Adrenal Insufficiency and Thyrotoxicosis Following Combined Immune Checkpoint Inhibitor Use: A Case Report and Literature Review.

Destructive thyroiditis and secondary adrenal insufficiency are major endocrinological immune-related adverse events of immune checkpoint inhibitors (ICIs). However, the timing at which each event occurs most frequently after drug administration varies, and cases where multiple events occur simultaneously are rare. We encountered a patient who concurrently suffered from thyrotoxicosis and adrenal insufficiency. An 80-year-old woman with a history of type 2 diabetes mellitus (DM) was diagnosed with stage IVA squamous cell carcinoma of the lungs. Treatment with a combination of nivolumab and ipilimumab was initiated. Although she tested positive for thyroglobulin antibody and transient subclinical hyperthyroidism was observed after two courses, treatment with ICIs was continued. Four months later, treatment was discontinued due to drug-induced lung disease. One month after the last administration, the patient became unconscious and was admitted to another hospital, diagnosed with diabetic ketoacidosis, urinary tract infection, and sepsis. After acute-phase treatment, she was transferred to our hospital due to persistent fever and tachycardia. Thyrotoxicosis and adrenal insufficiency were observed, with high levels of free thyroxine, low thyroid-stimulating hormone (TSH), and cortisol levels. Treatment with extracellular fluids, potassium iodide, beta-blockers, and hydrocortisone was initiated, and the patient's condition improved. No other pituitary hormone deficiencies were observed. She was diagnosed with painless thyroiditis and secondary adrenal insufficiency based on the positive thyroglobulin antibody, negative TSH receptor antibody, decreased Doppler flow in thyroid ultrasonography, low adrenocorticotrophic hormone (ACTH), and low response of ACTH and cortisol to corticotropin-releasing hormone loading test. MRI revealed no abnormalities. We report a case of thyrotoxicosis and secondary adrenal insufficiency five months after the first administration of nivolumab and ipilimumab. Careful follow-up and early detection of endocrine disorders are critical in patients treated with a combination of ICIs.

Hypopituitarism with secondary adrenocortical insufficiency and arginine vasopressin deficiency due to hypophysitis after COVID-19 vaccination: a case report.

BACKGROUND: Although vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported. CASE PRESENTATION: An 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 µg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 µIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient's disease course was stable with continued thyroid and adrenal corticosteroid supplementation. CONCLUSIONS: Herein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination.

Association of pulse pressure and mean blood pressure to frailty, sarcopenia, and cognitive dysfunction in elderly outpatients with history of hypertension.

This study aimed to evaluate the relationship between pulse pressure (PP) and sarcopenia, frailty, and cognitive function in elderly patients with hypertension. We evaluated 435 elderly patients with a history of hypertension who visited the frail outpatient clinic between July 2015 and October 2021. Data at the 1-, 2-, and 3-year follow-ups were available for 222, 177, and 164 patients, respectively. Sarcopenia, frailty, and cognitive function, including Mini-Mental State Examination (MMSE) scores, were evaluated. The patients' mean age was 79.2 ± 6.3 years (male, 34.9%). PP and mean blood pressure (BP) were 60.1 ± 13.6 mmHg and 94.1 ± 13.0 mmHg, respectively. At baseline, lower PP was associated with probable dementia (MMSE score ≤23 points) (OR = 0.960 per 1 mmHg increase; 95% CI, 0.933-0.989; P = 0.006) in the model adjusted for conventional confounding factors and comorbidities, whereas higher PP was associated with low handgrip strength (OR = 1.018 per 1 mmHg increase; 95% CI, 1.001-1.036; P = 0.041). In multivariate-adjusted logistic regression analysis of patients with preserved handgrip strength at baseline, reductions in PP (OR = 0.844; 95% CI, 0.731-0.974; P = 0.020) and mean BP (OR = 0.861; 95% CI, 0.758-0.979; P = 0.022) were significantly associated with the incidence of low handgrip strength at 3 years. In conclusion, a higher PP induced by increased arterial stiffness was associated with lower handgrip strength, whereas a lower PP was associated with probable dementia. Reduced PP was associated with decreased handgrip strength after three years.

