Prevention of hip fractures in older adults residing in long-term care facilities with a hip airbag: a retrospective pilot study.

BACKGROUND: Hip and pelvic fractures do commonly occur among older adults. This pilot study aimed to evaluate the effect of introduction of the WOLK hip airbag on the incidence of hip fractures. METHODS: A retrospective study was performed among 969 participants residing within 11 long-term care facilities for older patients, belonging to one large healthcare organization in The Netherlands. The intervention concerned application of 45 WOLK hip-airbags, distributed among selected residents of the long-term care facilities. Inclusion criteria; physically active participants with a pelvic circumference between 90-125 cm able to wear the hip airbag. Exclusion criteria; participants who continuously removed the hip airbag themselves or participants who depended on a wheelchair for mobility. Main outcome measures were the occurrence of falls and hip, pelvic and other fractures. RESULTS: The incidence of hip and pelvic fractures declined from 3.3/100 person years to 1.8/100 person years during the study for an Incidence Rate Ratio (IRR) of 0.55 (95% confidence interval (95%CI) 0.34-0.87) in the entire study population. The incidence of other fractures did not decline during the study period (IRR 0.72;95%CI 0.37-1.40). The incidence of falls declined to some extent during the study (IRR 0.88; 95%CI 0.83-0.93). CONCLUSIONS: After introduction of the WOLK hip airbag a reduction of the incidence of hip and pelvic fractures by almost half was observed in older patients residing in long-term care facilities, even though only 45 hip airbags were distributed among the 969 residents. As selection bias cannot be ruled out in this study, the results of this pilot study warrant replication by a future clinical trial to determine true effectiveness of this intervention.

Associations of sleep duration and quality with serum and hepatic lipids: The Netherlands Epidemiology of Obesity Study.

Short and long sleep duration and poor sleep quality may affect serum and hepatic lipid content, but available evidence is inconsistent. Therefore, we aimed to investigate the associations of sleep duration and quality with serum and hepatic lipid content in a large population-based cohort of middle-aged individuals. The present cross-sectional study was embedded in the Netherlands Epidemiology of Obesity (NEO) study and consisted of 4260 participants (mean age, 55 years; proportion men, 46%) not using lipid-lowering agents. Self-reported sleep duration and quality were assessed using the Pittsburgh Sleep Quality Index questionnaire (PSQI). Outcomes of this study were fasting lipid profile (total cholesterol, low-density lipoprotein [LDL]-cholesterol, high-density lipoprotein [HDL]-cholesterol and triglycerides), postprandial triglyceride (response) levels, and hepatic triglyceride content (HTGC) as measured with magnetic resonance spectroscopy. We performed multivariable linear regression analyses, adjusted for confounders and additionally for measures that link to adiposity (e.g. body mass index [BMI] and sleep apnea). We observed that relative to the group with median sleep duration (≈7.0 hr of sleep), the group with shortest sleep (≈5.0 hr of sleep) had 1.5-fold higher HTGC (95% confidence interval [CI]: 1.0-2.2). The group with PSQI score ≥ 10 had a 1.1-fold (95% CI: 1.0-1.2) higher serum triglyceride level compared with the group with PSQI ≤ 5. However, these associations disappeared after adjustment for BMI and sleep apnea. Therefore, we concluded that previously observed associations of shorter sleep duration and poorer sleep quality with an adverse lipid profile, may be explained by BMI and sleep apnea, rather than by a direct effect of sleep on the lipid profile.

Cortical phase changes measured using 7-T MRI in subjects with subjective cognitive impairment, and their association with cognitive function.

