Animal models to study cognitive impairment of chronic kidney disease.

Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD), and its prevalence increases with progressive loss of kidney function. MCI is characterized by a decline in cognitive performance greater than expected for an individual age and education level but with minimal impairment of instrumental activities of daily living. Deterioration can affect one or several cognitive domains (attention, memory, executive functions, language, and perceptual motor or social cognition). Given the increasing prevalence of kidney disease, more and more people with CKD will also develop MCI causing an enormous disease burden for these individuals, their relatives, and society. However, the underlying pathomechanisms are poorly understood, and current therapies mostly aim at supporting patients in their daily lives. This illustrates the urgent need to elucidate the pathogenesis and potential therapeutic targets and test novel therapies in appropriate preclinical models. Here, we will outline the necessary criteria for experimental modeling of cognitive disorders in CKD. We discuss the use of mice, rats, and zebrafish as model systems and present valuable techniques through which kidney function and cognitive impairment can be assessed in this setting. Our objective is to enable researchers to overcome hurdles and accelerate preclinical research aimed at improving the therapy of people with CKD and MCI.

Translational research on cognitive impairment in chronic kidney disease.

Cognitive decline is common in patients with acute or chronic kidney disease. Several areas of brain function can be affected, including short and long-term memory, attention and inhibitory control, sleep, mood, eating control and motor function. Cognitive decline in kidney disease shares risk factors with cognitive dysfunction in people without kidney disease, such as diabetes, high blood pressure, sedentary lifestyle and unhealthy diet. However, additional kidney-specific risk factors may contribute, such as uremic toxins, electrolyte imbalances, chronic inflammation, acid-base disorders or endocrine dysregulation. Traditional and kidney-specific risk factors may interact to cause damage to the blood-brain barrier, induce vascular damage in the brain, and cause neurotoxicity or neuroinflammation. Here, we discuss recent insights into the pathomechanisms of cognitive decline from animal models and novel avenues for prevention and therapy. We focus on a several areas that influence cognition: blood-brain barrier disruption, the role of skeletal muscle, physical activity and the endocrine factor irisin, and the emerging therapeutic role of sodium-glucose transporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. Taken together, these studies demonstrate the importance of animal models in providing a mechanistic understanding of this complex condition and their potential to explain the mechanisms of novel therapies.

Efficacy of erythropoietin as a neuroprotective agent in CKD-associated cognitive dysfunction: A literature systematic review.

Patients with chronic kidney disease (CKD) often experience mild cognitive impairment and other neurocognitive disorders. Studies have shown that erythropoietin (EPO) and its receptor have neuroprotective effects in cell and animal models of nervous system disorders. Recombinant human EPO (rHuEPO), commonly used to treat anemia in CKD patients, could be a neuroprotective agent. In this systematic review, we aimed to assess the published studies investigating the cognitive benefits of rHuEPO treatment in individuals with reduced kidney function. We comprehensively searched Pubmed, Cochrane Library, Scopus, and Web of Science databases from 1990 to 2023. After selection, 24 studies were analyzed, considering study design, sample size, participant characteristics, intervention, and main findings. The collective results of these studies in CKD patients indicated that rHuEPO enhances brain function, improves performance on neuropsychological tests, and positively affects electroencephalography measurements. These findings suggest that rHuEPO could be a promising neuroprotective agent for managing CKD-related cognitive impairment.

Comprehensive Geriatric Assessment, Treatment Decisions, and Outcomes in Older Patients Eligible for Pancreatic Surgery.

