Andrea B. Maier

Handgrip strength as a predictor of functional, psychological and social health. A prospective population-based study among the oldest old

BACKGROUND muscle wasting is associated with a detrimental outcome in older people. Muscle strength measurements could be useful as part of a clinical evaluation of oldest old patients to determine who are most at risk of accelerated decline in the near future. OBJECTIVE this study aimed to assess if handgrip strength predicts changes in functional, psychological and social health among oldest old. DESIGN the Leiden 85-plus Study is a prospective population-based follow-up study. SUBJECTS five-hundred fifty-five, all aged 85 years at baseline, participated in the study. METHODS handgrip strength was measured with a handgrip strength dynamometer. Functional, psychological and social health were assessed annually. Baseline data on chronic diseases were obtained from the treating physician, pharmacist, electrocardiogram and blood sample analysis. RESULTS at age 85, lower handgrip strength was correlated with poorer scores in functional, psychological and social health domains (all, P < 0.001). Lower baseline handgrip strength predicted an accelerated decline in activities of daily living (ADL) and cognition (both, P <or= 0.001), but not in social health (P > 0.30). CONCLUSION poor handgrip strength predicts accelerated dependency in ADL and cognitive decline in oldest old. Measuring handgrip strength could be a useful instrument in geriatric practice to identify those oldest old patients at risk for this accelerated decline.

Handgrip strength and mortality in the oldest old population: the Leiden 85-plus study

Background: Poor muscular strength has been shown to be associated with increased morbidity and mortality in diverse samples of middle-aged and elderly people. However, the oldest old population (i.e., over 85 years) is underrepresented in such studies. Our objective was to assess the association between muscular strength and mortality in the oldest old population. Methods: We included 555 participants (65% women) from the Leiden 85-plus study, a prospective population-based study of all 85-year-old inhabitants of Leiden, Netherlands. We measured the handgrip strength of participants at baseline and again at age 89 years. We collected baseline data on comorbidities, functional status, levels of physical activity, and adjusted for potential confounders. During the follow-up period, we collected data on mortality. Results: During a follow-up period of 9.5 years (range 8.5–10.5 years), 444 (80%) participants died. Risk for all-cause mortality was elevated among participants in the lowest tertile of handgrip strength at age 85 years (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.00–1.82, p = 0.047) and the lowest two tertiles of handgrip strength at age 89 years (HR 2.04, CI 1.24–3.35, p = 0.005 and HR 1.73, CI 1.11–2.70, p = 0.016). We also observed significantly increased mortality among participants in the tertile with the highest relative loss of handgrip strength over four years (HR 1.72, CI 1.07–2.77, p = 0.026). Interpretation: Handgrip strength, a surrogate measurement of overall muscular strength, is a predictor of all-cause mortality in the oldest old population and may serve as a convenient tool for prognostication of mortality risk among elderly people.

Hallmark Features of Immunosenescence Are Absent in Familial Longevity

Seropositivity for CMV is one of the parameters of the “immune risk profile” associated with mortality in longitudinal studies of the very elderly and may accelerate immunosenescence. Thus, any genetic factors influencing human longevity may be associated with susceptibility to CMV and CMV-accelerated immunosenescence. To test this, we analyzed long-lived families in the Leiden Longevity Study (LLS) in which offspring enjoy a 30% reduced standardized mortality rate, possibly owing to genetic enrichment. Serum C-reactive protein levels and the frequency of different T cell subsets were compared between 97 LLS offspring and 97 controls (their partners, representing the normal population). We also determined the capacity of T cells to respond against immunodominant Ags from CMV in a smaller group of LLS subjects and controls. CMV infection was strongly associated with an age-related reduction in the frequency of naive T cells and an accumulation of CD45RA–re-expressing and late-differentiated effector memory T cells in the general population, but not in members of long-lived families. The latter also had significantly lower C-reactive protein levels, indicating a lower proinflammatory status compared with CMV-infected controls. Finally, T cells from a higher proportion of offspring mounted a proliferative response against CMV Ags, which was also of greater magnitude and broader specificity than controls. Our data suggest that these rare individuals genetically enriched for longevity are less susceptible to the characteristic CMV-associated age-driven immune alterations commonly considered to be hallmarks of immunosenescence, which might reflect better immunological control of the virus and contribute to their decreased mortality rate.