Studies have suggested that, in subjects with subjective cognitive impairment (SCI), Alzheimer's disease (AD)-like changes may occur in the brain. Recently, an in vivo study has indicated the potential of ultra-high-field MRI to visualize amyloid-beta (Aß)-associated changes in the cortex in patients with AD, manifested by a phase shift on T2 *-weighted MRI scans. The main aim of this study was to investigate whether cortical phase shifts on T2 *-weighted images at 7 T in subjects with SCI can be detected, possibly implicating the deposition of Aß plaques and associated iron. Cognitive tests and T2 *-weighted scans using a 7-T MRI system were performed in 28 patients with AD, 18 subjects with SCI and 27 healthy controls (HCs). Cortical phase shifts were measured. Univariate general linear modeling and linear regression analysis were used to assess the association between diagnosis and cortical phase shift, and between cortical phase shift and the different neuropsychological tests, adjusted for age and gender. The phase shift (mean, 1.19; range, 1.00-1.35) of the entire cortex in AD was higher than in both SCI (mean, 0.85; range, 0.73-0.99; p < 0.001) and HC (mean, 0.94; range, 0.79-1.10; p < 0.001). No AD-like changes, e.g. increased cortical phase shifts, were found in subjects with SCI compared with HCs. In SCI, a significant association was found between memory function (Wechsler Memory Scale, WMS) and cortical phase shift (ß = -0.544, p = 0.007). The major finding of this study is that, in subjects with SCI, an increased cortical phase shift measured at high field is associated with a poorer memory performance, although, as a group, subjects with SCI do not show an increased phase shift compared with HCs. This increased cortical phase shift related to memory performance may contribute to the understanding of SCI as it is still unclear whether SCI is a sign of pre-clinical AD. Copyright © 2014 John Wiley & Sons, Ltd.

The development, implementation and evaluation of a transitional care programme to improve outcomes of frail older patients after hospitalisation.

BACKGROUND: fragmented healthcare systems are poorly suited to treat the increasing number of older patients with multimorbidity. OBJECTIVE: to report on the development, implementation and evaluation of a regional transitional care programme, aimed at improving the recovery rate of frail hospitalised older patients. METHODS: the programme was drafted in co-creation with organisations representing older adults, care providers and knowledge institutes. Conducting an action research project, the incidence of adverse outcomes within 3 months after hospital admission, and long-term care expenses (LTCE) were compared between samples in 2010-11 (pre-programme) and 2012-13 (post-programme) in frail and non-frail patients. Hospitalised patients aged ≥70 years were included in four hospitals in the targeted region. RESULTS: developed innovations addressed (i) improved risk management; (ii) delivery of integrated, function-oriented care; (iii) specific geriatric interventions; and (iv) optimisation of transfers. The incidence of adverse outcomes was compared in 813 and 904 included patients respectively in the two samples. In frail patients, the incidence of adverse outcomes decreased from 49.2% (149/303) in the pre-programme sample to 35.5% (130/366) in the post-programme sample. The risk ratio (RR), adjusted for heterogeneity between hospitals, was 0.72 (95% CI: 0.60-0.87). In non-frail patients the incidence of adverse outcomes remained unchanged (RR: 1.02, 95% CI: 0.76-1.36). LTCE were similar in the two samples. CONCLUSIONS: by involving stakeholders in designing and developing the transitional care programme, commitment of healthcare providers was secured. Feasible innovations in integrated transitional care for frail older patients after hospitalisation were sustainably implemented from within healthcare organisations.

Prediction of 90-day mortality in older patients after discharge from an emergency department: a retrospective follow-up study.

BACKGROUND: Older people frequently attend the emergency department (ED) and have a high risk of poor outcome as compared to their younger counterparts. Our aim was to study routinely collected clinical parameters as predictors of 90-day mortality in older patients attending our ED. METHODS: We conducted a retrospective follow-up study at the Leiden University Medical Center (The Netherlands) among patients aged 70 years or older attending the ED in 2012. Predictors were age, gender, time and way of arrival, presenting complaint, consulting medical specialty, vital signs, pain score and laboratory testing. Cox regression analyses were performed to analyse the association between these predictors and 90-day mortality. RESULTS: Three thousand two hundred one unique patients were eligible for inclusion. Ninety-day mortality was 10.5 % for the total group. Independent predictors of mortality were age (hazard ratio [HR] 1.06, 95 % confidence interval [95 % CI] 1.04-1.08), referral from another hospital (HR 2.74, 95 % CI 1.22-6.11), allocation to a non-surgical specialty (HR: 1.55, 95 % CI 1.13-2.14), increased respiration rate (HR up to 2.21, 95 % CI 1.25-3.92), low oxygen saturation (HR up to 1.96, 95 % CI 1.19-3.23), hypothermia (HR 2.27, 95 % CI 1.28-4.01), fever (HR 0.43, 95 % CI 0.24-0.75), high pain score (HR 1.55, 95 % CI 1.03-2.32) and the indication to perform laboratory testing (HR 3.44, 95 % CI 2.13-5.56). CONCLUSIONS: Routinely collected parameters at the ED can predict 90-day mortality in older patients presenting to the ED. This study forms the first step towards creating a new and simple screening tool to predict and improve health outcome in acutely presenting older patients.