INTRODUCTION: Periampullary cancer has a poor prognosis. Surgical resection is a potentially curative but high-risk treatment. Comprehensive geriatric assessment (CGA) can inform treatment decisions, but has not yet been evaluated in older patients eligible for pancreatic surgery. METHODS: This prospective observational study included patients ≥ 70 years of age eligible for pancreatic surgery. Frailty was defined as impairment in at least two of five domains: somatic, psychological, functional, nutritional, and social. Outcomes included postoperative complications, functional decline, and mortality. RESULTS: Of the 88 patients included, 87 had a complete CGA. Sixty-five patients (75%) were frail and 22 (25%) were non-frail. Frail patients were more likely to receive nonsurgical treatment (43.1% vs. 9.1% p = 0.004). Fifty-seven patients underwent surgery, of which 52 (59%) underwent pancreaticoduodenectomy. The incidence of postoperative delirium was three times higher in frail patients (29.7% vs. 0%, p = 0.005). The risk of mortality was three times higher in frail patients (HR: 3.36, 95% CI: 1.43-7.89, p = 0.006). CONCLUSION: Frailty is common in older patients eligible for pancreatic surgery and is associated with treatment decision, a higher incidence of delirium and a three times higher risk of all-cause mortality. CGA can contribute to shared decision-making and optimize perioperative care in older patients.

Prevalence of Sarcopenia in Chronic Heart Failure and Modulating Role of Chronic Kidney Disease.

INTRODUCTION: Sarcopenia, heart failure (HF), and chronic kidney disease (CKD) are common among the older people. Our objective was to evaluate the frequency of sarcopenia, among community-dwelling older adults with HF, possible causative factors, and the additive factor of CKD. METHODS: A cross-sectional analysis of 1,420 older people living in the community was carried out. Participants (aged 75 years and more) came from a European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test, and bioelectrical impedance analysis was performed. Previous known HF was defined as physician-diagnosed HF registered in the patient's medical record or the use of HF-related medications, regardless of left ventricular ejection fraction (LVEF). Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate was calculated using Berlin Initiative Study (BIS) to define the stages of CKD. Two-year mortality was also collected. RESULTS: A total of 226 (15.9%) participants had a prior chronic HF diagnosis, with a median age of 80.0 (5.0), and 123 (54.4%) were women. Using EWGSOP2 definition, 11.5% HF and 10.7% in non-HF participants met diagnostic criteria for sarcopenia. In multivariate analyses, only a lower body mass index (BMI) (odds ratios [OR], 0.82; 95% confidence interval [CI], 0.73-0.93) and lower short physical performance battery score (OR, 0.81; 95% CI, 0.69-0.96) were associated with sarcopenia. Patients with HF and sarcopenia have a similar all-cause mortality risk but higher 2-year cardiovascular mortality risk (p = 0.047). DISCUSSION/CONCLUSION: One out of ten community-dwelling older adults with concurrent clinical stable chronic HF, without considering LVEF, have sarcopenia. Lower BMI and poor physical performance are associated with sarcopenia in this population, but not CKD.

Ageing meets kidney disease.

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for ˃3 months, with implications for health. The most used diagnostic criteria are a urinary albumin: creatinine ratio ≥30 mg/g or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Either of these diagnostic thresholds is associated with adverse health outcomes. GFR decreases with age and the prevalence of CKD is highest in older adults; moreover, the presence of CKD is associated with an increased risk of all-cause and cardiovascular death related to accelerated ageing in all age ranges, and the absolute increase in risk is highest for those aged ˃75 years. Indeed, premature death is a more common outcome than CKD progression to kidney failure requiring kidney replacement therapy. The progressive ageing of the world population contributes to the projection that CKD will become the second most common cause of death before the end of the century in countries with long life expectancy. The current collection of selected studies on kidney disease and ageing published in Age&Ageing, NDT and CKJ provides an overview of key topics, including cognitive decline, sarcopaenia, wasting and cardiovascular and non-cardiovascular morbidity and mortality, the management of kidney failure and gender differences in CKD progression.

Delirium in older patients with COVID-19: Prevalence, risk factors and clinical outcomes across the first three waves of the pandemic.

