Cerebrovascular Risk-Factors of Prevalent and Incident Brain Infarcts in the General Population: The AGES-Reykjavik Study.

BACKGROUND: Studies on the association of cerebrovascular risk factors to magnetic resonance imaging detected brain infarcts have been inconsistent, partly reflecting limits of assessment to infarcts anywhere in the brain, as opposed to specific brain regions. We hypothesized that risk-factors may differ depending on where the infarct is located in subcortical-, cortical-, and cerebellar regions. METHODS: Participants (n=2662, mean age 74.6±4.8) from the longitudinal population-based AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study underwent brain magnetic resonance imaging at baseline and on average 5.2 years later. We assessed the number and location of brain infarcts (prevalent versus incident). We estimated the risk-ratios of prevalent (PRR) and incident (IRR) infarcts by baseline cerebrovascular risk-factors using Poisson regression. RESULTS: Thirty-one percent of the study participants had prevalent brain infarcts and 21% developed new infarcts over 5 years. Prevalent subcortical infarcts were associated with hypertension (PRR, 2.7 [95% CI, 1.1-6.8]), systolic blood pressure (PRR, 1.2 [95% CI, 1.1-1.4]), and diabetes (PRR, 2.8 [95% CI, 1.9-4.1]); incident subcortical infarcts were associated with systolic (IRR, 1.2 [95% CI, 1.0-1.4]) and diastolic (IRR, 1.3 [95% CI, 1.0-1.6]) blood pressure. Prevalent and incident cortical infarcts were associated with carotid plaques (PRR, 1.8 [95% CI, 1.3-2.5] and IRR, 1.9 [95% CI, 1.3-2.9], respectively), and atrial fibrillation was significantly associated with prevalent cortical infarcts (PRR, 1.8 [95% CI, 1.2-2.7]). Risk-factors for prevalent cerebellar infarcts included hypertension (PRR, 2.45 [95% CI, 1.5-4.0]), carotid plaques (PRR, 1.45 [95% CI, 1.2-1.8]), and migraine with aura (PRR, 1.6 [95% CI, 1.1-2.2]). Incident cerebellar infarcts were only associated with any migraine (IRR, 1.4 [95% CI, 1.0-2.0]). CONCLUSIONS: The risk for subcortical infarcts tends to increase with small vessel disease risk-factors such as hypertension and diabetes. Risk for cortical infarcts tends to increase with atherosclerotic/coronary processes and risk for cerebellar infarcts with a more mixed profile of factors. Assessment of risk-factors by location of asymptomatic infarcts found on magnetic resonance imaging may improve the ability to target and optimize preventive therapeutic approaches to prevent stroke.

Social network and the risk for developing mild cognitive impairment and dementia among older adults.

BACKGROUND: This study aimed to investigate the longitudinal associations between social network (SN) and the risk of lower cognitive function, mild cognitive impairment (MCI), and dementia among cognitively normal individuals 65 years and older. METHODS: Data from the Age, Gene/Environment Susceptibility (AGES) Reykjavik Study on 2816 participants (aged 65 to 96 years) were used to examine the associations using multiple logistic and linear regression models. SN included questions on frequency of contact with family and friends as well as information on marital status, resulting in a score ranging from 0 (poor social network) to 3 (good social network). Cognitive function outcomes included the speed of processing (SP), executive function (EF) and memory function (MF). MCI and dementia were diagnosed using a detailed assessment according to international guidelines. RESULTS: At baseline 0.5, 7.0, 41.7 and 50.8% reported a score of 0, 1, 2 and 3, respectively. During a mean follow-up time of 5.2 years, 7.1% (n = 188) of cognitively intact participants developed MCI and 3.0% (n = 79) developed dementia. Longitudinal analyses demonstrated that participants who had low SN were significantly more likely to have declines in MF (ß = - 0.533, P = 0.014) compared to high SN. Social networks were not independently associated with the decline of SP and EF during follow-up. According to fully adjusted models using logistic regression, SN was significantly associated with incidence risk of MCI (OR = 2.030, P = 0.014 and OR = 1.847 P = 0.001). These associations were largely independent of other lifestyle factors, depression and genetic disposition. CONCLUSIONS: Community-dwelling older adults who have poor social networks have a higher risk of declining memory function as well as a higher risk of mild cognitive impairment than older adults who have a higher social network. This study included numbers of relevant covariates in the study analysis, thereby significantly contributing to the literature on cognitive aging.