Optimal screening for increased risk for adverse outcomes in hospitalised older adults.

BACKGROUND: Screening for frailty might help to prevent adverse outcomes in hospitalised older adults. OBJECTIVE: To identify the most predictive and efficient screening tool for frailty. DESIGN AND SETTING: Two consecutive observational prospective cohorts in four hospitals in the Netherlands. SUBJECTS: Patients aged ≥70 years, electively or acutely hospitalised for ≥2 days. METHODS: Screening instruments included in the Dutch Safety Management Programme [VeiligheidsManagementSysteem (VMS)] on four geriatric domains (ADL, falls, undernutrition and delirium) were used and the Identification of Seniors At Risk, the 6-item Cognitive Impairment Test and the Mini-Mental State Examination were assessed. Three months later, adverse outcomes including functional decline, high-healthcare demand or death were determined. Correlation and regression tree analyses were performed and predictive capacities were assessed. RESULTS: Follow-up data were available of 883 patients. All screening instruments were similarly predictive for adverse outcome (predictive power 0.58-0.66), but the percentage of positively screened patients (13-72%), sensitivity (24-89%) and specificity (35-91%) highly differed. The strongest predictive model for frailty was scoring positive on ≥3 VMS domains if aged 70-80 years; or being aged ≥80 years and scoring positive on ≥1 VMS domains. This tool classified 34% of the patients as frail with a sensitivity of 68% and a specificity of 74%. Comparable results were found in the validation cohort. CONCLUSIONS: The VMS-tool plus age (VMS+) offers an efficient instrument to identify frail hospitalised older adults at risk for adverse outcome. In clinical practice, it is important to weigh costs and benefits of screening given the rather low-predictive power of screening instruments.

Low cognitive status is associated with a lower ability to maintain standing balance in elderly outpatients.

BACKGROUND: Evidence is emerging that cognitive performance is involved in maintaining balance and thereby involved in falls in the elderly. OBJECTIVE: To investigate the association of cognitive status with measures of standing balance in elderly outpatients. METHODS: In a cross-sectional study, 197 community-dwelling elderly [mean age (SD) 81.9 (7.1) years] referred to a geriatric outpatient clinic were included and subsequently dichotomized into a group with low and normal cognitive status based on cut-off values of the Mini-Mental State Examination, Montreal Cognitive Assessment and Visual Association Test. The ability to maintain standing balance as well as the center of pressure (CoP) movement were assessed during 10 s of side-by-side, semi-tandem and tandem stance with eyes open and eyes closed. Logistic and linear regression were used to examine the association between cognitive status and measures of standing balance adjusted for age, gender and highest completed education. RESULTS: Low cognitive status in elderly outpatients was associated with a lower ability to maintain 10 s of balance in side-by-side stance with eyes closed [OR (95% CI): 3.57 (1.60; 7.97)] and in semi-tandem stance with eyes open and eyes closed [OR (95% CI): 3.93 (1.71; 9.00) and OR (95% CI): 2.32 (1.11; 4.82), respectively]. Cognitive status was not associated with CoP movement. CONCLUSION: Low cognitive status associates with a lower ability to maintain standing balance in more demanding standing conditions in elderly outpatients. This may have implications for routine geriatric screening strategies and interpretation of results of either standing balance or cognitive tests.

The Impact of Different Diagnostic Criteria on the Prevalence of Sarcopenia in Healthy Elderly Participants and Geriatric Outpatients.

BACKGROUND: A consensus on the diagnostic criteria for sarcopenia, a common syndrome in the elderly, has not been reached yet. Prevalence rates vary between studies due to the use of different criteria encompassing different measures, correction factors and cutoff points. OBJECTIVE: This study compared prevalence rates of sarcopenia using nine sets of diagnostic criteria applied in two different elderly populations. METHODS: The study population encompassed 308 healthy elderly participants (152 males, 156 females; mean age 74 years) and 123 geriatric outpatients (54 males, 69 females; mean age 81 years). Diagnostic criteria included relative muscle mass, absolute muscle mass, muscle strength and physical performance. RESULTS: Prevalence rates of sarcopenia varied between 0 and 15% in healthy elderly participants and between 2 and 34% in geriatric outpatients. CONCLUSION: This study clearly demonstrates the dependency of sarcopenia prevalence rates on the applied diagnostic criteria.

