Andrea L Metti

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Are you Andrea L Metti?

Claim your profile

Publications (10)45.12 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We aimed to examine trajectories of inflammatory markers and cognitive decline over 10 years. Cox proportional hazards models were used to examine the association between interleukin-6 and C-reactive protein (CRP) trajectory components (slope, variability, and baseline level) and cognitive decline among 1323 adults, aged 70-79 years in the Health, Aging, and Body Composition Study. We tested for interactions by sex and apolipoprotein E (APOE) genotype. In models adjusted for multiple covariates and comorbidities, extreme CRP variability was significantly associated with cognitive decline (hazard ratio [HR] 1.6, 95% confidence interval [CI]: 1.1-2.3). This association was modified by sex and APOE e4 (p < 0.001 for both), such that the association remained among women (HR = 1.8; 95% CI: 1.1, 3.0) and among those with no APOE e4 allele (HR = 1.6; 95% CI: 1.1, 2.5). There were no significant associations between slope or baseline level of CRP and cognitive decline nor between interleukin-6 and cognitive decline. We believe CRP variability likely reflects poor control of or greater changes in vascular or metabolic disease over time, which in turn is associated with cognitive decline.
    Neurobiology of aging. 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives To determine the association between interleukin-6 (IL-6), IL-6 soluble receptor (sR), and soluble tumor necrosis factor receptor-1 (sTNF-R1) and cognitive status in the oldest-old women.DesignTwenty-year longitudinal cohort study.SettingFour clinical sites in the United States.ParticipantsWomen from the Study of Osteoporotic Fractures (N = 905; mean age 88.3 ± 2.8 at cognitive status adjudication).MeasurementsAt Year 20, cognitive status was adjudicated as normal, mild cognitive impairment (MCI), or dementia. Inflammatory markers were measured from blood serum at Years 10 and 16 in a random sample of women.ResultsOver 10 years, 199 (22.0%) women developed MCI and 145 (16.0%) dementia. There were no significant associations between IL-6 or sTNF-R1 and cognitive status. High IL-6-sR (≥37,401.36 pg/mL, highest tertile) at Year 16 was significantly associated with lower risk of dementia (odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.30–0.97) than in women with lower levels (<37,401.36 pg/mL, lower two tertiles). Women with high IL-6-sR at both time points (OR = 0.39, 95% CI = 0.17–0.89) or who transitioned to a high level (OR = 0.35, 95% CI = 0.14–0.88) had a lower risk of dementia.Conclusion In this cohort of white, high-functioning oldest-old women, a consistently high or an increasing level of IL-6-sR was associated with lower risk of dementia. Compared with other studies of younger-old adults, this suggests that the effect of inflammation on dementia may differ in younger-old and the oldest-old individuals. Understanding these differences will be crucial in interpreting results from ongoing clinical trials and in targeting therapeutic strategies to the oldest-old individuals.
    Journal of the American Geriatrics Society 03/2014; · 4.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Low literacy is common among the elderly and possibly more reflective of educational attainment than years of school completed. We examined the association between literacy and risk of likely dementia in older adults. Participants were 2,458 black and white elders (aged 71-82) from the Health, Aging and Body Composition study, who completed the Rapid Estimate of Adult Literacy in Medicine and were followed for 8 years. Participants were free of dementia at baseline; incidence of likely dementia was defined by hospital records, prescription for dementia medication, or decline in Modified Mini-Mental State Examination score. We conducted Cox proportional hazard models to evaluate the association between literacy and incidence of likely dementia. Demographics, education, income, comorbidities, lifestyle variables, and apolipoprotein E (APOE) ε4 status were included in adjusted analyses. Twenty-three percent of participants had limited literacy (<9th-grade level). Limited literacy, as opposed to adequate literacy (≥9th-grade level), was associated with greater incidence of likely dementia (25.5% vs17.0%; unadjusted hazard ratio [HR] = 1.75, 95% confidence interval 1.44-2.13); this association remained significant after adjustment. There was a trend for an interaction between literacy and APOE ε4 status (p = .07); the association between limited literacy and greater incidence of likely dementia was strong among ε4 noncarriers (unadjusted HR = 1.85) but nonsignificant among ε4 carriers (unadjusted HR = 1.25). Limited literacy is an important risk factor for likely dementia, especially among APOE ε4-negative older adults, and may prove fruitful to target in interventions aimed at reducing dementia risk.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 10/2013; · 4.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine whether anemia is associated with incident dementia in older adults. We studied 2,552 older adults (mean age 76.1 years; 38.9% black; 51.8% female) participating in the Health, Aging, and Body Composition study and free of dementia at baseline. We defined anemia using WHO criteria (hemoglobin concentration <13 g/dL for men and <12 g/dL for women). Dementia diagnosis was determined by dementia medication use, hospital records, or a change in Modified Mini-Mental State (3MS) score of more than 1.5 SD from mean. Discrete time Cox proportional hazard regression models were used to examine the hazard for developing dementia associated with anemia. Of 2,552 participants, 392 (15.4%) older adults had anemia at baseline. Over 11 years of follow-up, 455 (17.8%) participants developed dementia. In the unadjusted model, those with baseline anemia had an increased risk of dementia (23% vs 17%, hazard ratio = 1.64; 95% confidence interval 1.30, 2.07) compared to those without anemia. The association remained significant after adjusting for demographics, APOE ε4, baseline 3MS score, comorbidities, and renal function. Additional adjustment for other anemia measures (mean corpuscular volume, red cell distribution width), erythropoietin, and C-reactive protein did not appreciably change the results. There was no interaction by sex and race on risk of developing dementia. Among older adults, anemia is associated with an increased risk of developing dementia. Findings suggest that further study of anemia as a risk factor for dementia and a target for intervention for cognitive health is warranted.
