Vijay R. Varma

Serum ceramides increase the risk of Alzheimer disease: the Women's Health and Aging Study II.

Objectives: Previous studies have shown that high serum ceramides are associated with memory impairment and hippocampal volume loss, but have not examined dementia as an outcome. The aim of this study was to examine whether serum ceramides and sphingomyelins (SM) were associated with an increased risk of all-cause dementia and Alzheimer disease (AD). Methods: Participants included 99 women without dementia aged 70–79, with baseline serum SM and ceramides, enrolled in a longitudinal population-based study and followed for up to 6 visits over 9 years. Baseline lipids, in tertiles, were examined in relation to all-cause dementia and AD using discrete time Cox proportional survival analysis. Lipids were analyzed using electrospray ionization tandem mass spectrometry. Results: Twenty-seven (27.3%) of the 99 women developed incident dementia. Of these, 18 (66.7%) were diagnosed with probable AD. Higher baseline serum ceramides, but not SM, were associated with an increased risk of AD; these relationships were stronger than with all-cause dementia. Compared to the lowest tertile, the middle and highest tertiles of ceramide d18:1–C16:0 were associated with a 10-fold (95% confidence interval [CI] 1.2–85.1) and 7.6-fold increased risk of AD (95% CI 0.9–62.1), respectively. The highest tertiles of ceramide d18:1–C24:0 (hazard ratio [HR] = 5.1, 95% CI 1.1–23.6) and lactosylceramide (HR = 9.8, 95% CI 1.2–80.1) were also associated with risk of AD. Total and high-density lipoprotein cholesterol and triglycerides were not associated with dementia or AD. Conclusions: Results from this preliminary study suggest that particular species of serum ceramides are associated with incident AD and warrant continued examination in larger studies.

Low-intensity daily walking activity is associated with hippocampal volume in older adults

Hippocampal atrophy is associated with memory impairment and dementia and serves as a key biomarker in the preclinical stages of Alzheimers disease. Physical activity, one of the most promising behavioral interventions to prevent or delay cognitive decline, has been shown to be associated with hippocampal volume; specifically increased aerobic activity and fitness may have a positive effect on the size of the hippocampus. The majority of older adults, however, are sedentary and have difficulty initiating and maintaining exercise programs. A modestly more active lifestyle may nonetheless be beneficial. This study explored whether greater objectively measured daily walking activity was associated with larger hippocampal volume. We additionally explored whether greater low‐intensity walking activity, which may be related to leisure‐time physical, functional, and social activities, was associated with larger hippocampal volume independent of exercise and higher‐intensity walking activity. Segmentation of hippocampal volumes was performed using Functional Magnetic Resonance Imaging of the Brains Software Library (FSL), and daily walking activity was assessed using a step activity monitor on 92, nondemented, older adult participants. After controlling for age, education, body mass index, cardiovascular disease risk factors, and the Mini Mental State Exam, we found that a greater amount, duration, and frequency of total daily walking activity were each associated with larger hippocampal volume among older women, but not among men. These relationships were specific to hippocampal volume, compared with the thalamus, used as a control brain region, and remained significant for low‐intensity walking activity, independent of moderate‐ to vigorous‐intensity activity and self‐reported exercise. This is the first study, to our knowledge, to explore the relationship between objectively measured daily walking activity and hippocampal volume in an older adult population. Findings suggest the importance of examining whether increasing nonexercise, lifestyle physical activities may produce measurable cognitive benefits and affect hippocampal volume through molecular pathways unique to those related to moderate‐intensity exercise.

Impact of the Baltimore Experience Corps Trial on cortical and hippocampal volumes.

There is a substantial interest in identifying interventions that can protect and buffer older adults from atrophy in the cortex and particularly, the hippocampus, a region important to memory. We report the 2‐year effects of a randomized controlled trial of an intergenerational social health promotion program on older mens and womens brain volumes.

Cardiovascular risks and brain function: a functional magnetic resonance imaging study of executive function in older adults

Cardiovascular (CV) risk factors, such as hypertension, diabetes, and hyperlipidemia are associated with cognitive impairment and risk of dementia in older adults. However, the mechanisms linking them are not clear. This study aims to investigate the association between aggregate CV risk, assessed by the Framingham general cardiovascular risk profile, and functional brain activation in a group of community-dwelling older adults. Sixty participants (mean age: 64.6 years) from the Brain Health Study, a nested study of the Baltimore Experience Corps Trial, underwent functional magnetic resonance imaging using the Flanker task. We found that participants with higher CV risk had greater task-related activation in the left inferior parietal region, and this increased activation was associated with poorer task performance. Our results provide insights into the neural systems underlying the relationship between CV risk and executive function. Increased activation of the inferior parietal region may offer a pathway through which CV risk increases risk for cognitive impairment.

Low-Intensity Walking Activity is Associated with Better Health

Recommended levels of physical activity may represent challenging targets for many older adults at risk for disability, leading to the importance of evaluating whether low-intensity activity is associated with health benefits. We examined the cross-sectional association between low-intensity walking activity (<100 steps/min) and health and physical function in a group of older adults. Participants (N = 187; age = 66.8; 91.4% African American; 76.5% female) wore a StepWatch Activity Monitor to measure components of low-intensity walking activity. Only 7% of participants met physical activity guidelines and moderate-intensity activity (≥100 steps/min) contributed only 10% of the total steps/day and 2% of the total min/day. Greater amount, frequency, and duration of low-intensity activity were associated with better self-report and performance-based measures of physical function, better quality of life, and fewer depressive symptoms (ps < .05). The cross-sectional relationship between low-intensity activity and health outcomes important to independent function suggests that we further explore the longitudinal benefits of low-intensity activity.