Increased number of microinfarcts in Alzheimer disease at 7-T MR imaging.

PURPOSE: To assess the prevalence and number of cortical microinfarcts in patients with Alzheimer disease (AD) by using a 7-T magnetic resonance (MR) imaging system, to assess the independent association of cortical microinfarcts with cognitive dysfunction, and to investigate potential confounding effects of the coexisting presence of cerebral amyloid angiopathy (CAA). MATERIALS AND METHODS: The local institutional review board approved this study. In all cases, informed consent was obtained. High-spatial-resolution fluid-attenuated inversion recovery and T2*-weighted images were acquired in 14 AD patients and 18 control subjects to assess the presence of microinfarcts and microbleeds. Presence of CAA was assessed according to the Boston criteria. Image analysis was performed independently by two reviewers. Mann-Whitney U test was performed to assess differences in number of microinfarcts between groups. Negative binomial regression models were used to assess the association between diagnosis of AD and diagnosis of CAA and number of microinfarcts, between diagnosis of AD and number of microbleeds and number of microinfarcts, and between cognitive function and number of microinfarcts, all corrected for age and sex. RESULTS: Interobserver agreement was excellent for detecting microinfarcts (κ = 0.91) (P < .001). Patients with AD demonstrated higher number (P = .005) of microinfarcts (mean, 7.2) compared with control subjects (mean, 1.8). Negative binomial regression models showed an independent association between AD and number of microinfarcts (P = .006) and a trend for CAA and microinfarcts (P = .052). A negative correlation was found between cognitive function and the number of microinfarcts (P = .009). CONCLUSION: Patients with AD show more microinfarcts than do control subjects, the number of microinfarcts correlates with global cognitive performance, and the presence of microinfarcts was mainly AD rather than CAA related.

Systemic inflammatory markers in relation to cognitive function and measures of brain atrophy: a Mendelian randomization study.

Observational studies have implied associations between multiple cytokines and cognitive decline, anti-inflammatory drugs however did not yield any protective effects on cognitive decline. We aimed to assess the associations of systemic inflammation, as measured by multiple cytokine and growth factor, with cognitive performance and brain atrophy using two-sample Mendelian randomization (MR). Independent genetic instruments (p < 5e - 8 and p < 5e - 6) for 41 systemic inflammatory markers were retrieved from a genome-wide association study conducted in 8293 Finnish participants. Summary statistics for gene-outcome associations were obtained for cognitive performance (N = 257,841) and for brain atrophy measures of cerebral cortical surface area and thickness (N = 51,665) and hippocampal volume (N = 33,536). To rule out the heterogeneity in the cognitive performance, we additionally included three domains: the fluid intelligence score (N = 108,818), prospective memory result (N = 111,099), and reaction time (N = 330,069). Main results were computed by inverse-variance weighting; sensitivity analyses taking pleiotropy and invalid instruments into account were performed by using weighted-median estimator, MR-Egger, and MR PRESSO. After correcting for multiple testing using false discovery rate, only genetically predicted (with p < 5e - 6 threshold) per-SD (standard deviation) higher IL-8 was associated with - 0.103 (- 0.155, - 0.051, padjusted = 0.004) mm3 smaller hippocampal volume and higher intelligence fluid score [ß: 0.103 SD (95% CI: 0.042, 0.165), padjusted = 0.041]. Sensitivity analyses generally showed similar results, and no pleiotropic effect, heterogeneity, or possible reverse causation was detected. Our results suggested a possible causal association of high IL-8 levels with better cognitive performance but smaller hippocampal volume among the general healthy population, highlighting the complex role of inflammation in dementia-related phenotypes. Further research is needed to elucidate mechanisms underlying these associations.

Apolipoprotein E genotype, lifestyle and coronary artery disease: Gene-environment interaction analyses in the UK Biobank population.