Association between Cognitive Impairment Severity and Polypharmacy in Older Patients with Atrial Fibrillation: A Retrospective Study Using Inpatient Data from a Specialised Geriatric Hospital.

This study aimed to investigate the association between cognitive impairment and polypharmacy in patients with atrial fibrillation prone to cognitive decline, and to elucidate if the Dementia Assessment Sheet for Community-based Integrated Care System 21-Items (DASC-21) severity classification indicates drug adjustment. This retrospective cohort study used the DASC-21 and Diagnosis Procedure Combination data at a specialised geriatric hospital with patients hospitalised between April 2019 and March 2022. The association between cognitive severity evaluated using the DASC-21 and polypharmacy was investigated using a multivariate logistic regression model. Data of 1191 inpatients (44.3% aged ≥85 years, 49.0% male) were analysed. Compared with severe cognitive impairment, mild (odds ratio [OR]: 3.33, 95% confidence interval [CI]: 1.29-8.57) and moderate (OR: 2.46, 95% CI: 1.06-5.72) impairments were associated with concurrent use of ≥6 medications. Antithrombotics were related to polypharmacy. The ORs did not change with 6, 8, or 10 medications (2.11 [95% CI: 1.51-2.95, p < 0.001], 2.42 [95% CI: 1.79-3.27, p < 0.001], and 2.01 [95% CI: 1.46-2.77, p < 0.001], respectively). DASC-21 severity was associated with polypharmacy in patients with atrial fibrillation, with a trend toward decreased polypharmacy from moderate to severe. The DASC-21 may serve as an indicator for drug adjustment in clinical practice.

Serum Growth Differentiation Factor 15 Levels Predict the Incidence of Frailty among Patients with Cardiometabolic Diseases.

INTRODUCTION: Frailty is a crucial health issue among older adults. Growth differentiation factor 15 (GDF15) is associated with inflammation, oxidative stress, insulin resistance, and mitochondrial dysfunction, which are possible pathogeneses of frailty. However, few longitudinal studies have investigated the association between GDF15 and the incidence of frailty. Therefore, we investigated whether high serum GDF15 levels are associated with the incidence of frailty. METHODS: A total of 175 older adults (mean age: 77 ± 6 years; 63% women) with cardiometabolic diseases and no frailty out of the two criteria at baseline participated. Individuals with severe renal impairment or severe cognitive impairment were excluded. Serum GDF15 levels were measured at baseline. Patients were asked to assess frailty status at baseline and annually during follow-up using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). We examined the association between GDF15 tertiles and each frailty measure during follow-up (median 38-39 months). In the multivariate Cox regression analysis, with the GDF15 tertile groups as the explanatory variables, hazard ratios (HRs) and 95% confidence intervals (CIs) for incident frailty were calculated after adjusting for covariates and using the lowest tertile group as the reference. RESULTS: During the follow-up period, 25.6% and 34.0% of patients developed frailty, as defined by the mCHS and KCL, respectively. The highest GDF15 tertile group had a significantly higher incidence of mCHS- or KCL-defined frailty than the lowest GDF15 tertile group. Multivariate Cox regression analysis revealed that the adjusted HRs for incident mCHS- and KCL-defined frailty in the highest GDF15 tertile group were 3.9 (95% CI: 1.3-12.0) and 2.7 (95% CI: 1.1-6.9), respectively. CONCLUSION: High serum GDF15 levels predicted the incidence of frailty among older adults with cardiometabolic diseases and could be an effective marker of the risk for frailty in interventions aimed at preventing frailty, such as exercise and nutrition.

Categorization using the Dementia Assessment Sheet for Community-Based Integrated Care System 8-items (DASC-8) based on cognitive function and activities of daily living predicts frailty, disability and mortality in older adults.