OBJECTIVES: Delirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient characteristics and outcomes through the pandemic. We evaluated whether the prevalence and risk factors for delirium, and the association of delirium with in-hospital mortality changed through the pandemic. METHODS: This study was part of the COVID-OLD study in 19 Dutch hospitals including patients ≥70 years in the first (spring 2020), second (autumn 2020) and third wave (autumn 2021). Multivariable logistic regression models were used to study risk factors for delirium, and in-hospital mortality. Differences in effect sizes between waves were studied by including interaction terms between wave and risk factor in logistic regression models. RESULTS: 1540, 884 and 370 patients were included in the first, second and third wave, respectively. Prevalence of delirium in the third wave (12.7%) was significantly lower compared to the first (22.5%) and second wave (23.5%). In multivariable-adjusted analyses, pre-existing memory problems was a consistent risk factor for delirium across waves. Previous delirium was a risk factor for delirium in the first wave (OR 4.02), but not in the second (OR 1.61) and third wave (OR 2.59, p-value interaction-term 0.028). In multivariable-adjusted analyses, delirium was not associated with in-hospital mortality in all waves. CONCLUSION: Delirium prevalence declined in the third wave, which might be the result of vaccination and improved treatment strategies. Risk factors for delirium remained consistent across waves, although some attenuation was seen in the second wave.

New horizons in cognitive and functional impairment as a consequence of cerebral small vessel disease.

Cerebral small vessel disease (cSVD) is a frequent finding in imaging of the brain in older adults, especially in the concomitance of cardiovascular disease risk factors. Despite the well-established link between cSVD and (vascular) cognitive impairment (VCI), it remains uncertain how and when these vascular alterations lead to cognitive decline. The extent of acknowledged markers of cSVD is at best modestly associated with the severity of clinical symptoms, but technological advances increasingly allow to identify and quantify the extent and perhaps also the functional impact of cSVD more accurately. This will facilitate a more accurate diagnosis of VCI, against the backdrop of concomitant other neurodegenerative pathology, and help to identify persons with the greatest risk of cognitive and functional deterioration. In this study, we discuss how better assessment of cSVD using refined neuropsychological and comprehensive geriatric assessment as well as modern image analysis techniques may improve diagnosis and possibly the prognosis of VCI. Finally, we discuss new avenues in the treatment of cSVD and outline how these contemporary insights into cSVD can contribute to optimise screening and treatment strategies in older adults with cognitive impairment and multimorbidity.

Diabetes and factors associated with cognitive and functional decline. The screening for CKD among older people across Europe (SCOPE) study.

BACKGROUND: Type 2 diabetes mellitus (DM) in older people is a heterogeneous condition that exhibits differential characteristics in comparison with younger adults. DM increases the risk of disability, is associated with dementia and loss of function, and cognition may often be interrelated and more pronounced in older patients with DM than in those without. AIMS: Our aim was to evaluate the incidence of functional and/or cognitive impairment in older adults with and without DM, and its associated factors in DM participants. METHODS: A 2-year prospective analysis was conducted in a European multicenter prospective cohort (SCOPE study). Older community-dwelling adults (aged ≥ 75 years) underwent a comprehensive geriatric assessment. New functional and/or cognitive decline was explored. RESULTS: Of 1611 participants, 335 (22.0%) had DM at baseline. The percentage of participants scoring at least one ADL impairment and/or cognitive impairment (MMSE < 24) was similar in both groups (9.6%). Factors associated with any new disability in participants with DM in the multivariate analysis were female sex (OR 3.28, 95% CI 1.42-7.56), history of stroke (OR 4.58, 95% CI 1.64-12.7), and greater IADL dependency (OR 1.08 95% CI 1.02-1.15). DISCUSSION: Association between DM and cognitive or functional decline in outpatients of 75 years and older was not found, but factors such as female gender, history of stroke, and IADL dependency could be related. CONCLUSION: Decline in functional and cognitive status of community-dwelling older adults with DM was similar to participants without DM in a short period of 2 years of follow-up, though several clinical factors may increase its risk in this population.

Changing haemodynamic status of patients referred for transcatheter aortic valve intervention during the COVID-19 pandemic.