BACKGROUND AND AIMS: The APOE ε4 genotype has a higher risk for developing coronary artery disease (CAD), but there is preliminary evidence that antioxidative lifestyle factors interact with APOE genotype on CAD risk. Here, we assessed the effect modification of physical activity, oily fish and polyunsaturated fatty acid (PUFA) intake with APOE genotype on risk of incident CAD. METHODS: The present study comprised 345,659 white European participants from UK Biobank (mean age: 56.5 years, 45.7% men) without a history of CAD. Information regarding physical activity, oily fish intake and PUFA intake was collected through questionnaires, and information on incident CAD through linkage with hospital admission records. Analyses were performed using Cox proportional hazard models adjusted for age and sex. RESULTS: Higher physical activity level and oily fish intake were both associated with a lower incidence of CAD. However, these associations were similar across the different APOE genotypes (p-values for interaction > 0.05). Most notable, higher PUFA intake was associated with a lower CAD risk in APOE ε4 genotype carriers (hazard ratio: 0.76, 95% confidence interval: 0.63-0.92), and not in APOE ε3/ε3 genotype carriers (0.90; 0.79, 1.02), but without statistical evidence for effect modification (p-valueinteraction = 0.137). CONCLUSIONS: While higher physical activity and high fish and PUFA intake were associated with a lower risk of incident CAD, no evidence for interaction of these lifestyle factors with APOE genotype was observed in UK Biobank participants. Interventions intended to reduce cardiovascular risk might therefore be similarly effective across the APOE genotype carriers.

Effect of erythropoietin levels on mortality in old age: the Leiden 85-plus Study.

BACKGROUND: The production of erythropoietin is triggered by impaired oxygen delivery to the kidney, either because of anemia or hypoxemia. High erythropoietin levels have been shown to predict the risk of death among patients with chronic heart failure. We investigated the prognostic value of elevated erythropoietin levels on mortality among very elderly people in the general population. METHODS: The Leiden 85-plus Study is a population-based prospective follow-up study involving 599 people aged 85 years in Leiden, the Netherlands, enrolled between September 1997 and September 1999. Erythropoietin levels were determined at age 86. For this analysis, we included 428 participants with a creatinine clearance of at least 30 mL/min. Mortality data, recorded until Feb. 1, 2008, were obtained from the municipal registry. RESULTS: During follow-up, 324 (75.7%) participants died. Compared with participants whose erythropoietin levels were in the lowest tertile (reference group), those whose levels were in the middle tertile had a 25% increased risk of death (hazard ratio [HR] 1.25, 95% confidence interval [CI] 0.95-1.64), and those whose levels were in the highest tertile had a 73% increased risk (HR 1.73, 95% CI 1.32-2.26) (p value for trend < 0.01). The association between erythropoietin levels and mortality remained largely unchanged after we adjusted for sex, creatinine clearance, hemoglobin level, comorbidity, smoking status and C-reactive protein level, and was similar for deaths from cardiovascular and noncardiovascular causes. INTERPRETATION: Among people aged 85 years and older, elevated erythropoietin levels were associated with an increased risk of death, independent of hemoglobin levels.

The Association between Habitual Sleep Duration and Sleep Quality with Glycemic Traits: Assessment by Cross-Sectional and Mendelian Randomization Analyses.

Evidence on whether habitual sleep duration and sleep quality are associated with increased insulin resistance is inconsistent. Here, we investigated the associations between different measures of habitual sleep with glycemic traits through cross-sectional and Mendelian randomization (MR) analyses. We assessed the associations of sleep duration and sleep quality with glycemic traits using multivariable linear regression models adjusted for potential confounders in 4672 middle-aged (45-65 years; 48% men) nondiabetic participants of the Netherlands Epidemiology of Obesity (NEO) study. Genetic variants for total, short, and long sleep duration were used as instrumental variables in MR analyses using summary-level data of glycemic traits in nondiabetic individuals (MAGIC; n = 58,074). In cross-sectional analyses, shortest sleepers (median 5.0 h of sleep per night) had 14.5% (95% confidence interval (CI): 2.0; 28.6%) higher fasting insulin level and 16.3% (95% CI: 2.7; 31.7%) higher HOMA-ß. Bad sleep quality was associated with higher insulin resistance (e.g., 14.3% (95% CI: 4.7; 24.9%) higher HOMA-IR). All these associations disappeared after adjustment for BMI and the risk of sleep apnea. MR analyses did not indicate a causal association between total, short or long sleep duration and glycemic traits. Therefore, our used measures of habitual sleep duration and sleep quality are unlikely to directly associate with insulin resistance.

