Sex-dependent effect of the BDNF Val66Met polymorphism on executive functioning and processing speed in older adults: evidence from the health ABC study

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may be an important source of heterogeneity seen in cognitive aging, although the specific relationship between this polymorphism and cognition remains controversial and may depend on the sex of participants. We assessed 2668 older black and white adults and fit linear mixed models to digit symbol substitution test (DSST) performance assessed in years 0 (baseline), 4, 7, and 9 to examine the interaction between sex and BDNF genotype on the intercept (i.e., estimated baseline DSST) and change in DSST over 9 years, adjusted for covariates. Sex interacted with BDNF genotype to predict DSST intercept (F[1,1599] = 7.4, p < 0.01) and 9-year change (F[1,1183] = 4.1, p = 0.04) in white participants only. Initially, white male Val/Val carriers had lower DSST scores (37.6, SE = 0.8) in comparison with male Met carriers (difference, -1.7; 95% CI, -3.2 to -0.3) and female Val/Val carriers (difference, -5.6; 95% CI, -6.8 to -4.3). White female Met carriers showed a slower rate of change (annual rate of change = -0.6, SE = 0.1) in comparison with female Val/Val carriers (difference, -0.2; 95% CI, -0.4 to -0.02) and male Met carriers (difference, -0.3; 95% CI, -0.5 to -0.02). Our findings suggest that BDNF Val66Met and sex should be considered in future endeavors aimed at treating or preventing neurodegenerative disorders

Weight Change, Body Composition, and Risk of Mobility Disability and Mortality in Older Adults: a Population-Based Cohort Study

OBJECTIVES: To examine associations between weight change, body composition, risk of mobility disability, and mortality in older adults. DESIGN: Prospective, longitudinal, population-based cohort. SETTING: The Health, Aging, and Body Composition Study. PARTICIPANTS: Women (n = 1,044) and men (n = 931) aged 70 to 79. MEASUREMENTS: Weight and lean and fat mass from dual-energy X-ray absorptiometry measured annually over 5 years. Weight was defined as stable (n = 664, reference), loss (n = 662), gain (n = 321), or cycling (gain and loss, n = 328) using change of 5% from year to year or from Year 1 to 6. Mobility disability (two consecutive reports of difficulty walking one-quarter mile or climbing 10 steps) and mortality were determined for 8 years after the weight change period. Associations were analyzed using Cox proportional hazards regression adjusted for covariates. RESULTS: During follow-up, 313 women and 375 men developed mobility disability, and 322 women and 378 men died. There was no risk of mobility disability or mortality with weight gain. Weight loss (hazard ratio (HR) = 1.88, 95% confidence interval (CI) = 1.40-2.53) and weight cycling (HR = 1.59, 95% CI = 1.11-2.29) were associated with mobility disability in women, and weight loss was associated with mobility disability in men (HR = 1.30, 95% CI = 1.01-1.69). Weight loss and weight cycling were associated with mortality risk in women (weight loss: HR = 1.47, 95% CI = 1.07-2.01; weight cycling: HR = 1.62, 95% CI = 1.15-2.30) and in men (weight loss: HR = 1.41, 95% CI = 1.09-1.83; weight cycling: HR = 1.50, 95% CI = 1.08-2.08). Adjustment for lean and fat mass and change in lean and fat mass from Year 1 to 6 attenuated the relationships between weight loss and mobility disability in men and between weight loss and mortality in men and women. CONCLUSION: Weight cycling and weight loss predict impending mobility disability and mortality in old age, underscoring the prognostic importance of weight history

Leptin, abdominal obesity, and onset of depression in older men and women.