Creativity, leisure activities, social engagement and cognitive impairment: the AGES-Reykjavík study.

BACKGROUND: Participation in leisure activities and extensive social network have been associated with lower risk of cognitive impairment (CI) and dementia. AIMS: We examined whether leisure activities (cognitive solitary, cognitive group, social, physical, or creative activities) and social involvement are associated with less incidence of CI or dementia. METHODS: Analyses were performed from data of 2933 cognitively intact individuals at baseline included in the AGES-REYKJAVIK study. Odds ratios (OR) were calculated for incident CI and dementia in relation to cognitive individual, cognitive group, social, physical, and creative leisure activities as well as social networks. Models were adjusted for a number of known risk factors for cognitive decline. RESULTS: In 5 years, 12% of the cohort were diagnosed with CI or dementia. All leisure activities were associated with reduced likelihood of cognitive decline in the raw model, but in adjusted models, cognitive solitary [OR 0.49 (Confidence Interval (CI) 0.38-0.64)], cognitive group [OR 0.50 (CI 0.30-0.82)], and creative activities [OR 0.53 (CI 0.35-0.83)] were significantly associated with less cognitive decline. Analyses examining creative leisure activities independently, controlling for all other activities, suggested individuals participating in creative activities exhibited less CI [OR 0.64 (CI 0.41-0.98)]. Among social networks variables, frequency of meeting with friends and relatives was associated with reduced likelihood of CI [OR 0.49 (CI 0.31-0.75)]. DISCUSSION: Cognitive and creative leisure activities and frequent gatherings with friends and relatives are associated with reduced incidence of CI in this older cohort. CONCLUSION: Creative leisure activities might have special benefit for cognitive ability.

Predicting unplanned hospital visits in older home care recipients: a cross-country external validation study.

BACKGROUND: Accurate identification of older persons at risk of unplanned hospital visits can facilitate preventive interventions. Several risk scores have been developed to identify older adults at risk of unplanned hospital visits. It is unclear whether risk scores developed in one country, perform as well in another. This study validates seven risk scores to predict unplanned hospital admissions and emergency department (ED) visits in older home care recipients from six countries. METHODS: We used the IBenC sample (n = 2446), a cohort of older home care recipients from six countries (Belgium, Finland, Germany, Iceland, Italy and The Netherlands) to validate four specific risk scores (DIVERT, CARS, EARLI and previous acute admissions) and three frailty indicators (CHESS, Fried Frailty Criteria and Frailty Index). Outcome measures were unplanned hospital admissions, ED visits or any unplanned hospital visits after 6 months. Missing data were handled by multiple imputation. Performance was determined by assessing calibration and discrimination (area under receiver operating characteristic curve (AUC)). RESULTS: Risk score performance varied across countries. In Iceland, for any unplanned hospital visits DIVERT and CARS reached a fair predictive value (AUC 0.74 [0.68-0.80] and AUC 0.74 [0.67-0.80]), respectively). In Finland, DIVERT had fair performance predicting ED visits (AUC 0.72 [0.67-0.77]) and any unplanned hospital visits (AUC 0.73 [0.67-0.77]). In other countries, AUCs did not exceed 0.70. CONCLUSIONS: Geographical validation of risk scores predicting unplanned hospital visits in home care recipients showed substantial variations of poor to fair performance across countries. Unplanned hospital visits seem considerably dependent on healthcare context. Therefore, risk scores should be validated regionally before applied to practice. Future studies should focus on identification of more discriminative predictors in order to develop more accurate risk scores.

Cigarette Smoking Is Associated With Lower Quadriceps Cross-sectional Area and Attenuation in Older Adults.