AIM: This longitudinal study aimed to determine whether categorization by the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) is associated with risk of frailty onset, disability, and mortality. METHODS: We analyzed longitudinal data from outpatients aged 65 years and older evaluated for the DASC-8 at the Frailty Clinic. The outcomes during the 3-year follow-up period were (Study A) frailty onset (Kihon Checklist ≥8) and (Study B) disability (new certification of nursing care needs) or mortality. Multivariate Cox regression analyses were performed to examine independent associations between the DASC-8 category and outcomes, and hazard ratios and 95% confidence intervals (CIs) were calculated after adjustment for age, sex, and the presence or absence of diabetes, hypertension, and dyslipidemia. RESULTS: (Study A) Out of the 216 patients without frailty in Categories I or II at baseline, 40 (20.4%) and 11 (55.0%) developed frailty, respectively. The adjusted hazard ratio was 3.62 (95% CI: 1.69-7.76, P < 0.001). (Study B) Out of the 350 patients who did not require long-term care at baseline, disability or death occurred for 20 (7.3%) in Category I, 14 (23.0%) in Category II, and 9 (56.3%) in Category III. The adjusted hazard ratios were 2.40 (Category I vs. II; 95% CI: 1.13-5.11, P = 0.023) and 5.43 (Category I vs. III; 95% CI: 2.23-13.3, P < 0.001). CONCLUSION: Categorization according to DASC-8 is associated with the risk of frailty, disability, and mortality in older patients. Geriatr Gerontol Int 2024; 24: 150-155.

Relationship between blood pressure and cognitive impairment in elderly outpatients with cardiometabolic diseases.

AIM: The aim of this study was to clarify the relationship between high or low blood pressure (BP) and cognitive function in elderly outpatients with cardiometabolic diseases. METHODS: We evaluated the association between BP and the Dementia Assessment Sheet for Community-based Integrated Care System-21 items (DASC-21), Mini Mental State Examination (MMSE), and Montreal Cognitive Assessment Tool (MoCA) (N = 677). RESULTS: The patients' mean age was 79.2 ± 6.3 years (male 35.3%), and BP was 132.1 ± 18.1/73.5 ± 12.2 mmHg. Systolic BP (SBP) was linearly related to the DASC-21 score (r = -0.122, P = 0.004), but not to the MMSE score (P = 0.101) or MoCA score (P = 0.802). Multiple linear regression analysis showed that lower SBP was significantly related to the DASC-21 score, even after controlling for confounding factors (B = -0.411 per 10 mmHg; 95% confidence interval [CI], -0.673 to -0.149; P = 0.002). Moreover, logistic regression analysis showed that lower SBP was associated with DASC-21 ≥ 31 (odds ratio = 0.838 per 10 mmHg, P = 0.048). An MMSE score ≤23 was significantly associated with higher SBP in patients without a history of hypertension but with lower SBP in those with hypertension, those on hypertensive medication, and those with dyslipidemia. CONCLUSION: Higher BP was associated with a higher prevalence of probable dementia in those without a history of hypertension, even in late life. In those with hypertension and those taking antihypertensives with comorbidities of stroke or heart failure, lower BP was associated with probable dementia, which was largely dependent on reduced activities of daily living, as measured by the DASC-21 score. Geriatr Gerontol Int 2024; 24: 110-117.

Multimorbidity, consisting of a combination of chronic diseases and geriatric syndromes, predicts the risk of difficulty in discharge home in older patients admitted to acute care hospital.

AIM: To determine whether multimorbidity, consisting of chronic diseases and geriatric syndromes, is associated with home discharge difficulties in older patients. METHODS: A total of 522 older adults (mean age: 85 ± 7 years) who were admitted to an acute care hospital were enrolled. Multimorbidity was assessed by calculating the number of 16 chronic conditions (CCs): 8 chronic diseases (cardiac diseases, diabetes mellitus, chronic kidney disease, respiratory diseases, gastrointestinal diseases, anemia, dementia, and Parkinson disease) and 8 geriatric syndromes (depression, constipation, chronic pain, polypharmacy, dysphagia, underweight, hypoalbuminemia, and functional limitations). The patients were divided into four groups based on the number of CCs. The outcome was difficulty in discharging home (transfer to other facilities or in-hospital death). Multivariate logistic regression analysis was performed to assess independent associations between four CC groups and failure to discharge home after adjusting for age, sex, living alone, and Barthel index and odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: Of the 522 patients, 18.8% were transferred to other facilities or died. The proportion of poor outcome in those with 0-2, 3-4, 5-6, and ≥7 CCs was 4.4%, 14.8%, 25.5%, and 37.5%, respectively. Logistic regression analysis after adjusting for covariates revealed that multimorbidity increased the risk of difficulty in discharging home (OR, 2.9 [95% CI, 1.1-8.0] for 3-4 CCs; OR, 4.9 [95% CI, 1.8-13.5] for 5-6 CCs; OR, 8.7 [95% CI, 3.1-24.6] for ≥7 CCs). CONCLUSION: Multimorbidity, consisting of chronic diseases and geriatric syndromes, predicted difficulty in discharge home in older patients. Geriatr Gerontol Int 2024; 24: 300-305.

