Prevalence of polypharmacy in community-dwelling older adults from seven centres in five European countries : A cross-sectional study of DO-HEALTH

Objective To investigate the prevalence of polypharmacy and characteristics associated with polypharmacy in older adults from seven European cities. Design Cross-sectional study of baseline data from DO-HEALTH. Setting and participants DO-HEALTH enrolled 2157 community-dwelling adults age 70 and older from seven centres in Europe. Participants were excluded if they had major health problems or Mini-Mental State Examination Score <24 at baseline. Primary outcome measures Extensive information on prescription and over-the-counter medications were recorded. Polypharmacy was defined as the concomitant use of five or more medications, excluding vitamins or dietary supplements. Bivariate and multivariable logistic regression was used to test the association of sociodemographic factors (age, sex, years of education, living situation and city) and health-related indicators (number of comorbidities, cognitive function, frailty status, body mass index (BMI), prior fall, self-rated health and smoking status) with polypharmacy. Results 27.2% of participants reported polypharmacy ranging from 16.4% in Geneva to 60.8% in Coimbra. In the multivariable logistic regression analyses, older age (OR 1.07; 95% CI 1.04 to 1.10), greater BMI (OR 1.09; 95% CI 1.06 to 1.12) and increased number of comorbidities (OR 2.13; 95% CI 1.92 to 2.36) were associated with polypharmacy. Women were less likely to report polypharmacy than men (OR 0.65; 95% CI 0.51 to 0.84). In comparison to participants from Zurich, participants from Coimbra were more likely to report polypharmacy (OR 2.36; 95% CI 1.56 to 3.55), while participants from Geneva or Toulouse were less likely to report polypharmacy ((OR 0.36; 95% CI 0.22 to 0.59 and OR 0.64; 95% CI 0.42 to 0.96), respectively). Living situation, smoking status, years of education, prior fall, cognitive function, self-rated health and frailty status were not significantly associated with polypharmacy. Conclusion Polypharmacy is common among relatively healthy older adults, with moderate variability across seven European cities. Independent of several confounders, being a woman, older age, greater BMI and greater number of comorbidities were associated with increased odds for polypharmacy. Trial registration number NCT01745263

Prevalence of polypharmacy in community-dwelling older adults from seven centres in five European countries: a cross-sectional study of DO-HEALTH.

OBJECTIVE To investigate the prevalence of polypharmacy and characteristics associated with polypharmacy in older adults from seven European cities. DESIGN Cross-sectional study of baseline data from DO-HEALTH. SETTING AND PARTICIPANTS DO-HEALTH enrolled 2157 community-dwelling adults age 70 and older from seven centres in Europe. Participants were excluded if they had major health problems or Mini-Mental State Examination Score <24 at baseline. PRIMARY OUTCOME MEASURES Extensive information on prescription and over-the-counter medications were recorded. Polypharmacy was defined as the concomitant use of five or more medications, excluding vitamins or dietary supplements. Bivariate and multivariable logistic regression was used to test the association of sociodemographic factors (age, sex, years of education, living situation and city) and health-related indicators (number of comorbidities, cognitive function, frailty status, body mass index (BMI), prior fall, self-rated health and smoking status) with polypharmacy. RESULTS 27.2% of participants reported polypharmacy ranging from 16.4% in Geneva to 60.8% in Coimbra. In the multivariable logistic regression analyses, older age (OR 1.07; 95% CI 1.04 to 1.10), greater BMI (OR 1.09; 95% CI 1.06 to 1.12) and increased number of comorbidities (OR 2.13; 95% CI 1.92 to 2.36) were associated with polypharmacy. Women were less likely to report polypharmacy than men (OR 0.65; 95% CI 0.51 to 0.84). In comparison to participants from Zurich, participants from Coimbra were more likely to report polypharmacy (OR 2.36; 95% CI 1.56 to 3.55), while participants from Geneva or Toulouse were less likely to report polypharmacy ((OR 0.36; 95% CI 0.22 to 0.59 and OR 0.64; 95% CI 0.42 to 0.96), respectively). Living situation, smoking status, years of education, prior fall, cognitive function, self-rated health and frailty status were not significantly associated with polypharmacy. CONCLUSION Polypharmacy is common among relatively healthy older adults, with moderate variability across seven European cities. Independent of several confounders, being a woman, older age, greater BMI and greater number of comorbidities were associated with increased odds for polypharmacy. TRIAL REGISTRATION NUMBER NCT01745263

Prevalence and incidence of iron deficiency in European community-dwelling older adults : An observational analysis of the DO-HEALTH trial

Background and aim Iron deficiency is associated with increased morbidity and mortality in older adults. However, data on its prevalence and incidence among older adults is limited. The aim of this study was to investigate the prevalence and incidence of iron deficiency in European community-dwelling older adults aged ≥ 70 years. Methods Secondary analysis of the DO-HEALTH trial, a 3-year clinical trial including 2157 community-dwelling adults aged ≥ 70 years from Austria, France, Germany, Portugal and Switzerland. Iron deficiency was defined as soluble transferrin receptor (sTfR) > 28.1 nmol/L. Prevalence and incidence rate (IR) of iron deficiency per 100 person-years were examined overall and stratified by sex, age group, and country. Sensitivity analysis for three commonly used definitions of iron deficiency (ferritin  1.5) were also performed. Results Out of 2157 participants, 2141 had sTfR measured at baseline (mean age 74.9 years; 61.5% women). The prevalence of iron deficiency at baseline was 26.8%, and did not differ by sex, but by age (35.6% in age group ≥ 80, 29.3% in age group 75–79, 23.2% in age group 70–74); P  1.5. Occurrences of iron deficiency were observed with IR per 100 person-years of 9.2 (95% CI 8.3–10.1) and did not significantly differ by sex or age group. The highest IR per 100 person-years was observed in Austria (20.8, 95% CI 16.1–26.9), the lowest in Germany (6.1, 95% CI 4.7–8.0). Regarding the other definitions of iron deficiency, the IR per 100 person-years was 4.5 (95% CI 4.0–4.9) for ferritin  1.5. Conclusions Iron deficiency is frequent among relatively healthy European older adults, with people aged ≥ 80 years and residence in Austria and Portugal associated with the highest risk

