Luigi Ferrucci

National Institute on Aging, Baltimore, Maryland, United States

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Publications (816)5981.75 Total impact

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    ABSTRACT: An increasing number of aging researchers believes that multi-system physiological dysregulation may be a key biological mechanism of aging, but evidence of this has been sparse. Here, we used biomarker data on nearly 33 000 individuals from four large datasets to test for the presence of multi-system dysregulation. We grouped 37 biomarkers into six a priori groupings representing physiological systems (lipids, immune, oxygen transport, liver function, vitamins, and electrolytes), then calculated dysregulation scores for each system in each individual using statistical distance. Correlations among dysregulation levels across systems were generally weak but significant. Comparison of these results to dysregulation in arbitrary 'systems' generated by random grouping of biomarkers showed that a priori knowledge effectively distinguished the true systems in which dysregulation proceeds most independently. In other words, correlations among dysregulation levels were higher using arbitrary systems, indicating that only a priori systems identified distinct dysregulation processes. Additionally, dysregulation of most systems increased with age and significantly predicted multiple health outcomes including mortality, frailty, diabetes, heart disease, and number of chronic diseases. The six systems differed in how well their dysregulation scores predicted health outcomes and age. These findings present the first unequivocal demonstration of integrated multi-system physiological dysregulation during aging, demonstrating that physiological dysregulation proceeds neither as a single global process nor as a completely independent process in different systems, but rather as a set of system-specific processes likely linked through weak feedback effects. These processes - probably many more than the six measured here - are implicated in aging.
    Aging cell 09/2015; DOI:10.1111/acel.12402 · 6.34 Impact Factor
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    ABSTRACT: Polymorphisms in the vitamin D receptor (VDR) gene are some of the most studied in relation to skeletal muscle traits and significant associations have been observed by multiple groups. One such paper by our group provided the first evidence of a genetic association with sarcopenia in men, but that finding has yet to be replicated in an independent cohort. In the present study, we examined multiple VDR polymorphisms in relation to skeletal muscle traits and sarcopenia in 864 men and women across the adult age span. In addition to VDR genotypes and haplotypes, measurements of skeletal muscle strength and fat-free mass (FFM) were determined in all subjects and a measure of sarcopenia was calculated. We observed significant associations between Fok1 and Bsm1 genotypes and skeletal muscle strength in men and women, though these associations were modest and no significant associations were observed for these polymorphisms and muscle mass traits nor for Bsm1-Taq1 haplotype with muscle strength. Fok1 FF genotype was associated with an increased the risk of sarcopenia in older women compared to f-allele carriers (1.3-fold higher risk). These results support previous findings that VDR genetic variation appears to impact skeletal muscle strength and risk for sarcopenia but the influence is modest.
    Aging - Clinical and Experimental Research 09/2015; DOI:10.1007/s40520-015-0447-8 · 1.22 Impact Factor
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    Stéphanie M van den Berg · Marleen H M de Moor · Karin J H Verweij · Robert F Krueger · Michelle Luciano · Alejandro Arias Vasquez · Lindsay K Matteson · Jaime Derringer · Tõnu Esko · Najaf Amin · [...] · Hans J Grabe · Brenda W J H Penninx · Cornelia M van Duijn · David M Evans · David Schlessinger · Nancy L Pedersen · Antonio Terracciano · Matt McGue · Nicholas G Martin · Dorret I Boomsma
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    Stéphanie M van den Berg · Marleen H M de Moor · Karin J H Verweij · Robert F Krueger · Michelle Luciano · Alejandro Arias Vasquez · Lindsay K Matteson · Jaime Derringer · Tõnu Esko · Najaf Amin · [...] · Hans J Grabe · Brenda W J H Penninx · Cornelia M van Duijn · David M Evans · David Schlessinger · Nancy L Pedersen · Antonio Terracciano · Matt McGue · Nicholas G Martin · Dorret I Boomsma