The cross-sectional area of erector spinae muscle and the liver-to-spleen ratio are associated with frailty in older patients with diabetes: a cross-sectional study.

BACKGROUND: Older patients with diabetes mellitus are more susceptible to frailty. Although some imaging markers of appendicular skeletal muscle mass obtained using dual-energy X-ray absorptiometry or computed tomography (CT) imaging can reflect frailty status, the association between imaging indices obtained by abdominal CT scans and frailty in older inpatients has not been reported. METHODS: A total of 151 older inpatients with diabetes mellitus (median age, 79 years; men, 42%) who underwent abdominal CT scans close to the admission date were studied to examine the associations between abdominal CT indices and frailty. Two frailty definitions were used: the modified Cardiovascular Health Study (mCHS) criteria and Kihon Checklist (KCL) criteria. Using the imaging analysis software SYNAPSE VINCENT®, we compared the cross-sectional areas (CSA) of four truncal muscles (erector spinae, iliopsoas, rectus abdominis, and abdominal oblique muscles) and the liver-to-spleen ratio (L/S), the ratio of the CT values of the liver and spleen between frail and non-frail patients. The muscle areas that showed the strongest associations with frailty were also investigated in relation to grip strength and walking speed. Finally, multivariate binominal logistic regression analyses were performed to assess the independent associations of CSA of muscle and L/S with the prevalence of frailty. RESULTS: The prevalence of frailty defined by the mCHS and KCL criteria was 55% and 52%, respectively. The CSA of the erector spinae muscle was most significantly associated with frailty, and was significantly smaller in both sexes of mCHS-defined frail patients and in men with KCL-defined frailty. The CSA of erector spinae muscle was also positively correlated with grip strength and walking speed. In contrast, the L/S was higher in men with KCL-defined frailty. Multivariate logistic regression analyses revealed that the CSA of the erector spinae muscle was independently associated with mCHS-defined frailty in women, and the L/S was associated with KCL-defined frailty in men. CONCLUSIONS: The CSA of erector spinae muscle and low liver fat content could be indices of frailty in older patients with diabetes.

Impact of a history of cardiovascular disease and physical activity habits on the incidence of functional disability.

We examined the impact of a history of coronary artery disease (CAD) or cerebrovascular disease (CVD) and physical activity habits on functional disability among community-dwelling Japanese adults. This population-based retrospective cohort study included 10,661 people aged 39-98 years in Japan (5054, men). Median follow-up was 3.7 years. During the study period, 209 functional disabilities occurred in the overall study population. In multivariable analysis, a history of CVD (hazard ratio [HR] 1.57 [95% CI: 1.00-2.45]) and no physical activity habit (HR 1.74 [1.27-2.39]) presented increased risks for functional disability. HRs for functional disability among patients with a CVD history with and without a physical activity habit were 1.68 (0.75-3.74) and 2.65 (1.49-4.71), respectively, compared with individuals without a history of CVD with a physical activity habit. Similar results were observed for CAD. We found no significant difference in the incidence of functional disability between the group with a history of CAD or CVD and physical activity habits and the group with no history of CAD or CVD and without physical activity habits. Physical activity habits had a favorable influence on avoiding functional disability regardless of a history of CAD or CVD. Future prospective studies are needed to clarify these associations.

Abnormal Development of Microbiota May Be a Risk Factor for Febrile Urinary Tract Infection in Infancy.