ObjectiveThe mechanisms that underlie the association between abdominal obesity and depression risk in older persons are not well known, but the "leptin hypothesis" of depression suggests that leptin resistance may be involved in mood regulation. We tested whether high circulatory concentration of leptin, alone and in combination with visceral adiposity, is associated with onset of depression in a sample of older persons.MethodParticipants were 1,220 men and 1,282 women aged 70-79 years and enrolled in the Health, Aging, and Body Composition study. Serum concentration of leptin and abdominal visceral fat, ascertained by computed tomography, were assessed at baseline (April 1997-June 1998). Onset of depression, the primary outcome measure, was defined as a Center for Epidemiologic Studies-depression scale 10-item score ≥ 10 and/or new antidepressant medication use at any annual visit over a 5-year follow-up.ResultsHigher leptin level was associated with the risk of depression onset in men with high levels of visceral fat (hazard ratio [HR] = 1.25; 95% CI, 1.06-1.46; P = .01) but not in those with normal visceral fat (HR = 0.98; 95% CI, 0.80-1.19; P = .80) (leptin-by-visceral fat, P = .04). No interaction between leptin and visceral fat was detected in the analysis focusing on women (P = .90).ConclusionsIn older men, high leptin level was associated with an increased onset of depressive symptoms, especially in the presence of abdominal obesity, suggesting that underlying leptin resistance may play a role in this link. Differences in visceral fat levels and metabolic consequences may explain the absence of this association in women. These findings suggest a potential biological link between depression, obesity, and their joint association with negative health outcomes

Leptin, abdominal obesity, and onset of depression in older men and women

OBJECTIVE: The mechanisms that underlie the association between abdominal obesity and depression risk in older persons are not well known, but the “leptin hypothesis” of depression suggests that leptin resistance may be involved in mood regulation. We tested whether high circulatory concentration of leptin, alone and in combination with visceral adiposity, is associated with onset of depression in a sample of older persons. METHOD: Participants were 1220 men and 1282 women aged 70–79 years, enrolled in the Health, Aging and Body Composition study. Plasma concentration of leptin and abdominal visceral fat ascertained by computed tomography were assessed at baseline (April 1997 – June 1998). Onset of depression was defined as a Center for Epidemiological Studies-Depression Scale 10-item score ≥ 10 and/or new antidepressant medication use at any annual visit over a 5-year follow-up. RESULTS: Higher leptin was associated with the risk of depression onset in men with high visceral fat (HR=1.25,95%CI=1.06–1.46, p=0.01) but not in those with normal visceral fat (HR=0.98,95%CI=0.80–1.19, p=0.80) (leptin*visceral fat p=0.04). No interaction between leptin and visceral fat was detected in the analysis focusing on women (p=0.90). CONCLUSION: In older men, high leptin was associated with an increased onset of depressive symptoms especially in the presence of abdominal obesity, suggesting that underlying leptin resistance may play a role in this link. Differences in visceral fat levels and metabolic consequences may explain the absence of this association in women. These findings suggest a potential biological link between depression, obesity and their joint association with negative health outcomes

Surveying predictors of late-life longitudinal change in daily activity energy expenditure.

BackgroundTotal daily energy expenditure (TEE) is composed of resting metabolic rate (RMR), post-prandial thermogenesis and activity energy expenditure (AEE). Higher AEE is strongly associated with lower mortality and physical limitations among older adults, but factors that predict changes in AEE in septu and octogenarians are not clearly understood.ObjectiveTo identify factors associated with late-life longitudinal change in AEE.DesignEnergy expenditure was re-assessed in 83 participants (average age at baseline, 74.4±3.2 years)-an average of 7.5±0.54 years since the baseline measure. RMR was measured using indirect calorimetry and the thermic effect of meals was estimated at 10% of TEE. AEE was calculated as: TEE(0.9)-RMR. Participants were categorized into two groups according to the estimated day-to-day precision of the doubly-labeled water technique. Those who were within 10% or increased relative to their initial AEE measurement were categorized as having preserved AEE. Participants who declined greater than 10% of their initial measurement were categorized as having reduced AEE. A variety of socio-demographic, functional and mental factors, body composition, community and personal behaviors, blood measurements and health conditions were evaluated between groups at baseline and changes during follow-up.ResultsDaily AEE declined 106.61±293.25 kcal, which equated to a 14.63±40.57 kcal/d decrease per year. Fifty-nine percent (n = 49) preserved their AEE and 41% (n = 34) declined. Those who demonstrated a decline in AEE were older, had lower walking speed at baseline and showed a higher lean mass loss during follow up. Otherwise, groups were similar for socio-demographic characteristics, body composition, mental and physical function, health conditions and community and personal behaviors at baseline and change in these factors during follow-up.ConclusionsThis study demonstrates that AEE declines through the 8th decade of life and is associated with age, lower walking speed at baseline and lean mass loss. Additionally, there are a significant number of individuals who appear to be resilient to these declines despite having health events that are expected to have a negative impact on their physical activity

Surveying predictors of late-life longitudinal change in daily activity energy expenditure.