Prevalence and incidence of iron deficiency in European community-dwelling older adults: an observational analysis of the DO-HEALTH trial

Background and aim Iron deficiency is associated with increased morbidity and mortality in older adults. However, data on its prevalence and incidence among older adults is limited. The aim of this study was to investigate the prevalence and incidence of iron deficiency in European community-dwelling older adults aged ≥ 70 years. Methods Secondary analysis of the DO-HEALTH trial, a 3-year clinical trial including 2157 community-dwelling adults aged ≥ 70 years from Austria, France, Germany, Portugal and Switzerland. Iron deficiency was defined as soluble transferrin receptor (sTfR) > 28.1 nmol/L. Prevalence and incidence rate (IR) of iron deficiency per 100 person-years were examined overall and stratified by sex, age group, and country. Sensitivity analysis for three commonly used definitions of iron deficiency (ferritin  1.5) were also performed. Results Out of 2157 participants, 2141 had sTfR measured at baseline (mean age 74.9 years; 61.5% women). The prevalence of iron deficiency at baseline was 26.8%, and did not differ by sex, but by age (35.6% in age group ≥ 80, 29.3% in age group 75–79, 23.2% in age group 70–74); P  1.5. Occurrences of iron deficiency were observed with IR per 100 person-years of 9.2 (95% CI 8.3–10.1) and did not significantly differ by sex or age group. The highest IR per 100 person-years was observed in Austria (20.8, 95% CI 16.1–26.9), the lowest in Germany (6.1, 95% CI 4.7–8.0). Regarding the other definitions of iron deficiency, the IR per 100 person-years was 4.5 (95% CI 4.0–4.9) for ferritin  1.5. Conclusions Iron deficiency is frequent among relatively healthy European older adults, with people aged ≥ 80 years and residence in Austria and Portugal associated with the highest risk

Heterogeneous patterns of brain atrophy in Alzheimer's disease

Alzheimer’s disease (AD) is the most common cause of dementia. It is characterized by loss of memory and other cognitive functions. Although it is a heterogeneous condition, it has been studied as one disease for many decades. Neuropathological data and a large body of in vivo neuroimaging literature challenge the hypothesis that AD is a single entity, supporting the hypothesis of AD as a heterogeneous disease. In this thesis, we set out to understand some aspects of the heterogeneity in AD and aging with the help of atrophy and WM integrity markers from magnetic resonance imaging (MRI). The main aim of the thesis was to investigate the potential use of statistical and machine learning models for the assessment of heterogeneous conditions. In Study I, we utilized whole brain atrophy markers and cross-sectional cluster analysis to characterize the neurodegeneration variability in a large AD dementia cohort (299 amnestic AD patients). The clusters of patients that we discovered presented with distinct atrophy patterns. Some of them exist due to disease severity, but we identified topologically variable atrophy patterns too. Patients of the different clusters had distinct cognitive symptoms and clinical progression. Then, we designed a pipeline that will help us to assess heterogeneous populations when longitudinal neuroimaging and clinical data are available (Study II).We tested this pipeline in atrophy data from a small dataset of AD patients to assess its usefulness in MRI data and heterogeneous conditions. The model fitted the data well and we concluded that it can be used in larger scale analyses. Moreover, larger numbers of participants with long follow-up period should increase its freedom in searching for heterogeneity in longitudinal neuroimaging trajectories. After this methodological study, we used a very large dataset that consisted of neuroimaging, cerebrospinal fluid (CSF), and clinical data. We split our data in discovery and prediction datasets. The discovery dataset included positive clinically diagnosed AD dementia patients and negative cognitively unimpaired individuals (CU). Based on this dataset (Study III), we aimed to understand whether the observed heterogeneity in AD is caused by sampling patient’s data at different disease stages, or if it resembles distinct neurodegeneration subtypes. We modelled longitudinal brain atrophy data anchored to the clinical dementia onset. Our findings show that all the previously reported atrophy subtypes do exist but some of them reflect disease stages rather than subtypes. Most importantly, our modeling managed to summarize the observed heterogeneity in neurodegeneration with two unique pathways (mediotemporal and cortical). These two pathways have distinct cognitive signatures and were evaluated in a large independent AD dataset. Heterogeneity within the pathways exist and is likely caused by a complex interaction between protective/risk factors and concomitant non-AD pathologies. Some findings indicate that WM changes may precede grey matter atrophy in AD. In Study IV we investigated whether more than one WM profile exists in the aging population. We wanted to understand their association with AD pathophysiological changes and relate them to the risk of developing dementia. We discovered four distinct WM integrity patterns with different spatial WM integrity distribution in aging. Those patterns were related to different longitudinal cognitive profiles and specific white matter tracts informed about cluster assignments. In conclusion, heterogeneity can be observed not only in AD, but also in the population including healthy individuals. In this thesis, we identified distinct pathways of brain atrophy and WM integrity. Understanding the heterogeneous patterns of the different pathophysiological markers during ageing and the course of AD, will ultimately lead to the development of disease modifying (personalized) treatments