    Neurology 07/2013; · 8.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE Hypoglycemia commonly occurs in patients with diabetes mellitus (DM) and may negatively influence cognitive performance. Cognitive impairment in turn can compromise DM management and lead to hypoglycemia. OBJECTIVE To prospectively evaluate the association between hypoglycemia and dementia in a biracial cohort of older adults with DM. DESIGN AND SETTING Prospective population-based study. PARTICIPANTS We studied 783 older adults with DM (mean age, 74.0 years; 47.0% of black race/ethnicity; and 47.6% female) who were participating in the prospective population-based Health, Aging, and Body Composition Study beginning in 1997 and who had baseline Modified Mini-Mental State Examination scores of 80 or higher. MAIN OUTCOME MEASURES Dementia diagnosis was determined during the follow-up period from hospital records indicating an admission associated with dementia or the use of prescribed dementia medications. Hypoglycemic events were determined during the follow-up period by hospital records. RESULTS During the 12-year follow-up period, 61 participants (7.8%) had a reported hypoglycemic event, and 148 (18.9%) developed dementia. Those who experienced a hypoglycemic event had a 2-fold increased risk for developing dementia compared with those who did not have a hypoglycemic event (34.4% vs 17.6%, P < .001; multivariate-adjusted hazard ratio, 2.1; 95% CI, 1.0-4.4). Similarly, older adults with DM who developed dementia had a greater risk for having a subsequent hypoglycemic event compared with participants who did not develop dementia (14.2% vs 6.3%, P < .001; multivariate-adjusted hazard ratio, 3.1; 95% CI, 1.5-6.6). Further adjustment for stroke, hypertension, myocardial infarction, and cognitive change scores produced similar results. CONCLUSION AND RELEVANCE Among older adults with DM, there seems to be a bidirectional association between hypoglycemia and dementia.
    JAMA Internal Medicine 06/2013; · 13.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been hypothesized that cellular damage caused by oxidative stress is associated with late-life depression but epidemiological evidence is limited. In the present study we evaluated the association between urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), a biomarker of lipid peroxidation, and depressed mood in a large sample of community-dwelling older adults. Participants were selected from the Health, Aging and Body Composition study, a community-based longitudinal study of older persons (aged 70-79 years). The present analyses was based on a subsample of 1027 men and 948 women free of mobility disability. Urinary concentration of 8-iso-PGF2α was measured by radioimmunoassay methods and adjusted for urinary creatinine. Depressed mood was defined as a score greater than 5 on the 15-item Geriatric Depression Scale and/or use of antidepressant medications. Depressed mood was present in 3.0% of men and 5.5% of women. Depressed men presented higher urinary concentrations of 8-iso-PGF2α than non-depressed men even after adjustment for multiple sociodemographic, lifestyle and health factors (p = 0.03, Cohen's d = 0.30). This association was not present in women (depressed status-by-sex interaction p = 0.04). Our study showed that oxidative damage may be linked to depression in older men from a large sample of the general population. Further studies are needed to explore whether the modulation of oxidative stress may break down the link between late-life depression and its deleterious health consequences.
    PLoS ONE 06/2013; 8(6):65406-. · 3.53 Impact Factor
  • Andrea L Metti, Jane A Cauley
    [Show abstract] [Hide abstract]
    ABSTRACT: Dementia is a huge public health concern today owing to the exponentially increasing number of older adults it affects each year, and there has been a large number of investigators looking at potential biomarkers of dementia. Peripheral inflammatory markers have emerged as one potential class of markers that may be useful in predicting those individuals at a greater risk of developing dementia, or in expounding the underlying mechanisms or pathways of this complex disease. Although some evidence has been promising, indicating that peripheral inflammatory markers are indeed crucial in brain changes that occur in both normal aging and in dementia, results have been mixed on their usefulness for predicting dementia or cognitive decline in older adults. Here, the authors present a review of existing studies investigating inflammatory markers as potential biomarkers of dementia, highlighting some strengths and limitations of the current research and discuss the future directions for this field.
    Neurodegenerative disease management. 12/2012; 2(6):609-622.