INTRODUCTION: In addition to well-established links with cardiovascular and respiratory diseases, cigarette smoking may affect skeletal muscle; however, associations with quadriceps atrophy, density, and function are unknown. This study explored the associations of current and former smoking with quadriceps muscle area and attenuation as well as muscle force (assessed as knee extension peak torque) and rate of torque development-a measure of muscle power in older adults. METHODS: Data from 4469 older adults, aged 66-95 years at baseline in the Age, Gene/Environment Susceptibility-Reykjavik Study with measurements of thigh computed tomography, isometric knee extension testing, self-reported smoking history, and potential covariates were analyzed. RESULTS: Sex differences were observed in these data; therefore, our final analyses are stratified by sex. In men, both former smokers and current smokers had lower muscle area (with ß= -0.10, 95% confidence interval [CI] = -0.17 to -0.03 and ß = -0.19, 95% CI = -0.33 to -0.05, respectively) and lower muscle attenuation (ie, higher fat infiltration, ß = -0.08, 95% CI = -0.16 to -0.01 and ß = -0.17, 95% CI = -0.34 to -0.01, respectively) when compared with never smokers. Smoking status was not associated with male peak torque or rate of torque development. In women, current smoking was associated with lower muscle attenuation (ß = -0.24, 95% CI = -0.34 to -0.13) compared to never smoking. Among female smokers (current and former), muscle attenuation and peak torque were lower with increasing pack-years. CONCLUSIONS: Results suggest that cigarette smoking is related to multiple muscle properties at older age and that these relationships may be different among men and women. IMPLICATIONS: This article presents novel data, as it examined for the first time the relationship between smoking and computed tomography-derived quadriceps muscle size (cross-sectional area) and attenuation. This study suggests that current cigarette smoking is related to higher muscle fat infiltration, which may have significant health implications for the older population, because of its known association with poor physical function, falls, and hip fractures.

Multi-sensory training and wrist fractures: a randomized, controlled trial.

BACKGROUND: Asymmetric vestibular function, decreased plantar sensation, postural control and functional ability have been associated with fall-related wrist fractures. OBJECTIVE: To investigate whether multi-sensory training (MST) improves postural control, vestibular function, foot sensation and functional ability among people with fall-related wrist fractures compared to wrist stabilization training (WT). METHODS: This was an assessor-blinded, randomized controlled trial. Ninety-eight participants, age 50-75 years, were randomized to MST or WT. Pre- and post-training measurements: Head Shake Test (HST), Video-Head Impulse Test (vHIT), Semmes-Weinstein Monofilaments (SWF), Biothesiometer (BT), Sensory Organization Test (SOT), 10-m Walk Test (10MWT), Five Times Sit to Stand Test (FTSTS), Activities-Specific Balance Confidence (ABC) and Dizziness Handicap Inventory Scales (DHI). The training period was 12 weeks, with six supervised sessions by a physical therapist and daily home exercises for both groups. RESULTS: There were significant endpoint differences in SOT (p = 0.01) between the two groups, in favor of the MST group, but no changes were seen in other outcome variables. Subgroup analysis with participants below normal baseline SOT composite scores indicated that the MST was more effective in improving 10MWT fast (p = 0.04), FTSTS (p = 0.04), SWF (p = 0.04) and SOT scores (p = 0.04) than the WT. CONCLUSIONS: MST improves postural control among people with a fall-related wrist fracture. The results further suggest that the program is more effective for those with SOT balance scores below age-related norms.

Development of a novel benchmark method to identify and characterize best practices in home care across six European countries: design, baseline, and rationale of the IBenC project.