Thyroid status and mortality in nonagenarians from long-lived families and the general population.

The relationship between thyroid status and longevity has been investigated extensively. However, data on thyroid status and survival in old age is scarce. In this study we investigated associations of different parameters of thyroid status with mortality in nonagenarians, and whether these associations were different in nonagenarians from long-lived families than in nonagenarians from the general population. In total, 805 nonagenarians from the Leiden Longevity Study and 259 nonagenarians from the Leiden 85-plus Study were followed up to collect mortality data. At baseline, levels of thyrotropin (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured. In nonagenarians from long-lived families and from the general population, associations between thyroid parameters and mortality were similar. We found no interaction between study population and parameters of thyroid status on mortality (P-values>0.70). The results from both studies were combined to derive generalizable associations. Hazard ratios (HRs) for the highest compared to lowest tertiles were determined, resulting in TSH HR 0.91 (P=0.25), fT4 HR 1.22 (P=0.02), fT3 HR 0.74 (P=1.31e-4), and fT3/fT4 HR 0.66 (P=5.64e-7). In conclusion, higher fT3/fT4 ratios, higher levels of fT3, and lower levels of fT4 were associated with lower mortality rate in nonagenarians and independent of familial longevity status.

Left Ventricular Hypertrophy and Cognitive Decline in Old Age.

BACKGROUND: Patients with advanced heart failure run a greater risk of dementia. Whether early cardiac structural changes also associate with cognitive decline is yet to be determined. OBJECTIVE: We tested whether left ventricular hypertrophy (LVH) derived from electrocardiogram associates with cognitive decline in older subjects at risk of cardiovascular disease. METHODS: We included 4,233 participants (mean age 75.2 years, 47.8% male) from PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). LVH was assessed from baseline electrocardiograms by measuring the Sokolow-Lyon index. Higher levels of Sokolow-Lyon index indicate higher degrees of LVH. Cognitive domains involving selective attention, processing speed, and immediate and delayed memory were measured at baseline and repeated during a mean follow-up of 3.2 years. RESULTS: At baseline, LVH was not associated with worse cognitive function. During follow-up, participants with higher levels of LVH had a steeper decline in cognitive function including in selective attention (p = 0.009), processing speed (p = 0.010), immediate memory (p < 0.001), and delayed memory (p = 0.002). These associations were independent of cardiovascular risk factors, co-morbidities, and medications. CONCLUSION: LVH assessed by electrocardiogram associates with steeper decline in cognitive function of older subjects independent of cardiovascular risk factors and co-morbidities. This study provides further evidence on the link between subclinical cardiac structural changes and cognitive decline in older subjects.

Assessment of maximal handgrip strength: how many attempts are needed?

BACKGROUND: Handgrip strength (HGS) is used to identify individuals with low muscle strength (dynapenia). The influence of the number of attempts on maximal HGS is not yet known and may differ depending on age and health status. This study aimed to assess how many attempts of HGS are required to obtain maximal HGS. METHODS: Three cohorts (939 individuals) differing in age and health status were included. HGS was assessed three times and explored as continuous and dichotomous variable. Paired t-test, intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to test reproducibility of HGS. The number of individuals with misclassified dynapenia at attempts 1 and 2 with respect to attempt 3 were assessed. RESULTS: Results showed the same pattern in all three cohorts. Maximal HGS at attempts 1 and 2 was higher than at attempt 3 on population level (P < 0.001 for all three cohorts). ICC values between all attempts were above 0.8, indicating moderate to high reproducibility. Bland-Altman analysis showed that 41.0 to 58.9% of individuals had the highest HGS at attempt 2 and 12.4 to 37.2% at attempt 3. The percentage of individuals with a maximal HGS above the gender-specific cut-off value at attempt 3 compared with attempts 1 and 2 ranged from 0 to 50.0%, with a higher percentage of misclassification in middle-aged and older populations. CONCLUSIONS: Maximal HGS is dependent on the number of attempts, independent of age and health status. To assess maximal HGS, at least three attempts are needed if HGS is considered to be a continuous variable. If HGS is considered as a discrete variable to assess dynapenia, two attempts are sufficient to assess dynapenia in younger populations. Misclassification should be taken into account in middle-aged and older populations.