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Studies that have investigated the association between markers of inflammation and risk of dementia are conflicting. Therefore, the researchers conducted a systematic review and meta-analysis of observational studies with the hypothesis that an increased level of peripheral proinflammatory markers would be associated with risk of all-cause dementia or Alzheimer's disease (AD). METHODS: The researchers conducted a literature search of observational studies indexed in the PubMed and PsycInfo databases. Selected studies included those with at least one peripheral inflammatory biomarker and its association with risk of all-cause dementia or AD. Random effects models were used to generate pooled hazard ratios (HRs) comparing the top versus bottom quantile of inflammatory marker level. Heterogeneity was assessed using the I (2) statistic. RESULTS: Seven studies were identified, combining for a total 5,717 participants, 746 cases of all-cause dementia and 565 cases of AD. An increased level of C-reactive protein was associated with a 45% increased risk of all-cause dementia (HR: 1.45; 95% CI: 1.10, 1.91). Similarly, a higher level of interleukin-6 was associated with a 32% increased risk (HR: 1.32; 95% CI: 1.06, 1.64) of all-cause dementia. For AD alone, the association with C-reactive protein was less pronounced (HR: 1.21; 95% CI: 1.03, 1.42) and interleukin-6 was not associated with risk of AD (HR: 1.06; 95% CI: 0.83, 1.35). No significant heterogeneity was found in any of the meta-analyses (I (2) = 0%-40%, p ≥ .16). CONCLUSIONS: An increased peripheral level of inflammatory markers is associated with a modest increase in risk of all-cause dementia. Evidence for an association with risk of AD alone is limited.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2012; · 4.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plasma amyloid β-42 (Aβ42) and Aβ42/Aβ40 are increasingly recognized as biomarkers for dementia, with low levels indicating increased risk. Little is known about the demographic and medical correlates of plasma Aβ40 or Aβ42. In 997 community-dwelling, nondemented older adults from the Health, Aging, and Body Composition Study, we determined the cross-sectional association between a wide range of demographic and medical variables with Aβ40 and Aβ42. In multivariate stepwise linear regression models, Aβ40 was significantly associated with race (β=-14.70, F=22.01, P<0.0001), age (β=1.34, F=6.39, P=0.01), creatinine (β=52.91, F=151.77, P<0.0001), and the serum brain-derived neurotrophic factor (β=-0.0004, F=7.34, P=0.007); Aβ42 was significantly associated with race (β=-3.72, F=30.83, P<0.0001), sex (β=1.39, F=4.32, P=0.04), education (β=1.50, F=4.78, P=0.03), apolipoprotein E e4 genotype (β=-2.82, F=16.57, P<0.0001), and creatinine (β=9.32, F=120.09, P<0.0001). These correlates should be considered as potential confounders in future studies investigating plasma Aβ as a biomarker of dementia. Understanding fully how these correlates mediate or modify the association between plasma Aβ and dementia will be a fundamental step in determining the biological pathways through which plasma Aβ40 and Aβ42 are associated with dementia, and in determining their full potential as biomarkers.
    Alzheimer disease and associated disorders 06/2012; · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Older adults with depression have an increased risk of developing dementia. Low plasma beta-amyloid 42 (Aβ42) and Aβ42/Aβ40 have emerged as promising biomarkers of dementia. The association between depression and plasma Aβ is unclear. METHODS: In this longitudinal study of 988 community-dwelling elders from the Health Aging and Body Composition study, depression was assessed with the Center for Epidemiologic Studies-Depression Scale 10-item version. We determined the association between Aβ42 and Aβ42/Aβ40 tertile and depression at baseline and over 9 years. We also stratified the models to determine if apolipoprotein E e4 allele status modified the associations. RESULTS: Mean baseline age was 74.0 ± 3.0 years, 51 (5.2%) participants had depression, 545 (55.2%) were women, 531 (53.7%) were black, and 286 (30.7%) had one or more apolipoprotein E e4 allele. At baseline, there was no association between Aβ42/Aβ40 or Aβ42 and depression. Over 9 years, 220 (23.5%) participants developed depression. In adjusted Cox proportional hazards models, among those with one or more e4 allele, low Aβ42/Aβ40 was associated with an increased risk of developing depression over time (low 10.8% vs high 3.2%, hazard ratio = 2.38, 95% confidence interval: 1.15-4.92). Among those with no e4 allele, there was no association between Aβ42/Aβ40 and risk of depression over time (13.3% vs 17.5%, hazard ratio = 0.80, 95% confidence interval: 0.52-1.23; p value for interaction = .003). CONCLUSIONS: The association between low plasma Aβ42/Aβ40 and increased risk of incident depression among those with one or more apolipoprotein E e4 allele implies a synergistic relationship similar to that found with dementia. Future work should investigate the interrelationships among plasma Aβ42/Aβ40, depression, and dementia.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 04/2012; · 4.31 Impact Factor