Alison Kleppinger

T Cell Responses Are Better Correlates of Vaccine Protection in the Elderly

It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination. This study prospectively evaluated the relationship between the development of influenza illness, and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure (CHF). Adults age 60 years and older (90 subjects), and 10 healthy young adult controls received the 2003-04 trivalent inactivated influenza vaccine. Laboratory diagnosed influenza (LDI) was documented in 9 of 90 older adults. Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness (LDI subjects) and those who would not (non-LDI subjects). In contrast, PBMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects. The mean IFN-γ:IL-10 ratio in influenza A/H3N2-stimulated PBMC was 10-fold lower in LDI vs non-LDI subjects. Pre-and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI. In non-CHF subjects with LDI, granzyme B levels increased to high levels at the time of influenza infection. In conclusion, measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people. Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults.

Effects of Transdermal Testosterone on Bone and Muscle in Older Men with Low Bioavailable Testosterone Levels, Low Bone Mass, and Physical Frailty

OBJECTIVES: To investigate the effects of testosterone supplementation on bone, body composition, muscle, physical function, and safety in older men.

Initiation and Maintenance of Exercise Behavior in Older Women: Predictors from the Social Learning Model

The purpose of the present study was to determine the extent to which modifiable social learning constructs predicted long-term adherence to an exercise program in older individuals. Participants were 189 women aged 59 to 78 years and diagnosed with low bone density. Exercise behavior was assessed at 3-month intervals. Self-efficacy, readiness for change, orientation toward exercise, social support in general, and support specifically for exercise were measured at baseline and at 12-month follow-up. Analyses indicated that initial adoption of exercise behavior was best predicted by readiness to change. Maintenance was predicted by self-efficacy for exercise, and exercise behavior at 12 months was predicted by social support for exercise. The results were seen as supportive of the stages and processes of change model of health behavior change. Implications of the findings for interventions to enhance adoption and maintenance of exercise programs by older women are discussed.

Granzyme B: Correlates with protection and enhanced CTL response to influenza vaccination in older adults.

This study compared serum antibody titers and granzyme B (GrzB) levels in virus-stimulated peripheral blood mononuclear cells following influenza vaccination. Twelve of 239 older adults who subsequently developed laboratory-diagnosed influenza illness (LDI) had significantly lower GrzB levels compared to subjects without LDI (p=0.004). Eight subjects with LDI in the previous year showed an enhanced GrzB response to vaccination (p=0.02). Serum antibody titers following vaccination did not distinguish those older adults who developed LDI from those who did not. These results suggest that GrzB levels could be combined with antibody titers to more effectively predict vaccine efficacy in older adults.

Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial

BACKGROUND Soy foods contain several components (isoflavones and amino acids) that potentially affect bone. Few long-term, large clinical trials of soy as a means of improving bone mineral density (BMD) in late postmenopausal women have been conducted. OBJECTIVE Our goal was to evaluate the long-term effect of dietary soy protein and/or soy isoflavone consumption on skeletal health in late postmenopausal women. DESIGN We conducted a randomized, double-blind, placebo-controlled clinical trial in 131 healthy ambulatory women aged >60 y. Ninety-seven women completed the trial. After a 1-mo baseline period, subjects were randomly assigned into 1 of 4 intervention groups: soy protein (18 g) + isoflavone tablets (105 mg isoflavone aglycone equivalents), soy protein + placebo tablets, control protein + isoflavone tablets, and control protein + placebo tablets. RESULTS Consumption of protein powder and isoflavone pills did not differ between groups, and compliance with the study powder and pills was 80-90%. No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers. However, there were significant negative correlations between total dietary protein (per kg) and markers of bone turnover (P < 0.05). CONCLUSIONS Because soy protein and isoflavones (either alone or together) did not affect BMD, they should not be considered as effective interventions for preserving skeletal health in older women. The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover. This trial was registered at ClinicalTrials.gov as NCT00668447.