Febrile urinary tract infection (fUTI) is common in infants, but specific risk factors for developing it remain unclear. As most fUTIs are caused by ascending infections of intestinal bacteria, dysbiosis-an imbalance in gut microbial communities-may increase fUTI risk. This study was conducted to test the hypothesis that abnormal development of gut microbiota during infancy increases the risk of developing fUTI. Stool samples were collected from 28 infants aged 3-11 months with first-onset fUTI (fUTI group) and 51 healthy infants of the same age (HC group). After bacterial DNA extraction, 16S rRNA expression was measured and the diversity of gut microbiota and constituent bacteria were compared between the two groups. The alpha diversity of gut microbiota (median Shannon index and Chao index) was significantly lower in the fUTI group (3.0 and 42.5) than in the HC group (3.7 and 97.0; p < 0.001). The beta diversity also formed different clusters between the two groups (p < 0.001), suggesting differences in their microbial composition. The linear discriminant analysis effect size showed that the fUTI group proportionally featured significantly more Escherichia-Shigella in the gut microbiota (9.5%) than the HC group (3.1%; p < 0.001). In summary, abnormal gut microbiota development during infancy may increase the risk of fUTI.

Spontaneous pneumoperitoneum and diabetic ketoacidosis in fulminant type 1 diabetes: a case report.

A 41-year-old woman was referred to our emergency department with a 3-day history of upper abdominal pain. We diagnosed her with diabetic ketoacidosis (DKA) after laboratory tests indicated a blood glucose level of 569 mg/dL, positive urine ketone bodies and metabolic acidosis. Plain computed tomography (CT) scan revealed free gas surrounding the porta hepatis and gastric pylorus, which disappeared on the subsequent contrast-enhanced CT scan. Upper gastrointestinal endoscopy demonstrated no perforations; therefore, we assumed that the free gas was caused by spontaneous pneumoperitoneum. The patient had fulminant type 1 diabetes mellitus, as evidenced by her glycated hemoglobin A1c level of 6.9%, reduced insulin secretion and negative islet-specific autoantibodies. Pneumoperitoneum did not recur with conservative treatment, and DKA improved with intravenous fluids and insulin administration. Conservative management of DKA with spontaneous pneumoperitoneum may be considered if the patient's general condition is stable and there are no signs of peritoneal irritation.

Efficacy and Safety of 6-Month High Dietary Protein Intake in Hospitalized Adults Aged 75 or Older at Nutritional Risk: An Exploratory, Randomized, Controlled Study.

The aim of this study was to investigate the effects of increased dietary protein in daily-life settings in Japan for 6 months on the activities of daily living (ADL) in adults aged 75 or older at nutritional risk. The study was an open-label, exploratory, randomized controlled trial conducted at seven hospitals in Japan. The study participants were adults aged 75 or older who were hospitalized for treatable cancer, pneumonia, fractures, and/or urinary-tract infection at nutritional risk. The primary outcome was change in grip strength, skeletal muscle, and ADL indices (Barthel index, Lawton score). One hundred sixty-nine patients were randomly assigned to the intensive care (IC) or standard care (SC) group; the protein intake goals (g/kgw/day) were 1.5 for IC and 1.0 for SC. There was a significant improvement in grip strength only in the IC group (1.1 kg: 95% CI 0.1 to 2.1) (p = 0.02). While the skeletal muscle index and ADL indices were not significantly improved in either group, the improvement ratio tended to be greater in the IC group. There was no decrease in renal function in either group. Thus, intervention of increased dietary protein in daily-life settings for 6 months in adults aged 75 or older with treatable cancer, pneumonia, fractures, and/or urinary-tract infection and at nutritional risk may be effective in ameliorating loss of muscle strength.

Association between physical performance during sit-to-stand motion and frailty in older adults with cardiometabolic diseases: a cross-sectional, longitudinal study.