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    Stéphanie M van den Berg · Marleen H M de Moor · Karin J H Verweij · Robert F Krueger · Michelle Luciano · Alejandro Arias Vasquez · Lindsay K Matteson · Jaime Derringer · Tõnu Esko · Najaf Amin · [...] · Hans J Grabe · Brenda W J H Penninx · Cornelia M van Duijn · David M Evans · David Schlessinger · Nancy L Pedersen · Antonio Terracciano · Matt McGue · Nicholas G Martin · Dorret I Boomsma
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    ABSTRACT: Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
    Behavior Genetics 09/2015; DOI:10.1007/s10519-015-9735-5 · 3.21 Impact Factor
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    ABSTRACT: Background: Although the "anti-aging hormone" klotho is associated with sarcopenia in mice, the relationship between klotho and muscle strength in older adults is not well known. Methods: Plasma klotho concentrations were measured in 2,734 older adults, aged 71-80 years, who participated in the Health, Aging and Body Composition Study, a prospective observational cohort study conducted in Memphis, TN and Pittsburgh, PA. Knee extension strength was measured using isokinetic dynamometry at baseline and follow-up 2 and 4 years later. Knee extension strength was normalized for weight. Results: At baseline, participants in the highest tertile of plasma klotho had higher knee extension strength (β = .72, standard error [SE] = .018, p < .0001) compared with those in the lowest tertile in a multivariable linear regression model adjusting for age, sex, race, smoking, study site, C-reactive protein, interleukin-6, and diabetes. Participants in the highest tertile of plasma klotho at baseline had less of a decline in knee strength over 4 years of follow-up (β = -.025, SE = .011, p = .02) compared with those in the lowest tertile in a multivariable linear regression model adjusting for the same covariates above. Conclusions: Plasma klotho concentrations were an independent predictor of changes in knee strength over time in older adults. Further studies are needed to identify the biological mechanisms by which circulating klotho could modify skeletal muscle strength.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2015; DOI:10.1093/gerona/glv077 · 5.42 Impact Factor
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    ABSTRACT: Patterns of DNA methylation (DNAm) that track with aging have been identified. However, the relevance of these patterns for aging outcomes remains unclear. Longitudinal epigenome-wide DNAm information was obtained from the InCHIANTI study, a large representative European population. DNAm was evaluated using the Illumina HumanMethylation450 array on blood samples collected at baseline and 9-year follow-up: observations from 499 participants with paired longitudinal blood sample and information on differential blood count were included in analyses. A total of 56,579 markers were significantly associated with age in cross-sectional analysis of DNAm at year 9, 31,252 markers were changed significantly over the 9-year follow-up, and 16,987 markers were both cross-sectionally associated with age and significantly changed over time. Rates of change at 76 markers and year 9 level of DNAm at 88 markers were identified as strongly associated with mortality in Cox proportional hazard models adjusted for age and relevant covariates (mean follow-up time 4.4 years). Less than 0.05% of markers associated with age or that changed over time were also associated with mortality after adjusting for chronological age. Although the influence of DNAm on health and longevity remains unclear, these findings confirm that aging is associated cross-sectionally and longitudinally with robust and consistent patterns of methylation change.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2015; DOI:10.1093/gerona/glv118 · 5.42 Impact Factor
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    ABSTRACT: Sarcopenia is associated with increased risk of adverse outcomes in older people. Aim of the study was to explore the predictive value of the European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic algorithm in terms of disability, hospitalization, and mortality and analyze the specific role of grip strength and walking speed as diagnostic criteria for sarcopenia. Longitudinal analysis of 538 participants enrolled in the InCHIANTI study. Sarcopenia was defined as having low muscle mass plus low grip strength or low gait speed (EWGSOP criteria). Muscle mass was assessed using bioimpedance analysis. Cox proportional and logistic regression models were used to assess risk of death, hospitalization, and disability for sarcopenic people and to investigate the individual contributions of grip strength and walking speed to the predictive value of the EWGSOP's algorithm. Prevalence of EWGSOP-defined sarcopenia at baseline was 10.2%. After adjusting