INTRODUCTION: Delays in the diagnosis and referral of aortic stenosis (AS) during the coronavirus disease 2019 (COVID-19) pandemic may have affected the haemodynamic status of AS patients. We aimed to compare clinical and haemodynamic characteristics of severe AS patients referred for transcatheter aortic valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) before the pandemic versus two subsequent periods. METHODS: This study compared three 1­year historical cohorts: a pre-COVID-19 group (PCOV), a 1st-year COVID-19 group (COV-Y1) and a 2nd-year COVID-19 group (COV-Y2). The main parameters were baseline New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP). Demographics, procedural characteristics and 30-day clinical outcomes were assessed. The transition time between heart team decision and TAVI was examined. Pairwise group comparisons were performed (PCOV vs COV-1Y and COV-1Y vs COV-2Y). RESULTS: A total of 720 patients were included with 266, 249 and 205 patients in the PCOV, COV-Y1 and COV-Y2 groups, respectively. BAV was performed in 28 patients (4%). NYHA class did not differ across the cohorts. Compared to PCOV, LVEF was slightly lower in COV-Y1 (58% (49-60%) vs 57% (45-60%), p = 0.03); no difference was observed when comparing COV-Y1 and COV-Y2. LVEDP was higher in COV-Y1 than in PCOV (20 mm Hg (16-26 mm Hg) vs 17 mm Hg (13-24 mm Hg), p = 0.01). No difference was found when comparing LVEDP between COV-Y1 and COV-Y2. Thirty-day mortality did not differ between groups. Transition time was reduced in the COVID era. Duration of hospital stay declined over the study period. CONCLUSIONS: Patients undergoing TAVI during the COVID-19 pandemic had more advanced AS illustrated by lower LVEF and higher LVEDP, but there were no differences in clinical outcome. The TAVI pathway became more efficient.

Delirium in older COVID-19 patients: Evaluating risk factors and outcomes.

OBJECTIVES: A high incidence of delirium has been reported in older patients with Coronavirus disease 2019 (COVID-19). We aimed to identify determinants of delirium, including the Clinical Frailty Scale, in hospitalized older patients with COVID-19. Furthermore, we aimed to study the association of delirium independent of frailty with in-hospital outcomes in older COVID-19 patients. METHODS: This study was performed within the framework of the multi-center COVID-OLD cohort study and included patients aged ≥60 years who were admitted to the general ward because of COVID-19 in the Netherlands between February and May 2020. Data were collected on demographics, co-morbidity, disease severity, and geriatric parameters. Prevalence of delirium during hospital admission was recorded based on delirium screening using the Delirium Observation Screening Scale (DOSS) which was scored three times daily. A DOSS score ≥3 was followed by a delirium assessment by the ward physician In-hospital outcomes included length of stay, discharge destination, and mortality. RESULTS: A total of 412 patients were included (median age 76, 58% male). Delirium was present in 82 patients. In multivariable analysis, previous episode of delirium (Odds ratio [OR] 8.9 [95% CI 2.3-33.6] p = 0.001), and pre-existent memory problems (OR 7.6 [95% CI 3.1-22.5] p < 0.001) were associated with increased delirium risk. Clinical Frailty Scale was associated with increased delirium risk (OR 1.63 [95%CI 1.40-1.90] p < 0.001) in univariable analysis, but not in multivariable analysis. Patients who developed delirium had a shorter symptom duration and lower levels of C-reactive protein upon presentation, whereas vital parameters did not differ. Patients who developed a delirium had a longer hospital stay and were more often discharged to a nursing home. Delirium was associated with mortality (OR 2.84 [95% CI1.71-4.72] p < 0.001), but not in multivariable analyses. CONCLUSIONS: A previous delirium and pre-existent memory problems were associated with delirium risk in COVID-19. Delirium was not an independent predictor of mortality after adjustment for frailty.

Ageing meets kidney disease.

