Megan M. Marron

The relationship between interleukin-1 receptor antagonist and cognitive function in older adults with bipolar disorder

Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin‐1 receptor antagonist (IL‐1RA) was increased in elderly BD subjects; (ii) whether IL‐1RA was associated with worse neurocognitive function; and (iii) whether IL‐1RA was associated with white matter integrity.

Longer lithium exposure is associated with better white matter integrity in older adults with bipolar disorder

Bipolar disorder (BD) is associated with cognitive dysfunction and structural brain abnormalities. In human and non‐human studies, lithium has been related to neuroprotective and neurotrophic effects. We explored whether lithium treatment is related to better brain integrity and cognitive function in older adults with BD.

Association of Baseline Sleep Quality With Trajectories of Depressive Symptoms in Patients Undergoing Interferon Treatment.

Objective Some patients with hepatitis C starting interferon-&agr; (IFN-&agr;) therapy experience depression, although many patients do not develop depressive symptoms. We have found that poor sleep is associated with increased depressive symptoms on average. It is unknown whether this association holds generally or is driven by a specific, distinct subgroup. This investigation first determined whether patterns of change in depressive symptoms form clinically meaningful, distinct subgroups and then tested the extent to which sleep disturbances are associated with a less favorable depression trajectory. Method Group-based trajectory modeling was used on 124 patients with hepatitis C who started IFN-&agr; therapy. The Pittsburgh Sleep Quality Index (PSQI) assessed pretreatment sleep, the Beck Depression Inventory minus the sleep question assessed depression over time, and the Structured Clinical Interview for DSM-IV provided categorical diagnoses. Results Three distinct subgroups were found, where each subgroup shared similar patterns of depressive symptoms over time. The groups were characterized as “nondepressed,” “slow increase,” and “rapid increase.” The nondepressed subgroup (44.4%) experienced low depressive symptoms with little change over time. In comparison, all rapid increasers (11.3%) were diagnosed as having a mood disorder by 12 weeks of treatment. The PSQI was strongly associated with group membership, where the odds of developing a rapid increase was elevated 39% for every unit-score increase in the PSQI compared with individuals who remained nondepressed (odds ratio = 1.39, 95% confidence interval = 1.07–1.80, adjusted for depression at baseline). Conclusions Only a distinct subpopulation of people is notably vulnerable to a developing a rapid increase in depression symptoms during IFN-&agr; therapy. This group may be identifiable by their markedly poor sleep before IFN-&agr; therapy.

Age, Race, and Gender Factors in Incident Disability

Background Incident disability rates enable the comparison of risk across populations. Understanding these by age, sex, and race is important for planning for the care of older adults and targeting prevention. Methods We calculated incident disability rates among older adults in the Cardiovascular Health Study, a study of 5,888 older adults aged ≥ 65 years over 6 years of follow-up. Disability was defined in the following two ways: (i) self-report of disability (severe difficulty or inability) in any of six Activities of Daily Living (ADL), and (ii) mobility difficulty (any difficulty walking half a mile or climbing 10 steps). Incident disability rates were calculated as events per 100 person years for age, gender, and race groups. Results The incidence of ADL disability, and mobility difficulty were 2.7 (2.5-2.8), and 9.8 (9.4-10.3) events per 100 person years. Women, older participants, and blacks had higher rates in both domains. Conclusion Incidence rates are considerably different based on the domain examined as well as age, race, and gender composition of the population. Prevention efforts should focus on high risk populations and attempt to ameliorate factors that increase risk in these groups.

Mortality in Relation to Changes in a Healthy Aging Index: The Health, Aging, and Body Composition Study