BACKGROUND: Europe's ageing society leads to an increased demand for long-term care, thereby putting a strain on the sustainability of health care systems. The 'Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of Community Care' (IBenC) project aims to develop a new benchmark methodology based on quality of care and cost of care utilization to identify best practices in home care. The study's baseline data, methodology, and rationale are reported. METHODS: Home care organizations in Belgium, Finland, Germany, Iceland, Italy, and the Netherlands, home care clients of 65 years and over receiving home care, and professionals working in these organizations were included. Client data were collected according to a prospective longitudinal design with the interRAI Home Care instrument. Assessments were performed at baseline, after six and 12 months by trained (research) nurses. Characteristics of home care organizations and professionals were collected cross-sectionally with online surveys. RESULTS: Thirty-eight home care organizations, 2884 home care clients, and 1067 professionals were enrolled. Home care clients were mainly female (66.9%), on average 82.9 years (± 7.3). Extensive support in activities of daily living was needed for 41.6% of the sample, and 17.6% suffered cognitive decline. Care professionals were mainly female (93.4%), and over 45 years (52.8%). Considerable country differences were found. CONCLUSION: A unique, international, comprehensive database is established, containing in-depth information on home care organizations, their clients and staff members. The variety of data enables the development of a novel cost-quality benchmark method, based on interRAI-HC data. This benchmark can be used to explore relevant links between organizational efficiency and organizational and staff characteristics.

Dynamic sitting: Measurement and associations with metabolic health.

Dynamic sitting, such as fidgeting and desk work, might be associated with health, but remains difficult to identify out of accelerometry data. We examined, in a laboratory study, whether dynamic sitting can be identified out of triaxial activity counts. Among 18 participants (56% men, 27.3 ± 6.5 years), up to 236 counts per minute were recorded in the anteroposterior and mediolateral axes during dynamic sitting using a hip-worn accelerometer. Subsequently, we examined in 621 participants (38% men, 80.0 ± 4.7 years) from the AGES-Reykjavik Study whether dynamic sitting was associated with cardio-metabolic health. Compared to participants who recorded the fewest dynamic sitting minutes (Q1), those with more dynamic sitting minutes had a lower BMI (Q2 = -1.39 (95%CI = -2.33;-0.46); Q3 = -1.87 (-2.82;-0.92); Q4 = -3.38 (-4.32;-2.45)), a smaller waist circumference (Q2 = -2.95 (-5.44;-0.46); Q3 = -3.47 (-6.01;-0.93); Q4 = -8.21 (-10.72;-5.71)), and a lower odds for the metabolic syndrome (Q2 = 0.74 [0.45;1.20] Q3 = 0.58 [0.36;0.95]; Q4 = 0.36 [0.22;0.59]). Our findings suggest that dynamic sitting might be identified using accelerometry and that this behaviour was associated with health. This might be important given the large amounts of time people spend sitting. Future studies with a focus on validation, causation and physiological pathways are needed to further examine the possible relevance of dynamic sitting.

A mutation in APP protects against Alzheimer's disease and age-related cognitive decline.

The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-ß precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease ß-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the ß-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.

Interactions between drugs and geriatric syndromes in nursing home and home care: results from Shelter and IBenC projects.

AIM: Drugs may interact with geriatric syndromes by playing a role in the continuation, recurrence or worsening of these conditions. Aim of this study is to assess the prevalence of interactions between drugs and three common geriatric syndromes (delirium, falls and urinary incontinence) among older adults in nursing home and home care in Europe. METHODS: We performed a cross-sectional multicenter study among 4023 nursing home residents participating in the Services and Health for Elderly in Long-TERm care (Shelter) project and 1469 home care patients participating in the Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of community care (IBenC) project. Exposure to interactions between drugs and geriatric syndromes was assessed by 2015 Beers criteria. RESULTS: 790/4023 (19.6%) residents in the Shelter Project and 179/1469 (12.2%) home care patients in the IBenC Project presented with one or more drug interactions with geriatric syndromes. In the Shelter project, 288/373 (77.2%) residents experiencing a fall, 429/659 (65.1%) presenting with delirium and 180/2765 (6.5%) with urinary incontinence were on one or more interacting drugs. In the IBenC project, 78/172 (45.3%) participants experiencing a fall, 80/182 (44.0%) presenting with delirium and 36/504 (7.1%) with urinary incontinence were on one or more interacting drugs. CONCLUSION: Drug-geriatric syndromes interactions are common in long-term care patients. Future studies and interventions aimed at improving pharmacological prescription in the long-term care setting should assess not only drug-drug and drug-disease interactions, but also interactions involving geriatric syndromes.

Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the General Population: The AGES-Reykjavik Study (Age Gene/Environment Susceptibility-Reykjavik Study).

BACKGROUND AND PURPOSE: The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from longitudinal population studies is scarce. We investigated the incidence of infarcts in cortical, subcortical, cerebellar, and overall brain regions and how prevalent and incident infarcts associate with cognitive change and incident dementia. METHODS: Participants (n=2612, 41% men, mean age 74.6±4.8) underwent brain magnetic resonance imaging for the assessment of infarcts and cognitive testing at baseline and on average 5.2 years later. Incident dementia was assessed according to the international guidelines. RESULTS: Twenty-one percent of the study participants developed new infarcts. The risk of incident infarcts in men was higher than the risk in women (1.8; 95% confidence interval, 1.5-2.3). Persons with both incident and prevalent infarcts showed steeper cognitive decline and had almost double relative risk of incident dementia (1.7; 95% confidence interval, 1.3-2.2) compared with those without infarcts. Persons with new subcortical infarcts had the highest risk of incident dementia compared with those without infarcts (2.6; 95% confidence interval, 1.9-3.4). CONCLUSIONS: Men are at greater risk of developing incident brain infarcts than women. Persons with incident brain infarcts decline faster in cognition and have an increased risk of dementia compared with those free of infarcts. Incident subcortical infarcts contribute more than cortical and cerebellar infarcts to incident dementia which may indicate that infarcts of small vessel disease origin contribute more to the development of dementia than infarcts of embolic origin in larger vessels.

Associations of fat and muscle tissue with cognitive status in older adults: the AGES-Reykjavik Study.

Background/Objective: studies on the association of dementia with specific body composition (BC) components are scarce. Our aim was to investigate associations of BC measures with different levels of cognitive function in late-life. Methods: we studied 5,169 participants (mean age 76 years, 42.9% men) in the AGES-Reykjavik Study of whom 485 (9.4%) were diagnosed with mild cognitive impairment (MCI) and 307 (5.9%) with dementia. Visceral fat, abdominal and thigh subcutaneous fat, and thigh muscle were assessed by computed tomography. MCI and dementia were based on clinical assessment and a consensus meeting; those without MCI or dementia were categorised as normal. Multinomial regression models assessed the associations stratified by sex and in additional analyses by midlife body mass index (BMI). Results: among women, there was a decreased likelihood of dementia per SD increase in abdominal subcutaneous fat (OR 0.72; 95% CI: 0.59-0.88), thigh subcutaneous fat (0.81; 0.67-0.98) and thigh muscle (0.63; 0.52-0.76), but not visceral fat, adjusting for demographics, vascular risk factors, stroke and depression. Inverse associations of fat with dementia were attenuated by weight change from midlife and were strongest in women with midlife BMI <25. In men, one SD increase in thigh muscle was associated with a decreased likelihood of dementia (0.75; 0.61-0.92). BC was not associated with MCI in men or women. Conclusion: a higher amount of abdominal and thigh subcutaneous fat were associated with a lower likelihood of dementia in women only, while more thigh muscle was associated with a lower likelihood of dementia in men and women.

Muscle Quality and Myosteatosis: Novel Associations With Mortality Risk: The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.