for potential confounders, sarcopenia was associated with disability (odds ratio 3.15; 95% confidence interval [CI] 1.41-7.05), hospitalization (hazard ratio [HR] 1.57; 95% CI 1.03-2.41), and mortality (HR 1.88; 95% CI 0.91-3.91). The association between an alternative sarcopenic phenotype, defined only by the presence of low muscle mass and low grip strength, and both disability and mortality were similar to the association with the phenotypes defined by low muscle mass and low walking speed or by the EWGSOP algorithm. The EWGSOP's phenotype is a good predictor of incident disability, hospitalization and death. Assessment of only muscle weakness, in addition to low muscle mass, provided similar predictive value as compared to the original algorithm. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail:
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2015; DOI:10.1093/gerona/glv129 · 5.42 Impact Factor
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    ABSTRACT: Introduction: Macrostructural white matter damage (WMD) is associated with less uniform and slower walking in older adults. The effect of age and subclinical microstructural WM degeneration (a potentially earlier phase of WM ischemic damage) on walking patterns and speed is less clear. This study examines the effect of age on the associations of regional microstructural WM integrity with walking variability and speed, independent of macrostructural WMD. Methods: This study involved 493 participants (n=51 young; n=209 young-old; n=233 old-old) from the Baltimore Longitudinal Study of Aging. All completed a 400-meter walk test and underwent a concurrent brain MRI with diffusion tensor imaging. Microstructural WM integrity was measured as fractional anisotropy (FA). Walking variability was measured as trend-adjusted variation in time over ten 40-meter laps (lap time variation, LTV). Fast-paced walking speed was assessed as mean lap time (MLT). Multiple linear regression models of FA predicting LTV and MLT were adjusted for age, sex, height, weight, and WM hyperintensities. Results Independent of WM hyperintensities, lower FA in the body of the corpus callosum was associated with higher LTV and longer MLT only in the young-old. Lower FA in superior longitudinal, inferior fronto-occipital, and uncinate fasciculi, the anterior limb of the internal capsule, and the anterior corona radiate was associated with longer MLT only in the young-old. Conclusion: While macrostructural WMD is known to predict more variable and slower walking in older adults, microstructural WM disruption is independently associated with variable and poorer fast-paced walking only in the young-old. Disrupted regional WM integrity may be a subclinical contributor to variable and abnormal walking at an earlier phase of aging.
    Brain Imaging and Behavior 09/2015; DOI:10.1007/s11682-015-9449-6 · 4.60 Impact Factor
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    ABSTRACT: The extent and clinical significance of stem and progenitor cell (SPC) increases in response to lower-extremity ischemia in people with peripheral artery disease (PAD) are unclear. We compared changes in SPC levels immediately following a treadmill exercise test between individuals with and without PAD. Among participants with PAD, we determined whether more severe PAD was associated with greater increases in SPCs following treadmill exercise-induced lower-extremity ischemia. We measured SPC levels in 25 participants with PAD and 20 without PAD before and immediately after a treadmill exercise test. Participants with PAD, compared to participants without PAD, had greater increases in CD34(+)CD45(dim) (+0.08±0.03 vs -0.06±0.04, p=0.008), CD34(+)CD45(dim)CD133(+) (+0.08±0.05 vs -0.08±0.04, p=0.014), CD34(+)CD45(dim)CD31(+) (+0.10±0.03 vs -0.07±0.04, p=0.002), and CD34(+)CD45(dim)ALDH(+) SPCs (+0.18±0.07 vs -0.05±0.08, p=0.054) measured as a percentage of all white blood cells. Among participants with PAD, those with any increases in the percent of SPCs immediately after the treadmill exercise test compared to those with no change or a decrease in SPCs had lower baseline ankle-brachial index values (0.65±0.17 vs 0.90±0.19, p=0.004) and shorter treadmill times to onset of ischemic leg symptoms (2.17±1.54 vs 5.25±3.72 minutes, p=0.012). In conclusion, treadmill exercise-induced lower-extremity ischemia is associated with acute increases in circulating SPCs among people with PAD. More severe PAD is associated with a higher prevalence of SPC increases in response to lower-extremity ischemia. Further prospective study is needed to establish the prognostic significance of ischemia-related increases in SPCs among patients with PAD. © The Author(s) 2015.