Background Baseline scores on a Healthy Aging Index (HAI), including 5 key physiological domains, strongly predict health outcomes. This study aimed to characterize 9-year changes in a HAI and explore their relationship to subsequent mortality. Methods Data are from the Health, Aging and Body Composition study of well-functioning adults aged 70-79. A HAI, which ranges from 0-10, was constructed at year 1 and year 10 of the study including systolic blood pressure, forced expiratory volume, digit symbol substitution test, cystatin C and fasting glucose. The relationships between the HAI at year 1 and year 10 and the change between years and subsequent mortality until year 17 were estimated from Cox proportional hazards models. Results 2264 participants had complete data on a HAI at year 1, of these 1122 had complete data at year 10. HAI scores tended to increase (i.e., get worse) over 9-year follow-up, from (mean (SD)) 4.3 (2.1) to 5.7 (2.1); mean within person change 1.5 (1.6). After multivariable adjustment HAI score was related to mortality from year 1 (Hazard Ratio (95% Confidence Interval) =1.17 (1.13 - 1.21) per unit) and year 10 (1.20 (1.14 - 1.27) per unit). The change between years was also related to mortality (1.08 (1.02 - 1.15) per unit change). Conclusions HAI scores tended to increase with advancing age and stratified mortality rates among participants remaining at year 10. The HAI may prove useful to understand changes in health with aging.

Racial Differences in Cause-Specific Mortality Between Community-Dwelling Older Black and White Adults: Racial differences in mortality in older adults

To understand which causes of death are higher in black than white community‐dwelling older adults and determine whether differences in baseline risk factors explain racial differences in mortality.

A novel healthy blood pressure phenotype in the Long Life Family Study

Background: Hypertension tends to run in families and has both genetic and environmental determinants. We assessed the hypothesis that a novel healthy blood pressure (BP) phenotype is also familial and sought to identify its associated factors. Methods: We developed a healthy BP phenotype in the Long Life Family Study, a cohort of two-generation families selected for longevity. Participants from the offspring generation (n = 2211, ages 32–88) were classified as having healthy BP if their age-adjusted and sex-adjusted SBP z-score was between −1.5 and −0.5. Offspring on antihypertensive medications were classified as not having healthy BP. Families with at least two offspring (n = 419 families) were defined as meeting the healthy BP phenotype if at least two and at least 50% of their offspring had healthy BP. Results: Among 2211 offspring, 476 (21.5%) met the healthy BP phenotype. When examining the 419 families, only 44 (10.5%) families met the criteria for the healthy BP phenotype. Both offspring and probands from families with healthy BP performed better on neuropsychological tests that place demands on complex attention and executive function when compared with offspring and probands from remaining families. Among families with the healthy BP phenotype compared with families without, a higher proportion of offspring met the American Heart Association definition of ideal cardiovascular health (10.8 versus 3.8%, respectively; driven by BP, smoking status, and BMI components). Conclusion: In this cohort of familial longevity, few families had a novel healthy BP phenotype in multiple members. Families with this healthy BP phenotype may represent a specific pathway to familial longevity.

Metabolite Profiles of Healthy Aging Index Are Associated With Cardiovascular Disease in African Americans: The Health, Aging, and Body Composition Study

Background Metabolic dysfunction is a hallmark of differential aging, specifically in African Americans. Investigation of systemic metabolic state, multiorgan aging, and long-term cardiovascular outcome in African Americans has not been reported. Methods We studied 291 African American males in the Health, Aging, and Body Composition (Health ABC) study to identify circulating metabolites related to the Newman healthy aging index (HAI; a multiparametric score comprised of blood pressure, blood glucose, neurocognitive function, creatinine, and forced vital capacity). We examined the relationship of selected metabolites differential abundant at the extremes of HAI with long-term survival from cardiovascular mortality. Results The median age was 73 years. We identified 19 metabolites differentially expressed in blood in 86 study participants at the extremes of HAI (HAI 0-3: N = 30 vs 8-10: N = 56). At a median follow-up of 10 years, 78 participants (27 per cent) died from cardiovascular causes. After adjustment for age, body mass index, presence of prevalent cardiovascular disease, creatinine, and HAI, six of these 19 metabolites were associated with long-term cardiovascular mortality. Although several metabolites had been previously reported in Caucasians (eg, isocitrate), we identified several metabolites with unreported association with cardiac disease. Metabolites associated with HAI and cardiac death in African Americans specified pathways relevant to nitric oxide, oxidative stress, mitochondrial function, urea cycle, and gut microbial metabolism. Conclusions Metabolite profiling in African Americans identified known and novel metabolic pathways linked to HAI and cardiovascular death. Further investigation in larger patient cohorts is required to uncover race-based signatures of cardiovascular disease with aging.