Dehydroepiandrosterone Combined with Exercise Improves Muscle Strength and Physical Function in Frail Older Women

OBJECTIVES: To investigate the effects of dehydroepiandrosterone (DHEA) combined with exercise on bone mass, strength, and physical function in older, frail women.

Functional Impact of Relative Versus Absolute Sarcopenia in Healthy Older Women

OBJECTIVES: To determine whether adjustment of muscle mass for height2 or for body mass represents a more‐relevant predictor of physical performance.

The 6-minute walk is associated with frailty and predicts mortality in older adults with heart failure

Heart failure (HF) may contribute to the development of functional decline and frailty in older adults. Sixty HF patients with an ejection fraction ≤ 40% evaluated in 2004 and 2005 were reevaluated in 2008. Six-minute walk distance (6MW), frailty score, and biomarkers (25-hydroxyvitamin D, C-reactive protein, and interleukin-6 [IL-6]) were measured. Participants were categorized at baseline and follow-up into 3 groups: nonfrail/normal endurance (NF/NE), nonfrail/low endurance (NF/LE) and frail/low endurance (F/LE). Survival time was assessed according to frailty/endurance status and associated predictors of mortality. Forty-three men, 17 women (mean age, 78 ± 12 years) were contacted. At follow-up, 20 had died, 20 participated, and 20 did not participate. There were no changes in frailty/endurance status over time (McNemar;P=.19). Deaths occurred in 18% of NF/NE, 45% of NF/LE, and 60% of F/LE persons. The NF/NE group had greater survival rates than the NF/LE (  P=.032) and F/LE (  P=.014) groups. The 6MW and frailty score were independently predictive of mortality, with hazard ratios of 0.82 (95% confidence interval, 0.72-0.94) and 1.64 (95% confidence interval, 1.19-2.26), respectively, as was New York Heart Association class and IL-6. Backward stepwise Cox regression revealed that 6MW and frailty each were associated with mortality (P=.005) and highly correlated. Physical function is an important predictor of mortality in older adults with HF. The 6MW may be useful as a measure of frailty.

Self-reported dietary intake of omega-3 fatty acids and association with bone and lower extremity function.

OBJECTIVES: To assess the relationship between self‐reported omega‐3 fatty acid (O3FA) intake and bone mineral density (BMD) and lower extremity function in older adults.

Dementia care consultation for family caregivers: Collaborative model linking an Alzheimer's association chapter with primary care physicians

Objective: The primary objective is to report on the efficacy of an individualized dementia care consultation intervention for family caregivers of patients with diagnosed dementia living in the community. The secondary objective is to present evidence on the intervention process to inform the feasibility and sustainability of the model featuring collaboration between primary care physicians and a voluntary sector organization. Method: Randomization was based on primary care physician practice site. In the intervention group, dementia care consultants located at an Alzheimers association chapter provided individualized counseling and support over a 12-month period, and sent copies of care plans developed with family caregivers to referring primary care physicians. In the control group, family caregivers received educational and community resource information but no care consultation. Nursing home admission of patients during the 12-month study period was the primary outcome; secondary outcomes included measures of caregiver self-efficacy for managing dementia, caregiver depressive symptoms, and caregiver burden. Results: A total of 84 family caregivers participated. After adjusting for baseline characteristics, patients whose family caregivers were in the intervention group were less likely than their control group counterparts to be admitted to a nursing home (Adjusted odds ratio = 0.40; 95% C.I. = 0.14–1.18; p = 0.10). No other outcomes were significantly different between treatment groups; however, intervention group caregivers reporting greater satisfaction with the intervention showed improved self-efficacy for managing dementia compared to their less satisfied counterparts. Medical record reviews found that care plans were found in most patient records, but that only 27% of intervention group caregivers reported discussing these care plans with physicians. Three different individuals occupied the dementia care consultant position during the study period, and this turnover led to family caregiver dissatisfaction. Conclusion: The dementia care consultation intervention showed favorable effects on nursing home admission and on caregiver outcomes among intervention group caregivers more satisfied with the intervention, but there are important barriers to sustaining this collaboration between primary care physicians and a voluntary sector organization such as an Alzheimers association chapter.