    Vascular Medicine 08/2015; DOI:10.1177/1358863X15600255 · 1.79 Impact Factor
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    ABSTRACT: To determine whether weight loss in older adults may be a marker of impending burden of multimorbidity regardless of initial weight, testing the hypotheses that obesity but not overweight in elderly adults is associated with greater number of diseases than normal weight and that obese older adults who lose weight over time have the greatest burden of multimorbidity. Longitudinal cohort study (Invecchiare in Chianti Study). Community. Individuals aged 60 and older at baseline followed for an average of 4 years (N = 1,025). Multimorbidity was measured as number of diagnosed diseases. Baseline body mass index (BMI) was categorized as normal weight (<25.0 kg/m(2) ), overweight (25.0-29.9 kg/m(2) ), and obese (≥30.0 kg/m(2) ). Loss of weight was defined as decrease over time in BMI of at least 0.15 kg/m(2) per year. Age, sex, and education were covariates. Baseline obesity was cross-sectionally associated with high multimorbidity and greater longitudinal increase of multimorbidity than normal weight (P = .005) and overweight (P < .001). Moreover, obese participants who lost weight over follow-up had a significantly greater increase in multimorbidity than other participants, including obese participants who maintained or gained weight over time (P = .005). In nonobese participants, changes in weight had no effect on changes in multimorbidity over time. Sensitivity analyses confirmed that one specific disease did not drive the association and that competing mortality did not bias the association. Loss of weight in obese older persons is a strong biomarker of impending expansion of multimorbidity. Older obese individuals who lose weight should receive thoughtful medical attention. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.
    Journal of the American Geriatrics Society 08/2015; DOI:10.1111/jgs.13608 · 4.57 Impact Factor
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    ABSTRACT: To investigate the relationship between vestibular loss associated with aging and age-related decline in visuospatial function. Cross-sectional analysis within a prospective cohort study. Baltimore Longitudinal Study of Aging (BLSA). Community-dwelling BLSA participants with a mean age of 72 (range 26-91) (N = 183). Vestibular function was measured using vestibular-evoked myogenic potentials. Visuospatial cognitive tests included Card Rotations, Purdue Pegboard, Benton Visual Retention Test, and Trail-Making Test Parts A and B. Tests of executive function, memory, and attention were also considered. Participants underwent vestibular and cognitive function testing. In multiple linear regression analyses, poorer vestibular function was associated with poorer performance on Card Rotations (P = .001), Purdue Pegboard (P = .005), Benton Visual Retention Test (P = 0.008), and Trail-Making Test Part B (P = .04). Performance on tests of executive function and verbal memory were not significantly associated with vestibular function. Exploratory factor analyses in a subgroup of participants who underwent all cognitive tests identified three latent cognitive abilities: visuospatial ability, verbal memory, and working memory and attention. Vestibular loss was significantly associated with lower visuospatial and working memory and attention factor scores. Significant consistent associations between vestibular function and tests of visuospatial ability were observed in a sample of community-dwelling adults. Impairment in visuospatial skills is often one of the first signs of dementia and Alzheimer's disease. Further longitudinal studies are needed to evaluate whether the relationship between vestibular function and visuospatial ability is causal. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.
