 3) and in the last month of life (month 1). We explored the factors associated with the decreased number of cardiovascular preventive drugs from month 12 to both month 3 and month 1. RESULTS: A total of 118 661 participants were included, and the majority were aged ≥90 years and women. The prevalence of cardiovascular preventive drugs decreased but remained common in month 1, which included antihypertensives (34.7%), antiplatelets (15.9%), oral anticoagulants (7.6%), antidiabetic drugs (7.3%) and lipid-lowering drugs (6.1%). The relative decrease from month 12 to month 1 was the largest for lipid-lowering drugs (44.8%) and the smallest for oral anticoagulants (13.6%). Among other drugs, laxatives (enema), antiemetics, oral corticosteroids, analgesics, expectorants, bronchodilators and antibiotics showed a large relative increase. Older age, duration of home medical care services for <1 year and diagnoses of cancer, dementia and Parkinson's disease were associated with a greater likelihood of a decreased number of cardiovascular preventive drugs. CONCLUSIONS: There is room for deprescribing to avoid inappropriate polypharmacy by balancing preventive and symptom management drugs in those receiving home medical care with a limited life expectancy.

GPR120 signaling controls amyloid-ß degrading activity of matrix metalloproteinases.

Alzheimer disease (AD) is characterized by the extensive deposition of amyloid-ß peptide (Aß) in the brain. Brain Aß level is regulated by a balance between Aß production and clearance. The clearance rate of Aß is decreased in the brains of sporadic AD patients, indicating that the dysregulation of Aß clearance mechanisms affects the pathological process of AD. Astrocytes are among the most abundant cells in the brain and are implicated in the clearance of brain Aß via their regulation of the blood-brain barrier, glymphatic system, and proteolytic degradation. The cellular morphology and activity of astrocytes are modulated by several molecules, including ω3 polyunsaturated fatty acids, such as docosahexaenoic acid, which is one of the most abundant lipids in the brain, via the G protein-coupled receptor GPR120/FFAR4. In this study, we analyzed the role of GPR120 signaling in the Aß-degrading activity of astrocytes. Treatment with the selective antagonist upregulated the matrix metalloproteinase (MMP) inhibitor-sensitive Aß-degrading activity in primary astrocytes. Moreover, the inhibition of GPR120 signaling increased the levels of Mmp2 and Mmp14 mRNAs, and decreased the expression levels of tissue inhibitor of metalloproteinases 3 (Timp3) and Timp4, suggesting that GPR120 negatively regulates the astrocyte-derived MMP network. Finally, the intracerebral injection of GPR120 specific antagonist substantially decreased the levels of Tris-buffered saline-soluble Aß in male AD model mice, and this effect was canceled by the coinjection of an MMP inhibitor. These data indicate that astrocytic GPR120 signaling negatively regulates the Aß degrading activity of MMPs.SIGNIFICANT STATEMENTThe level of amyloid ß (Aß) in the brain is a crucial determinant of the development of Alzheimer disease. Here we found that astrocytes, which are the most abundant cell type in the central nervous system, harbors degrading activity against amyloid ß, which is regulated by GPR120 signaling. GPR120 is involved in the inflammatory response and obesity in peripheral organs. However, the pathophysiological role of GPR120 in Alzheimer disease remains unknown. We found that selective inhibition of GPR120 signaling in astrocytes increased the Aß-degrading activity of matrix metalloproteases. Our results suggest that GPR120 in astrocytes is a novel therapeutic target for the development of anti-Aß therapeutics.

Cognitive function has a stronger correlation with perceived age than with chronological age.

AIM: The perceived age of older adults, as measured by their facial appearance, has been shown to be a robust biomarker of aging predictive of survival, telomere length and DNA methylation, and reportedly correlates with carotid atherosclerosis and bone status. This study aimed to determine whether metrics of dementia, including general cognition, vitality, depressive state and self-supportability, have stronger correlations with perceived age than with chronological age. METHODS: This study included 124 patients who were admitted to the Department of Geriatric Medicine, The University of Tokyo Hospital, on account of being suspected of cognitive decline. The Mini-Mental State Examination, Vitality Index, Geriatric Depression Scale-15, instrumental activities of daily living and Barthel Index were carried out. Five experienced geriatricians and five experienced clinical psychologists determined the perceived age of participants based on photographs. RESULTS: The average values of the 10 raters showed excellent reliability (intraclass correlation coefficient (3, 10) = 0.941). Steiger's test revealed that perceived age showed a significantly better correlation with the Mini-Mental State Examination (female) and Vitality Index (total, female) than did chronological age, but not with Geriatric Depression Scale-15, instrumental activities of daily living or the Barthel Index. CONCLUSIONS: Perceived age was shown to be a reliable biomarker for cognitive assessment. Geriatr Gerontol Int 2020; 20: 779-784.

Loss of kallikrein-related peptidase 7 exacerbates amyloid pathology in Alzheimer's disease model mice.

Deposition of amyloid-ß (Aß) as senile plaques is one of the pathological hallmarks in the brains of Alzheimer's disease (AD) patients. In addition, glial activation has been found in AD brains, although the precise pathological role of astrocytes remains unclear. Here, we identified kallikrein-related peptidase 7 (KLK7) as an astrocyte-derived Aß degrading enzyme. Expression of KLK7 mRNA was significantly decreased in the brains of AD patients. Ablation of Klk7 exacerbated the thioflavin S-positive Aß pathology in AD model mice. The expression of Klk7 was upregulated by Aß treatment in the primary astrocyte, suggesting that Klk7 is homeostatically modulated by Aß-induced responses. Finally, we found that the Food and Drug Administration-approved anti-dementia drug memantine can increase the expression of Klk7 and Aß degradation activity specifically in the astrocytes. These data suggest that KLK7 is an important enzyme in the degradation and clearance of deposited Aß species by astrocytes involved in the pathogenesis of AD.

Dysregulated Metabolism of the Amyloid-ß Protein and Therapeutic Approaches in Alzheimer Disease.

Amyloid-ß protein (Aß) is the main component of senile plaques in the brains of Alzheimer disease (AD) patients. Aß is proteolytically derived from amyloid-ß precursor protein by ß- and γ-secretases. Secreted Aß is then eliminated from the central nervous system by multiple clearance mechanisms, including phagocytosis, immune responses, and proteolytic degradation. These dynamic metabolic processes, which are referred to as Aß economy, regulate steady-state brain Aß levels. Familial AD-linked genetic mutations augment the production and aggregation of Aß. In contrast, rare genetic variants that reduce Aß production were protective against AD. Moreover, decreased Aß clearance has been demonstrated in sporadic AD patients, suggesting that dysregulation of Aß economy contributes to the development of AD. Thus, several approaches to inhibit the production as well as to enhance the clearance of Aß have been investigated as potential therapeutics against AD. In this manuscript, we introduce the molecules and cellular mechanisms involved in the regulation of Aß economy and discuss the current understanding of these processes in the development of therapeutics against AD. J. Cell. Biochem. 118: 4183-4190, 2017. © 2017 Wiley Periodicals, Inc.