Handgrip strength at midlife and familial longevity

Low handgrip strength has been linked with premature mortality in diverse samples of middle-aged and elderly subjects. The value of handgrip strength as marker of "exceptional" human longevity has not been previously explored. We postulated that the genetic influence on extreme survival might also be involved in the muscular strength determination pathway. Therefore, the objective of this study was to assess the muscle strength in a sample of middle-aged adults who are genetically enriched for exceptional survival and comparing them to a control group. We included 336 offspring of the nonagenarian from the Leiden Longevity Study who were enriched for heritable exceptional longevity, and 336 of their partners were used as controls. The Leiden Longevity study was a prospective follow up study of long-living siblings pairs together with their offspring and their partners. Handgrip strength was used as a proxy for overall muscle strength. No significant difference in handgrip strength was seen between the offspring of the nonagenarian and their partners after adjustment for potential confounders including body compositions, sum score of comorbidities, medication use, smoking and alcohol history. The main determinants of midlife handgrip strength were age, gender, total body percentage fat and relative appendicular lean mass. Although midlife handgrip strength has previously been shown to be an important prognostic indicator of survival, it is not a marker of exceptional familial longevity in middleaged adults. This finding suggests that genetic component of susceptibility to extreme survival is likely to be separate from that of muscular strength

Cytomegalovirus seropositivity is associated with glucose regulation in the oldest old. Results from the Leiden 85-plus Study

Background: Cytomegalovirus (CMV) infection has been reported to contribute to the pathogenesis of type 1 diabetes and post-transplantation diabetes. However, CMV infection has not been evaluated as a possible risk factor for type 2 diabetes. Our aim was to investigate potential associations between CMV seropositivity, CMV IgG antibody level and glucose regulation in the oldest old.Results: CMV seropositive subjects were more likely to have type 2 diabetes (17.2% vs 7.9%, p = 0.016), had a higher level of HbA1c (p = 0.014) and higher non-fasting glucose (p = 0.024) in the oldest olds. These associations remained significant after adjustment for possible confounders. CMV IgG antibody level was not significantly associated with glucose regulation (all p > 0.05).Conclusions: In the oldest old, CMV seropositivity is significantly associated with various indicators of glucose regulation. This finding suggests that CMV infection might be a risk factor for the development of type 2 diabetes in the elderly

Serum triiodothyronine levels and inflammatory cytokine production capacity

Increasing evidence suggests that pro-inflammatory cytokines are at play in lowering peripheral thyroid hormone levels during critical illness. Conversely, thyroid hormones have been suggested to enhance production of inflammatory cytokines. In view of these considerations, we hypothesized a mutual association between triiodothyronine and pro-inflammatory cytokines. Therefore we evaluated the relation between both circulating and induced inflammatory markers and serum thyroid function parameters in the Leiden 85-plus Study. We found that higher circulating levels of inflammatory markers were associated with lower levels of free serum triiodothyronine. In turn, higher serum free triiodothyronine levels were related to higher production capacity of pro-inflammatory cytokines after stimulation with lipopolysaccharide. By combining in vivo and ex vivo data, we were able to demonstrate for the first time the existence of a potential feedback mechanism between thyroid function and immune production capacity. We conclude that maintenance of normal thyroid function might be important for a preserved immune response in elderly human populations

Randomised Controlled Trial of Unsolicited Occupational Therapy in Community-Dwelling Elderly People: The LOTIS Trial

OBJECTIVE: The objective of this trial, the Leiden 85-Plus Occupational Therapy Intervention Study (LOTIS), was to assess whether unsolicited occupational therapy, as compared to no therapy, can decelerate the increase in disability in high-risk elderly people. DESIGN: This was a randomised controlled trial with 2-y follow-up. SETTING: The study took place in the municipality of Leiden in the Netherlands. PARTICIPANTS: The participants were 402 community-dwelling 85-y-old people, with a Mini-Mental State Examination score of >18 points at baseline. INTERVENTIONS: Participants in the intervention group were visited by an occupational therapist who provided training and education about assistive devices that were already present and who gave recommendations and information about procedures, possibilities, and costs of assistive devices and community-based services. Control participants were not visited by an occupational therapist. OUTCOME MEASURES: The primary outcome measure was the score achieved on the Groningen Activity Restriction Scale. Secondary outcome measures included self-evaluations of well-being and feelings of loneliness. RESULTS: The participants were evenly divided between the two groups: 202 participants were allocated to the intervention group and 200 participants to the control group. Of the 202 participants randomised to occupational therapy, 55 participants declined the proposed intervention. An occupational therapist indicated that of the remaining 147 participants, 66 (45%) needed an occupational therapy intervention. A total of 44 new assistive devices and five community-based services were implemented. During follow-up there was a progressive increase in disability in the intervention group (mean annual increase, 2.0 points; SE 0.2; p < 0.001) and control group (mean annual increase, 2.1 points; SE 0.2; p < 0.001). The increase in disability was not significantly different between study groups (0.08 points; 95% CI, −1.1–1.2; p = 0.75). There was also no difference between study groups for any of the secondary outcome measures. CONCLUSION: Unsolicited occupational therapy in high-risk elderly participants does not decelerate the increase in disability over time