    Journal of the American Geriatrics Society 08/2015; DOI:10.1111/jgs.13609 · 4.57 Impact Factor
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    ABSTRACT: Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function. We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking ¼ - ½ mile or climbing 10 steps within 3 years. Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to ≥1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10% to 1% in men, and from 15% to 1% in women, while mobility difficulty trended from 47% to 4% in men and 40% to 6% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81) and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82), women: 0.73 (0.67-0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve. In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail:
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2015; DOI:10.1093/gerona/glv126 · 5.42 Impact Factor
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    ABSTRACT: The hormone klotho, encoded by the gene klotho, is primarily expressed in the kidney and choroid plexus of the brain. Higher klotho concentrations and certain genetic variants of klotho have been linked to better cognition; however, it is unknown whether klotho relates prospectively to slower cognitive decline in older adults. Plasma klotho was measured in 833 participants aged 55 or older without dementia enrolled in InCHIANTI, a prospective cohort study comprising Italian adults. Cognition was measured by Mini-Mental State Examination (MMSE) and Trail-Making Tests A and B (Trails A and Trails B) at enrollment and at 3 and 6 years after enrollment. We assessed whether klotho concentrations measured at the 3-year visit related to cognition and cognitive decline. Each additional natural logarithm of klotho (pg/mL) was associated with 35% lower risk of meaningful decline in MMSE, defined as decline exceeding three points (relative risk = 0.65; 95% confidence interval 0.45, 0.95; p value = .02), and 0.75-point smaller average 3-year decline (baseline to 3-year visit) in MMSE (95% confidence interval 0.02, 1.48; p value = .04). No statistically significant associations were found between klotho and declining Trails A (relative risk = 0.99; 95% confidence interval 0.75, 1.32; p value = .97) and B (relative risk = 1.02; 95% confidence interval 0.84, 1.24; p value = .82). Higher plasma klotho concentrations were associated with lower risk of meaningful decline and smaller average decline in MMSE. We did not observe such findings with Trails A and B, perhaps because they test executive function and motor skills, whereas MMSE measures global cognition. Future studies should investigate mechanisms through which klotho may affect domain-specific cognitive changes. Published by Oxford University Press on behalf of the Gerontological Society of America 2015.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2015; DOI:10.1093/gerona/glv140 · 5.42 Impact Factor
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    ABSTRACT: We examined whether physical activity in early adulthood, late midlife, and old age as well as cumulative physical activity history are associated with changes in physical functioning and mortality in old age. Data are from participants aged 65 years or older enrolled in the InCHIANTI study who were followed up from 1998-2000 to 2007-2008 (n = 1,149). At baseline, participants recalled their physical activity levels at ages 20-40, 40-60, and in the previous year, and they were categorized as physically inactive, moderately active, and physically active. Physical performance was assessed with the Short Physical Performance Battery and self-reported mobility disability was evaluated at the 3-, 6- and 9-year follow-up. Mortality follow-up was assessed until the end of 2010. Physical inactivity at baseline was associated with greater decline in Short Physical Performance Battery score (mean 9-year change: -2.72, 95% CI: -3.08, -2.35 vs -0.98, 95% -1.57, -0.39) and greater rate of incident mobility disability (hazard ratio 4.66, 95% CI 1.14-19.07) and mortality (hazard ratio 2.18, 95% CI 1.01-4.70) compared to physically active participants at baseline. Being physically active throughout adulthood was associated with smaller decline in physical performance as well as with lower risk of incident mobility disability and premature death compared with those who had been less active during their adult life. Higher cumulative physical activity over the life course was associated with less decline in physical performance and reduced rate of incident mobility disability and mortality in older ages. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail:
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2015; DOI:10.1093/gerona/glv111 · 5.42 Impact Factor
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    ABSTRACT: Background: The frailty phenotype (FP) proposed by Fried and colleagues (Fried LP, Tangen CM, Walston J, et al.; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146-M156.) requires the administration of performance tests (gait speed, handgrip strength) not always feasible in routine clinical practice. Furthermore, the discriminative capacity of the instrument has been rarely investigated. Aim of this study was to evaluate the discriminative capacity of the FP and compare it with a modified version including only anamnestic information. Methods: Data are from 890 participants of the InCHIANTI study without impairment in activities of daily living (ADL) at baseline (mean age 74 years, women 55%). Frailty was defined by (a) the presence of ≥3 criteria of the FP, and (b) having ≥2 criteria of an anamnestic FP (AFP), not including gait speed and handgrip strength. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were used to evaluate the discriminative capacity of both definitions for incident disability (ie, loss of at least one ADL), incidence of "accelerated" disability (loss of >2 ADL) over a 6-year follow-up, and 5-years mortality. Results: FP and AFP yielded a frailty prevalence of 6.4% and 6.5%, respectively; only 32 patients were considered frail by both indices (kappa: .53). For incident disability, FP showed sensitivity = .194, specificity = .963, PPV = .400, and NPV = .903. Similarly, AFP had sensitivity = .129, specificity = .949, PPV = .245, and NPV = .894. Consistent results were found for accelerated disability and mortality. Conclusions: In our sample, both FP and AFP showed low sensitivity in identifying older people who would die or develop disability, but they could well discriminate people who would not experience adverse outcomes.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2015; DOI:10.1093/gerona/glv096 · 5.42 Impact Factor
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    ABSTRACT: Background: In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. Methods: We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998-2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. Results: After adjustment for age, α-carotene (β ± SE = -0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = -0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = -1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = -0.29 ± 0.08, p = 0.0009), and E2 persisted whereas the relationship between α-carotene and T/E2 ratio was attenuated (β ± SE = 0.22 ± 0.12, p = 0.07). In a fully adjusted model (Model 3), only β-carotene (β ± SE = -0.05 ± 0.02, p = 0.03) was significantly and inversely associated with E2 levels independent of α-carotene. No association was found between retinol, total non-pro-vitamin A carotenoids, lutein, zeaxanthin, and lycopene, and E2 levels. Conclusions: In older women, β-carotene levels are independently and inversely associated with E2.