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for >3 months, with implications for health. The most used diagnostic criteria are a urinary albumin: creatinine ratio ≥30 mg/g or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Either of these diagnostic thresholds is associated with adverse health outcomes. GFR decreases with age and the prevalence of CKD is highest in older adults; moreover, the presence of CKD is associated with an increased risk of all-cause and cardiovascular death related to accelerated ageing in all age ranges, and the absolute increase in risk is highest for those aged >75 years. Indeed, premature death is a more common outcome than CKD progression to kidney failure requiring kidney replacement therapy. The progressive ageing of the world population contributes to the projection that CKD will become the second most common cause of death before the end of the century in countries with long life expectancy. The current collection of selected studies on kidney disease and ageing published in Age&Ageing, NDT and CKJ provides an overview of key topics, including cognitive decline, sarcopaenia, wasting and cardiovascular and non-cardiovascular morbidity and mortality, the management of kidney failure and gender differences in CKD progression.

The relevance of geriatric assessments on the association between chronic kidney disease stages and mortality among older people: a secondary analysis of a multicentre cohort study.

BACKGROUND: age-adapted definition of chronic kidney disease (CKD) does not take individual risk factors into account. We aimed at investigating whether functional impairments influence CKD stage at which mortality increases among older people. METHODS: our series consisted of 2,372 outpatients aged 75 years or more enrolled in a multicentre international prospective cohort study. The study outcome was 24-month mortality. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Geriatric assessments included handgrip strength, short physical performance battery (SPPB), cognitive impairment, dependency in basic activities of daily living (BADL) and risk of malnutrition. Analysis was carried out by Cox regression, before and after stratification by individual functional impairments. Survival trees including kidney function and functional impairments were also investigated, and their predictivity assessed by C-index. RESULTS: overall, mortality was found to increase starting from eGFR = 30-44.9 ml/min/1.73 m2 (hazard ratio [HR] = 3.28, 95% confidence interval [CI] = 1.81-5.95) to ACR = 30-300 mg/g (HR = 1.96, 95%CI = 1.23-3.10). However, in survival trees, an increased risk of mortality was observed among patients with impaired handgrip and eGFR = 45-59.9 ml/min/1.73 m2, as well as patients with ACR < 30 mg/g and impaired handgrip and SPPB. Survival tree leaf node membership had greater predictive accuracy (C-index = 0.81, 95%CI = 0.78-0.84 for the eGFR survival tree and C-index = 0.77, 95%CI = 0.71-0.81 for the ACR survival tree) in comparison with that of individual measures of kidney function. CONCLUSIONS: physical performance helps to identify a proportion of patients at an increased risk of mortality despite a mild-moderate impairment in kidney function and improves predictive accuracy of individual measures of kidney function.

Characteristics and outcomes of older patients hospitalised for COVID-19 in the first and second wave of the pandemic in The Netherlands: the COVID-OLD study.

BACKGROUND: as the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed. OBJECTIVE: to investigate differences in characteristics, disease presentation and outcomes of older hospitalised COVID-19 patients between the first and second pandemic wave in The Netherlands. METHODS: this was a multicentre retrospective cohort study in 16 hospitals in The Netherlands including patients aged ≥ 70 years, hospitalised for COVID-19 in Spring 2020 (first wave) and Autumn 2020 (second wave). Data included Charlson comorbidity index (CCI), disease severity and Clinical Frailty Scale (CFS). Main outcome was in-hospital mortality. RESULTS: a total of 1,376 patients in the first wave (median age 78 years, 60% male) and 946 patients in the second wave (median age 79 years, 61% male) were included. There was no relevant difference in presence of comorbidity (median CCI 2) or frailty (median CFS 4). Patients in the second wave were admitted earlier in the disease course (median 6 versus 7 symptomatic days; P < 0.001). In-hospital mortality was lower in the second wave (38.1% first wave versus 27.0% second wave; P < 0.001). Mortality risk was 40% lower in the second wave compared with the first wave (95% confidence interval: 28-51%) after adjustment for differences in patient characteristics, comorbidity, symptomatic days until admission, disease severity and frailty. CONCLUSIONS: compared with older patients hospitalised in the first COVID-19 wave, patients in the second wave had lower in-hospital mortality, independent of risk factors for mortality.The better prognosis likely reflects earlier diagnosis, the effect of improvement in treatment and is relevant for future guidelines and treatment decisions.