BackgroundTotal daily energy expenditure (TEE) is composed of resting metabolic rate (RMR), post-prandial thermogenesis and activity energy expenditure (AEE). Higher AEE is strongly associated with lower mortality and physical limitations among older adults, but factors that predict changes in AEE in septu and octogenarians are not clearly understood.ObjectiveTo identify factors associated with late-life longitudinal change in AEE.DesignEnergy expenditure was re-assessed in 83 participants (average age at baseline, 74.4±3.2 years)-an average of 7.5±0.54 years since the baseline measure. RMR was measured using indirect calorimetry and the thermic effect of meals was estimated at 10% of TEE. AEE was calculated as: TEE(0.9)-RMR. Participants were categorized into two groups according to the estimated day-to-day precision of the doubly-labeled water technique. Those who were within 10% or increased relative to their initial AEE measurement were categorized as having preserved AEE. Participants who declined greater than 10% of their initial measurement were categorized as having reduced AEE. A variety of socio-demographic, functional and mental factors, body composition, community and personal behaviors, blood measurements and health conditions were evaluated between groups at baseline and changes during follow-up.ResultsDaily AEE declined 106.61±293.25 kcal, which equated to a 14.63±40.57 kcal/d decrease per year. Fifty-nine percent (n = 49) preserved their AEE and 41% (n = 34) declined. Those who demonstrated a decline in AEE were older, had lower walking speed at baseline and showed a higher lean mass loss during follow up. Otherwise, groups were similar for socio-demographic characteristics, body composition, mental and physical function, health conditions and community and personal behaviors at baseline and change in these factors during follow-up.ConclusionsThis study demonstrates that AEE declines through the 8th decade of life and is associated with age, lower walking speed at baseline and lean mass loss. Additionally, there are a significant number of individuals who appear to be resilient to these declines despite having health events that are expected to have a negative impact on their physical activity

The influence of abdominal visceral fat on inflammatory pathways and mortality risk in obstructive lung disease

BACKGROUND: Low-grade systemic inflammation, particularly elevated IL-6, predicts mortality in chronic obstructive pulmonary disease (COPD). Although altered body composition, especially increased visceral fat (VF) mass, could be a significant contributor to low-grade systemic inflammation, this remains unexplored in COPD. OBJECTIVE: The objective was to investigate COPD-specific effects on VF and plasma adipocytokines and their predictive value for mortality. DESIGN: Within the Health, Aging, and Body Composition (Health ABC) Study, an observational study in community-dwelling older persons, we used propensity scores to match n = 729 persons with normal lung function to n = 243 persons with obstructive lung disease (OLD; defined as the ratio of forced expiratory volume in 1 s to forced vital capacity < lower limit of normal). Matching was based on age, sex, race, clinic site, BMI, and smoking status. Within this well-balanced match, we compared computed tomography-acquired visceral fat area (VFA) and plasma adipocytokines, analyzed independent associations of VFA and OLD status on plasma adipocytokines, and studied their predictive value for 9.4-y mortality. RESULTS: Whereas whole-body fat mass was comparable between groups, persons with OLD had increased VFA and higher plasma IL-6, adiponectin, and plasminogen activator inhibitor 1 (PAI-1). Both OLD status and VFA were independently positively associated with IL-6. Adiponectin was positively associated with OLD status but negatively associated with VFA. PAI-1 was no longer associated with OLD status after VFA was accounted for. Participants with OLD had increased risk of all-cause, respiratory, and cardiovascular mortality, of which IL-6 was identified as an independent predictor. CONCLUSION: Our data suggest that excessive abdominal visceral fat contributes to increased plasma IL-6, which, in turn, is strongly associated with all-cause and cause-specific mortality in older persons with OLD