Muscle composition may affect mortality risk, but prior studies have been limited to specific samples or less precise determination of muscle composition. We evaluated associations of thigh muscle composition, determined using computed tomography imaging, and knee extension strength with mortality risk among 4,824 participants aged 76.4 (standard deviation (SD), 5.5) years from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study (2002-2006). Cox proportional hazards models were used to estimate hazard ratios. After 8.8 years of follow-up, there were 1,942 deaths. For men, each SD-increment increase in muscle lean area, muscle quality, and strength was associated with lower mortality risk, with decreases ranging between 11% and 22%. Each SD-increment increase in intermuscular adipose tissue and intramuscular adipose tissue was associated with higher mortality risk (hazard ratio (HR) = 1.13 (95% confidence interval (CI): 1.06, 1.22) and HR = 1.23 (95% CI: 1.15, 1.30), respectively). For women, each SD-increment increase in muscle lean area, muscle quality, and strength was associated with lower mortality risk, with decreases ranging between 12% and 19%. Greater intramuscular adipose tissue was associated with an 8% higher mortality risk (HR = 1.08, 95% CI: 1.01, 1.16). This study shows that muscle composition is associated with mortality risk. These results also show the importance of improving muscle strength and area and lowering muscle adipose tissue infiltration.

Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age.

The genetic contribution to the variation in human lifespan is ∼ 25%. Despite the large number of identified disease-susceptibility loci, it is not known which loci influence population mortality. We performed a genome-wide association meta-analysis of 7729 long-lived individuals of European descent (≥ 85 years) and 16 121 younger controls (<65 years) followed by replication in an additional set of 13 060 long-lived individuals and 61 156 controls. In addition, we performed a subset analysis in cases aged ≥ 90 years. We observed genome-wide significant association with longevity, as reflected by survival to ages beyond 90 years, at a novel locus, rs2149954, on chromosome 5q33.3 (OR = 1.10, P = 1.74 × 10(-8)). We also confirmed association of rs4420638 on chromosome 19q13.32 (OR = 0.72, P = 3.40 × 10(-36)), representing the TOMM40/APOE/APOC1 locus. In a prospective meta-analysis (n = 34 103), the minor allele of rs2149954 (T) on chromosome 5q33.3 associates with increased survival (HR = 0.95, P = 0.003). This allele has previously been reported to associate with low blood pressure in middle age. Interestingly, the minor allele (T) associates with decreased cardiovascular mortality risk, independent of blood pressure. We report on the first GWAS-identified longevity locus on chromosome 5q33.3 influencing survival in the general European population. The minor allele of this locus associates with low blood pressure in middle age, although the contribution of this allele to survival may be less dependent on blood pressure. Hence, the pleiotropic mechanisms by which this intragenic variation contributes to lifespan regulation have to be elucidated.

Variant of TREM2 associated with the risk of Alzheimer's disease.

BACKGROUND: Sequence variants, including the ε4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer's disease. Few rare variants affecting the risk of late-onset Alzheimer's disease have been found. METHODS: We obtained the genome sequences of 2261 Icelanders and identified sequence variants that were likely to affect protein function. We imputed these variants into the genomes of patients with Alzheimer's disease and control participants and then tested for an association with Alzheimer's disease. We performed replication tests using case-control series from the United States, Norway, The Netherlands, and Germany. We also tested for a genetic association with cognitive function in a population of unaffected elderly persons. RESULTS: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42×10(-10)). The mutation had a frequency of 0.46% in controls 85 years of age or older. We observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P=2.1×10(-12) in combined discovery and replication samples). We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers (P=0.003). CONCLUSIONS: Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes. (Funded by the National Institute on Aging and others.).

Mortality in Older Persons with Retinopathy and Concomitant Health Conditions: The Age, Gene/Environment Susceptibility-Reykjavik Study.