BACKGROUND: Although physical performance tests of the lower extremities are used to assess sarcopenia and frailty, little is known about the mechanisms by which the parameters of ground reaction force (GRF) measured during sit-to-stand motion affect the frailty status in older adults. We aimed to examine the association between GRF parameters during sit-to-stand motion and the incidence of frailty in older adults. METHODS: This longitudinal study evaluated 319 outpatients aged ≥ 65 years with cardiometabolic diseases. The GRF parameters were measured using a motor function analyzer, in which the power, speed, and balance scores were calculated. Frailty was diagnosed using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). The independent associations between scores and frailty indices were assessed using multivariate binomial logistic regression analyses. Cox regression analysis was used to examine whether power and speed scores were associated with the incidence of frailty after adjusting for covariates. RESULTS: Logistic regression analyses adjusted for covariates showed that the power and speed scores were associated with frailty according to the mCHS criteria (power: OR = 0.37, 95% CI = 0.22-0.63; speed: OR = 0.64, 95% CI = 0.52-0.79) and KCL criteria (power: OR = 0.40, 95% CI = 0.26-0.62; speed: OR = 0.81, 95% CI = 0.69-0.96) at baseline. Receiver operating characteristic analyses revealed that the area under the curve values of power and speed scores for discriminating mCHS-defined frailty were 0.72 and 0.73. The Cox regression analysis showed that the speed score predicted the incidence of mCHS-defined (HR = 0.45, 95% CI = 0.22-0.92, P = 0.029) and KCL-defined (HR = 0.77, 95% CI = 0.60-0.99, P = 0.039) frailty, whereas the power score was associated with the incidence of KCL-defined frailty (HR = 0.72, 95% CI = 0.55-0.95, P = 0.02) after adjusting for covariates. CONCLUSIONS: The speed and power scores measured during sit-to-stand motion are predictive of frailty in older adults with cardiometabolic disease. Therefore, the GRF parameters measured during sit-to-stand motion could be an important indicator of frailty. Further studies are necessary to examine whether the GRF parameters can be improved by exercise or whether the changes in these parameters are associated with the improvement of frailty status.

Changes in blood pressure associated with frailty and sarcopenia in elderly outpatients with cardiometabolic diseases.

AIM: We aimed to examine the relationship between changes in clinic blood pressure (BP) and frailty and sarcopenia in elderly outpatients with cardiometabolic disease. METHODS: In 691 elderly outpatients with cardiometabolic diseases, the associations of frailty according to the modified Japanese Cardiovascular Health Study score (J-CHS) and Kihon Checklist (KCL) criteria with clinic BP were evaluated at baseline and followed up for 3 years. RESULTS: Among the patients (79.2 ± 6.3 years, male 35.6%), 30.4% had frailty by the J-CHS criteria and 38.0% by the KCL criteria. A J-curve relationship was observed between BP and frailty; the prevalence of frailty was the lowest in patients with systolic BP (SBP) 119.5-130.5 mmHg and in those with diastolic BP (DBP) 72.0-80.5 mmHg. Frailty by the J-CHS criteria correlated with lower DBP (OR = 0.892 per 5 mmHg increase, 95% confidence interval [CI] 0.819-0.972, P = 0.009), whereas that by the KCL criteria correlated with lower SBP (OR = 0.872 per 10 mmHg increase, 95% CI 0.785-0.969, P = 0.011) in multivariate-adjusted models. In patients with frailty by the J-CHS criteria at baseline, changes in DBP (OR = 0.921 per 1 mmHg change, 95% CI 0.851-0.996, P = 0.038) were associated with sustained frailty 1 year later. Changes in DBP were associated with progression to a slow walking speed 1 year later (OR = 0.939, 95% CI 0.883-0.999, P = 0.047). Changes in SBP (OR = 0.928, 95% CI 0.878-0.981, P = 0.008) and DBP (OR = 0.926, 95% CI 0.859-0.997, P = 0.042) were associated with progression to a weak hand grip strength 3 years later. CONCLUSION: A J-curve relationship was observed between frailty and BP, and a decline in BP was associated with progression to a slow walking speed and weak hand grip strength in elderly outpatients with cardiometabolic diseases. Geriatr Gerontol Int 2023; 23: 506-516.

Determinants of depressive symptoms in older outpatients with cardiometabolic diseases in a Japanese frailty clinic: Importance of bidirectional association between depression and frailty.