A Systematic Review of Strategies for Preventing Delirium in Patients Undergoing Vascular Surgery.

BACKGROUND: Elderly patients undergoing vascular surgery are at a risk of developing postoperative delirium, which is associated with high mortality. Delirium prevention is difficult and is investigated in surgical patients from various specialisms, but little is known about delirium prevention in vascular surgery. For this reason we performed a systematic review on strategies for delirium prevention in patients undergoing elective surgery for peripheral arterial disease or for an aneurysm of the abdominal aorta. METHODS: This systematic review included studies describing strategies for preventing delirium in patients undergoing elective surgery for peripheral arterial disease or for an aneurysm of the abdominal aorta. The search was conducted using the keywords 'vascular surgery,' 'prevention,' and 'delirium' and was last run on October 21, 2021 in the electronic databases PubMed, MEDLINE, Embase, Web of Science, the Cochrane library, and Emcare. Risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials and the ROBINS-1 tool for observational studies. RESULTS: Four studies including 565 patients were included in the systematic review. A significant decrease in the incidence of delirium was reported by a study investigating the effect of comprehensive geriatric assessments within patients undergoing surgery for an aneurysm of the abdominal aorta or lower limb bypass surgery (24% in the control group vs. 11% in the intervention group, P = 0.018) and in the total group of a study evaluating the effect of outpatient clinic multimodal prehabilitation for patients with an aneurysm of the abdominal aorta (11.7% in the control group vs. 8.2% in the intervention group, P = 0.043, Odds Ratio = 0.56). A nonsignificant decrease in delirium incidence was described for patients receiving a multidisciplinary quality improvement at the vascular surgical ward (21.4% in the control group vs. 14.6% in the intervention group, P = 0.17). The study concerning the impact of the type of anesthesia on delirium in 11 older vascular surgical patients, of which 3 developed delirium, did not differentiate between the different types of anesthesia the patients received. CONCLUSIONS: Despite the high and continuous increasing incidence of delirium in the growing elderly vascular population, little is known about effective preventive strategies. An approach to address multiple risk factors simultaneously seems to be promising in delirium prevention, whether through multimodal prehabilitation or comprehensive geriatric assessments. Several strategies including prehabilitation programs have been proven to be successful in other types of surgery and more research is required to evaluate effective preventive strategies and prehabilitation programs in vascular surgical patients.

Factors associated with polypharmacy and the high risk of medication-related problems among older community-dwelling adults in European countries: a longitudinal study.

BACKGROUND: Polypharmacy can be defined as using five or more medications simultaneously. "Medication-related problems", an extension of polypharmacy, includes inappropriate prescribing, poor adherence, overdosage, underdosage, inappropriate drug selection, inadequate monitoring, adverse drug effects, and drug interactions. Polypharmacy and the high risk of medication-related problems among older people are associated with adverse health consequences due to drug-drug interactions, drug-disease interactions, and adverse drug effects. This study aims to assess the factors associated with polypharmacy and the high risk of medication-related problems among community-dwelling older people in the Netherlands, Greece, Croatia, Spain, United Kingdom. METHOD: This longitudinal study used baseline and follow-up data from 1791 participants of the Urban Health Center European project. Polypharmacy and the risk of medication-related problems were evaluated at baseline and follow-up using the Medication Risk Questionnaire. We studied factors in the domains (a) sociodemographic characteristics, (b) lifestyle and nutrition, and (c) health and health care use. Hierarchical logistic regression analyses were used to examine the factors associated with polypharmacy and the high risk of medication-related problems. RESULTS: Mean age was 79.6 years (SD ± 5.6 years); 60.8% were women; 45.2% had polypharmacy, and 41.8% had a high risk of medication-related problems. Women participants had lower odds of polypharmacy (OR = 0.55;95%CI:0.42-0.72) and a high risk of medication-related problems (OR = 0.50; 95%CI:0.39-0.65). Participants with a migration background (OR = 1.67;95%CI:1.08-2.59), overweight (OR = 1.37; 95%CI:1.04-1.79) and obesity (OR = 1.78;95%CI:1.26-2.51) compared to 'normal weight', with lower physical HRQoL (OR = 0.96, 95%CI:0.95-0.98), multi-morbidity (OR = 3.73, 95%CI:2.18-6.37), frailty (OR = 1.69, 95%CI:1.24-2.30), visited outpatient services (OR = 1.77, 95%CI: 1.09-2.88) had higher odds of polypharmacy. The associations with the high risk of medication-related problems were similar. CONCLUSIONS: Multiple factors in demography, lifestyle, nutrition, and health care use are associated with polypharmacy and the high risk of medication-related problems. Polypharmacy is a single element that may reflect the number of medications taken. The broader content of medication-related problems should be considered to assess the context of medication use among older people comprehensively. These provide starting points to improve interventions to reduce polypharmacy and high risk of medication-related problems. In the meantime, health professionals can apply these insights to identify subgroups of patients at a high risk of polypharmacy and medication-related problems. TRIAL REGISTRATION: The intervention of the UHCE project was registered in the ISRCTN registry as ISRCTN52788952. The date of registration is 13/03/2017.