Copy number variation associates with mortality in long-lived individuals:a genome-wide assessment

Pathophysiology, epidemiology and therapy of agein

Adverse environmental conditions influence age-related innate immune responsiveness

BACKGROUND-: The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether age-related innate immune responses are similar or differ between populations living under very diverse environmental conditions. METHODS-: We compared cross-sectional age-related changes in ex vivo innate cytokine responses in a population living under affluent conditions in the Netherlands (age 20–68 years old, n = 304) and a population living under adverse environmental conditions in Ghana (age 23–95 years old, n = 562). RESULTS-: We found a significant decrease in LPS-induced Interleukin (IL)-10 and Tumor Necrosis Factor (TNF) production with age in the Dutch population. In Ghana a similar age-related decline in IL-10 responses to LPS, as well as to zymosan, or LPS plus zymosan, was observed. TNF production, however, did not show an age-associated decline, but increased significantly with age in response to co-stimulation with LPS and zymosan. CONCLUSION-: We conclude that the decline in innate cytokine responses is an intrinsic ageing phenomenon, while pathogen exposure and/or selective survival drive pro-inflammatory responses under adverse living conditions

Difficulties in recruitment for a randomized controlled trial involving hysterosalpingography

BACKGROUND: The usefulness of hysterosalpingography (HSG) as routine investigation in the fertility work-up prior to laparoscopy and dye had been assessed in a randomized controlled trial. Recruiting subjects to the study was more difficult than anticipated. The objective of this study was to explore possible reasons for non-participation in the trial. METHODS: All newly referred subfertile women admitted to the Reproductive Medicine Clinic of Leiden University Medical Centre between 1 April 1997 and 31 December 1999, were eligible for the study. The reasons for non-participation were evaluated by scrutinizing the medical records. RESULTS: Out of 759 women, a total of 127 (17%) agreed to participate in the trial. The most important reason for non-participation was because of exclusion criteria (73%). Other reasons were inattentive clinicians (3%) and patient-associated reasons (24%). Patient refusal and indecisiveness to enroll in the study were the most common patient-associated reasons. The most frequently stated reason for trial refusal was reluctance to undergo laparoscopy and dye mainly due to issues related to anesthesia and scheduling of procedure. CONCLUSION: Almost three-quarters of recruitment difficulties in this study were due to unavoidable reasons. To overcome the remaining avoidable reasons for non-participation, attention should be paid to appropriate instruction of the study protocol to the participating doctors and to provide adequate information, in layman's terms, to the patients. Reminding patients by notes or telephone calls for attending the clinic are helpful. It may be contingent upon tracing the reasons of clinicians and patients for non-participation to improve enrollment during a trial

No Excess Mortality in Patients Aged 50 Years and Older Who Received Treatment for Ductal Carcinoma In Situ of the Breast

Background. The incidence of ductal carcinoma in situ (DCIS) has increased at a fast rate.The aim of this study was to assess the incidence and treatment in the Netherlands and estimate the excess mortality risk of DCIS. Methods. From the Netherlands Cancer Registry, adult female patients (diagnosed 1997–2005) with DCIS were selected. Treatment was described according to age. Relative mortality at 10 years of follow-up was calculated by dividing observed mortality over expected mortality. Expected mortality was calculated using the matched Dutch general population. Results. Overall, 8421 patients were included in this study. For patients aged 50–64, and 65–74 an increase in breast-conserving surgery was observed over time (P < 0.001). For patients over 75 years of age, 8.0% did not undergo surgery; this percentage remained stable over time (P = 0.07). Overall, treated patients aged >50 years experienced no excess mortality regardless of treatment (relative mortality 1.0). Conclusion. The present population-based study of almost 8500 patients showed no excess mortality in surgically treated women over 50 years with DCIS