    Nutrients 08/2015; 7(8):6506-19. DOI:10.3390/nu7085296 · 3.27 Impact Factor
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    ABSTRACT: We determined whether poorer 6-minute walk performance and lower physical activity levels are associated with higher rates of ischemic heart disease (IHD) events in people with lower extremity peripheral artery disease (PAD). Five hundred ten PAD participants were identified from Chicago-area medical centers and followed prospectively for 19.0±9.5 months. At baseline, participants completed the 6-minute walk and reported number of blocks walked during the past week (physical activity). IHD events were systematically adjudicated and consisted of new myocardial infarction, unstable angina, and cardiac death. For 6-minute walk, IHD event rates were 25/170 (14.7%) for the third (poorest) tertile, 10/171 (5.8%%) for the second tertile, and 6/169 (3.5%) for the first (best) tertile (P=0.003). For physical activity, IHD event rates were 21/154 (13.6%) for the third (poorest) tertile, 15/174 (8.6%) for the second tertile, and 5/182 (2.7%) for the first (best) tertile (P=0.001). Adjusting for age, sex, race, smoking, body mass index, comorbidities, and physical activity, participants in the poorest 6-minute walk tertile had a 3.28-fold (95% CI 1.17 to 9.17, P=0.024) higher hazard for IHD events, compared with those in the best tertile. Adjusting for confounders including 6-minute walk, participants in the poorest physical activity tertile had a 3.72-fold (95% CI 1.24 to 11.19, P=0.019) higher hazard for IHD events, compared with the highest tertile. Six-minute walk and physical activity predict IHD event rates in PAD. Further study is needed to determine whether interventions that improve 6-minute walk, physical activity, or both can reduce IHD events in PAD. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 07/2015; 4(7). DOI:10.1161/JAHA.115.001846 · 4.31 Impact Factor
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    ABSTRACT: Recent studies point out the role of the age-related decline of anabolic hormones, especially testosterone, in the onset of "anemia of aging". Some of testosterone erythropoietic activities are mediated by Insulin-Like Growth Factor (IGF)-1, which also seems to have independent erythropoietic effects. However, the association between IGF-1, anemia and hemoglobin (Hb) has been poorly investigated in older population. We used data from a representative sample of 953 subjects ≥65 yrs of the InCHIANTI Study, not on GH or erythropoietin therapy and without hematological malignancy and cancer. Anemia was defined according to the WHO criteria by Hb level ≤13 g/dL in men and ≤12 g/dL in women. Backward multiple regression analyses including age, IGF Binding Protein (IGFBP)-3, testosterone, comorbidities, inflammatory markers, anemia-related measures were used to address the relationship between IGF-1 and Hb and between IGF-1 and anemia in the two sexes. 46/410 men (11.2%) and 71/543 women (13.0%) were defined as anemic. After adjustment for age, anemic men (100±54 vs 130±56, p<0.001) and women (89.1±48 vs 110±52, p=0.001) exhibited lower IGF-1 levels than non-anemic counterpart. IGF-1 levels were independently and negatively associated with anemia in men (β±SE=-0.0005±0.0002, p=0.04) but not in women (β±SE=-0.0002±0.0002, p=0.40). In both men (β±SE=0.002±0.001, p=0.03) and women (β±SE=0.002± 0.0009, p=0.03) IGF-1 levels were independently and positively associated with Hb levels. In older men, but not in women, IGF-1 levels are negatively associated with anemia. IGF-1 levels are independent and positive determinants of Hb concentration in both sexes.