Diabetes, sarcopenia and chronic kidney disease; the Screening for CKD among Older People across Europe (SCOPE) study.

BACKGROUND: Sarcopenia may be more present in older adults with diabetes (DM). Accordingly, we evaluated the prevalence of sarcopenia and its associated risk factors among community-dwelling older adults with DM. METHODS: A cross-sectional analysis of older people living in the community was carried out. Participants (aged 75 years and more) came from an European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test and bioelectrical impedance analysis was performed. Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate (eGFR) was calculated using Berlin Initiative Study (BIS) to define the stages of chronic kidney disease (CKD). Previous known DM was defined as physician-diagnosed DM registered in the patient's medical record or the use of DM-related medications. Hemoglobin A1c levels and specific DM therapies administered were collected. Time elapsed from the first diagnosis of DM was not collected and, therefore, was not included in the analyses. RESULTS: A total of 1,420 subjects were evaluated with a median age of 79.0 (6.0) years, of which 804 (56.6%) were women and 615 (43.3%) men; 315 (22.2%) participants had prior DM diagnosis, with a median age of 80.0 (6.0), 146 (46.3%) were women. Using EWGSOP2 definition, 150 (10.6%) participants in the SCOPE study met diagnostic criteria for sarcopenia. Participants without diabetes had more often normal results in the 3 sarcopenia components than participants with diabetes [887 (80.31%) vs. 227 (72.1%), p = 0.002], highlighting higher percentages of severe sarcopenia in participants with diabetes [27 (8.6%) vs. 58 (5.2%), p = 0.028]. Confirmed or severe sarcopenia was detected in 41 (13%) participants with diabetes and 109 (9.8%) participants without diabetes (p = 0.108). According to BIS equation, sarcopenia was not significantly more prevalent in the more advanced stages of CKD (p = 0.845). In multivariate analyses, older age (odds ratios [OR], 1.17; 95% confidence interval [CI], 1.08-1.27), and lower body mass index (OR, 0.79; 95% CI, 0.71-0.89 were associated with the presence of sarcopenia. CONCLUSIONS: One tenth of all older community-dwelling subjects have sarcopenia. Older age and being thinner, but not worse renal function, were associated with higher prevalence of sarcopenia in older older adults with diabetes.

The recognition and management of neuropsychiatric symptoms in early Alzheimer's disease: a qualitative study among Dutch memory clinic physicians.