PURPOSE: To assess the impact of retinopathy on mortality in older persons with concomitant health conditions. DESIGN: Population-based prospective cohort study. PARTICIPANTS: A total of 4966 individuals aged 67 to 96 years (43.2% were male) from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS). METHODS: Retinopathy was evaluated from digital fundus images (2002-2006) using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Mortality was assessed through September 2013 (cause of death assigned through 2009). Cox proportional hazards regression models, with age as the time scale, estimated the association between retinopathy and death while controlling for risk factors and the presence of concomitant health conditions. MAIN OUTCOME MEASURES: Mortality from all causes and cardiovascular disease (CVD). RESULTS: Among the 4966 participants, 503 (10.1%) had diabetes and 614 (12.4%) had retinopathy at baseline. A subset of these (136 [2.7%]) had both diabetes and retinopathy. After a median follow-up of 8.6 years, 1763 persons died, 276 (45.0%) with retinopathy and 1487 (34.2%) without retinopathy, of whom 76 and 162 persons, respectively, also had diabetes. There were 366 deaths from CVD through 2009, 72 (11.7%) in persons with retinopathy and 294 (6.8%) in those without retinopathy. In multivariable analyses, retinopathy was significantly associated with all-cause mortality (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.10-1.43; P < 0.01) and CVD-related mortality (HR, 1.57; 95% CI, 1.20-2.06; P < 0.01). Findings were more striking in men: all-cause HR, 1.33 (95% CI, 1.11-1.60) and CVD HR, 1.81 (95% CI, 1.25-2.63). Risk of mortality was further increased among those with retinopathy concomitant with microalbuminuria (all-cause HR, 1.70; 95% CI, 1.03-2.23, and CVD HR, 2.04; 95% CI, 1.27-3.28) and those with retinopathy, microalbuminuria, and diabetes (all-cause HR, 2.01; 95% CI, 1.22-3.31, and CVD HR, 5.24; 95% CI, 1.91-14.42). History of clinical stroke increased the risk of CVD-related mortality among persons with retinopathy (HR, 3.30; 95% CI, 2.05-5.32), particularly those with retinopathy and diabetes (HR, 5.38; 95% CI, 1.80-16.06). CONCLUSIONS: Even minimal retinopathy was a significant predictor of increased mortality in older persons, particularly men, irrespective of diabetes status. Persons with retinopathy may warrant closer clinical management of general health.

Associations between arterial stiffness, depressive symptoms and cerebral small vessel disease: cross-sectional findings from the AGES-Reykjavik Study.

BACKGROUND: Arterial stiffness may contribute to depression via cerebral microvascular damage, but evidence for this is scarce. We therefore investigated whether arterial stiffness is associated with depressive symptoms and whether cerebral small vessel disease contributes to this association. METHODS: This cross-sectional study included a subset of participants from the AGES-Reykjavik study second examination round, which was conducted from 2007 to 2011. Arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]), depressive symptoms (15-item geriatric depression scale [GDS-15]) and cerebral small vessel disease (MRI) were determined. Manifestations of cerebral small vessel disease included higher white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces and lower total brain parenchyma volume. RESULTS: We included 2058 participants (mean age 79.6 yr; 59.0% women) in our analyses. Higher CFPWV was associated with a higher GDS-15 score, after adjustment for potential confounders (ß 0.096, 95% confidence interval [CI] 0.005-0.187). Additional adjustment for white matter hyperintensity volume or subcortical infarcts attenuated the association between CFPWV and the GDS-15 score, which became nonsignificant (p > 0.05). Formal mediation tests showed that the attenuating effects of white matter hyperintensity volume and subcortical infarcts were statistically significant. Virchow-Robin spaces, cerebral microbleeds and cerebral atrophy did not explain the association between CFPWV and depressive symptoms. LIMITATIONS: Our study was limited by its cross-sectional design, which precludes any conclusions about causal mediation. Depressive symptoms were assessed by a self-report questionnaire. CONCLUSION: Greater arterial stiffness is associated with more depressive symptoms; this association is partly accounted for by white matter hyperintensity volume and subcortical infarcts. This study supports the hypothesis that arterial stiffness leads to depression in part via cerebral small vessel disease.

Physical activity and incidence of sarcopenia: the population-based AGES-Reykjavik Study.