INTRODUCTION: Frailty and depression may play important roles in the management of older patients with cardiometabolic diseases. We explored the determinants of depressive symptoms and their association with frailty among patients with cardiometabolic diseases (hypertension, diabetes, and atrial fibrillation) in a cross-sectional study. METHODS: A total of 633 outpatients aged 65 years or older with cardiometabolic disease and suspected symptoms of frailty participated in this study. Depressive symptoms, physical activity, and social network were assessed using the Geriatric Depression Scale (GDS)-15, International Physical Activity Questionnaire, and Lubben Social Network Scale-6 (LSNS-6), respectively. Frailty was evaluated using the Kihon Checklist (KCL) based on the Comprehensive Geriatric Assessment (CGA), the modified Cardiovascular Health Study (mCHS), and the Clinical Frailty Scale (CFS). Binomial logistic regression analysis was used to examine the determinants of depressive symptoms and their association with frailty. RESULTS: Depressive symptoms with GDS-15 scores ≥ 5 were present in 43.6% of the patients. In logistic regression, after adjusting for covariates, the determinants of depressive symptoms in all patients were lack of social network, low years of education, and frailty. In contrast, in logistic regression with frailty as the dependent variable, depressive symptoms were independently associated KCL-defined frailty (OR = 6.28, 95% CI: 4.13-9.55) and mCHS-defined frailty (OR = 2.66, 95% CI: 1.70-4.17), but not with CFS. Similarly, significant associations between depression and frailty were observed in patients with hypertension, diabetes, or atrial fibrillation. CONCLUSIONS: Lack of social networks, low education, and frailty based on the KCL and mCHS were important determinants of depressive symptoms in all patients. The relatively strong associations between depressive symptoms and frailty based on CGA in patients with hypertension, diabetes, or atrial fibrillation suggest that the assessment of depressive symptoms is of great importance in clinical practice in those patients at high risk of frailty.

Association between white matter alterations on diffusion tensor imaging and incidence of frailty in older adults with cardiometabolic diseases.

Diffusion tensor imaging (DTI) can be used for the early detection of abnormal changes in the integrity of cerebral white matter tracts, and we have previously reported that these changes are associated with indices of early atherosclerotic lesions. Although these changes have been demonstrated to be associated with the incidence of frailty in older adults, no studies have investigated this relationship in patients at high risk for vascular disease. In this longitudinal study, we followed outpatients with cardiometabolic diseases for a maximum of 6 years (median, 3 years) and evaluated the association of baseline DTI data of seven white matter tracts with the incidence of frailty. The modified version of the Cardiovascular Health Study criteria and the Kihon Checklist were used as indices of frailty; fractional anisotropy (FA) and mean diffusivity (MD) were used as indices of white matter changes. Patients who developed frailty based on both indices had low FA and high MD in many of the tracts tested, with the most significant difference found in the MD of the anterior thalamic radiation (ATR). Cox proportional hazard model analysis revealed a significantly high risk of frailty defined by both indices in the groups with high MD values in the left ATR. Similar results were found in patients with diabetes mellitus but not in those without diabetes mellitus. Therefore, abnormalities in the integrity of the left ATR could be associated with the progression of frailty in older adults with cardiometabolic disease, particularly those with diabetes mellitus.

Relationship between the Thyroid Function and Cognitive Impairment in the Elderly in Japan.

Objective The reference ranges of serum thyroid hormone levels are determined by the values of normal subjects aged 15 or 20 to 60 years old in Japan and may differ from the values in elderly patients. In addition, the relationship between the thyroid function and cognitive function remains controversial. We assessed the thyroid function of elderly subjects ≥60 years old and its impact on the cognitive function in Japanese adults. Methods We compared the thyroid function by age group and gender and investigated the effects of cognitive impairment on the thyroid function. This study was a cross-sectional, multi-institutional joint study. Patients The serum concentrations of thyroid hormones in 1,136 patients were measured; however, those taking thyroid hormones, anti-thyroid drugs, and steroid hormones were excluded. Among them, 1,016 cases in which the cognitive function was evaluated were divided into five groups according to their free thyroxine (FT4) levels. Results Excluding overt thyroid dysfunction (5.8%), the average age of the 1,070 remaining patients was 77.5 years old. The rate of cognitive impairment was lowest at FT4 levels of 1.1-1.2 ng/dL and highest at FT4 levels <0.9 ng/dL for both genders. Thyroid-stimulating hormone (TSH) levels in the elderly varied widely by age group and gender. The upper limit of the reference range of TSH for those ≥60 years old may be higher (7.7-9.2 mIU/L for men; 8.2-8.6 mIU/L for women) than the current range for those <60 years old (4.23 mIU/L). Conclusion The thyroid function seemed to be slightly higher (lower TSH and higher FT4) in the population without cognitive impairment than in those with cognitive impairment, except for men in their 90s.