    Endocrine Practice 07/2015; DOI:10.4158/EP14100.OR · 2.81 Impact Factor

Publication Stats

39k Citations
5,981.75 Total Impact Points


  • 1994–2015
    • National Institute on Aging
      • • Clinical Research Branch (CRB)
      • • Laboratory of Personality and Cognition (LPC)
      • • Laboratory of Epidemiology, Demography and Biometry (LEDB)
      Baltimore, Maryland, United States
  • 2014
    • Universiteit Twente
      • Group of Behavioural Sciences
      Enschede, Overijssel, Netherlands
    • California Pacific Medical Center Research Institute
      • Research Institute
      San Francisco, California, United States
  • 2003–2014
    • National Institutes of Health
      • • Clinical Research Branch (CRB)
      • • Laboratory of Epidemiology, Demography, and Biometry (LEDB)
      베서스다, Maryland, United States
    • Catholic University of the Sacred Heart
      • School of Geriatrics
      Milano, Lombardy, Italy
  • 2013
    • Karolinska Institutet
      Сольна, Stockholm, Sweden
    • Florida State University
      • Department of Geriatrics
      Tallahassee, Florida, United States
  • 2010–2013
    • Queen's University
      • School of Rehabilitation Therapy
      Kingston, Ontario, Canada
    • University Hospital of Parma
      Parma, Emilia-Romagna, Italy
    • University of Lausanne
      • Faculté de biologie et de médecine (FBM)
      Lausanne, VD, Switzerland
    • Università degli studi di Parma
      • Department of Clinical and Experimental Medicine
      Parma, Emilia-Romagna, Italy
  • 2012
    • William Penn University
      Filadelfia, Pennsylvania, United States
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
  • 2007–2012
    • Johns Hopkins Medicine
      • • Department of Otolaryngology - Head and Neck Surgery
      • • Department of Urology
      • • Department of Medicine
      Baltimore, Maryland, United States
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
    • VU University Medical Center
      • Department of Psychiatry
      Amsterdamo, North Holland, Netherlands
    • Università degli Studi di Perugia
      • Department of Clinical and Experimental Medicine
      Perugia, Umbria, Italy
    • Second University of Naples
      • Faculty of Medicine and Surgery
      Caserta, Campania, Italy
    • Unità Locale Socio Sanitaria Padova ULSS 16
      Padua, Veneto, Italy
  • 2011
    • Boston University
      • Department of Biostatistics
      Boston, Massachusetts, United States
    • University of Exeter
      • Peninsula College of Medicine and Dentistry
      Exeter, England, United Kingdom
  • 2005–2011
    • University of Naples Federico II
      • Department of Molecular Medicine and Medical Biotechnology
      Napoli, Campania, Italy
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
  • 2009
    • Case Western Reserve University
      • School of Medicine
      Cleveland, Ohio, United States
    • National Eye Institute
      Maryland, United States
  • 2004–2009
    • Johns Hopkins University
      • • Department of Medicine
      • • Division of Geriatric Medicine and Gerontology
      Baltimore, Maryland, United States
  • 2008
    • Grays Harbor Community Hospital
      Aberdeen, Washington, United States
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      Chieta, Abruzzo, Italy
    • Saint Louis University
      Saint Louis, Michigan, United States
  • 2007–2008
    • University of Washington Seattle
      • Department of Rehabilitation Medicine
      Seattle, Washington, United States
  • 1996–2008
    • INRCA Istituto Nazionale di Ricovero e Cura per Anziani
      • Gerontological Research Department
      Ancona, The Marches, Italy
  • 2006
    • University of Pennsylvania
      • Center for Clinical Epidemiology and Biostatistics
      Philadelphia, Pennsylvania, United States
  • 2002–2003
    • Italian National Research Council
      Oristany, Sardinia, Italy
  • 1997
    • INRIM Istituto Nazionale di Ricerca Metrologica
      Torino, Piedmont, Italy
  • 1986–1995
    • University of Florence
      • Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
      Florens, Tuscany, Italy