CMV and Immunosenescence: from basics to clinics

Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates “immunosenescence”. This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.

Patterns of muscle strength loss with age in the general population and patients with a chronic inflammatory state

Abstract Background There is growing recognition of the serious consequences of sarcopenia on the functionality and autonomy in old age. Recently, the age-related changes in several inflammatory mediators have been implicated in the pathogenesis of sarcopenia. The purposes of this systematic review were two-fold: (1) to describe the patterns of muscle strength loss with age in the general population, and (2) to quantify the loss of muscle strength in rheumatoid arthritis as representative for an underlying inflammatory state. Handgrip strength was used as a proxy for overall muscle strength. Results Results from 114 studies (involving 90,520 subjects) and 71 studies (involving 10,529 subjects) were combined in a meta-analysis for the general and rheumatoid arthritis population respectively and standardized at an equal sex distribution. For the general population we showed that between the ages of 25 years and 95 years mean handgrip strength declined from 45.5kg to 23.2kg for males and from 27.1kg to 12.8kg for females. We noted a steeper handgrip strength decline after 50 years of age (rate of 0.37kg/year). In the rheumatoid arthritis population handgrip strength was not associated with chronological age between the ages of 35 years and 65 years and was as low as 20.2kg in male and 15.1 in female. Rheumatoid arthritis disease duration was inversely associated with handgrip strength. Conclusions This meta-analysis shows distinct patterns of age-related decrease of handgrip strength in the general population. Handgrip strength is strongly associated with the presence and duration of an inflammatory state as rheumatoid arthritis. The putative link between age-related inflammation and sarcopenia mandates further study as it represents a potential target for intervention to maintain functional independence in old age.

High Blood Pressure and Resilience to Physical and Cognitive Decline in the Oldest Old: The Leiden 85-Plus Study

To evaluate the association between various blood pressure (BP) measures at age 85 and future decline in physical and cognitive function the oldest old.

The number of p16INK4a positive cells in human skin reflects biological age.

Cellular senescence is a defense mechanism in response to molecular damage which accumulates with aging. Correspondingly, the number of senescent cells has been reported to be greater in older than in younger subjects and furthermore associates with age‐related pathologies. Inter‐individual differences exist in the rate at which a person ages (biological age). Here, we studied whether younger biological age is related to fewer senescent cells in middle‐aged individuals with the propensity for longevity, using p16INK4a as a marker for cellular senescence. We observed that a younger biological age associates with lower levels of p16INK4a positive cells in human skin.

Gene expression analysis of mTOR pathway: association with human longevity

mTOR signalling is implicated in the development of disease and in lifespan extension in model organisms. This pathway has been associated with human diseases such as diabetes and cancer, but has not been investigated for its impact on longevity per se. Here, we investigated whether transcriptional variation within the mTOR pathway is associated with human longevity using whole‐blood samples from the Leiden Longevity Study. This is a unique cohort of Dutch families with extended survival across generations, decreased morbidity and beneficial metabolic profiles in middle‐age. By comparing mRNA levels of nonagenarians and middle‐aged controls, the mTOR signalling gene set was found to associate with old age (P = 4.6 × 10−7). Single gene analysis showed that seven of 40 mTOR pathway genes had a significant differential expression of at least 5%. Of these, the RPTOR (Raptor) gene was found to be differentially expressed also when the offspring of nonagenarians was compared with their spouses, indicating association with familial longevity in middle‐age. This association was not explained by variation between the groups in the prevalence of type 2 diabetes and cancer or glucose levels. Thus, the mTOR pathway not only plays a role in the regulation of disease and aging in animal models, but also in human health and longevity.

More than half of hip fracture patients do not regain mobility in the first postoperative year

Aim:  To measure functional recovery and determine risk factors for failure to return to the prefracture level of mobility of hip fracture patients 1 year postoperatively.

High prevalence of cytomegalovirus DNA in plasma samples of blood donors in connection with seroconversion

BACKGROUND: Human cytomegalovirus (CMV) is considered to latently infect blood cells. Transfusion‐transmitted infection (TT‐CMV) of immunocompromised patients occurs despite the use of CMV‐seronegative or leukoreduced units.