BACKGROUND: Timely recognition and treatment of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) dementia may improve quality of life, reduce caregiver burden, and delay disease progression. However, management of NPS in early AD dementia remains challenging. To date, little is known about the specific challenges for memory clinic-based physicians. The aims of this qualitative study were to obtain insights regarding the recognition and treatment of NPS in AD dementia in the memory clinic, to identify challenges experienced by physicians while managing NPS, and to examine the attitudes of memory clinic physicians on the role of the memory clinic in the care for NPS in early AD dementia. METHODS: Semi-structured interviews were conducted with 13 physicians working at a memory clinic in the Netherlands (n = 7 neurologist, n = 6 geriatrician, 46% female). The data were analyzed by two independent researchers using thematic analysis. RESULTS: We observed large variation among Dutch memory clinic physicians regarding care practices, expertise, and attitudes on the role of the memory clinic considering NPS in AD dementia. The most prominent challenges that memory clinic physicians experienced while managing NPS included that the outpatient setting complicates the recognition and treatment of NPS, a lack of experience, knowledge, and/or resources to adequately apply non-pharmacological interventions, and a lack of consensus among physicians on the role of the memory clinic in NPS recognition and management. CONCLUSIONS: We identified challenges that need to be addressed to improve the early recognition and adequate management of NPS in AD dementia at the memory clinic.

Orthostatic Hypotension: A Prodromal Marker of Parkinson's Disease?

BACKGROUND: Orthostatic hypotension is common in patients with Parkinson's disease (PD). However, it remains unknown whether orthostatic hypotension is a marker of prodromal PD or more advanced disease. The objectives of this study were to assess whether orthostatic hypotension is a prodromal marker of PD in the general population. METHODS: This study was embedded in the Rotterdam Study, a large prospective population-based cohort in the Netherlands. We measured orthostatic hypotension in 6910 participants. First, we determined the relation between prevalent PD and orthostatic hypotension using logistic regression. Second, we followed PD-free participants for the occurrence of PD until 2016 and studied the association between orthostatic hypotension and the risk of PD using Cox proportional hazards models. All models were adjusted for age and sex. RESULTS: At baseline, the mean age ± standard deviation of the study population was 69.0 ± 8.8 years, and 59.1% were women. Orthostatic hypotension was present in 1245 participants (19.8%), and 62 participants (1.0%) had PD at the time of orthostatic hypotension measurement. Participants with PD were significantly more likely to have orthostatic hypotension (odds ratio, 1.88; 95% confidence interval, 1.09-3.24). During a median (interquartile range) follow-up of 16.1 years (8.5-22.7 years), 122 participants were diagnosed with incident PD. Orthostatic hypotension at baseline was not associated with an increased risk of PD (hazard ratio, 0.97; 95% confidence interval, 0.59-1.58). CONCLUSIONS: Our study suggests that orthostatic hypotension is common in patients with PD, but that orthostatic hypotension is not associated with an increased risk of PD and thus is not a prodromal marker of PD in the general population. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Albuminuria as a risk factor for mild cognitive impairment and dementia-what is the evidence?

Kidney dysfunction can profoundly influence many organ systems, and recent evidence suggests a potential role for increased albuminuria in the development of mild cognitive impairment (MCI) or dementia. Epidemiological studies conducted in different populations have demonstrated that the presence of increased albuminuria is associated with a higher relative risk of MCI or dementia both in cross-sectional analyses and in studies with long-term follow-up. The underlying pathophysiological mechanisms of albuminuria's effect are as yet insufficiently studied, with several important knowledge gaps still present in a complex relationship with other MCI and dementia risk factors. Both the kidney and the brain have microvascular similarities that make them sensitive to endothelial dysfunction involving different mechanisms, including oxidative stress and inflammation. The exact substrate of MCI and dementia is still under investigation, however available experimental data indicate that elevated albuminuria and low glomerular filtration rate are associated with significant neuroanatomical declines in hippocampal function and grey matter volume. Thus, albuminuria may be critical in the development of cognitive impairment and its progression to dementia. In this review, we summarize the available evidence on albuminuria's link to MCI and dementia, point to existing gaps in our knowledge and suggest actions to overcome them. The major question of whether interventions that target increased albuminuria could prevent cognitive decline remains unanswered. Our recommendations for future research are aimed at helping to plan clinical trials and to solve the complex conundrum outlined in this review, with the ultimate goal of improving the lives of patients with chronic kidney disease.