BACKGROUND: the prevalence of sarcopenia increases with age. Physical activity might slow the rate of muscle loss and therewith the incidence of sarcopenia. OBJECTIVE: to examine the association of physical activity with incident sarcopenia over a 5-year period. DESIGN: data from the population-based Age, Gene/Environment, Susceptibility-Reykjavik Study were used. SETTING: people residing in the Reykjavik area at the start of the study. SUBJECTS: the study included people aged 66-93 years (n = 2309). METHODS: the amount of moderate-vigorous physical activity (MVPA) was assessed by a self-reported questionnaire. Sarcopenia was identified using the European Working Group on Sarcopenia in Older People algorithm, including muscle mass (computed tomography imaging), grip strength (computerised dynamometer) and gait speed (6 m). RESULTS: mean age of the participants was 74.9 ± 4.7 years. The prevalence of sarcopenia was 7.3% at baseline and 16.8% at follow-up. The incidence proportion of sarcopenia over 5 years was 14.8% in the least-active individuals and 9.0% in the most-active individuals. Compared with the least-active participants, those reporting a moderate-high amount of MVPA had a significantly lower likelihood of incident sarcopenia (OR = 0.64, 95% CI 0.45-0.91). Participants with a high amount of MVPA had higher baseline levels of muscle mass, strength and walking speed, but baseline MVPA was not associated with the rate of muscle loss. CONCLUSION: a higher amount of MVPA seems to contribute to counteracting the development of sarcopenia. To delay the onset of sarcopenia and its potential adverse outcomes, attention should be paid to increasing physical activity levels in older adults.

Substantial between-country differences in organising community care for older people in Europe-a review.

BACKGROUND: The European population is aging. The main drivers of public spending on health care for people of 65 years and older are hospital admission and admission to long-term care facilities. High quality community care can be a cost-effective and quality solution to respond to the impact of ageing populations on health-care systems. It is unclear how well countries are equipped to provide affordable and quality community care. The aim of this article is to describe and compare community care delivery with care-dependent older people in Europe. METHODS: This study is conducted within the European Union-financed IBenC project [Identifying best practices for care-dependent elderly byBenchmarkingCosts and outcomes of community care (FP7)] in which six European countries are involved. To compare the community care delivery with care-dependent older people in these countries, we performed a systematic comparison of macro indicators using metadata complemented with data from multinational surveys. RESULTS: Data on the following dimensions are described and compared: population of the country, governmental expenditures on health, sources of community health services funding, governmental vision and regulation on community care, community care organisations and care professionals, eligibility criteria for and equity in receiving care and the involvement of informal care. CONCLUSION: : Because of the variations in the European community care contexts, the growing demand for community care as a cost-effective and quality solution to the care burden of aging populations will have country-specific impacts. When learning from other countries' best practices, in addition to researchers, policy makers should take full account of local and national care contexts.

Convergent validity of the interRAI-HC for societal costs estimates in comparison with the RUD Lite instrument in community dwelling older adults.

BACKGROUND: The interRAI-Home Care (interRAI-HC) instrument is commonly used in routine care to assess care and service needs, resource utilisation and health outcomes of community dwelling home care clients. Potentially, the interRAI-HC can also be used to calculate societal costs in economic evaluations. The purpose of this study was to assess the convergent validity of the interRAI-HC instrument in comparison with the RUD Lite instrument for the calculation of societal costs among care-dependent community dwelling older adults. METHODS: A within-subject design was used. Participants were 65 years and older and received professional community care in five countries. The RUD Lite was administered by trained (research) nurses or self-reports within 4 weeks after the interRAI-HC assessment. Agreement between the interRAI-HC and RUD Lite estimates was assessed using Spearman's correlation coefficients. We hypothesised that there was strong correlation (Spearman's ρ > 0.5) between resource utilisation estimates, costs of care estimates and total societal cost estimates derived from both instruments. RESULTS: Strong correlation was found between RUD Lite and interRAI-HC resource utilisation assessments for eight out of ten resource utilisation items. Total societal costs according to the RUD Lite were statistically significantly lower than according to the interRAI-HC (mean difference €-804, 95 % CI -1340; -269). The correlation between the instruments for total societal costs and all six cost categories was strong. CONCLUSIONS: The interRAI-HC has good convergent validity as compared with the RUD-Lite instrument to estimate societal cost of resource utilisation in community dwelling older adults. Since interRAI-HC assessments are part of routine care in many community care organisations and countries already, this finding may increase the feasibility of performing economic evaluations among community dwelling older adults.