Lipoprotein particle profiles mark familial and sporadic human longevity.

BACKGROUND: Genetic and biochemical studies have indicated an important role for lipid metabolism in human longevity. Ashkenazi Jewish centenarians and their offspring have large low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles as compared with control individuals. This profile also coincided with a lower prevalence of disease. Here, we investigate whether this observation can be confirmed for familial longevity in an outbred European population and whether it can be extended to sporadic longevity in the general population. METHODS AND FINDINGS: NMR-measured lipoprotein profiles were analyzed in 165 families from the Leiden Longevity Study, consisting of 340 long-lived siblings (females >91 y, males >89 y), 511 of their offspring, and 243 partners of the offspring. Offspring had larger (21.3 versus 21.1 nm; p = 0.020) and fewer (1,470 versus 1,561 nmol/l; p = 0.011) LDL particles than their same-aged partners. This effect was even more prominent in the long-lived siblings (p < 10(-3)) and could be pinpointed to a reduction specifically in the concentration of small LDL particles. No differences were observed for HDL particle phenotypes. The mean LDL particle sizes in 259 90-y-old singletons from a population-based study were similar to those in the long-lived siblings and thus significantly larger than in partners of the offspring, suggesting that the relevance of this phenotype extends beyond familial longevity. A low concentration of small LDL particles was associated with better overall health among both long-lived siblings (p = 0.003) and 90-y-old singletons (p = 0.007). CONCLUSIONS: Our study indicates that LDL particle profiles mark both familial and sporadic human longevity already in middle age.

Chromosome 4q25, microsomal transfer protein gene, and human longevity: novel data and a meta-analysis of association studies.

Recently, chromosome 4q25 was linked to exceptional human longevity, and a haplotype of the positional candidate microsomal transfer protein (MTP) gene was associated to the phenotype in U.S. Caucasians. We investigated whether linkage to 4q25 could be detected in 164 nonagenarian sibships of the Leiden Longevity Study. Additionally, we compared the MTP -493G/T and Q95H allele and haplotype frequencies in the Leiden Longevity Study (379 nonagenarians, 525 of their offspring, and 251 partners of their offspring) and in the Leiden 85-Plus Study (655 octogenarians and 244 young controls). The latter study population was followed for at least 7 years, providing the opportunity to perform also prospective analyses using the longitudinal data. We found neither evidence for linkage at 4q25 nor association of the MTP locus with longevity in nonagenarian individuals. Meta-analyses of all previous studies implied that the association in U.S. Caucasians may have its source in admixture of the U.S. control population rather than in the genetic effect of the locus on exceptional longevity.

Common Ground? The Concordance of Sarcopenia and Frailty Definitions.

OBJECTIVES: This study aimed to explore the concordance between definitions of sarcopenia and frailty in a clinically relevant population of geriatric outpatients. DESIGN: Data were retrieved from a cross-sectional study. SETTING: The study was performed in a geriatric outpatient clinic of a middle-sized teaching hospital. PARTICIPANTS: The study included 299 geriatric outpatients (mean age 82.4, SD 7.1) who were consecutively referred to the outpatient clinic. MEASUREMENTS: Prevalence rates and subsequent concordance evolving from 3 definitions of sarcopenia and 2 definitions of frailty were compared. Definitions of sarcopenia included the European Working Group on Sarcopenia in Older People (gait speed, handgrip strength, muscle mass), International Working Group on Sarcopenia (gait speed, muscle mass) and the definition by Janssen (muscle mass). Definitions of frailty included the Fried frailty phenotype (weight loss, exhaustion, physical inactivity, handgrip strength, walk time) and the definition of Rockwood (use of walking aid, activities of daily living, incontinence, and cognitive impairment). RESULTS: Prevalence rates for sarcopenia varied between 17% and 22% and between 29% and 33% for frailty. There was little concordance in intraindividual prevalence rates of sarcopenia and frailty using different definitions. None of the outpatients was classified as having sarcopenia and frailty according to all applied definitions. Outpatients with sarcopenia were more likely to be frail than frail outpatients to be sarcopenic. CONCLUSION: This study clearly indicates that sarcopenia and frailty are 2 separate conditions based on the current definitions. It is important to diagnose sarcopenia and frailty as separate entities, as each may require specific treatment.