Blunted diurnal decline of cortisol among older adults with low socioeconomic status

Low socioeconomic status (SES) is associated with increased risk for adverse health outcomes; those with low SES are thought to experience greater environmental disadvantage and exposure to chronic stress over the life course. The effects of chronic stress on health have been measured by cortisol levels and variations in their diurnal pattern. However, the patterns of association between SES and cortisol have been equivocal in older adults. This paper examined in 98 older adults participating in the Brain Health Substudy of the Baltimore Experience Corps Trial baseline patterns of diurnal variation in salivary cortisol associated with lower versus higher SES using total income and perceived SES relative to others. For each measure, participants stratified into lower versus higher SES showed a more blunted rate of decline in diurnal salivary cortisol over the day in adjusted models (P values ≤ 0.05). There were no SES‐related differences in awakening cortisol, cortisol‐awakening response, or area under the curve. These findings confirm prior evidence of a biologic pathway through which socioeconomic disadvantage is linked to biologic vulnerability, and through which the impact of volunteer service in Experience Corps may be measured.

Effect of Community Volunteering on Physical Activity A Randomized Controlled Trial

INTRODUCTION Older adults with a high number of chronic conditions and who live in environments that do not promote physical activity have great difficulty initiating and adhering to exercise programs. Novel lifestyle activity interventions that can effectively increase physical activity may address disparities in health in these populations. This study evaluates the effects of the Baltimore Experience Corps program, a community-based volunteer program, on walking activity in older adults. METHODS The Baltimore Experience Corps Trial is a sex-stratified RCT that recruited participants from 2006 to 2009. Older adult participants aged ≥60 years (n=123) were from a nested objective physical activity trial within the larger Baltimore Experience Corps Trial. Participants randomized to the intervention group were placed as volunteers within the Baltimore public school system for 2 years. The primary study outcome was objectively measured total amount of walking activity measured in steps/day. Differences between intervention and control groups were measured at 12 and 24 months using linear mixed effects models. Data were analyzed in 2014. RESULTS At 24 months, women, but not men, in the intervention group showed an increased amount of walking activity, averaging 1,500.3 (95% CI=77.6, 2,922.9) greater steps/day compared with the control group. Women in the control group showed a decline of 1,191.6 (95% CI=-2243.7, -139.5) steps/day at 24 months compared to baseline. CONCLUSIONS A community-based volunteer intervention increased walking activity among older women, who were at elevated risk for both inactivity and adverse health outcomes. TRIAL REGISTRATION This study is registered at www.clinicaltrials.gov NCT00380562.

Evidence for brain glucose dysregulation in Alzheimer's disease

It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimers disease (AD) pathogenesis.

African Americans and Clinical Research: Evidence Concerning Barriers and Facilitators to Participation and Recruitment Recommendations

Purpose of the Study The goal of the study was to examine barriers and facilitators to clinical research participation among African Americans, as well as recommendations for overcoming these. Design and Methods Eight focus groups were conducted consisting of 64 individuals. These focus groups targeted 2 groups of individuals: (a) community members, including both individuals involved in research and individuals not involved in research, and (b) community leaders, including clergy, community health care providers and service providers who may influence decisions to participate in research. Results Among participants in both groups, the most common barriers to participation included fear and mistrust of research due to multiple factors, such as a lack of information about research and prevailing knowledge of historical occurrences. Facilitators to research participation included intrinsic factors, such as a desire to help others, and extrinsic factors, such as familiarity with the research recruiter. The focus groups also directly engaged participants in discussions of strategies that might improve recruitment, such as the importance of providing personal stories that enable community members to understand the potential benefits of research. Implications Findings from these focus groups address the mandate from funding agencies that emphasize the importance of including racially diverse populations in clinical research studies, and offer potential solutions for increasing the recruitment and retention of minority participants.

Experience Corps Baltimore: Exploring the Stressors and Rewards of High-intensity Civic Engagement

PURPOSE Experience Corps (EC) represents a high-intensity, intergenerational civic engagement activity where older adults serve as mentors and tutors in elementary schools. Although high-intensity volunteer opportunities are designed to enhance the health and well being of older adult volunteers, little is known about the negative and positive aspects of volunteering unique to intergenerational programs from the volunteers perspective. DESIGN AND METHODS Stressors and rewards associated with volunteering in EC were explored in 8 focus group discussions with 46 volunteers from EC Baltimore. Transcripts were coded for frequently expressed themes. RESULTS Participants reported stressors and rewards within 5 key domains: intergenerational (childrens problem behavior, working with and helping children, observing/facilitating improvement or transformation in a child, and developing a special connection with a child); external to EC (poor parenting and childrens social stressors); interpersonal (challenges in working with teachers and bonding/making social connections); personal (enjoyment, self-enhancement/achievement, and being/feeling more active); and structural (satisfaction with the structural elements of the EC program). IMPLICATIONS Volunteers experienced unique intergenerational stressors related to childrens problem behavior and societal factors external to the EC program. Overall, intergenerational, interpersonal, and personal rewards from volunteering, as well as program structure may have balanced the stress associated with volunteering. A better understanding of stressors and rewards from high-intensity volunteer programs may enhance our understanding of how intergenerational civic engagement volunteering affects well being in later life and may inform project modifications to maximize such benefits for future volunteers and those they serve.